WASHINGTON — A diagnostic test to predict preeclampsia does not effectively rule in or out this pregnancy complication in women with systemic lupus erythematosus (SLE) and proteinuria, according to new research presented at the annual meeting of the American College of Rheumatology (ACR).

“If you have a patient who has proteinuria during pregnancy, I’m not sure we know what to do with this test,” said Megan Clowse, MD, MPH, associate professor of medicine and chief of the Division of Rheumatology and Immunology at Duke University School of Medicine in Durham, North Carolina. She led the research and presented the work.

The results “are probably a step in the right direction to understanding that we need more biochemical markers for differentiating preeclampsia [in this patient population],” Leanna Wise, MD, of the Keck School of Medicine at the University of Southern California, Los Angeles, said in an interview. She comoderated the session where the research was presented. “It exposed that we have a lot of gray areas in which we need to do more research.”

The test is a ratio of two biomarkers that measure spiral artery and placental health: Soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF). In the general population, a sFlt-1/PlGF ratio ≤ 38 effectively rules out the short-term risk for preeclampsia, whereas a ratio ≥ 85 is moderately predictive of preeclampsia. However, it was not known how this test would fare in pregnant women with SLE who are already at a higher risk for the complication.

To answer this question, Clowse and colleagues pulled patient data from an ongoing prospective registry of lupus pregnancies. The analysis included patients with a confirmed SLE diagnosis who had enrolled in the registry prior to 30 weeks’ gestation. All participants had provided a serum sample prior to 16 weeks’ gestation and had singleton pregnancies.

In an extensive chart review, preeclampsia was determined by a roundtable of six experts: Two rheumatologists, two maternal-fetal medicine doctors, and two nephrologists.

The analysis included 79 pregnancies, of which 30% developed preeclampsia. Nearly half (47%) of the participants identified as Black or African American. About 30% had a history of lupus nephritis, and half of these patients had active disease during their pregnancy. About half of the women reported that this was their first pregnancy, and an additional 17% of women reported a prior episode of preeclampsia. Most patients were on aspirin (92%) and hydroxychloroquine (87%), and another 43% were prescribed prednisone and 37% were taking azathioprine.

Researchers assessed whether a low sFlt-1/PlGF ratio (≤ 38) was associated with the absence of preeclampsia at 4- and 8-weeks post–blood draw, as well as during the entire pregnancy. They also tested if a high ratio (≥ 85) was associated with the development of preeclampsia within 4- and 8-weeks post–blood draw and through the entire pregnancy.

Across all pregnancies in the cohort, those with sFlt-1/PlGF ≤ 38 were unlikely to develop preeclampsia at 4 weeks post draw (negative predictive value [NPV], 98%) and 8 weeks post draw (NPV, 96%). Still, 20% of patients with this low ratio went on to develop preeclampsia at some point during their pregnancy.

Similar to the general population, sFlt-1/PlGF ≥ 85 was only moderately predictive of preeclampsia. Over half of all patients with this high ratio developed preeclampsia, but more than 40% did not.

Researchers also stratified patients by urine protein:creatinine ratio (UPCR) at the time of their rheumatology visit, defining proteinuria as a UPCR ≥ 300 mg/g.

In patients without proteinuria (n = 63), a low sFlt-1/PlGF ratio ruled out preeclampsia over the next 8 weeks, but a high sFlt-1/PlGF ratio was not usefully predictive of preeclampsia.

 

Low Ratio to Rule Out Preeclampsia ‘Reassuring’

The high reliability in ruling out preeclampsia in this subset of patients with a low sFlt-1/PlGF ratio is “reassuring,” Wise said, and suggests that these patients are “relatively safe moving forward,” given regular follow-up.

In the small group of patients with proteinuria (n = 16), 44% ultimately developed preeclampsia. One third of patients with sFlt-1/PlGF ≤ 38 developed preeclampsia in 8 weeks, and half experienced preeclampsia at some point during their pregnancy. Among the patients with sFlt-1:PlGF ≥ 85, 56% developed preeclampsia during their pregnancy.

“The negative predictive values are not really great, and the positive predictive values are not really very useful,” Clowse said. For a pregnant patient with proteinuria, “I don’t think that a high [ratio] is going to tell us that she definitely has preeclampsia today or tomorrow. I also am not convinced yet that a low [ratio] tells us that she’s out of the woods. So, I think we definitely need more research on what to do with this test in patients with proteinuria.”

Clowse is a consultant and has received research support/grants from GSK and UCB. She also reported consulting for AstraZeneca. Wise is a consultant for Aurinia Pharmaceuticals and has received honoraria from AstraZeneca, Aurinia Pharmaceuticals, and GSK.

A version of this article first appeared on Medscape.com.

WASHINGTON — A diagnostic test to predict preeclampsia does not effectively rule in or out this pregnancy complication in women with systemic lupus erythematosus (SLE) and proteinuria, according to new research presented at the annual meeting of the American College of Rheumatology (ACR).

“If you have a patient who has proteinuria during pregnancy, I’m not sure we know what to do with this test,” said Megan Clowse, MD, MPH, associate professor of medicine and chief of the Division of Rheumatology and Immunology at Duke University School of Medicine in Durham, North Carolina. She led the research and presented the work.

The results “are probably a step in the right direction to understanding that we need more biochemical markers for differentiating preeclampsia [in this patient population],” Leanna Wise, MD, of the Keck School of Medicine at the University of Southern California, Los Angeles, said in an interview. She comoderated the session where the research was presented. “It exposed that we have a lot of gray areas in which we need to do more research.”

The test is a ratio of two biomarkers that measure spiral artery and placental health: Soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF). In the general population, a sFlt-1/PlGF ratio ≤ 38 effectively rules out the short-term risk for preeclampsia, whereas a ratio ≥ 85 is moderately predictive of preeclampsia. However, it was not known how this test would fare in pregnant women with SLE who are already at a higher risk for the complication.

To answer this question, Clowse and colleagues pulled patient data from an ongoing prospective registry of lupus pregnancies. The analysis included patients with a confirmed SLE diagnosis who had enrolled in the registry prior to 30 weeks’ gestation. All participants had provided a serum sample prior to 16 weeks’ gestation and had singleton pregnancies.

In an extensive chart review, preeclampsia was determined by a roundtable of six experts: Two rheumatologists, two maternal-fetal medicine doctors, and two nephrologists.

The analysis included 79 pregnancies, of which 30% developed preeclampsia. Nearly half (47%) of the participants identified as Black or African American. About 30% had a history of lupus nephritis, and half of these patients had active disease during their pregnancy. About half of the women reported that this was their first pregnancy, and an additional 17% of women reported a prior episode of preeclampsia. Most patients were on aspirin (92%) and hydroxychloroquine (87%), and another 43% were prescribed prednisone and 37% were taking azathioprine.

Researchers assessed whether a low sFlt-1/PlGF ratio (≤ 38) was associated with the absence of preeclampsia at 4- and 8-weeks post–blood draw, as well as during the entire pregnancy. They also tested if a high ratio (≥ 85) was associated with the development of preeclampsia within 4- and 8-weeks post–blood draw and through the entire pregnancy.

Across all pregnancies in the cohort, those with sFlt-1/PlGF ≤ 38 were unlikely to develop preeclampsia at 4 weeks post draw (negative predictive value [NPV], 98%) and 8 weeks post draw (NPV, 96%). Still, 20% of patients with this low ratio went on to develop preeclampsia at some point during their pregnancy.

Similar to the general population, sFlt-1/PlGF ≥ 85 was only moderately predictive of preeclampsia. Over half of all patients with this high ratio developed preeclampsia, but more than 40% did not.

Researchers also stratified patients by urine protein:creatinine ratio (UPCR) at the time of their rheumatology visit, defining proteinuria as a UPCR ≥ 300 mg/g.

In patients without proteinuria (n = 63), a low sFlt-1/PlGF ratio ruled out preeclampsia over the next 8 weeks, but a high sFlt-1/PlGF ratio was not usefully predictive of preeclampsia.

 

Low Ratio to Rule Out Preeclampsia ‘Reassuring’

The high reliability in ruling out preeclampsia in this subset of patients with a low sFlt-1/PlGF ratio is “reassuring,” Wise said, and suggests that these patients are “relatively safe moving forward,” given regular follow-up.

In the small group of patients with proteinuria (n = 16), 44% ultimately developed preeclampsia. One third of patients with sFlt-1/PlGF ≤ 38 developed preeclampsia in 8 weeks, and half experienced preeclampsia at some point during their pregnancy. Among the patients with sFlt-1:PlGF ≥ 85, 56% developed preeclampsia during their pregnancy.

“The negative predictive values are not really great, and the positive predictive values are not really very useful,” Clowse said. For a pregnant patient with proteinuria, “I don’t think that a high [ratio] is going to tell us that she definitely has preeclampsia today or tomorrow. I also am not convinced yet that a low [ratio] tells us that she’s out of the woods. So, I think we definitely need more research on what to do with this test in patients with proteinuria.”

Clowse is a consultant and has received research support/grants from GSK and UCB. She also reported consulting for AstraZeneca. Wise is a consultant for Aurinia Pharmaceuticals and has received honoraria from AstraZeneca, Aurinia Pharmaceuticals, and GSK.

A version of this article first appeared on Medscape.com.

WASHINGTON — A diagnostic test to predict preeclampsia does not effectively rule in or out this pregnancy complication in women with systemic lupus erythematosus (SLE) and proteinuria, according to new research presented at the annual meeting of the American College of Rheumatology (ACR).

“If you have a patient who has proteinuria during pregnancy, I’m not sure we know what to do with this test,” said Megan Clowse, MD, MPH, associate professor of medicine and chief of the Division of Rheumatology and Immunology at Duke University School of Medicine in Durham, North Carolina. She led the research and presented the work.

The results “are probably a step in the right direction to understanding that we need more biochemical markers for differentiating preeclampsia [in this patient population],” Leanna Wise, MD, of the Keck School of Medicine at the University of Southern California, Los Angeles, said in an interview. She comoderated the session where the research was presented. “It exposed that we have a lot of gray areas in which we need to do more research.”

The test is a ratio of two biomarkers that measure spiral artery and placental health: Soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF). In the general population, a sFlt-1/PlGF ratio ≤ 38 effectively rules out the short-term risk for preeclampsia, whereas a ratio ≥ 85 is moderately predictive of preeclampsia. However, it was not known how this test would fare in pregnant women with SLE who are already at a higher risk for the complication.

To answer this question, Clowse and colleagues pulled patient data from an ongoing prospective registry of lupus pregnancies. The analysis included patients with a confirmed SLE diagnosis who had enrolled in the registry prior to 30 weeks’ gestation. All participants had provided a serum sample prior to 16 weeks’ gestation and had singleton pregnancies.

In an extensive chart review, preeclampsia was determined by a roundtable of six experts: Two rheumatologists, two maternal-fetal medicine doctors, and two nephrologists.

The analysis included 79 pregnancies, of which 30% developed preeclampsia. Nearly half (47%) of the participants identified as Black or African American. About 30% had a history of lupus nephritis, and half of these patients had active disease during their pregnancy. About half of the women reported that this was their first pregnancy, and an additional 17% of women reported a prior episode of preeclampsia. Most patients were on aspirin (92%) and hydroxychloroquine (87%), and another 43% were prescribed prednisone and 37% were taking azathioprine.

Researchers assessed whether a low sFlt-1/PlGF ratio (≤ 38) was associated with the absence of preeclampsia at 4- and 8-weeks post–blood draw, as well as during the entire pregnancy. They also tested if a high ratio (≥ 85) was associated with the development of preeclampsia within 4- and 8-weeks post–blood draw and through the entire pregnancy.

Across all pregnancies in the cohort, those with sFlt-1/PlGF ≤ 38 were unlikely to develop preeclampsia at 4 weeks post draw (negative predictive value [NPV], 98%) and 8 weeks post draw (NPV, 96%). Still, 20% of patients with this low ratio went on to develop preeclampsia at some point during their pregnancy.

Similar to the general population, sFlt-1/PlGF ≥ 85 was only moderately predictive of preeclampsia. Over half of all patients with this high ratio developed preeclampsia, but more than 40% did not.

Researchers also stratified patients by urine protein:creatinine ratio (UPCR) at the time of their rheumatology visit, defining proteinuria as a UPCR ≥ 300 mg/g.

In patients without proteinuria (n = 63), a low sFlt-1/PlGF ratio ruled out preeclampsia over the next 8 weeks, but a high sFlt-1/PlGF ratio was not usefully predictive of preeclampsia.

 

Low Ratio to Rule Out Preeclampsia ‘Reassuring’

The high reliability in ruling out preeclampsia in this subset of patients with a low sFlt-1/PlGF ratio is “reassuring,” Wise said, and suggests that these patients are “relatively safe moving forward,” given regular follow-up.

In the small group of patients with proteinuria (n = 16), 44% ultimately developed preeclampsia. One third of patients with sFlt-1/PlGF ≤ 38 developed preeclampsia in 8 weeks, and half experienced preeclampsia at some point during their pregnancy. Among the patients with sFlt-1:PlGF ≥ 85, 56% developed preeclampsia during their pregnancy.

“The negative predictive values are not really great, and the positive predictive values are not really very useful,” Clowse said. For a pregnant patient with proteinuria, “I don’t think that a high [ratio] is going to tell us that she definitely has preeclampsia today or tomorrow. I also am not convinced yet that a low [ratio] tells us that she’s out of the woods. So, I think we definitely need more research on what to do with this test in patients with proteinuria.”

Clowse is a consultant and has received research support/grants from GSK and UCB. She also reported consulting for AstraZeneca. Wise is a consultant for Aurinia Pharmaceuticals and has received honoraria from AstraZeneca, Aurinia Pharmaceuticals, and GSK.

A version of this article first appeared on Medscape.com.

WASHINGTON — Women with rheumatoid arthritis (RA) experience improved fertility when treated using a treat-to-target (T2T) approach aimed at remission, according to a new research presented at the annual meeting of the American College of Rheumatology.

In the study, more than half the women following this T2T approach were able to conceive within 3 months, which is “nearly equal to the general population,” said presenter and senior author Radboud Dolhain, MD, PhD, who heads the Department of Rheumatology at Erasmus University Medical Center in Rotterdam, the Netherlands.

Compared with 10%-15% of the general population, as many as 42% of patients with RA are not able to get pregnant within 1 year of unprotected intercourse.

“For people who are thinking about pregnancy or want to plan for pregnancy, talking with them about the importance of making sure their RA is well-treated is an essential aspect,” said Mehret Birru Talabi, MD, PhD, director of the Women’s and Reproductive Health Rheumatology Clinic at the University of Pittsburgh Medical Center in Pennsylvania. She was not involved with the research.

“This is a nice, relatively large study that’s demonstrating [that] if you actually treat the patient and treat them effectively, their time to pregnancy is lower,” she said.

 

Study Details

The analysis compared time to pregnancy between two cohorts of women with RA who aimed to become pregnant. Women were, on average, around 32 years old in both groups, and nearly 60% had not been pregnant before.

The first cohort was part of the Pregnancy-Induced Amelioration of RA (PARA) study, conducted by Erasmus University Medical Center from 2002 to 2010, in which patients were treated by their own rheumatologists with standard of care at the time. Of the 245 women included, 36% were on no medication, and one fourth were taking nonsteroidal anti-inflammatory drugs (NSAIDs). One third of patients were prescribed sulfasalazine, 6% were on hydroxychloroquine, and 4% were prescribed a tumor necrosis factor (TNF) inhibitor. Of the PARA patients prescribed prednisone, about half used a dose > 7.5 mg/d.

The second cohort was part of the Preconception Counseling in Active RA (PreCARA) study, conducted at Erasmus University Medical Center from 2012 to 2023. PreCARA patients were treated with the T2T approach aimed at remission/low disease activity and avoiding use of NSAIDs and high-dose prednisone (> 7.5 mg/d). Of the 215 women in the cohort, 69% were on sulfasalazine, 65% were on hydroxychloroquine, 53% were taking a TNF inhibitor, 45% took prednisone, and 13% took NSAIDs. For patients prescribed prednisone, 75% used a daily dose ≤ 7.5 mg/d. Only six patients were not taking any medication.

In the preconception period, the median Disease Activity Score in 28 joints using C-reactive protein was 2.33 in the PreCARA cohort and 3.84 in the PARA cohort.

The median time to pregnancy was 84 days in the PreCARA cohort, compared with 196 days in the PARA cohort. Compared with 42% of women in the PARA cohort, less than a quarter of women in the PreCARA cohort did not conceive within 1 year of trying. There was no difference between the two groups in the use of assisted reproductive techniques.

In an additional analysis, Dolhain and colleagues found that time to pregnancy in the PreCARA cohort was most associated with maternal age and nulliparity.

“You also will find [this association] in every cohort in time to pregnancy, and it underscores the robustness of our data,” Dolhain said. “We didn’t find any association [with time to pregnancy] anymore with disease activity, the use of NSAIDs, and the use of prednisone.”

 

Study ‘Will Make Patients Feel More Confident in Their Decisions’

Discussions about continuing medication before and during pregnancy can be a “tension point” for some patients, Talabi said, and these types of studies provide further evidence to reassure patients that this approach can help them reach their reproductive goals.

The study is “very clinically translatable, where you can show [patients] the benefit of continuing their medications” in the preconception period and during pregnancy, added Catherine Sims, MD, a rheumatologist at Duke Health in Durham, North Carolina, who is focused on reproductive rheumatology and preventive health.

“What we try to drive home is that the health of the mother directly translates to the health of the pregnancy and that includes medications, and that is okay because now we have shown that pregnancies are safe while taking these medications,” she said. “I think [this study] will make patients feel more confident in their decisions, which is a big, important piece of it.”

Sims is a consultant for Amgen and conducted research funded by GlaxoSmithKline. Dolhain and Talabi had no relevant disclosures.

A version of this article first appeared on Medscape.com.

WASHINGTON — Women with rheumatoid arthritis (RA) experience improved fertility when treated using a treat-to-target (T2T) approach aimed at remission, according to a new research presented at the annual meeting of the American College of Rheumatology.

In the study, more than half the women following this T2T approach were able to conceive within 3 months, which is “nearly equal to the general population,” said presenter and senior author Radboud Dolhain, MD, PhD, who heads the Department of Rheumatology at Erasmus University Medical Center in Rotterdam, the Netherlands.

Compared with 10%-15% of the general population, as many as 42% of patients with RA are not able to get pregnant within 1 year of unprotected intercourse.

“For people who are thinking about pregnancy or want to plan for pregnancy, talking with them about the importance of making sure their RA is well-treated is an essential aspect,” said Mehret Birru Talabi, MD, PhD, director of the Women’s and Reproductive Health Rheumatology Clinic at the University of Pittsburgh Medical Center in Pennsylvania. She was not involved with the research.

“This is a nice, relatively large study that’s demonstrating [that] if you actually treat the patient and treat them effectively, their time to pregnancy is lower,” she said.

 

Study Details

The analysis compared time to pregnancy between two cohorts of women with RA who aimed to become pregnant. Women were, on average, around 32 years old in both groups, and nearly 60% had not been pregnant before.

The first cohort was part of the Pregnancy-Induced Amelioration of RA (PARA) study, conducted by Erasmus University Medical Center from 2002 to 2010, in which patients were treated by their own rheumatologists with standard of care at the time. Of the 245 women included, 36% were on no medication, and one fourth were taking nonsteroidal anti-inflammatory drugs (NSAIDs). One third of patients were prescribed sulfasalazine, 6% were on hydroxychloroquine, and 4% were prescribed a tumor necrosis factor (TNF) inhibitor. Of the PARA patients prescribed prednisone, about half used a dose > 7.5 mg/d.

The second cohort was part of the Preconception Counseling in Active RA (PreCARA) study, conducted at Erasmus University Medical Center from 2012 to 2023. PreCARA patients were treated with the T2T approach aimed at remission/low disease activity and avoiding use of NSAIDs and high-dose prednisone (> 7.5 mg/d). Of the 215 women in the cohort, 69% were on sulfasalazine, 65% were on hydroxychloroquine, 53% were taking a TNF inhibitor, 45% took prednisone, and 13% took NSAIDs. For patients prescribed prednisone, 75% used a daily dose ≤ 7.5 mg/d. Only six patients were not taking any medication.

In the preconception period, the median Disease Activity Score in 28 joints using C-reactive protein was 2.33 in the PreCARA cohort and 3.84 in the PARA cohort.

The median time to pregnancy was 84 days in the PreCARA cohort, compared with 196 days in the PARA cohort. Compared with 42% of women in the PARA cohort, less than a quarter of women in the PreCARA cohort did not conceive within 1 year of trying. There was no difference between the two groups in the use of assisted reproductive techniques.

In an additional analysis, Dolhain and colleagues found that time to pregnancy in the PreCARA cohort was most associated with maternal age and nulliparity.

“You also will find [this association] in every cohort in time to pregnancy, and it underscores the robustness of our data,” Dolhain said. “We didn’t find any association [with time to pregnancy] anymore with disease activity, the use of NSAIDs, and the use of prednisone.”

 

Study ‘Will Make Patients Feel More Confident in Their Decisions’

Discussions about continuing medication before and during pregnancy can be a “tension point” for some patients, Talabi said, and these types of studies provide further evidence to reassure patients that this approach can help them reach their reproductive goals.

The study is “very clinically translatable, where you can show [patients] the benefit of continuing their medications” in the preconception period and during pregnancy, added Catherine Sims, MD, a rheumatologist at Duke Health in Durham, North Carolina, who is focused on reproductive rheumatology and preventive health.

“What we try to drive home is that the health of the mother directly translates to the health of the pregnancy and that includes medications, and that is okay because now we have shown that pregnancies are safe while taking these medications,” she said. “I think [this study] will make patients feel more confident in their decisions, which is a big, important piece of it.”

Sims is a consultant for Amgen and conducted research funded by GlaxoSmithKline. Dolhain and Talabi had no relevant disclosures.

A version of this article first appeared on Medscape.com.

WASHINGTON — Women with rheumatoid arthritis (RA) experience improved fertility when treated using a treat-to-target (T2T) approach aimed at remission, according to a new research presented at the annual meeting of the American College of Rheumatology.

In the study, more than half the women following this T2T approach were able to conceive within 3 months, which is “nearly equal to the general population,” said presenter and senior author Radboud Dolhain, MD, PhD, who heads the Department of Rheumatology at Erasmus University Medical Center in Rotterdam, the Netherlands.

Compared with 10%-15% of the general population, as many as 42% of patients with RA are not able to get pregnant within 1 year of unprotected intercourse.

“For people who are thinking about pregnancy or want to plan for pregnancy, talking with them about the importance of making sure their RA is well-treated is an essential aspect,” said Mehret Birru Talabi, MD, PhD, director of the Women’s and Reproductive Health Rheumatology Clinic at the University of Pittsburgh Medical Center in Pennsylvania. She was not involved with the research.

“This is a nice, relatively large study that’s demonstrating [that] if you actually treat the patient and treat them effectively, their time to pregnancy is lower,” she said.

 

Study Details

The analysis compared time to pregnancy between two cohorts of women with RA who aimed to become pregnant. Women were, on average, around 32 years old in both groups, and nearly 60% had not been pregnant before.

The first cohort was part of the Pregnancy-Induced Amelioration of RA (PARA) study, conducted by Erasmus University Medical Center from 2002 to 2010, in which patients were treated by their own rheumatologists with standard of care at the time. Of the 245 women included, 36% were on no medication, and one fourth were taking nonsteroidal anti-inflammatory drugs (NSAIDs). One third of patients were prescribed sulfasalazine, 6% were on hydroxychloroquine, and 4% were prescribed a tumor necrosis factor (TNF) inhibitor. Of the PARA patients prescribed prednisone, about half used a dose > 7.5 mg/d.

The second cohort was part of the Preconception Counseling in Active RA (PreCARA) study, conducted at Erasmus University Medical Center from 2012 to 2023. PreCARA patients were treated with the T2T approach aimed at remission/low disease activity and avoiding use of NSAIDs and high-dose prednisone (> 7.5 mg/d). Of the 215 women in the cohort, 69% were on sulfasalazine, 65% were on hydroxychloroquine, 53% were taking a TNF inhibitor, 45% took prednisone, and 13% took NSAIDs. For patients prescribed prednisone, 75% used a daily dose ≤ 7.5 mg/d. Only six patients were not taking any medication.

In the preconception period, the median Disease Activity Score in 28 joints using C-reactive protein was 2.33 in the PreCARA cohort and 3.84 in the PARA cohort.

The median time to pregnancy was 84 days in the PreCARA cohort, compared with 196 days in the PARA cohort. Compared with 42% of women in the PARA cohort, less than a quarter of women in the PreCARA cohort did not conceive within 1 year of trying. There was no difference between the two groups in the use of assisted reproductive techniques.

In an additional analysis, Dolhain and colleagues found that time to pregnancy in the PreCARA cohort was most associated with maternal age and nulliparity.

“You also will find [this association] in every cohort in time to pregnancy, and it underscores the robustness of our data,” Dolhain said. “We didn’t find any association [with time to pregnancy] anymore with disease activity, the use of NSAIDs, and the use of prednisone.”

 

Study ‘Will Make Patients Feel More Confident in Their Decisions’

Discussions about continuing medication before and during pregnancy can be a “tension point” for some patients, Talabi said, and these types of studies provide further evidence to reassure patients that this approach can help them reach their reproductive goals.

The study is “very clinically translatable, where you can show [patients] the benefit of continuing their medications” in the preconception period and during pregnancy, added Catherine Sims, MD, a rheumatologist at Duke Health in Durham, North Carolina, who is focused on reproductive rheumatology and preventive health.

“What we try to drive home is that the health of the mother directly translates to the health of the pregnancy and that includes medications, and that is okay because now we have shown that pregnancies are safe while taking these medications,” she said. “I think [this study] will make patients feel more confident in their decisions, which is a big, important piece of it.”

Sims is a consultant for Amgen and conducted research funded by GlaxoSmithKline. Dolhain and Talabi had no relevant disclosures.

A version of this article first appeared on Medscape.com.

Sarah Cigna, MD, sees patients every week with vulvovaginal pain and vulvar dermatoses. She’s an ob.gyn. with a focus on sexual health — often the first physician seen by patients with vulvar pain or itch — and she believes collaboration with dermatologists is essential, especially for complex cases in what she calls a neglected, data-poor area of medicine.

She also recommends that dermatologists have a good understanding of the vestibule, “one of the most important structures in vulvar medicine,” and that they become equipped to recognize generalized and localized causes of vulvar pain and/or itch.

“The problem is, we don’t talk about [vulvovaginal pain and itch] ... it’s taboo and we’re not taught about it in medical school,” Cigna, assistant professor of obstetrics and gynecology at The George Washington University (GWU), Washington, DC, said in a grand rounds lecture held recently at the GWU School of Medicine and Health Sciences Department of Dermatology.

“There are dermatologists who don’t have much training in vulvar dermatology, and a lot of gyns don’t get as much training” as they should, she said in an interview after the lecture. “So who’s looking at people’s vulvar skin and figuring out what’s going on and giving them effective treatments and evidence-based education?”

Cigna and dermatologist Emily Murphy, MD, will be co-directors of a joint ob.gyn-dermatology Vulvar Dermatology Clinic at GWU that will be launched in 2025, with monthly clinics for particularly challenging cases where the etiology is unclear or treatment is ineffective. “We want to collaborate in a more systematic way and put our heads together and think creatively about what will improve patient care,” Cigna said in the interview.

Dermatologists have valuable expertise in the immunology and genetic factors involved in skin disorders, Cigna said. Moreover, Murphy, assistant professor of dermatology and director of the Vulvar Health Program at GWU, said in an interview, dermatologists “are comfortable in going to off-label systemic medications that ob.gyns may not use that often” and bring to the table expertise in various types of procedures.

Murphy recently trained with Melissa Mauskar, MD, associate of dermatology and obstetrics and gynecology at the University of Texas Southwestern, Dallas, and founder and director of the Gynecologic Dermatology Clinic there. “It’s so important for dermatologists to be involved. It just takes some extra training that residents aren’t getting right now,” said Murphy, a member of the newly formed Vulvar Dermatoses Research Consortium.

In her grand rounds lecture, Cigna offered pearls to dermatologists for approaching a history and exam and covered highlights of the diagnosis and treatment of various problems, from vulvar Candida infections and lichen simplex chronicus to vulvar lichen sclerosus (LS), vulvar lichen planus (LP), vulvar Crohn’s disease, pudendal neuralgia, and pelvic floor muscle spasm, as well as the role of mast cell proliferation in vulvar issues.

 

Approaching the History and Exam

A comprehensive history covers the start, duration, and location of pain and/or itching as well as a detailed timeline (such as timing of potential causes, including injuries or births) and symptoms (such as burning, cutting, aching, and stinging). The question of whether pain “is on the outside, at the entrance, or deeper inside” is “crucial, especially for those in dermatology,” Cigna emphasized.

“And if you’re seeing a patient for a vulvar condition, please ask them about sex. Ask, is this affecting your sexual or intimate life with your partner because this can also give you a clue about what’s going on and how you can help them,” she told the audience of dermatologists.

Queries about trauma history (physical and emotional/verbal), competitive sports (such as daily cycling, equestrian, and heavy weight lifting), endometriosis/gynecologic surgery, connective tissue disorders (such as Ehler-Danlos syndrome), and irritable bowel syndrome are all potentially important to consider. It is important to ask about anxiety, depression, and obsessive-compulsive disorder, which do not cause — but are highly associated with — vulvar dermatoses, she said.

A surprisingly large number of people with vulvovaginal issues are being diagnosed with Ehler-Danlos syndrome, so “I’m always asking, are you hypermobile because this might be affecting the musculoskeletal system, which might be affecting the pelvis,” Cigna said. “Anything that affects the pelvis can affect the vulva as well.”

The pelvic examination should be “offered” rather than assumed to be part of the exam, as part of a trauma-informed approach that is crucial for earning trust, she advised. “Just saying, ‘we’re going to talk, and then I can offer you an exam if you like’…patients like it. It helps them feel safer and more open.”

Many diagnoses are differentiated by eliciting pain on the anterior vs the posterior half of the vulvar vestibule — the part of the vulva that lies between the labia minora and is composed of nonkeratinized tissue with embryonic origins in the endoderm. “If you touch on the keratinized skin (of the vulva) and they don’t have pain, but on the vestibule they do have pain, and there is no pain inside the vagina, this suggests there is a vestibular problem,” said Cigna.

Pain/tenderness isolated to the posterior half of the vestibule suggests a muscular cause, and pain in both the posterior and anterior parts of the vestibule suggests a cause that is more systemic or diffuse, which could be a result of a hormonal issue such as one related to oral contraceptives or decreased testosterone, or a nerve-related process.

Cigna uses gentle swipes of a Q-tip moistened with water or gel to examine the vulva rather than a poke or touch, with the exception being the posterior vestibule, which overlies muscle insertion sites. “Make sure to get a baseline in remote areas such as the inner thigh, and always distinguish between ‘scratchy/sensitive’ sensations and pain,” she said, noting the value of having the patient hold a mirror on her inner thigh.

 

Causes of Vulvar Itch: Infectious and Noninfectious

With vulvar candidiasis, a common infectious cause of vulvar itch, “you have to ask if they’re also itching on the inside because if you treat them with a topical and you don’t treat the vaginal yeast infection that may be co-occurring, they’ll keep reseeding their vulvar skin,” Cigna said, “and it will never be fully treated.”

Candida albicans is the most common cause of vulvar or vulvovaginal candidiasis, and resistance to antifungals has been rising. Non-albicans Candida “tends to have even higher resistance rates,” she said. Ordering a sensitivity panel along with the culture is helpful, but “comprehensive vaginal biome” panels are generally not useful. “It’s hard to correlate the information clinically,” she said, “and there’s not always a lot of information about susceptibilities, which is what I really like to know.”

Cigna’s treatments for vaginal infections include miconazole, terconazole, and fluconazole (and occasionally, itraconazole or voriconazole — a “decision we don’t take lightly”). Vulvar treatments include nystatin ointment, clotrimazole cream, and miconazole cream. Often, optimal treatment involves addressing “both inside and out,” she said, noting the importance of also killing yeast in undergarment fabric.

“In my experience, Diflucan [oral fluconazole] doesn’t treat persistent vulvar cutaneous skin yeast well, so while I might try Diflucan, I typically use something topical as well,” she said. “And with vaginal yeast, we do use boric acid from time to time, especially for non-albicans species because it tends to be a little more effective.”

Noninfectious causes of vulvar itch include allergic, neuropathic, and muscular causes, as well as autoimmune dermatoses and mast cell activation syndrome. Well known in dermatology are acute contact dermatitis and lichen simplex chronicus — both characterized by induration, thickening, and a “puffy” erythematous appearance, and worsening of pruritus at night. What may be less appreciated is the long list of implicated allergens , including Always menstrual pads made of a plastic-containing “dry weave” material, Cigna said. There are at least several cotton-only, low-preservative feminine products available on the market, she noted.

 

Common Autoimmune Vulvar Dermatoses: LS and LP

Vulvar LS has traditionally been thought to affect mainly prepubertal and postmenopausal women, but the autoimmune condition is now known to affect more reproductive-age people with vulvas than previously appreciated, Cigna said.

And notably, in an observational web-based study of premenopausal women (aged 18-50 years) with biopsy-confirmed vulvar LS, the leading symptom was not itch but dyspareunia and tearing with intercourse. This means “we’re missing people,” said Cigna, an author of the study. “We think the reason we’re not seeing itch as commonly in this population is that itch is likely mediated by the low estrogen state of pre- and postmenopausal people.”

Vulvar LS also occurs in pregnancy, with symptoms that are either stable or decrease during pregnancy and increase in the postpartum period, as demonstrated in a recently published online survey.

Patients with vulvar LS can present with hypopigmentation, lichenification, and scarring and architectural changes, the latter of which can involve clitoral phimosis, labial resorption, and narrowing of the introitus. (The vaginal mucosa is unaffected.) The presentation can be subtle, especially in premenopausal women, and differentiation between LS, vitiligo, and yeast is sometimes necessary.

A timely biopsy-driven definitive diagnosis is important because vulvar LS increases the risk for cancer if it’s not adequately treated and because long-term steroid use can affect the accuracy of pathology reports. “We really care about keeping this disease in remission as much as possible,” Cigna said. Experts in the field recommend long-term maintenance therapy with a mid-ultra-potent steroid one to three times/week or an alternative. “I’ve just started using ruxolitinib cream, a Janus kinase (JAK) inhibitor, and tacrolimus, a calcineurin inhibitor,” she said.

With vulvar LP, based on current evidence, the risk for malignant transformation is low, but “it crosses into the vagina and can cause vaginal adhesions, so if you’re diagnosing someone with lichen planus, you need to make sure you’re talking with them about dilators, and if you’re not comfortable, send them to [gyn],” she said.

The use of vulvoscopy is important for one’s ability to see the fine Wickham’s striae that often characterize vulvar LP, she noted. Medical treatments for vulvar LP include topical calcineurin inhibitors, high-potency steroids, and JAK inhibitors.

Surgical treatment of vulvar granuloma fissuratum caused by vulvar LS is possible (when the patient is in complete remission, to prevent koebnerization), with daily post-op application of clobetasol and retraction of tissues, noted Cigna, the author of a study on vulvar lysis of adhesions.

With both LS and LP, Cigna said, “don’t forget (consideration of) hormones” as an adjunctive treatment, especially in postmenopausal women. “Patients in a low hormone state will have more flares.”

 

Vulvar Crohn’s

“We all have to know how to look for this,” Cigna said. “Unilateral or asymmetric swelling is classic, but don’t rule out the diagnosis if you see symmetric swelling.” Patients also typically have linear “knife-like” fissures or ulcerations, the vulva “is very indurated,” and “swelling is so intense, the patients are miserable,” she said.

Vulvar Crohn’s disease may precede intestinal disease in 20%-30% of patients, so referral to a gastroenterologist — and ideally subsequent collaboration — is important, as vulvar manifestations are treated with systemic medications typical for Crohn’s.

A biopsy is required for diagnosis, and the pathologist should be advised to look for lichenified squamous mucosa with the Touton giant cell reaction. “Vulvar Crohn’s is a rare enough disorder that if you don’t have an experienced or informed pathologist looking at your specimen, they may miss it because they won’t be looking for it,” Cigna added in the interview. “You should be really clear about what you’re looking for.”

 

Neuropathic Itch, Pelvic Floor Muscle Spasm

Patients with pudendal neuralgia — caused by an injured, entrapped, or irritated pudendal nerve (originating from S2-S4) — typically present with chronic vulvar and pelvic pain that is often unprovoked and worsens with sitting. Itching upon touch is often another symptom, and some patients describe a foreign body sensation. The cause is often trauma (such as an accident or childbirth-related) as opposed to myofascial irritation, Cigna explained in her lecture.

“Your exam will be largely normal, with no skin findings, so patients will get sent away if you don’t know to look for pudendal neuralgia by pressing on the pudendal nerve or doing (or referring for) a diagnostic nerve block,” Cigna added in the interview.

Persistent genital arousal disorder (PGAD) is “more global” in that it can also originate not only from the pudendal nerve but also from nerve roots higher in the spine or even from the brain. “People feel a sense of arousal, but some describe it as an itch,” Cigna said in her lecture, referring to a 2021 consensus document on PGAD/genito-pelvic dysesthesia by the International Society for the Study of Women’s Sexual Health as a valuable resource for understanding and managing the condition.

Diagnosis and treatment usually start with a pudendal nerve block with a combination of steroid and anesthetic. If this does not relieve arousal/itching, the next step may be an MRI to look higher in the spine.

 

Pelvic Floor Muscle Spasm

Vulvar pain, skin itching, and irritation can be symptoms of pelvic floor muscle spasm. “Oftentimes people come to me and say, ‘I have a dermatologic problem,’” Cigna said. “The skin may look red and erythematous, but it’s probably more likely a muscle problem when you’re not finding anything, and no amount of steroid will help the itch go away when the problem lies underneath.”

Co-occurring symptoms can include vaginal dryness, clitoral pain, urethral discomfort, bladder pain/irritation, increased urgency, constipation, and anal fissures. The first-line treatment approach is pelvic floor therapy.

“Pelvic floor therapy is not just for incontinence. It’s also for pain and discomfort from muscles,” she said, noting that most patients with vulvar disorders are referred for pelvic floor therapy. “Almost all of them end up having pelvic floor dysfunction because the pelvic floor muscles spasm whenever there’s pain or inflammation.”

 

A Cautionary Word on Vulvodynia, and a Mast Cell Paradigm to Explore

Vulvodynia is defined as persistent pain of at least 3 months’ duration with no clear cause. “These are the patients with no skin findings,” Cigna said. But in most cases, she said, careful investigation identifies causes that are musculoskeletal, hormonal, or nerve-related.

“It’s a term that’s thrown around a lot — it’s kind of a catchall. Yet it should be a small minority of patients who truly have a diagnosis of vulvodynia,” she said.

In the early stages of investigation is the idea that mast cell proliferation and mast cell activation may play a role in some cases of vulvar and vestibular pain and itching. “We see that some patients with vulvodynia and vestibulodynia have mast cells that are increased in number in the epithelium and beneath the epithelium, and nerve staining shows an increased number of nerve endings traveling into the epithelium,” Cigna said.

“We do diagnose some people clinically” based on urticaria and other symptoms suggestive of mast cell proliferation/activation (such as flushing, abdominal cramping, diarrhea, hypotensive syncope or near syncope, and tachycardia), and “then we send them to the allergist for testing,” Cigna said.

Cigna and Murphy have no relevant financial disclosures.

 

A version of this article appeared on Medscape.com.

Sarah Cigna, MD, sees patients every week with vulvovaginal pain and vulvar dermatoses. She’s an ob.gyn. with a focus on sexual health — often the first physician seen by patients with vulvar pain or itch — and she believes collaboration with dermatologists is essential, especially for complex cases in what she calls a neglected, data-poor area of medicine.

She also recommends that dermatologists have a good understanding of the vestibule, “one of the most important structures in vulvar medicine,” and that they become equipped to recognize generalized and localized causes of vulvar pain and/or itch.

“The problem is, we don’t talk about [vulvovaginal pain and itch] ... it’s taboo and we’re not taught about it in medical school,” Cigna, assistant professor of obstetrics and gynecology at The George Washington University (GWU), Washington, DC, said in a grand rounds lecture held recently at the GWU School of Medicine and Health Sciences Department of Dermatology.

“There are dermatologists who don’t have much training in vulvar dermatology, and a lot of gyns don’t get as much training” as they should, she said in an interview after the lecture. “So who’s looking at people’s vulvar skin and figuring out what’s going on and giving them effective treatments and evidence-based education?”

Cigna and dermatologist Emily Murphy, MD, will be co-directors of a joint ob.gyn-dermatology Vulvar Dermatology Clinic at GWU that will be launched in 2025, with monthly clinics for particularly challenging cases where the etiology is unclear or treatment is ineffective. “We want to collaborate in a more systematic way and put our heads together and think creatively about what will improve patient care,” Cigna said in the interview.

Dermatologists have valuable expertise in the immunology and genetic factors involved in skin disorders, Cigna said. Moreover, Murphy, assistant professor of dermatology and director of the Vulvar Health Program at GWU, said in an interview, dermatologists “are comfortable in going to off-label systemic medications that ob.gyns may not use that often” and bring to the table expertise in various types of procedures.

Murphy recently trained with Melissa Mauskar, MD, associate of dermatology and obstetrics and gynecology at the University of Texas Southwestern, Dallas, and founder and director of the Gynecologic Dermatology Clinic there. “It’s so important for dermatologists to be involved. It just takes some extra training that residents aren’t getting right now,” said Murphy, a member of the newly formed Vulvar Dermatoses Research Consortium.

In her grand rounds lecture, Cigna offered pearls to dermatologists for approaching a history and exam and covered highlights of the diagnosis and treatment of various problems, from vulvar Candida infections and lichen simplex chronicus to vulvar lichen sclerosus (LS), vulvar lichen planus (LP), vulvar Crohn’s disease, pudendal neuralgia, and pelvic floor muscle spasm, as well as the role of mast cell proliferation in vulvar issues.

 

Approaching the History and Exam

A comprehensive history covers the start, duration, and location of pain and/or itching as well as a detailed timeline (such as timing of potential causes, including injuries or births) and symptoms (such as burning, cutting, aching, and stinging). The question of whether pain “is on the outside, at the entrance, or deeper inside” is “crucial, especially for those in dermatology,” Cigna emphasized.

“And if you’re seeing a patient for a vulvar condition, please ask them about sex. Ask, is this affecting your sexual or intimate life with your partner because this can also give you a clue about what’s going on and how you can help them,” she told the audience of dermatologists.

Queries about trauma history (physical and emotional/verbal), competitive sports (such as daily cycling, equestrian, and heavy weight lifting), endometriosis/gynecologic surgery, connective tissue disorders (such as Ehler-Danlos syndrome), and irritable bowel syndrome are all potentially important to consider. It is important to ask about anxiety, depression, and obsessive-compulsive disorder, which do not cause — but are highly associated with — vulvar dermatoses, she said.

A surprisingly large number of people with vulvovaginal issues are being diagnosed with Ehler-Danlos syndrome, so “I’m always asking, are you hypermobile because this might be affecting the musculoskeletal system, which might be affecting the pelvis,” Cigna said. “Anything that affects the pelvis can affect the vulva as well.”

The pelvic examination should be “offered” rather than assumed to be part of the exam, as part of a trauma-informed approach that is crucial for earning trust, she advised. “Just saying, ‘we’re going to talk, and then I can offer you an exam if you like’…patients like it. It helps them feel safer and more open.”

Many diagnoses are differentiated by eliciting pain on the anterior vs the posterior half of the vulvar vestibule — the part of the vulva that lies between the labia minora and is composed of nonkeratinized tissue with embryonic origins in the endoderm. “If you touch on the keratinized skin (of the vulva) and they don’t have pain, but on the vestibule they do have pain, and there is no pain inside the vagina, this suggests there is a vestibular problem,” said Cigna.

Pain/tenderness isolated to the posterior half of the vestibule suggests a muscular cause, and pain in both the posterior and anterior parts of the vestibule suggests a cause that is more systemic or diffuse, which could be a result of a hormonal issue such as one related to oral contraceptives or decreased testosterone, or a nerve-related process.

Cigna uses gentle swipes of a Q-tip moistened with water or gel to examine the vulva rather than a poke or touch, with the exception being the posterior vestibule, which overlies muscle insertion sites. “Make sure to get a baseline in remote areas such as the inner thigh, and always distinguish between ‘scratchy/sensitive’ sensations and pain,” she said, noting the value of having the patient hold a mirror on her inner thigh.

 

Causes of Vulvar Itch: Infectious and Noninfectious

With vulvar candidiasis, a common infectious cause of vulvar itch, “you have to ask if they’re also itching on the inside because if you treat them with a topical and you don’t treat the vaginal yeast infection that may be co-occurring, they’ll keep reseeding their vulvar skin,” Cigna said, “and it will never be fully treated.”

Candida albicans is the most common cause of vulvar or vulvovaginal candidiasis, and resistance to antifungals has been rising. Non-albicans Candida “tends to have even higher resistance rates,” she said. Ordering a sensitivity panel along with the culture is helpful, but “comprehensive vaginal biome” panels are generally not useful. “It’s hard to correlate the information clinically,” she said, “and there’s not always a lot of information about susceptibilities, which is what I really like to know.”

Cigna’s treatments for vaginal infections include miconazole, terconazole, and fluconazole (and occasionally, itraconazole or voriconazole — a “decision we don’t take lightly”). Vulvar treatments include nystatin ointment, clotrimazole cream, and miconazole cream. Often, optimal treatment involves addressing “both inside and out,” she said, noting the importance of also killing yeast in undergarment fabric.

“In my experience, Diflucan [oral fluconazole] doesn’t treat persistent vulvar cutaneous skin yeast well, so while I might try Diflucan, I typically use something topical as well,” she said. “And with vaginal yeast, we do use boric acid from time to time, especially for non-albicans species because it tends to be a little more effective.”

Noninfectious causes of vulvar itch include allergic, neuropathic, and muscular causes, as well as autoimmune dermatoses and mast cell activation syndrome. Well known in dermatology are acute contact dermatitis and lichen simplex chronicus — both characterized by induration, thickening, and a “puffy” erythematous appearance, and worsening of pruritus at night. What may be less appreciated is the long list of implicated allergens , including Always menstrual pads made of a plastic-containing “dry weave” material, Cigna said. There are at least several cotton-only, low-preservative feminine products available on the market, she noted.

 

Common Autoimmune Vulvar Dermatoses: LS and LP

Vulvar LS has traditionally been thought to affect mainly prepubertal and postmenopausal women, but the autoimmune condition is now known to affect more reproductive-age people with vulvas than previously appreciated, Cigna said.

And notably, in an observational web-based study of premenopausal women (aged 18-50 years) with biopsy-confirmed vulvar LS, the leading symptom was not itch but dyspareunia and tearing with intercourse. This means “we’re missing people,” said Cigna, an author of the study. “We think the reason we’re not seeing itch as commonly in this population is that itch is likely mediated by the low estrogen state of pre- and postmenopausal people.”

Vulvar LS also occurs in pregnancy, with symptoms that are either stable or decrease during pregnancy and increase in the postpartum period, as demonstrated in a recently published online survey.

Patients with vulvar LS can present with hypopigmentation, lichenification, and scarring and architectural changes, the latter of which can involve clitoral phimosis, labial resorption, and narrowing of the introitus. (The vaginal mucosa is unaffected.) The presentation can be subtle, especially in premenopausal women, and differentiation between LS, vitiligo, and yeast is sometimes necessary.

A timely biopsy-driven definitive diagnosis is important because vulvar LS increases the risk for cancer if it’s not adequately treated and because long-term steroid use can affect the accuracy of pathology reports. “We really care about keeping this disease in remission as much as possible,” Cigna said. Experts in the field recommend long-term maintenance therapy with a mid-ultra-potent steroid one to three times/week or an alternative. “I’ve just started using ruxolitinib cream, a Janus kinase (JAK) inhibitor, and tacrolimus, a calcineurin inhibitor,” she said.

With vulvar LP, based on current evidence, the risk for malignant transformation is low, but “it crosses into the vagina and can cause vaginal adhesions, so if you’re diagnosing someone with lichen planus, you need to make sure you’re talking with them about dilators, and if you’re not comfortable, send them to [gyn],” she said.

The use of vulvoscopy is important for one’s ability to see the fine Wickham’s striae that often characterize vulvar LP, she noted. Medical treatments for vulvar LP include topical calcineurin inhibitors, high-potency steroids, and JAK inhibitors.

Surgical treatment of vulvar granuloma fissuratum caused by vulvar LS is possible (when the patient is in complete remission, to prevent koebnerization), with daily post-op application of clobetasol and retraction of tissues, noted Cigna, the author of a study on vulvar lysis of adhesions.

With both LS and LP, Cigna said, “don’t forget (consideration of) hormones” as an adjunctive treatment, especially in postmenopausal women. “Patients in a low hormone state will have more flares.”

 

Vulvar Crohn’s

“We all have to know how to look for this,” Cigna said. “Unilateral or asymmetric swelling is classic, but don’t rule out the diagnosis if you see symmetric swelling.” Patients also typically have linear “knife-like” fissures or ulcerations, the vulva “is very indurated,” and “swelling is so intense, the patients are miserable,” she said.

Vulvar Crohn’s disease may precede intestinal disease in 20%-30% of patients, so referral to a gastroenterologist — and ideally subsequent collaboration — is important, as vulvar manifestations are treated with systemic medications typical for Crohn’s.

A biopsy is required for diagnosis, and the pathologist should be advised to look for lichenified squamous mucosa with the Touton giant cell reaction. “Vulvar Crohn’s is a rare enough disorder that if you don’t have an experienced or informed pathologist looking at your specimen, they may miss it because they won’t be looking for it,” Cigna added in the interview. “You should be really clear about what you’re looking for.”

 

Neuropathic Itch, Pelvic Floor Muscle Spasm

Patients with pudendal neuralgia — caused by an injured, entrapped, or irritated pudendal nerve (originating from S2-S4) — typically present with chronic vulvar and pelvic pain that is often unprovoked and worsens with sitting. Itching upon touch is often another symptom, and some patients describe a foreign body sensation. The cause is often trauma (such as an accident or childbirth-related) as opposed to myofascial irritation, Cigna explained in her lecture.

“Your exam will be largely normal, with no skin findings, so patients will get sent away if you don’t know to look for pudendal neuralgia by pressing on the pudendal nerve or doing (or referring for) a diagnostic nerve block,” Cigna added in the interview.

Persistent genital arousal disorder (PGAD) is “more global” in that it can also originate not only from the pudendal nerve but also from nerve roots higher in the spine or even from the brain. “People feel a sense of arousal, but some describe it as an itch,” Cigna said in her lecture, referring to a 2021 consensus document on PGAD/genito-pelvic dysesthesia by the International Society for the Study of Women’s Sexual Health as a valuable resource for understanding and managing the condition.

Diagnosis and treatment usually start with a pudendal nerve block with a combination of steroid and anesthetic. If this does not relieve arousal/itching, the next step may be an MRI to look higher in the spine.

 

Pelvic Floor Muscle Spasm

Vulvar pain, skin itching, and irritation can be symptoms of pelvic floor muscle spasm. “Oftentimes people come to me and say, ‘I have a dermatologic problem,’” Cigna said. “The skin may look red and erythematous, but it’s probably more likely a muscle problem when you’re not finding anything, and no amount of steroid will help the itch go away when the problem lies underneath.”

Co-occurring symptoms can include vaginal dryness, clitoral pain, urethral discomfort, bladder pain/irritation, increased urgency, constipation, and anal fissures. The first-line treatment approach is pelvic floor therapy.

“Pelvic floor therapy is not just for incontinence. It’s also for pain and discomfort from muscles,” she said, noting that most patients with vulvar disorders are referred for pelvic floor therapy. “Almost all of them end up having pelvic floor dysfunction because the pelvic floor muscles spasm whenever there’s pain or inflammation.”

 

A Cautionary Word on Vulvodynia, and a Mast Cell Paradigm to Explore

Vulvodynia is defined as persistent pain of at least 3 months’ duration with no clear cause. “These are the patients with no skin findings,” Cigna said. But in most cases, she said, careful investigation identifies causes that are musculoskeletal, hormonal, or nerve-related.

“It’s a term that’s thrown around a lot — it’s kind of a catchall. Yet it should be a small minority of patients who truly have a diagnosis of vulvodynia,” she said.

In the early stages of investigation is the idea that mast cell proliferation and mast cell activation may play a role in some cases of vulvar and vestibular pain and itching. “We see that some patients with vulvodynia and vestibulodynia have mast cells that are increased in number in the epithelium and beneath the epithelium, and nerve staining shows an increased number of nerve endings traveling into the epithelium,” Cigna said.

“We do diagnose some people clinically” based on urticaria and other symptoms suggestive of mast cell proliferation/activation (such as flushing, abdominal cramping, diarrhea, hypotensive syncope or near syncope, and tachycardia), and “then we send them to the allergist for testing,” Cigna said.

Cigna and Murphy have no relevant financial disclosures.

 

A version of this article appeared on Medscape.com.

Sarah Cigna, MD, sees patients every week with vulvovaginal pain and vulvar dermatoses. She’s an ob.gyn. with a focus on sexual health — often the first physician seen by patients with vulvar pain or itch — and she believes collaboration with dermatologists is essential, especially for complex cases in what she calls a neglected, data-poor area of medicine.

She also recommends that dermatologists have a good understanding of the vestibule, “one of the most important structures in vulvar medicine,” and that they become equipped to recognize generalized and localized causes of vulvar pain and/or itch.

“The problem is, we don’t talk about [vulvovaginal pain and itch] ... it’s taboo and we’re not taught about it in medical school,” Cigna, assistant professor of obstetrics and gynecology at The George Washington University (GWU), Washington, DC, said in a grand rounds lecture held recently at the GWU School of Medicine and Health Sciences Department of Dermatology.

“There are dermatologists who don’t have much training in vulvar dermatology, and a lot of gyns don’t get as much training” as they should, she said in an interview after the lecture. “So who’s looking at people’s vulvar skin and figuring out what’s going on and giving them effective treatments and evidence-based education?”

Cigna and dermatologist Emily Murphy, MD, will be co-directors of a joint ob.gyn-dermatology Vulvar Dermatology Clinic at GWU that will be launched in 2025, with monthly clinics for particularly challenging cases where the etiology is unclear or treatment is ineffective. “We want to collaborate in a more systematic way and put our heads together and think creatively about what will improve patient care,” Cigna said in the interview.

Dermatologists have valuable expertise in the immunology and genetic factors involved in skin disorders, Cigna said. Moreover, Murphy, assistant professor of dermatology and director of the Vulvar Health Program at GWU, said in an interview, dermatologists “are comfortable in going to off-label systemic medications that ob.gyns may not use that often” and bring to the table expertise in various types of procedures.

Murphy recently trained with Melissa Mauskar, MD, associate of dermatology and obstetrics and gynecology at the University of Texas Southwestern, Dallas, and founder and director of the Gynecologic Dermatology Clinic there. “It’s so important for dermatologists to be involved. It just takes some extra training that residents aren’t getting right now,” said Murphy, a member of the newly formed Vulvar Dermatoses Research Consortium.

In her grand rounds lecture, Cigna offered pearls to dermatologists for approaching a history and exam and covered highlights of the diagnosis and treatment of various problems, from vulvar Candida infections and lichen simplex chronicus to vulvar lichen sclerosus (LS), vulvar lichen planus (LP), vulvar Crohn’s disease, pudendal neuralgia, and pelvic floor muscle spasm, as well as the role of mast cell proliferation in vulvar issues.

 

Approaching the History and Exam

A comprehensive history covers the start, duration, and location of pain and/or itching as well as a detailed timeline (such as timing of potential causes, including injuries or births) and symptoms (such as burning, cutting, aching, and stinging). The question of whether pain “is on the outside, at the entrance, or deeper inside” is “crucial, especially for those in dermatology,” Cigna emphasized.

“And if you’re seeing a patient for a vulvar condition, please ask them about sex. Ask, is this affecting your sexual or intimate life with your partner because this can also give you a clue about what’s going on and how you can help them,” she told the audience of dermatologists.

Queries about trauma history (physical and emotional/verbal), competitive sports (such as daily cycling, equestrian, and heavy weight lifting), endometriosis/gynecologic surgery, connective tissue disorders (such as Ehler-Danlos syndrome), and irritable bowel syndrome are all potentially important to consider. It is important to ask about anxiety, depression, and obsessive-compulsive disorder, which do not cause — but are highly associated with — vulvar dermatoses, she said.

A surprisingly large number of people with vulvovaginal issues are being diagnosed with Ehler-Danlos syndrome, so “I’m always asking, are you hypermobile because this might be affecting the musculoskeletal system, which might be affecting the pelvis,” Cigna said. “Anything that affects the pelvis can affect the vulva as well.”

The pelvic examination should be “offered” rather than assumed to be part of the exam, as part of a trauma-informed approach that is crucial for earning trust, she advised. “Just saying, ‘we’re going to talk, and then I can offer you an exam if you like’…patients like it. It helps them feel safer and more open.”

Many diagnoses are differentiated by eliciting pain on the anterior vs the posterior half of the vulvar vestibule — the part of the vulva that lies between the labia minora and is composed of nonkeratinized tissue with embryonic origins in the endoderm. “If you touch on the keratinized skin (of the vulva) and they don’t have pain, but on the vestibule they do have pain, and there is no pain inside the vagina, this suggests there is a vestibular problem,” said Cigna.

Pain/tenderness isolated to the posterior half of the vestibule suggests a muscular cause, and pain in both the posterior and anterior parts of the vestibule suggests a cause that is more systemic or diffuse, which could be a result of a hormonal issue such as one related to oral contraceptives or decreased testosterone, or a nerve-related process.

Cigna uses gentle swipes of a Q-tip moistened with water or gel to examine the vulva rather than a poke or touch, with the exception being the posterior vestibule, which overlies muscle insertion sites. “Make sure to get a baseline in remote areas such as the inner thigh, and always distinguish between ‘scratchy/sensitive’ sensations and pain,” she said, noting the value of having the patient hold a mirror on her inner thigh.

 

Causes of Vulvar Itch: Infectious and Noninfectious

With vulvar candidiasis, a common infectious cause of vulvar itch, “you have to ask if they’re also itching on the inside because if you treat them with a topical and you don’t treat the vaginal yeast infection that may be co-occurring, they’ll keep reseeding their vulvar skin,” Cigna said, “and it will never be fully treated.”

Candida albicans is the most common cause of vulvar or vulvovaginal candidiasis, and resistance to antifungals has been rising. Non-albicans Candida “tends to have even higher resistance rates,” she said. Ordering a sensitivity panel along with the culture is helpful, but “comprehensive vaginal biome” panels are generally not useful. “It’s hard to correlate the information clinically,” she said, “and there’s not always a lot of information about susceptibilities, which is what I really like to know.”

Cigna’s treatments for vaginal infections include miconazole, terconazole, and fluconazole (and occasionally, itraconazole or voriconazole — a “decision we don’t take lightly”). Vulvar treatments include nystatin ointment, clotrimazole cream, and miconazole cream. Often, optimal treatment involves addressing “both inside and out,” she said, noting the importance of also killing yeast in undergarment fabric.

“In my experience, Diflucan [oral fluconazole] doesn’t treat persistent vulvar cutaneous skin yeast well, so while I might try Diflucan, I typically use something topical as well,” she said. “And with vaginal yeast, we do use boric acid from time to time, especially for non-albicans species because it tends to be a little more effective.”

Noninfectious causes of vulvar itch include allergic, neuropathic, and muscular causes, as well as autoimmune dermatoses and mast cell activation syndrome. Well known in dermatology are acute contact dermatitis and lichen simplex chronicus — both characterized by induration, thickening, and a “puffy” erythematous appearance, and worsening of pruritus at night. What may be less appreciated is the long list of implicated allergens , including Always menstrual pads made of a plastic-containing “dry weave” material, Cigna said. There are at least several cotton-only, low-preservative feminine products available on the market, she noted.

 

Common Autoimmune Vulvar Dermatoses: LS and LP

Vulvar LS has traditionally been thought to affect mainly prepubertal and postmenopausal women, but the autoimmune condition is now known to affect more reproductive-age people with vulvas than previously appreciated, Cigna said.

And notably, in an observational web-based study of premenopausal women (aged 18-50 years) with biopsy-confirmed vulvar LS, the leading symptom was not itch but dyspareunia and tearing with intercourse. This means “we’re missing people,” said Cigna, an author of the study. “We think the reason we’re not seeing itch as commonly in this population is that itch is likely mediated by the low estrogen state of pre- and postmenopausal people.”

Vulvar LS also occurs in pregnancy, with symptoms that are either stable or decrease during pregnancy and increase in the postpartum period, as demonstrated in a recently published online survey.

Patients with vulvar LS can present with hypopigmentation, lichenification, and scarring and architectural changes, the latter of which can involve clitoral phimosis, labial resorption, and narrowing of the introitus. (The vaginal mucosa is unaffected.) The presentation can be subtle, especially in premenopausal women, and differentiation between LS, vitiligo, and yeast is sometimes necessary.

A timely biopsy-driven definitive diagnosis is important because vulvar LS increases the risk for cancer if it’s not adequately treated and because long-term steroid use can affect the accuracy of pathology reports. “We really care about keeping this disease in remission as much as possible,” Cigna said. Experts in the field recommend long-term maintenance therapy with a mid-ultra-potent steroid one to three times/week or an alternative. “I’ve just started using ruxolitinib cream, a Janus kinase (JAK) inhibitor, and tacrolimus, a calcineurin inhibitor,” she said.

With vulvar LP, based on current evidence, the risk for malignant transformation is low, but “it crosses into the vagina and can cause vaginal adhesions, so if you’re diagnosing someone with lichen planus, you need to make sure you’re talking with them about dilators, and if you’re not comfortable, send them to [gyn],” she said.

The use of vulvoscopy is important for one’s ability to see the fine Wickham’s striae that often characterize vulvar LP, she noted. Medical treatments for vulvar LP include topical calcineurin inhibitors, high-potency steroids, and JAK inhibitors.

Surgical treatment of vulvar granuloma fissuratum caused by vulvar LS is possible (when the patient is in complete remission, to prevent koebnerization), with daily post-op application of clobetasol and retraction of tissues, noted Cigna, the author of a study on vulvar lysis of adhesions.

With both LS and LP, Cigna said, “don’t forget (consideration of) hormones” as an adjunctive treatment, especially in postmenopausal women. “Patients in a low hormone state will have more flares.”

 

Vulvar Crohn’s

“We all have to know how to look for this,” Cigna said. “Unilateral or asymmetric swelling is classic, but don’t rule out the diagnosis if you see symmetric swelling.” Patients also typically have linear “knife-like” fissures or ulcerations, the vulva “is very indurated,” and “swelling is so intense, the patients are miserable,” she said.

Vulvar Crohn’s disease may precede intestinal disease in 20%-30% of patients, so referral to a gastroenterologist — and ideally subsequent collaboration — is important, as vulvar manifestations are treated with systemic medications typical for Crohn’s.

A biopsy is required for diagnosis, and the pathologist should be advised to look for lichenified squamous mucosa with the Touton giant cell reaction. “Vulvar Crohn’s is a rare enough disorder that if you don’t have an experienced or informed pathologist looking at your specimen, they may miss it because they won’t be looking for it,” Cigna added in the interview. “You should be really clear about what you’re looking for.”

 

Neuropathic Itch, Pelvic Floor Muscle Spasm

Patients with pudendal neuralgia — caused by an injured, entrapped, or irritated pudendal nerve (originating from S2-S4) — typically present with chronic vulvar and pelvic pain that is often unprovoked and worsens with sitting. Itching upon touch is often another symptom, and some patients describe a foreign body sensation. The cause is often trauma (such as an accident or childbirth-related) as opposed to myofascial irritation, Cigna explained in her lecture.

“Your exam will be largely normal, with no skin findings, so patients will get sent away if you don’t know to look for pudendal neuralgia by pressing on the pudendal nerve or doing (or referring for) a diagnostic nerve block,” Cigna added in the interview.

Persistent genital arousal disorder (PGAD) is “more global” in that it can also originate not only from the pudendal nerve but also from nerve roots higher in the spine or even from the brain. “People feel a sense of arousal, but some describe it as an itch,” Cigna said in her lecture, referring to a 2021 consensus document on PGAD/genito-pelvic dysesthesia by the International Society for the Study of Women’s Sexual Health as a valuable resource for understanding and managing the condition.

Diagnosis and treatment usually start with a pudendal nerve block with a combination of steroid and anesthetic. If this does not relieve arousal/itching, the next step may be an MRI to look higher in the spine.

 

Pelvic Floor Muscle Spasm

Vulvar pain, skin itching, and irritation can be symptoms of pelvic floor muscle spasm. “Oftentimes people come to me and say, ‘I have a dermatologic problem,’” Cigna said. “The skin may look red and erythematous, but it’s probably more likely a muscle problem when you’re not finding anything, and no amount of steroid will help the itch go away when the problem lies underneath.”

Co-occurring symptoms can include vaginal dryness, clitoral pain, urethral discomfort, bladder pain/irritation, increased urgency, constipation, and anal fissures. The first-line treatment approach is pelvic floor therapy.

“Pelvic floor therapy is not just for incontinence. It’s also for pain and discomfort from muscles,” she said, noting that most patients with vulvar disorders are referred for pelvic floor therapy. “Almost all of them end up having pelvic floor dysfunction because the pelvic floor muscles spasm whenever there’s pain or inflammation.”

 

A Cautionary Word on Vulvodynia, and a Mast Cell Paradigm to Explore

Vulvodynia is defined as persistent pain of at least 3 months’ duration with no clear cause. “These are the patients with no skin findings,” Cigna said. But in most cases, she said, careful investigation identifies causes that are musculoskeletal, hormonal, or nerve-related.

“It’s a term that’s thrown around a lot — it’s kind of a catchall. Yet it should be a small minority of patients who truly have a diagnosis of vulvodynia,” she said.

In the early stages of investigation is the idea that mast cell proliferation and mast cell activation may play a role in some cases of vulvar and vestibular pain and itching. “We see that some patients with vulvodynia and vestibulodynia have mast cells that are increased in number in the epithelium and beneath the epithelium, and nerve staining shows an increased number of nerve endings traveling into the epithelium,” Cigna said.

“We do diagnose some people clinically” based on urticaria and other symptoms suggestive of mast cell proliferation/activation (such as flushing, abdominal cramping, diarrhea, hypotensive syncope or near syncope, and tachycardia), and “then we send them to the allergist for testing,” Cigna said.

Cigna and Murphy have no relevant financial disclosures.

 

A version of this article appeared on Medscape.com.

TOPLINE:

Exposure to fine particulate matter (PM_2.5) during pregnancy is associated with an increased risk for spontaneous preterm birth, with peak vulnerability in the second trimester. Lower socioeconomic status, limited green space exposure, and extreme heat amplify this risk, whereas living around more trees provides protective effects.

METHODOLOGY:

• The researchers conducted a population-based retrospective cohort study to examine the associations of exposures to total PM_2.5 and five constituents (black carbon, nitrate, organic matter, and sulfate) during pregnancy with spontaneous preterm birth.
• They included 409,037 singleton live births from the Kaiser Permanente Southern California health care system between 2008 and 2018, with mothers having a mean age of 30.3 years at delivery (51% Hispanic).
• Daily total PM_2.5 concentrations and monthly data on the constituents in California were obtained; mean exposures during the entire pregnancy and in each trimester were calculated.
• Spontaneous preterm births were identified through the evaluation of preterm labor visits and were defined as a delivery occurring before 37 weeks following the onset of spontaneous labor, without pregnancy complications, and within 7 days of the last preterm labor visit.
• The analysis also examined the effect of factors such as race and ethnicity, education, median household income, exposure to green spaces, wildfire smoke, and temperature.

TAKEAWAY:

• Each 2.76 µg/m³ increase in total PM_2.5 exposure during pregnancy raised the risk for spontaneous preterm birth by 15% (P < .001), with black carbon showing the highest risk (adjusted odds ratio [aOR], 1.15; 95% CI, 1.12-1.18; P < .001).
• Exposure to PM_2.5 during the second trimester showed the highest association with spontaneous preterm birth (aOR, 1.10; P < .001), followed by that during the third (aOR, 1.09; P < .001) and first (aOR, 1.07; P < .001) trimesters.
• Individuals with lower education levels showed a higher risk for spontaneous preterm birth than those with more than 4 years of college education (P = .003).
• Exposure to extreme heat (P < .001) and lower exposure to total green space (P = .003) increased the risk for spontaneous preterm abortion.

IN PRACTICE:

“Targeted and preventive public health interventions among these subpopulations with high risk may be critical for minimizing the burden of spontaneous preterm birth,” the authors wrote.

SOURCE:

The study was led by Anqi Jiao of the program in public health at the Department of Environmental and Occupational Health at the University of California, Irvine. It was published online in JAMA Network Open.

LIMITATIONS:

According to the authors, exposure misclassification was inevitable as individual exposure to PM_2.5 was estimated according to census tract-level data without considering personal activity patterns. Only five major PM_2.5 constituents were measured due to data availability. Additionally, street-view green space data were considered spatial snapshots, which cannot capture temporal variations, possibly leading to exposure misclassification and biased associations in either direction.

DISCLOSURES:

The study was supported by the National Institute of Environmental Health Sciences and the California Air Resources Board. One author reported receiving research funding from pharmaceutical and biopharmaceutical companies, which was paid to the institute. Another author reported receiving grants from a medical technology company outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Exposure to fine particulate matter (PM_2.5) during pregnancy is associated with an increased risk for spontaneous preterm birth, with peak vulnerability in the second trimester. Lower socioeconomic status, limited green space exposure, and extreme heat amplify this risk, whereas living around more trees provides protective effects.

METHODOLOGY:

• The researchers conducted a population-based retrospective cohort study to examine the associations of exposures to total PM_2.5 and five constituents (black carbon, nitrate, organic matter, and sulfate) during pregnancy with spontaneous preterm birth.
• They included 409,037 singleton live births from the Kaiser Permanente Southern California health care system between 2008 and 2018, with mothers having a mean age of 30.3 years at delivery (51% Hispanic).
• Daily total PM_2.5 concentrations and monthly data on the constituents in California were obtained; mean exposures during the entire pregnancy and in each trimester were calculated.
• Spontaneous preterm births were identified through the evaluation of preterm labor visits and were defined as a delivery occurring before 37 weeks following the onset of spontaneous labor, without pregnancy complications, and within 7 days of the last preterm labor visit.
• The analysis also examined the effect of factors such as race and ethnicity, education, median household income, exposure to green spaces, wildfire smoke, and temperature.

TAKEAWAY:

• Each 2.76 µg/m³ increase in total PM_2.5 exposure during pregnancy raised the risk for spontaneous preterm birth by 15% (P < .001), with black carbon showing the highest risk (adjusted odds ratio [aOR], 1.15; 95% CI, 1.12-1.18; P < .001).
• Exposure to PM_2.5 during the second trimester showed the highest association with spontaneous preterm birth (aOR, 1.10; P < .001), followed by that during the third (aOR, 1.09; P < .001) and first (aOR, 1.07; P < .001) trimesters.
• Individuals with lower education levels showed a higher risk for spontaneous preterm birth than those with more than 4 years of college education (P = .003).
• Exposure to extreme heat (P < .001) and lower exposure to total green space (P = .003) increased the risk for spontaneous preterm abortion.

IN PRACTICE:

“Targeted and preventive public health interventions among these subpopulations with high risk may be critical for minimizing the burden of spontaneous preterm birth,” the authors wrote.

SOURCE:

The study was led by Anqi Jiao of the program in public health at the Department of Environmental and Occupational Health at the University of California, Irvine. It was published online in JAMA Network Open.

LIMITATIONS:

According to the authors, exposure misclassification was inevitable as individual exposure to PM_2.5 was estimated according to census tract-level data without considering personal activity patterns. Only five major PM_2.5 constituents were measured due to data availability. Additionally, street-view green space data were considered spatial snapshots, which cannot capture temporal variations, possibly leading to exposure misclassification and biased associations in either direction.

DISCLOSURES:

The study was supported by the National Institute of Environmental Health Sciences and the California Air Resources Board. One author reported receiving research funding from pharmaceutical and biopharmaceutical companies, which was paid to the institute. Another author reported receiving grants from a medical technology company outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Exposure to fine particulate matter (PM_2.5) during pregnancy is associated with an increased risk for spontaneous preterm birth, with peak vulnerability in the second trimester. Lower socioeconomic status, limited green space exposure, and extreme heat amplify this risk, whereas living around more trees provides protective effects.

METHODOLOGY:

• The researchers conducted a population-based retrospective cohort study to examine the associations of exposures to total PM_2.5 and five constituents (black carbon, nitrate, organic matter, and sulfate) during pregnancy with spontaneous preterm birth.
• They included 409,037 singleton live births from the Kaiser Permanente Southern California health care system between 2008 and 2018, with mothers having a mean age of 30.3 years at delivery (51% Hispanic).
• Daily total PM_2.5 concentrations and monthly data on the constituents in California were obtained; mean exposures during the entire pregnancy and in each trimester were calculated.
• Spontaneous preterm births were identified through the evaluation of preterm labor visits and were defined as a delivery occurring before 37 weeks following the onset of spontaneous labor, without pregnancy complications, and within 7 days of the last preterm labor visit.
• The analysis also examined the effect of factors such as race and ethnicity, education, median household income, exposure to green spaces, wildfire smoke, and temperature.

TAKEAWAY:

• Each 2.76 µg/m³ increase in total PM_2.5 exposure during pregnancy raised the risk for spontaneous preterm birth by 15% (P < .001), with black carbon showing the highest risk (adjusted odds ratio [aOR], 1.15; 95% CI, 1.12-1.18; P < .001).
• Exposure to PM_2.5 during the second trimester showed the highest association with spontaneous preterm birth (aOR, 1.10; P < .001), followed by that during the third (aOR, 1.09; P < .001) and first (aOR, 1.07; P < .001) trimesters.
• Individuals with lower education levels showed a higher risk for spontaneous preterm birth than those with more than 4 years of college education (P = .003).
• Exposure to extreme heat (P < .001) and lower exposure to total green space (P = .003) increased the risk for spontaneous preterm abortion.

IN PRACTICE:

“Targeted and preventive public health interventions among these subpopulations with high risk may be critical for minimizing the burden of spontaneous preterm birth,” the authors wrote.

SOURCE:

The study was led by Anqi Jiao of the program in public health at the Department of Environmental and Occupational Health at the University of California, Irvine. It was published online in JAMA Network Open.

LIMITATIONS:

According to the authors, exposure misclassification was inevitable as individual exposure to PM_2.5 was estimated according to census tract-level data without considering personal activity patterns. Only five major PM_2.5 constituents were measured due to data availability. Additionally, street-view green space data were considered spatial snapshots, which cannot capture temporal variations, possibly leading to exposure misclassification and biased associations in either direction.

DISCLOSURES:

The study was supported by the National Institute of Environmental Health Sciences and the California Air Resources Board. One author reported receiving research funding from pharmaceutical and biopharmaceutical companies, which was paid to the institute. Another author reported receiving grants from a medical technology company outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Women with polycystic ovary syndrome (PCOS) have 26% higher nulliparity rates and give birth at more advanced ages despite similar family aspirations and higher rates of fertility treatment. Later PCOS diagnosis is associated with double the rate of advanced maternal age at childbirth.

METHODOLOGY:

• A prospective cohort study followed 14,247 Australian women from 1996 (age, 18-23 years) to 2021 (age, 43-48 years), comparing 981 women with self-reported PCOS against 13,266 without PCOS.
• Participants completed surveys approximately every 3 years, with data collection including childbirth events, fertility issues, and treatment history from 20 weeks of gestational age, including stillbirths.
• Analysis focused on comparing parity, maternal age at deliveries, and factors associated with advanced maternal age between groups, with adjustments made for education level, area of residence, marital status, body mass index group, hypertension, and type 2 diabetes.

TAKEAWAY:

• Compared with women without PCOS, those with PCOS had fewer births (1.9 ± 1.2 vs 1.7 ± 1.3; P < .001) and higher nulliparity rates (18% vs 23%; P = .003).
• PCOS was associated with increased odds of advanced maternal age at first childbirth (adjusted odds ratio [aOR], 1.34; 95% CI, 1.04-1.75) and higher rates of gestational diabetes (aOR, 3.90; 95% CI, 2.99-5.10).
• Late PCOS diagnosis was linked to increased odds of advanced maternal age at first childbirth (aOR, 1.98; 95% CI, 1.22-3.22), emphasizing the importance of early diagnosis.
• Compared with women without PCOS, those with PCOS were older at first childbirth (28.8 ± 5.5 vs 29.5 ± 5.5 years) and second childbirth (31.1 ± 5.0 vs 32.1 ± 5.2 years) (P < .001 for both).

IN PRACTICE:

“Women with PCOS have increased infertility and have higher rates of seeking and using ovulation induction and IVF than those without PCOS. Moreover, women with PCOS are older at both first and second childbirth, have longer interconception periods, are of advanced maternal age, and have higher nulliparity and lower fecundity compared with women without PCOS,” the authors of the study wrote.

SOURCE:

This study was led by Maria Forslund, MD, PhD, Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg in Sweden. It was published online in American Journal of Obstetrics & Gynecology.

LIMITATIONS:

This study relied on self-reported PCOS diagnosis, though these data were previously validated in the cohort. While dropouts from the study were common, a previous modeling study showed no serious bias in estimates of associations between risk factors and health outcomes in the longitudinal models.

DISCLOSURES:

Forslund received support from the Swedish Medical Society (SLS-984944; SLS986952). The study was funded by the Australian Government’s Department of Health and Aged Care. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

Women with polycystic ovary syndrome (PCOS) have 26% higher nulliparity rates and give birth at more advanced ages despite similar family aspirations and higher rates of fertility treatment. Later PCOS diagnosis is associated with double the rate of advanced maternal age at childbirth.

METHODOLOGY:

• A prospective cohort study followed 14,247 Australian women from 1996 (age, 18-23 years) to 2021 (age, 43-48 years), comparing 981 women with self-reported PCOS against 13,266 without PCOS.
• Participants completed surveys approximately every 3 years, with data collection including childbirth events, fertility issues, and treatment history from 20 weeks of gestational age, including stillbirths.
• Analysis focused on comparing parity, maternal age at deliveries, and factors associated with advanced maternal age between groups, with adjustments made for education level, area of residence, marital status, body mass index group, hypertension, and type 2 diabetes.

TAKEAWAY:

• Compared with women without PCOS, those with PCOS had fewer births (1.9 ± 1.2 vs 1.7 ± 1.3; P < .001) and higher nulliparity rates (18% vs 23%; P = .003).
• PCOS was associated with increased odds of advanced maternal age at first childbirth (adjusted odds ratio [aOR], 1.34; 95% CI, 1.04-1.75) and higher rates of gestational diabetes (aOR, 3.90; 95% CI, 2.99-5.10).
• Late PCOS diagnosis was linked to increased odds of advanced maternal age at first childbirth (aOR, 1.98; 95% CI, 1.22-3.22), emphasizing the importance of early diagnosis.
• Compared with women without PCOS, those with PCOS were older at first childbirth (28.8 ± 5.5 vs 29.5 ± 5.5 years) and second childbirth (31.1 ± 5.0 vs 32.1 ± 5.2 years) (P < .001 for both).

IN PRACTICE:

“Women with PCOS have increased infertility and have higher rates of seeking and using ovulation induction and IVF than those without PCOS. Moreover, women with PCOS are older at both first and second childbirth, have longer interconception periods, are of advanced maternal age, and have higher nulliparity and lower fecundity compared with women without PCOS,” the authors of the study wrote.

SOURCE:

This study was led by Maria Forslund, MD, PhD, Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg in Sweden. It was published online in American Journal of Obstetrics & Gynecology.

LIMITATIONS:

This study relied on self-reported PCOS diagnosis, though these data were previously validated in the cohort. While dropouts from the study were common, a previous modeling study showed no serious bias in estimates of associations between risk factors and health outcomes in the longitudinal models.

DISCLOSURES:

Forslund received support from the Swedish Medical Society (SLS-984944; SLS986952). The study was funded by the Australian Government’s Department of Health and Aged Care. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

Women with polycystic ovary syndrome (PCOS) have 26% higher nulliparity rates and give birth at more advanced ages despite similar family aspirations and higher rates of fertility treatment. Later PCOS diagnosis is associated with double the rate of advanced maternal age at childbirth.

METHODOLOGY:

• A prospective cohort study followed 14,247 Australian women from 1996 (age, 18-23 years) to 2021 (age, 43-48 years), comparing 981 women with self-reported PCOS against 13,266 without PCOS.
• Participants completed surveys approximately every 3 years, with data collection including childbirth events, fertility issues, and treatment history from 20 weeks of gestational age, including stillbirths.
• Analysis focused on comparing parity, maternal age at deliveries, and factors associated with advanced maternal age between groups, with adjustments made for education level, area of residence, marital status, body mass index group, hypertension, and type 2 diabetes.

TAKEAWAY:

• Compared with women without PCOS, those with PCOS had fewer births (1.9 ± 1.2 vs 1.7 ± 1.3; P < .001) and higher nulliparity rates (18% vs 23%; P = .003).
• PCOS was associated with increased odds of advanced maternal age at first childbirth (adjusted odds ratio [aOR], 1.34; 95% CI, 1.04-1.75) and higher rates of gestational diabetes (aOR, 3.90; 95% CI, 2.99-5.10).
• Late PCOS diagnosis was linked to increased odds of advanced maternal age at first childbirth (aOR, 1.98; 95% CI, 1.22-3.22), emphasizing the importance of early diagnosis.
• Compared with women without PCOS, those with PCOS were older at first childbirth (28.8 ± 5.5 vs 29.5 ± 5.5 years) and second childbirth (31.1 ± 5.0 vs 32.1 ± 5.2 years) (P < .001 for both).

IN PRACTICE:

“Women with PCOS have increased infertility and have higher rates of seeking and using ovulation induction and IVF than those without PCOS. Moreover, women with PCOS are older at both first and second childbirth, have longer interconception periods, are of advanced maternal age, and have higher nulliparity and lower fecundity compared with women without PCOS,” the authors of the study wrote.

SOURCE:

This study was led by Maria Forslund, MD, PhD, Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg in Sweden. It was published online in American Journal of Obstetrics & Gynecology.

LIMITATIONS:

This study relied on self-reported PCOS diagnosis, though these data were previously validated in the cohort. While dropouts from the study were common, a previous modeling study showed no serious bias in estimates of associations between risk factors and health outcomes in the longitudinal models.

DISCLOSURES:

Forslund received support from the Swedish Medical Society (SLS-984944; SLS986952). The study was funded by the Australian Government’s Department of Health and Aged Care. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

New recommendations from the WikiGuidelines Group offer strategies for the prevention, diagnosis, and management of urinary tract infections (UTIs) in children and adults.

While the guideline covers a range of clinical topics, including prophylaxis and antimicrobial stewardship, many key clinical questions remain unanswered because of a lack of high-quality evidence, according to lead author Zachary Nelson, PharmD, MPH, of HealthPartners and Park Nicollet Health Services, St. Louis Park, Minnesota, and colleagues.

“This guideline fills a critical gap by providing pragmatic, broadly applicable recommendations tailored for generalist care and systems-based practice,” Nelson and colleagues wrote in JAMA Network Open. “Our guidance is rooted in the best available evidence and is designed for clinicians from various backgrounds and healthcare environments. It emphasizes a patient-centered approach to the diagnosis, prevention, and treatment of UTIs and related genitourinary infections.”

The guideline panelists, including 54 experts from 12 countries, developed the document in accordance with Standards for Quality Improvement Reporting Excellence and the WikiGuidelines charter. The latter requires that “clear recommendations” are based on data from at least two concordant randomized clinical trials (RCTs), or one RCT plus one concordant prospective observational study.

This approach allowed the panel to provide clear recommendations for 6 out of 37 unique questions, while 3 other questions were partially answered. In other words, 75% of the questions lacked sufficient evidence for answers.

“These guidelines are important because they illuminate the clinical data and lack of data we have for approaching diagnosis and treatment of this common infection that leads to a wide array of morbidity and sometimes mortality, as well as significant cost burden to the healthcare system,” said coauthor Sarah Kurz, MD, clinical assistant professor of internal medicine at Michigan Medicine, Ann Arbor, in a written comment.

Jessica Hammett, MD, a urologist at Emory Healthcare, Atlanta, Georgia, who was not an author of the study, suggested that the guideline is additionally impactful because of the panel’s geographic diversity.

“It is an international collaboration that takes into account regional and international practice patterns and differences,” Hammett said in a written comment.

The key guideline recommendations are briefly summarized below.

Preventive Strategies for UTI

The guideline endorses cranberry products as preventive for UTI-prone women, children, and post-intervention patients, though data are insufficient to recommend them for older adults, those with bladder issues, or pregnant women.

Topical estrogen is recommended for postmenopausal women with recurrent UTIs, as it helps restore the vaginal microbiome with minimal systemic absorption. It may also benefit patients with breast cancer when nonhormonal alternatives fail.

For those with intact bladder anatomy, methenamine hippurate is suggested as a noninferior alternative to low-dose antibiotics for preventing recurrent UTIs.

“These findings confirm the best practice of starting postmenopausal women on vaginal estrogen to prevent UTIs, which is a treatment option that should be implemented more commonly,” Hammett said. “Interestingly as compared to the AUA guidelines, this paper recommends the use of cranberry supplementation and methenamine as antibiotic alternatives for preventing UTIs.”

 

Empirical Treatment Recommendations

According to the guideline, empirical treatment for UTIs should focus on antimicrobials with high urinary tract concentration and local pathogen efficacy.

Nitrofurantoin is recommended for uncomplicated cystitis, while trimethoprim/sulfamethoxazole (TMP/SMX) and first-generation cephalosporins are advised for pyelonephritis.

For intravenous therapy, ceftriaxone is preferred unless there are risk factors for multidrug resistance.

Recommended treatment durations include 5 days for nitrofurantoin, 3 days for TMP/SMX and fluoroquinolones, and a single dose for fosfomycin in acute cystitis cases. For acute pyelonephritis, fluoroquinolones are advised for 5-7 days, with dose-optimized beta-lactams for 7 days. Gram-negative bacteremia from urinary sources warrants a 7-day course.

 

Stewardship and Clinical Management

The guideline emphasizes antimicrobial stewardship, with support for antibiotic de-escalation and oral regimens where feasible, to reduce adverse effects and hospital stays. Although evidence is limited, the authors suggest thorough allergy assessment and selective reporting of susceptibility results to enhance antibiotic selection.

While data were insufficient to make clear recommendations about the treatment of asymptomatic bacteriuria, Nelson and colleagues suggested that this practice “risks side effects without benefit” while threatening antimicrobial sustainability.

Hammett agreed, noting that “[this] serves as an important reminder not to treat asymptomatic bacteriuria, as it increases side effects and bacterial resistance without any improvement as compared to placebo.”

 

Special Considerations for Urologic Procedures

Finally, patients undergoing urologic procedures, routine cystoscopy, and urodynamic studies generally do not require prophylactic antibiotics, according to the guideline. Single-dose antibiotic prophylaxis is recommended for low-risk nephrolithotomy patients, though high-risk individuals, such as those who are pregnant or post kidney transplant, may require extended prophylaxis.

Kurz suggested that the guideline consolidates and supports the foundation of evidence driving common practices.

“I don’t think these guidelines offer any strikingly new strategies, which is unsurprising, as they were created after a deep dive into existing literature,” Kurz said. “But more importantly, what I think they do is to highlight where and what the evidence is for many of the clinical strategies that are commonly employed. For example, in terms of prevention, it is common for primary care physicians, urologists, and infectious diseases doctors to recommend cranberry and hydration and to use methenamine. These guidelines highlight that there is sufficient quality and quantity of evidence to support these interventions.”

She also noted how the guidelines emphasize the need for symptoms to make a UTI diagnosis and advise against routine testing of asymptomatic individuals.

“Despite this not being new information, typical clinical practice is often out of step here, and this [guideline] reemphasizes the important factors when considering UTI diagnosis,” Kurz said.

Finally, she expressed frustration for the numerous knowledge gaps remaining in this area, which may be traced back to barriers ranging from the semantic to the more systemic.

“Some of the difficulty is lack of clear definitions and precise terminology regarding UTIs,” Kurz said, noting the unclear distinction between complicated and uncomplicated UTIs. “I would also argue that UTIs are a disease that predominantly affects women, and like many other diseases where this is the case, [they] tend to be less studied. Hopefully, this guideline’s spotlight on all that we do not know can inspire high-quality research to address these gaps, leading to optimal patient care along with decreased burden on the system as a whole in terms of cost and antimicrobial resistance.”

The study was funded by Merck. The WikiGuidelines Group that established this guideline is entirely voluntary and unpaid; the group intends to establish a nonprofit organization to support the development of other guidelines using this novel methodology and eventually intends to trademark the name WikiGuidelines. The authors disclosed relationships with Pfizer, Eumedica, GSK, and others.

A version of this article first appeared on Medscape.com.

New recommendations from the WikiGuidelines Group offer strategies for the prevention, diagnosis, and management of urinary tract infections (UTIs) in children and adults.

While the guideline covers a range of clinical topics, including prophylaxis and antimicrobial stewardship, many key clinical questions remain unanswered because of a lack of high-quality evidence, according to lead author Zachary Nelson, PharmD, MPH, of HealthPartners and Park Nicollet Health Services, St. Louis Park, Minnesota, and colleagues.

“This guideline fills a critical gap by providing pragmatic, broadly applicable recommendations tailored for generalist care and systems-based practice,” Nelson and colleagues wrote in JAMA Network Open. “Our guidance is rooted in the best available evidence and is designed for clinicians from various backgrounds and healthcare environments. It emphasizes a patient-centered approach to the diagnosis, prevention, and treatment of UTIs and related genitourinary infections.”

The guideline panelists, including 54 experts from 12 countries, developed the document in accordance with Standards for Quality Improvement Reporting Excellence and the WikiGuidelines charter. The latter requires that “clear recommendations” are based on data from at least two concordant randomized clinical trials (RCTs), or one RCT plus one concordant prospective observational study.

This approach allowed the panel to provide clear recommendations for 6 out of 37 unique questions, while 3 other questions were partially answered. In other words, 75% of the questions lacked sufficient evidence for answers.

“These guidelines are important because they illuminate the clinical data and lack of data we have for approaching diagnosis and treatment of this common infection that leads to a wide array of morbidity and sometimes mortality, as well as significant cost burden to the healthcare system,” said coauthor Sarah Kurz, MD, clinical assistant professor of internal medicine at Michigan Medicine, Ann Arbor, in a written comment.

Jessica Hammett, MD, a urologist at Emory Healthcare, Atlanta, Georgia, who was not an author of the study, suggested that the guideline is additionally impactful because of the panel’s geographic diversity.

“It is an international collaboration that takes into account regional and international practice patterns and differences,” Hammett said in a written comment.

The key guideline recommendations are briefly summarized below.

Preventive Strategies for UTI

The guideline endorses cranberry products as preventive for UTI-prone women, children, and post-intervention patients, though data are insufficient to recommend them for older adults, those with bladder issues, or pregnant women.

Topical estrogen is recommended for postmenopausal women with recurrent UTIs, as it helps restore the vaginal microbiome with minimal systemic absorption. It may also benefit patients with breast cancer when nonhormonal alternatives fail.

For those with intact bladder anatomy, methenamine hippurate is suggested as a noninferior alternative to low-dose antibiotics for preventing recurrent UTIs.

“These findings confirm the best practice of starting postmenopausal women on vaginal estrogen to prevent UTIs, which is a treatment option that should be implemented more commonly,” Hammett said. “Interestingly as compared to the AUA guidelines, this paper recommends the use of cranberry supplementation and methenamine as antibiotic alternatives for preventing UTIs.”

 

Empirical Treatment Recommendations

According to the guideline, empirical treatment for UTIs should focus on antimicrobials with high urinary tract concentration and local pathogen efficacy.

Nitrofurantoin is recommended for uncomplicated cystitis, while trimethoprim/sulfamethoxazole (TMP/SMX) and first-generation cephalosporins are advised for pyelonephritis.

For intravenous therapy, ceftriaxone is preferred unless there are risk factors for multidrug resistance.

Recommended treatment durations include 5 days for nitrofurantoin, 3 days for TMP/SMX and fluoroquinolones, and a single dose for fosfomycin in acute cystitis cases. For acute pyelonephritis, fluoroquinolones are advised for 5-7 days, with dose-optimized beta-lactams for 7 days. Gram-negative bacteremia from urinary sources warrants a 7-day course.

 

Stewardship and Clinical Management

The guideline emphasizes antimicrobial stewardship, with support for antibiotic de-escalation and oral regimens where feasible, to reduce adverse effects and hospital stays. Although evidence is limited, the authors suggest thorough allergy assessment and selective reporting of susceptibility results to enhance antibiotic selection.

While data were insufficient to make clear recommendations about the treatment of asymptomatic bacteriuria, Nelson and colleagues suggested that this practice “risks side effects without benefit” while threatening antimicrobial sustainability.

Hammett agreed, noting that “[this] serves as an important reminder not to treat asymptomatic bacteriuria, as it increases side effects and bacterial resistance without any improvement as compared to placebo.”

 

Special Considerations for Urologic Procedures

Finally, patients undergoing urologic procedures, routine cystoscopy, and urodynamic studies generally do not require prophylactic antibiotics, according to the guideline. Single-dose antibiotic prophylaxis is recommended for low-risk nephrolithotomy patients, though high-risk individuals, such as those who are pregnant or post kidney transplant, may require extended prophylaxis.

Kurz suggested that the guideline consolidates and supports the foundation of evidence driving common practices.

“I don’t think these guidelines offer any strikingly new strategies, which is unsurprising, as they were created after a deep dive into existing literature,” Kurz said. “But more importantly, what I think they do is to highlight where and what the evidence is for many of the clinical strategies that are commonly employed. For example, in terms of prevention, it is common for primary care physicians, urologists, and infectious diseases doctors to recommend cranberry and hydration and to use methenamine. These guidelines highlight that there is sufficient quality and quantity of evidence to support these interventions.”

She also noted how the guidelines emphasize the need for symptoms to make a UTI diagnosis and advise against routine testing of asymptomatic individuals.

“Despite this not being new information, typical clinical practice is often out of step here, and this [guideline] reemphasizes the important factors when considering UTI diagnosis,” Kurz said.

Finally, she expressed frustration for the numerous knowledge gaps remaining in this area, which may be traced back to barriers ranging from the semantic to the more systemic.

“Some of the difficulty is lack of clear definitions and precise terminology regarding UTIs,” Kurz said, noting the unclear distinction between complicated and uncomplicated UTIs. “I would also argue that UTIs are a disease that predominantly affects women, and like many other diseases where this is the case, [they] tend to be less studied. Hopefully, this guideline’s spotlight on all that we do not know can inspire high-quality research to address these gaps, leading to optimal patient care along with decreased burden on the system as a whole in terms of cost and antimicrobial resistance.”

The study was funded by Merck. The WikiGuidelines Group that established this guideline is entirely voluntary and unpaid; the group intends to establish a nonprofit organization to support the development of other guidelines using this novel methodology and eventually intends to trademark the name WikiGuidelines. The authors disclosed relationships with Pfizer, Eumedica, GSK, and others.

A version of this article first appeared on Medscape.com.

New recommendations from the WikiGuidelines Group offer strategies for the prevention, diagnosis, and management of urinary tract infections (UTIs) in children and adults.

While the guideline covers a range of clinical topics, including prophylaxis and antimicrobial stewardship, many key clinical questions remain unanswered because of a lack of high-quality evidence, according to lead author Zachary Nelson, PharmD, MPH, of HealthPartners and Park Nicollet Health Services, St. Louis Park, Minnesota, and colleagues.

“This guideline fills a critical gap by providing pragmatic, broadly applicable recommendations tailored for generalist care and systems-based practice,” Nelson and colleagues wrote in JAMA Network Open. “Our guidance is rooted in the best available evidence and is designed for clinicians from various backgrounds and healthcare environments. It emphasizes a patient-centered approach to the diagnosis, prevention, and treatment of UTIs and related genitourinary infections.”

The guideline panelists, including 54 experts from 12 countries, developed the document in accordance with Standards for Quality Improvement Reporting Excellence and the WikiGuidelines charter. The latter requires that “clear recommendations” are based on data from at least two concordant randomized clinical trials (RCTs), or one RCT plus one concordant prospective observational study.

This approach allowed the panel to provide clear recommendations for 6 out of 37 unique questions, while 3 other questions were partially answered. In other words, 75% of the questions lacked sufficient evidence for answers.

“These guidelines are important because they illuminate the clinical data and lack of data we have for approaching diagnosis and treatment of this common infection that leads to a wide array of morbidity and sometimes mortality, as well as significant cost burden to the healthcare system,” said coauthor Sarah Kurz, MD, clinical assistant professor of internal medicine at Michigan Medicine, Ann Arbor, in a written comment.

Jessica Hammett, MD, a urologist at Emory Healthcare, Atlanta, Georgia, who was not an author of the study, suggested that the guideline is additionally impactful because of the panel’s geographic diversity.

“It is an international collaboration that takes into account regional and international practice patterns and differences,” Hammett said in a written comment.

The key guideline recommendations are briefly summarized below.

Preventive Strategies for UTI

The guideline endorses cranberry products as preventive for UTI-prone women, children, and post-intervention patients, though data are insufficient to recommend them for older adults, those with bladder issues, or pregnant women.

Topical estrogen is recommended for postmenopausal women with recurrent UTIs, as it helps restore the vaginal microbiome with minimal systemic absorption. It may also benefit patients with breast cancer when nonhormonal alternatives fail.

For those with intact bladder anatomy, methenamine hippurate is suggested as a noninferior alternative to low-dose antibiotics for preventing recurrent UTIs.

“These findings confirm the best practice of starting postmenopausal women on vaginal estrogen to prevent UTIs, which is a treatment option that should be implemented more commonly,” Hammett said. “Interestingly as compared to the AUA guidelines, this paper recommends the use of cranberry supplementation and methenamine as antibiotic alternatives for preventing UTIs.”

 

Empirical Treatment Recommendations

According to the guideline, empirical treatment for UTIs should focus on antimicrobials with high urinary tract concentration and local pathogen efficacy.

Nitrofurantoin is recommended for uncomplicated cystitis, while trimethoprim/sulfamethoxazole (TMP/SMX) and first-generation cephalosporins are advised for pyelonephritis.

For intravenous therapy, ceftriaxone is preferred unless there are risk factors for multidrug resistance.

Recommended treatment durations include 5 days for nitrofurantoin, 3 days for TMP/SMX and fluoroquinolones, and a single dose for fosfomycin in acute cystitis cases. For acute pyelonephritis, fluoroquinolones are advised for 5-7 days, with dose-optimized beta-lactams for 7 days. Gram-negative bacteremia from urinary sources warrants a 7-day course.

 

Stewardship and Clinical Management

The guideline emphasizes antimicrobial stewardship, with support for antibiotic de-escalation and oral regimens where feasible, to reduce adverse effects and hospital stays. Although evidence is limited, the authors suggest thorough allergy assessment and selective reporting of susceptibility results to enhance antibiotic selection.

While data were insufficient to make clear recommendations about the treatment of asymptomatic bacteriuria, Nelson and colleagues suggested that this practice “risks side effects without benefit” while threatening antimicrobial sustainability.

Hammett agreed, noting that “[this] serves as an important reminder not to treat asymptomatic bacteriuria, as it increases side effects and bacterial resistance without any improvement as compared to placebo.”

 

Special Considerations for Urologic Procedures

Finally, patients undergoing urologic procedures, routine cystoscopy, and urodynamic studies generally do not require prophylactic antibiotics, according to the guideline. Single-dose antibiotic prophylaxis is recommended for low-risk nephrolithotomy patients, though high-risk individuals, such as those who are pregnant or post kidney transplant, may require extended prophylaxis.

Kurz suggested that the guideline consolidates and supports the foundation of evidence driving common practices.

“I don’t think these guidelines offer any strikingly new strategies, which is unsurprising, as they were created after a deep dive into existing literature,” Kurz said. “But more importantly, what I think they do is to highlight where and what the evidence is for many of the clinical strategies that are commonly employed. For example, in terms of prevention, it is common for primary care physicians, urologists, and infectious diseases doctors to recommend cranberry and hydration and to use methenamine. These guidelines highlight that there is sufficient quality and quantity of evidence to support these interventions.”

She also noted how the guidelines emphasize the need for symptoms to make a UTI diagnosis and advise against routine testing of asymptomatic individuals.

“Despite this not being new information, typical clinical practice is often out of step here, and this [guideline] reemphasizes the important factors when considering UTI diagnosis,” Kurz said.

Finally, she expressed frustration for the numerous knowledge gaps remaining in this area, which may be traced back to barriers ranging from the semantic to the more systemic.

“Some of the difficulty is lack of clear definitions and precise terminology regarding UTIs,” Kurz said, noting the unclear distinction between complicated and uncomplicated UTIs. “I would also argue that UTIs are a disease that predominantly affects women, and like many other diseases where this is the case, [they] tend to be less studied. Hopefully, this guideline’s spotlight on all that we do not know can inspire high-quality research to address these gaps, leading to optimal patient care along with decreased burden on the system as a whole in terms of cost and antimicrobial resistance.”

The study was funded by Merck. The WikiGuidelines Group that established this guideline is entirely voluntary and unpaid; the group intends to establish a nonprofit organization to support the development of other guidelines using this novel methodology and eventually intends to trademark the name WikiGuidelines. The authors disclosed relationships with Pfizer, Eumedica, GSK, and others.

A version of this article first appeared on Medscape.com.

TOPLINE:

Long-term treatment with TransCon parathyroid hormone (PTH), a replacement therapy for hypoparathyroidism, demonstrates sustained efficacy and safety in patients with hypoparathyroidism over 52 weeks, with 95% of participants able to discontinue conventional therapy.

METHODOLOGY:

• Conventional therapy for hypoparathyroidism (active vitamin D and elemental calcium) alleviates symptoms of hypocalcemia, but it does not improve insufficient PTH levels and is linked to long-term complications, such as nephrocalcinosis, nephrolithiasis, and renal dysfunction.
• This phase 3 (PaTHway) trial aimed to investigate the long-term efficacy, safety, and tolerability of TransCon PTH (palopegteriparatide) in adults with hypoparathyroidism.
• Overall, 82 patients with chronic hypoparathyroidism (mean age, 48.6 years; 78% women; 93% White) were randomly assigned to receive TransCon PTH or placebo, both coadministered with conventional therapy for 26 weeks.
• At the 26-week visit, patients who completed the blinded treatment (n = 79) were assigned to receive only TransCon PTH with conventional therapy in an ongoing 156-week open-label extension.
• For this analysis at week 52, the main efficacy endpoint was the proportion of patients (n = 78) with normal serum calcium levels (8.3-10.6 mg/dL) and independence from conventional therapy (active vitamin D and therapeutic doses of calcium); safety assessments included serum chemistries, 24-hour urine calcium excretion, and treatment-emergent adverse events.

TAKEAWAY:

• At week 52, the majority of the patients receiving TransCon PTH achieved normal serum calcium levels within the normal range (86%) and independence from conventional therapy (95%). None required active vitamin D.
• In secondary endpoints, patients receiving TransCon PTH showed sustained improvement in Hypoparathyroidism Patient Experience Scale scores, reflecting better symptom management, enhanced functioning, and overall well-being through week 52.
• At week 52, the mean 24-hour urine calcium excretion in patients first randomized to TransCon PTH was 185.1 mg/d, remaining well below the upper limit of normal (≤ 250 mg/d), while the placebo group mean fell to 223.1 mg/d during the open-label extension of TransCon PTH.
• TransCon PTH was well-tolerated, with most treatment-emergent adverse events being mild or moderate and none leading to treatment discontinuation.

IN PRACTICE:

“These results suggest that TransCon PTH may improve outcomes and advance the standard of care for adults living with hypoparathyroidism,” the authors wrote.

SOURCE:

The study was led by Bart L. Clarke, MD, Mayo Clinic, Rochester, Minnesota. It was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The study’s limitations included the open-label design during the extension period, which may have introduced bias in patient-reported outcomes. Additionally, the study population was predominantly women and White, which may have limited the generalizability of the findings. Further research is needed to assess the long-term effects of TransCon PTH on renal complications. One patient died of fatal cardiac arrest deemed unrelated to the study drug.

DISCLOSURES:

The study was funded by Ascendis Pharma A/S. Seven authors declared being current or former employees of Ascendis Pharma. The other authors declared receiving grants, research funding, honoraria, serving as consultants, advisory board members, study investigators, and other ties with Ascendis Pharma and multiple other pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Long-term treatment with TransCon parathyroid hormone (PTH), a replacement therapy for hypoparathyroidism, demonstrates sustained efficacy and safety in patients with hypoparathyroidism over 52 weeks, with 95% of participants able to discontinue conventional therapy.

METHODOLOGY:

• Conventional therapy for hypoparathyroidism (active vitamin D and elemental calcium) alleviates symptoms of hypocalcemia, but it does not improve insufficient PTH levels and is linked to long-term complications, such as nephrocalcinosis, nephrolithiasis, and renal dysfunction.
• This phase 3 (PaTHway) trial aimed to investigate the long-term efficacy, safety, and tolerability of TransCon PTH (palopegteriparatide) in adults with hypoparathyroidism.
• Overall, 82 patients with chronic hypoparathyroidism (mean age, 48.6 years; 78% women; 93% White) were randomly assigned to receive TransCon PTH or placebo, both coadministered with conventional therapy for 26 weeks.
• At the 26-week visit, patients who completed the blinded treatment (n = 79) were assigned to receive only TransCon PTH with conventional therapy in an ongoing 156-week open-label extension.
• For this analysis at week 52, the main efficacy endpoint was the proportion of patients (n = 78) with normal serum calcium levels (8.3-10.6 mg/dL) and independence from conventional therapy (active vitamin D and therapeutic doses of calcium); safety assessments included serum chemistries, 24-hour urine calcium excretion, and treatment-emergent adverse events.

TAKEAWAY:

• At week 52, the majority of the patients receiving TransCon PTH achieved normal serum calcium levels within the normal range (86%) and independence from conventional therapy (95%). None required active vitamin D.
• In secondary endpoints, patients receiving TransCon PTH showed sustained improvement in Hypoparathyroidism Patient Experience Scale scores, reflecting better symptom management, enhanced functioning, and overall well-being through week 52.
• At week 52, the mean 24-hour urine calcium excretion in patients first randomized to TransCon PTH was 185.1 mg/d, remaining well below the upper limit of normal (≤ 250 mg/d), while the placebo group mean fell to 223.1 mg/d during the open-label extension of TransCon PTH.
• TransCon PTH was well-tolerated, with most treatment-emergent adverse events being mild or moderate and none leading to treatment discontinuation.

IN PRACTICE:

“These results suggest that TransCon PTH may improve outcomes and advance the standard of care for adults living with hypoparathyroidism,” the authors wrote.

SOURCE:

The study was led by Bart L. Clarke, MD, Mayo Clinic, Rochester, Minnesota. It was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The study’s limitations included the open-label design during the extension period, which may have introduced bias in patient-reported outcomes. Additionally, the study population was predominantly women and White, which may have limited the generalizability of the findings. Further research is needed to assess the long-term effects of TransCon PTH on renal complications. One patient died of fatal cardiac arrest deemed unrelated to the study drug.

DISCLOSURES:

The study was funded by Ascendis Pharma A/S. Seven authors declared being current or former employees of Ascendis Pharma. The other authors declared receiving grants, research funding, honoraria, serving as consultants, advisory board members, study investigators, and other ties with Ascendis Pharma and multiple other pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Long-term treatment with TransCon parathyroid hormone (PTH), a replacement therapy for hypoparathyroidism, demonstrates sustained efficacy and safety in patients with hypoparathyroidism over 52 weeks, with 95% of participants able to discontinue conventional therapy.

METHODOLOGY:

• Conventional therapy for hypoparathyroidism (active vitamin D and elemental calcium) alleviates symptoms of hypocalcemia, but it does not improve insufficient PTH levels and is linked to long-term complications, such as nephrocalcinosis, nephrolithiasis, and renal dysfunction.
• This phase 3 (PaTHway) trial aimed to investigate the long-term efficacy, safety, and tolerability of TransCon PTH (palopegteriparatide) in adults with hypoparathyroidism.
• Overall, 82 patients with chronic hypoparathyroidism (mean age, 48.6 years; 78% women; 93% White) were randomly assigned to receive TransCon PTH or placebo, both coadministered with conventional therapy for 26 weeks.
• At the 26-week visit, patients who completed the blinded treatment (n = 79) were assigned to receive only TransCon PTH with conventional therapy in an ongoing 156-week open-label extension.
• For this analysis at week 52, the main efficacy endpoint was the proportion of patients (n = 78) with normal serum calcium levels (8.3-10.6 mg/dL) and independence from conventional therapy (active vitamin D and therapeutic doses of calcium); safety assessments included serum chemistries, 24-hour urine calcium excretion, and treatment-emergent adverse events.

TAKEAWAY:

• At week 52, the majority of the patients receiving TransCon PTH achieved normal serum calcium levels within the normal range (86%) and independence from conventional therapy (95%). None required active vitamin D.
• In secondary endpoints, patients receiving TransCon PTH showed sustained improvement in Hypoparathyroidism Patient Experience Scale scores, reflecting better symptom management, enhanced functioning, and overall well-being through week 52.
• At week 52, the mean 24-hour urine calcium excretion in patients first randomized to TransCon PTH was 185.1 mg/d, remaining well below the upper limit of normal (≤ 250 mg/d), while the placebo group mean fell to 223.1 mg/d during the open-label extension of TransCon PTH.
• TransCon PTH was well-tolerated, with most treatment-emergent adverse events being mild or moderate and none leading to treatment discontinuation.

IN PRACTICE:

“These results suggest that TransCon PTH may improve outcomes and advance the standard of care for adults living with hypoparathyroidism,” the authors wrote.

SOURCE:

The study was led by Bart L. Clarke, MD, Mayo Clinic, Rochester, Minnesota. It was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The study’s limitations included the open-label design during the extension period, which may have introduced bias in patient-reported outcomes. Additionally, the study population was predominantly women and White, which may have limited the generalizability of the findings. Further research is needed to assess the long-term effects of TransCon PTH on renal complications. One patient died of fatal cardiac arrest deemed unrelated to the study drug.

DISCLOSURES:

The study was funded by Ascendis Pharma A/S. Seven authors declared being current or former employees of Ascendis Pharma. The other authors declared receiving grants, research funding, honoraria, serving as consultants, advisory board members, study investigators, and other ties with Ascendis Pharma and multiple other pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

What to Know About NOSE

Traditionally, a laparoscopic approach to bowel resection secondary to endometriosis means enlargement of the port site or more commonly, a Pfannenstiel incision to introduce an anvil. Both incisions raise the risk of postoperative complications including pain and incisional hernia. Moreover, recovery time is prolonged.

Natural orifice specimen extraction (NOSE) makes use of a natural orifice, the vagina or anus, to extract the specimen and introduce the anvil. Transanal extraction for the management of endometriosis-related bowel disease was first described by the late David Redwine, MD, in his 1996 publication in Fertility and Sterility.¹

The concern with use of vaginal NOSE surgery is rectovaginal fistula secondary to two incision lines in close opposition. Both transvaginal NOSE and transanal NOSE have been criticized for longer dissection of the mesorectum and thus longer resected specimen. Despite these concerns, over the past 10 years, articles have been published showing not only the feasibility of the NOSE technique, but excellent comparative outcomes, as well.^2-4

 

A recent systematic review and meta-analysis by Kar et al. comparing NOSE extraction to minilaparotomy in bowel resection due to endometriosis revealed no significant difference in complication rate, but significantly shorter operation duration, reduced length of stay, and less blood loss in the NOSE surgical arm.⁵

The most recent study to be published in the Journal of Minimally Invasive Gynecology involving total laparoscopic segmental resection with transanal NOSE for the treatment of colorectal endometriosis was written by the guest author of this edition of the Master Class in Gynecologic Surgery, Professor Mario Malzoni, Scientific Director of the Malzoni Research Hospital, the Center for Advanced Pelvic Surgery, in Avellino, Italy. In the JMIG article, and in this Master Class, Professor Malzoni, a world-renowned endometriosis specialist recognized for his extraordinary skill and multi-organ surgical work, discusses the difference between the standard bowel resection technique with that of NOSE, and reports on his experience with NOSE.⁶

It is a pleasure and honor to welcome my friend and colleague, Professor Mario Malzoni, to this edition of the Master Class in Gynecologic Surgery.

Dr. Charles E. Miller is Professor, Obstetrics & Gynecology, Department of Clinical Sciences, Rosalind Franklin University of Medicine and Science, North Chicago, and Director, Minimally Invasive Gynecologic Surgery, Advocate Lutheran General Hospital, Park Ridge, both in Illinois. Email him at obnews@mdedge.com.

References

1. Redwine DB et al. Laparoscopically assisted transvaginal segmental resection of the rectosigmoid colon for endometriosis. Fertil Steril. 1996 Jan;65(1):193-7.

2. Akladios C et al. Totally laparoscopic intracorporeal anastomosis with natural orifice specimen extraction (NOSE) techniques, particularly suitable for bowel endometriosis. J Minim Invasive Gynecol. 2014 Nov-Dec;21(6):1095-102.

3. Bokor A et al. Natural orifice specimen extraction during laparoscopic bowel resection for colorectal endometriosis: technique and outcome. J Minim Invasive Gynecol. 2018 Sep-Oct;25(6):1065-74.

4. Grigoriadis G et al. Natural orifice specimen extraction colorectal resection for deep endometriosis: A 50 case series. J Minim Invasive Gynecol. 2022 Sep;29(9):1054-62.

5. Kar E et al. Natural orifice specimen extraction as a promising alternative for minilaparotomy in bowel resection due to endometriosis: A systematic review and meta-analysis. J Minim Invasive Gynecol. 2024 Jul;31(7):574-83.e1.

6. Malzoni M et al. Total laparoscopic segmental resection with transanal natural orifice specimen extraction for treatment of colorectal endometriosis: Descriptive analysis from the TrEnd study database. J Minim Invasive Gynecol. 2024 Oct;18:S1553-4650(24)01453-5.

Laparoscopic Resection With Transanal NOSE for Deep Colorectal Endometriosis

When segmental sigmoid colon/rectal resection is indicated for treatment of deep infiltrating bowel endometriosis, a totally laparoscopic resection with intracorporeal anastomosis and transanal natural orifice specimen extraction (NOSE) can be safe, effective, and advantageous compared with an abdominal mini-laparotomy for extracorporeal anastomosis and specimen retrieval.

With advanced laparoscopic surgical skills, accurate preoperative ultrasound evaluation, and a high-quality perioperative care protocol (including high-quality bowel preparation), segmental resection with NOSE can offer better preservation of vascularization, smaller resection sizes, lower rates of postoperative pain, a shorter time for gas passage after surgery, decreased hospital stays, and lower rates of wound infection and incisional hernia.

We have seen such improved results in our high-volume center since shifting in April 2021 from our classical technique for segmental rectosigmoid resection¹ to a totally laparoscopic approach with NOSE. We first reported on this new technique in 2022 in a video article in the Journal of Minimally Invasive Gynecology,²and in October 2024, outcomes of 81 patients who underwent segmental sigmoid colon/rectal resection with intracorporeal anastomosis and transanal NOSE at our institution from April 2021 through March 2024 were reported in Journal of Minimally Invasive Gynecology.³Given our experience with this approach for deep endometriosis, I am convinced that NOSE should be preferred to transabdominal specimen extraction for segmental rectosigmoid resection. This is where the future lies for deep infiltrating endometriosis. Here, I share our outcomes and describe our technique.

Our Prior Approach With A Mini-Laparotomy

Our traditional laparoscopic approach for segmental colon/rectal resection of deep infiltrating endometriosis involved an abdominal mini-laparotomy (no more than 4 cm in length) for specimen retrieval, resection of the proximal rectum, and positioning of the head of a circular stapler for end-to-end anastomosis. (Connection of the two parts of the circular stapler for anastomosis was achieved via laparoscopy.)¹

Several factors allowed us to minimize potential complications, including standardization of our technique, the use of three-dimensional endoscopes, and indocyanine green fluorescence angiography to assess the perfusion of the bowel after the completion of anastomosis. Still, an unpublished analysis of 1050 segmental bowel resections performed over more than 17 years using our traditional technique showed that hospital stays averaged 8 days, time to first defecation averaged 7 days, and time to first passage of flatus averaged 1 day. 

Per the Clavien-Dindo classification system for surgical complications that was used at the time, 1.9% of these 1050 patients had grade 1 (minor) or grade 2 complications and 6% had grade 3 complications. Grade 2 complications were defined as needing intervention or a hospital stay more than twice the median for the procedure. Grade 3 complications were defined as leading to lasting disability or organ resection. 

In the meantime, in colorectal cancer surgery, published studies on NOSE versus conventional laparoscopy with transabdominal specimen extraction have consistently pointed to the benefits of NOSE. A 2022 review ⁴ of 19 studies involving over 3400 patients and a 2022 meta-analysis ⁵ of 21 randomized controlled trials involving more than 2000 patients both showed significantly reduced postoperative morbidity and no differences in oncologic outcomes. Among the notable differences in the 2022 meta-analysis was a relative risk of postoperative infection of 0.34 for patients treated with NOSE compared with conventional laparoscopic techniques. 

Among patients with deep rectal endometriosis, reported experience with intracorporeal anastomosis and NOSE for segmental resection is limited, with a few studies published between 2014 and 2022. Excluding anecdotal reports, only about 140 patients have been reported in the literature as having intracorporeal anastomosis and transanal NOSE for deep infiltrating bowel endometriosis. ³

Our Outcomes With A Totally Laparoscopic Approach

Our approach to evaluating our experience with totally laparoscopic resection with transanal NOSE has been to systematically collect data from consecutive patients and to analyze 1) complications of the technique, 2) conversion to the traditional technique/open surgery, and 3) endometriosis-free bowel resection margins and recurrence. Secondarily, we look at intraoperative blood loss, operative time, recovery of gastrointestinal function, hospital stay length, and reproductive outcomes.

Across 81 patients from our TrEnd study database (Surgical TReatment of women with deep ENDometriosis infiltrating the sigmoid colon and/or rectum) who received a totally laparoscopic standardized procedure involving intracorporeal anastomosis and transanal NOSE, we had no conversions even to mini-laparotomy, and no cases of protective colostomy or ileostomy. 

Complete endometriosis removal was achieved in 100% of cases, with final pathology showing endometriosis-free resection margins, and patients remained free of bowel endometriosis at a median follow-up of 21 months.³Our analysis also shows improved gastrointestinal function recovery (median time to first defecation of 4 days, compared to 7 days previously, with the same 1-day median time to first passage of flatus) and a significantly improved hospital length of stay to a median of 3 days (interquartile range, 3-4.5 days); the latter reflects in part the absence of infection.³There were no intra-operative complications. Postoperative Clavien-Dindo grade 3 complications occurred in three patients (3.7%), two of whom required reoperation (one for hemoperitoneum and one for ureteral injury) and one who experienced rectal anastomotic bleeding on postoperative day 1. (The two requiring reoperation had significant right lateral parametrial involvement and underwent nerve-sparing parametrectomy at the time of bowel resection).³Notably, 7 of the 81 patients had totally laparoscopic double segmental colorectal resection — 6 with simultaneous ileocecal valve and rectal resection, and 1 with simultaneous ileal and rectal resection. None of these seven patients had postoperative complications. (A report on the six surgeries for deep endometriosis infiltrating the ileocecal valve and rectum was also published this year in the journal Colorectal Disease.⁶) 

Median blood loss in the 81-patient cohort was 20 mL (IQR, 20-30 mL), and the median length of surgery was 160 minutes (IQR, 130-210 minutes). 

Bowel endometriotic nodules had a mean maximum diameter of 4.3 cm (3.5-5.5 cm), a mean depth of invasion of 9 mm (7-9 mm), a mean estimated stenosis of 40% (35%-50%), and a mean distance from the anal verge of 13 cm (10-15 cm).³ (The cohort in this analysis did not include patients who received concomitant hysterectomy and transvaginal NOSE.)

Specifics of the New Technique, Including Totally Intracorporeal Anastomosis

As in our previous technique, the surgical procedure starts with left and dorsal rectal mobilization. The left pelvic sidewall dissection begins with incision of the parietal peritoneum along the pelvic portions of the psoas muscle. The retroperitoneal connective tissue is dissected in order to identify the ureter, the hypogastric nerve, and the presacral parietal pelvic fascia (PPPF). Dissection is carried downward in front of the PPPF and medially to the left hypogastric nerve.

Right and ventral rectal mobilization begins with incision of the peritoneum along the gray avascular line, which is seen with upward retraction of the rectum. 

Again, for preservation of bowel and bladder function, the hypogastric nerve must be identified and preserved through dissection that displaces the nerve dorsally and laterally. 

Dissection proceeds to sharply divide the nodule into two parts (rectal and rectocervical components). The caudal boundary of ventral dissection is reached by incising the septum and opening the rectovaginal space. The lymphovascular fatty tissue surrounding the rectum is then excised and the rectal tube is denuded at the level of the distal resection margin. 

The distal and proximal resection margins are prepared and transected using a tissue-sealing device, and the resected rectal specimen is placed into a retrieval bag and pulled out through the anus (Figure 1). 

 

The totally intracorporeal side-to-end anastomosis is performed using a traditional circular stapler. Its anvil is inserted through the proximal resection line and exteriorized forward on the antimesenteric side of the sigmoid colon/rectum. The proximal and distal resection lines are closed with a 60-mm linear endo-stapler, and finally, the shaft of the circular stapler is inserted into the rectum, and the two parts of the stapler are joined. The stapler is then closed and fired (Figure 2). 

 

An air leak test is performed to check the quality of the rectal sutures. However, regardless of the results, we routinely apply interrupted stitches to the so-called “dog ears” in order to reduce tension along the anastomotic line. 

We also evaluate the microvascularization of the two parts of the bowel at the level of the reanastomosis using indocyanine green fluorescence angiography. Doing so allows us to avoid complications caused by anastomotic leakage. 

 

Patient Selection And Peri-Surgical Care

The decision to perform segmental resection as opposed to other more conservative laparoscopic excision techniques is made after skilled preoperative imaging reveals the number of lesions, the largest nodule diameter, the infiltration depth, and the circumference of bowel involvement.

A recently published international consensus statement⁷ on noninvasive imaging techniques for diagnosis of pelvic deep endometriosis and endometriosis classification systems concludes there is Level 1a evidence that preoperative imaging with transvaginal ultrasound (TVUS) can predict with good precision the size and degree of infiltration of deep endometriosis of the rectum (a Grade A statement, per the Oxford Centre for Evidence-Based Medicine levels of evidence). 

The consensus document was published across seven different journals by international and European societies, and the American Association of Gynecologic Laparoscopists (AAGL), each of which contributed to a multidisciplinary panel of gynecological surgeons, sonographers, and radiologists. 

At our center, we achieve precise preoperative evaluations with TVUS (other centers also employ MRI) and have long set clear preoperative indications for segmental resection. Based on our experience,⁸ a nodule ≥ 3 cm and infiltration of the tunica muscularis of the sigmoid colon/rectum ≥ 7 mm indicate the need for segmental resection. It is impossible to achieve surgical goals in such cases through shaving or discoid resection. 

Our perioperative care protocol for total laparoscopic segmental resection with transanal NOSE, described in our new paper,³ includes several components: antibiotic therapy (metronidazole 500 mg 12 hours before surgery; cefazolin 2 g plus metronidazole 500 mg 1 hour before skin incision; and cefazolin 1 g plus metronidazole 500 mg 12 hours after surgery); good intraoperative bowel preparation (mechanical with oral polyethylene glycol solution preoperatively, and rectal irrigation with a mixed solution of povidine-iodine and normal saline intraoperatively); and venous thromboembolism prophylaxis postoperatively for 28 days.

Moving Forward, A Word On Classification

Multicenter trials and research with longer follow-up times will be helpful in advancing the use of totally laparoscopic segmental colorectal resection for deep endometriosis. To enable better sharing of diagnostic and therapeutic results — and to advance the credibility of research — my hope is that the field will reach further agreement on endometriosis classification systems. This would also help with the development of standards for postgraduate education.

We have made significant strides in recognizing imaging as a standard for diagnosis and treatment, and I believe we currently have two very good endometriosis classification systems — the #Enzian classification system issued in 2021 and the AAGL 2021 Endometriosis Classification — that can be used in combination with imaging to reliably and consistently describe deep endometriosis.

Mario Malzoni, MD, is scientific director of the Malzoni Research Hospital, the Center for Advanced Pelvic Surgery, in Avellino, Italy. He reported having no disclosures relevant to this Master Class. 

References

1. Malzoni M et al. Surgical principles of segmental rectosigmoid resection and reanastomosis for deep infiltrating endometriosis. J Minim Invasive Gynecol. 2020;27(2):258. 

2. Malzoni M et al. Totally laparoscopic resection with transanal natural orifice specimen extraction for deep endometriosis infiltrating the rectum. J Minim Invasive Gynecol. 2022;29(1):19. 

3. Malzoni M et al. Total laparoscopic segmental resection with transanal natural orifice specimen extraction for treatment of colorectal endometriosis: Descriptive analysis from the TrEnd study database. J Minim Invasive Gynecol. 2024. (in press). 4. Brincat SD et al. Natural orifice versus transabdominal specimen extraction in laparoscopic surgery for colorectal cancer: meta-analysis. BJS Open 2022;6(3):zrac074.

5. Zhou Z et al. Laparoscopic natural orifice specimen extraction surgery versus conventional surgery in colorectal cancer: A meta-analysis of randomized controlled trials. Gastroenterol Res Pract. 2022 Jan 18;2022:6661651. 

6. Malzoni M et al. Simultaneous total laparoscopic double segmental resection with transanal natural orifice specimen extraction for deep endometriosis infiltrating the ileocaecal valve and rectum—A video vignette. Colorectal Dis 2024 Jul 25. 

7. Condous G et al. Noninvasive imaging techniques for diagnosis of pelvic deep endometriosis and endometriosis classification systems: An international consensus. J. Minim Invasive Gynecol. 2024;31(7):557-73. 

8. Malzoni M et al. Preoperative ultrasound indications determine excision technique for bowel surgery for deep infiltrating endometriosis: A single, high-volume center. J Minim Invasive Gynecol. 2020;27(5):1141-7.

What to Know About NOSE

Traditionally, a laparoscopic approach to bowel resection secondary to endometriosis means enlargement of the port site or more commonly, a Pfannenstiel incision to introduce an anvil. Both incisions raise the risk of postoperative complications including pain and incisional hernia. Moreover, recovery time is prolonged.

Natural orifice specimen extraction (NOSE) makes use of a natural orifice, the vagina or anus, to extract the specimen and introduce the anvil. Transanal extraction for the management of endometriosis-related bowel disease was first described by the late David Redwine, MD, in his 1996 publication in Fertility and Sterility.¹

The concern with use of vaginal NOSE surgery is rectovaginal fistula secondary to two incision lines in close opposition. Both transvaginal NOSE and transanal NOSE have been criticized for longer dissection of the mesorectum and thus longer resected specimen. Despite these concerns, over the past 10 years, articles have been published showing not only the feasibility of the NOSE technique, but excellent comparative outcomes, as well.^2-4

 

A recent systematic review and meta-analysis by Kar et al. comparing NOSE extraction to minilaparotomy in bowel resection due to endometriosis revealed no significant difference in complication rate, but significantly shorter operation duration, reduced length of stay, and less blood loss in the NOSE surgical arm.⁵

The most recent study to be published in the Journal of Minimally Invasive Gynecology involving total laparoscopic segmental resection with transanal NOSE for the treatment of colorectal endometriosis was written by the guest author of this edition of the Master Class in Gynecologic Surgery, Professor Mario Malzoni, Scientific Director of the Malzoni Research Hospital, the Center for Advanced Pelvic Surgery, in Avellino, Italy. In the JMIG article, and in this Master Class, Professor Malzoni, a world-renowned endometriosis specialist recognized for his extraordinary skill and multi-organ surgical work, discusses the difference between the standard bowel resection technique with that of NOSE, and reports on his experience with NOSE.⁶

It is a pleasure and honor to welcome my friend and colleague, Professor Mario Malzoni, to this edition of the Master Class in Gynecologic Surgery.

Dr. Charles E. Miller is Professor, Obstetrics & Gynecology, Department of Clinical Sciences, Rosalind Franklin University of Medicine and Science, North Chicago, and Director, Minimally Invasive Gynecologic Surgery, Advocate Lutheran General Hospital, Park Ridge, both in Illinois. Email him at obnews@mdedge.com.

References

1. Redwine DB et al. Laparoscopically assisted transvaginal segmental resection of the rectosigmoid colon for endometriosis. Fertil Steril. 1996 Jan;65(1):193-7.

2. Akladios C et al. Totally laparoscopic intracorporeal anastomosis with natural orifice specimen extraction (NOSE) techniques, particularly suitable for bowel endometriosis. J Minim Invasive Gynecol. 2014 Nov-Dec;21(6):1095-102.

3. Bokor A et al. Natural orifice specimen extraction during laparoscopic bowel resection for colorectal endometriosis: technique and outcome. J Minim Invasive Gynecol. 2018 Sep-Oct;25(6):1065-74.

4. Grigoriadis G et al. Natural orifice specimen extraction colorectal resection for deep endometriosis: A 50 case series. J Minim Invasive Gynecol. 2022 Sep;29(9):1054-62.

5. Kar E et al. Natural orifice specimen extraction as a promising alternative for minilaparotomy in bowel resection due to endometriosis: A systematic review and meta-analysis. J Minim Invasive Gynecol. 2024 Jul;31(7):574-83.e1.

6. Malzoni M et al. Total laparoscopic segmental resection with transanal natural orifice specimen extraction for treatment of colorectal endometriosis: Descriptive analysis from the TrEnd study database. J Minim Invasive Gynecol. 2024 Oct;18:S1553-4650(24)01453-5.

Laparoscopic Resection With Transanal NOSE for Deep Colorectal Endometriosis

When segmental sigmoid colon/rectal resection is indicated for treatment of deep infiltrating bowel endometriosis, a totally laparoscopic resection with intracorporeal anastomosis and transanal natural orifice specimen extraction (NOSE) can be safe, effective, and advantageous compared with an abdominal mini-laparotomy for extracorporeal anastomosis and specimen retrieval.

With advanced laparoscopic surgical skills, accurate preoperative ultrasound evaluation, and a high-quality perioperative care protocol (including high-quality bowel preparation), segmental resection with NOSE can offer better preservation of vascularization, smaller resection sizes, lower rates of postoperative pain, a shorter time for gas passage after surgery, decreased hospital stays, and lower rates of wound infection and incisional hernia.

We have seen such improved results in our high-volume center since shifting in April 2021 from our classical technique for segmental rectosigmoid resection¹ to a totally laparoscopic approach with NOSE. We first reported on this new technique in 2022 in a video article in the Journal of Minimally Invasive Gynecology,²and in October 2024, outcomes of 81 patients who underwent segmental sigmoid colon/rectal resection with intracorporeal anastomosis and transanal NOSE at our institution from April 2021 through March 2024 were reported in Journal of Minimally Invasive Gynecology.³Given our experience with this approach for deep endometriosis, I am convinced that NOSE should be preferred to transabdominal specimen extraction for segmental rectosigmoid resection. This is where the future lies for deep infiltrating endometriosis. Here, I share our outcomes and describe our technique.

Our Prior Approach With A Mini-Laparotomy

Our traditional laparoscopic approach for segmental colon/rectal resection of deep infiltrating endometriosis involved an abdominal mini-laparotomy (no more than 4 cm in length) for specimen retrieval, resection of the proximal rectum, and positioning of the head of a circular stapler for end-to-end anastomosis. (Connection of the two parts of the circular stapler for anastomosis was achieved via laparoscopy.)¹

Several factors allowed us to minimize potential complications, including standardization of our technique, the use of three-dimensional endoscopes, and indocyanine green fluorescence angiography to assess the perfusion of the bowel after the completion of anastomosis. Still, an unpublished analysis of 1050 segmental bowel resections performed over more than 17 years using our traditional technique showed that hospital stays averaged 8 days, time to first defecation averaged 7 days, and time to first passage of flatus averaged 1 day. 

Per the Clavien-Dindo classification system for surgical complications that was used at the time, 1.9% of these 1050 patients had grade 1 (minor) or grade 2 complications and 6% had grade 3 complications. Grade 2 complications were defined as needing intervention or a hospital stay more than twice the median for the procedure. Grade 3 complications were defined as leading to lasting disability or organ resection. 

In the meantime, in colorectal cancer surgery, published studies on NOSE versus conventional laparoscopy with transabdominal specimen extraction have consistently pointed to the benefits of NOSE. A 2022 review ⁴ of 19 studies involving over 3400 patients and a 2022 meta-analysis ⁵ of 21 randomized controlled trials involving more than 2000 patients both showed significantly reduced postoperative morbidity and no differences in oncologic outcomes. Among the notable differences in the 2022 meta-analysis was a relative risk of postoperative infection of 0.34 for patients treated with NOSE compared with conventional laparoscopic techniques. 

Among patients with deep rectal endometriosis, reported experience with intracorporeal anastomosis and NOSE for segmental resection is limited, with a few studies published between 2014 and 2022. Excluding anecdotal reports, only about 140 patients have been reported in the literature as having intracorporeal anastomosis and transanal NOSE for deep infiltrating bowel endometriosis. ³

Our Outcomes With A Totally Laparoscopic Approach

Our approach to evaluating our experience with totally laparoscopic resection with transanal NOSE has been to systematically collect data from consecutive patients and to analyze 1) complications of the technique, 2) conversion to the traditional technique/open surgery, and 3) endometriosis-free bowel resection margins and recurrence. Secondarily, we look at intraoperative blood loss, operative time, recovery of gastrointestinal function, hospital stay length, and reproductive outcomes.

Across 81 patients from our TrEnd study database (Surgical TReatment of women with deep ENDometriosis infiltrating the sigmoid colon and/or rectum) who received a totally laparoscopic standardized procedure involving intracorporeal anastomosis and transanal NOSE, we had no conversions even to mini-laparotomy, and no cases of protective colostomy or ileostomy. 

Complete endometriosis removal was achieved in 100% of cases, with final pathology showing endometriosis-free resection margins, and patients remained free of bowel endometriosis at a median follow-up of 21 months.³Our analysis also shows improved gastrointestinal function recovery (median time to first defecation of 4 days, compared to 7 days previously, with the same 1-day median time to first passage of flatus) and a significantly improved hospital length of stay to a median of 3 days (interquartile range, 3-4.5 days); the latter reflects in part the absence of infection.³There were no intra-operative complications. Postoperative Clavien-Dindo grade 3 complications occurred in three patients (3.7%), two of whom required reoperation (one for hemoperitoneum and one for ureteral injury) and one who experienced rectal anastomotic bleeding on postoperative day 1. (The two requiring reoperation had significant right lateral parametrial involvement and underwent nerve-sparing parametrectomy at the time of bowel resection).³Notably, 7 of the 81 patients had totally laparoscopic double segmental colorectal resection — 6 with simultaneous ileocecal valve and rectal resection, and 1 with simultaneous ileal and rectal resection. None of these seven patients had postoperative complications. (A report on the six surgeries for deep endometriosis infiltrating the ileocecal valve and rectum was also published this year in the journal Colorectal Disease.⁶) 

Median blood loss in the 81-patient cohort was 20 mL (IQR, 20-30 mL), and the median length of surgery was 160 minutes (IQR, 130-210 minutes). 

Bowel endometriotic nodules had a mean maximum diameter of 4.3 cm (3.5-5.5 cm), a mean depth of invasion of 9 mm (7-9 mm), a mean estimated stenosis of 40% (35%-50%), and a mean distance from the anal verge of 13 cm (10-15 cm).³ (The cohort in this analysis did not include patients who received concomitant hysterectomy and transvaginal NOSE.)

Specifics of the New Technique, Including Totally Intracorporeal Anastomosis

As in our previous technique, the surgical procedure starts with left and dorsal rectal mobilization. The left pelvic sidewall dissection begins with incision of the parietal peritoneum along the pelvic portions of the psoas muscle. The retroperitoneal connective tissue is dissected in order to identify the ureter, the hypogastric nerve, and the presacral parietal pelvic fascia (PPPF). Dissection is carried downward in front of the PPPF and medially to the left hypogastric nerve.

Right and ventral rectal mobilization begins with incision of the peritoneum along the gray avascular line, which is seen with upward retraction of the rectum. 

Again, for preservation of bowel and bladder function, the hypogastric nerve must be identified and preserved through dissection that displaces the nerve dorsally and laterally. 

Dissection proceeds to sharply divide the nodule into two parts (rectal and rectocervical components). The caudal boundary of ventral dissection is reached by incising the septum and opening the rectovaginal space. The lymphovascular fatty tissue surrounding the rectum is then excised and the rectal tube is denuded at the level of the distal resection margin. 

The distal and proximal resection margins are prepared and transected using a tissue-sealing device, and the resected rectal specimen is placed into a retrieval bag and pulled out through the anus (Figure 1). 

 

The totally intracorporeal side-to-end anastomosis is performed using a traditional circular stapler. Its anvil is inserted through the proximal resection line and exteriorized forward on the antimesenteric side of the sigmoid colon/rectum. The proximal and distal resection lines are closed with a 60-mm linear endo-stapler, and finally, the shaft of the circular stapler is inserted into the rectum, and the two parts of the stapler are joined. The stapler is then closed and fired (Figure 2). 

 

An air leak test is performed to check the quality of the rectal sutures. However, regardless of the results, we routinely apply interrupted stitches to the so-called “dog ears” in order to reduce tension along the anastomotic line. 

We also evaluate the microvascularization of the two parts of the bowel at the level of the reanastomosis using indocyanine green fluorescence angiography. Doing so allows us to avoid complications caused by anastomotic leakage. 

 

Patient Selection And Peri-Surgical Care

The decision to perform segmental resection as opposed to other more conservative laparoscopic excision techniques is made after skilled preoperative imaging reveals the number of lesions, the largest nodule diameter, the infiltration depth, and the circumference of bowel involvement.

A recently published international consensus statement⁷ on noninvasive imaging techniques for diagnosis of pelvic deep endometriosis and endometriosis classification systems concludes there is Level 1a evidence that preoperative imaging with transvaginal ultrasound (TVUS) can predict with good precision the size and degree of infiltration of deep endometriosis of the rectum (a Grade A statement, per the Oxford Centre for Evidence-Based Medicine levels of evidence). 

The consensus document was published across seven different journals by international and European societies, and the American Association of Gynecologic Laparoscopists (AAGL), each of which contributed to a multidisciplinary panel of gynecological surgeons, sonographers, and radiologists. 

At our center, we achieve precise preoperative evaluations with TVUS (other centers also employ MRI) and have long set clear preoperative indications for segmental resection. Based on our experience,⁸ a nodule ≥ 3 cm and infiltration of the tunica muscularis of the sigmoid colon/rectum ≥ 7 mm indicate the need for segmental resection. It is impossible to achieve surgical goals in such cases through shaving or discoid resection. 

Our perioperative care protocol for total laparoscopic segmental resection with transanal NOSE, described in our new paper,³ includes several components: antibiotic therapy (metronidazole 500 mg 12 hours before surgery; cefazolin 2 g plus metronidazole 500 mg 1 hour before skin incision; and cefazolin 1 g plus metronidazole 500 mg 12 hours after surgery); good intraoperative bowel preparation (mechanical with oral polyethylene glycol solution preoperatively, and rectal irrigation with a mixed solution of povidine-iodine and normal saline intraoperatively); and venous thromboembolism prophylaxis postoperatively for 28 days.

Moving Forward, A Word On Classification

Multicenter trials and research with longer follow-up times will be helpful in advancing the use of totally laparoscopic segmental colorectal resection for deep endometriosis. To enable better sharing of diagnostic and therapeutic results — and to advance the credibility of research — my hope is that the field will reach further agreement on endometriosis classification systems. This would also help with the development of standards for postgraduate education.

We have made significant strides in recognizing imaging as a standard for diagnosis and treatment, and I believe we currently have two very good endometriosis classification systems — the #Enzian classification system issued in 2021 and the AAGL 2021 Endometriosis Classification — that can be used in combination with imaging to reliably and consistently describe deep endometriosis.

Mario Malzoni, MD, is scientific director of the Malzoni Research Hospital, the Center for Advanced Pelvic Surgery, in Avellino, Italy. He reported having no disclosures relevant to this Master Class. 

References

1. Malzoni M et al. Surgical principles of segmental rectosigmoid resection and reanastomosis for deep infiltrating endometriosis. J Minim Invasive Gynecol. 2020;27(2):258. 

2. Malzoni M et al. Totally laparoscopic resection with transanal natural orifice specimen extraction for deep endometriosis infiltrating the rectum. J Minim Invasive Gynecol. 2022;29(1):19. 

3. Malzoni M et al. Total laparoscopic segmental resection with transanal natural orifice specimen extraction for treatment of colorectal endometriosis: Descriptive analysis from the TrEnd study database. J Minim Invasive Gynecol. 2024. (in press). 4. Brincat SD et al. Natural orifice versus transabdominal specimen extraction in laparoscopic surgery for colorectal cancer: meta-analysis. BJS Open 2022;6(3):zrac074.

5. Zhou Z et al. Laparoscopic natural orifice specimen extraction surgery versus conventional surgery in colorectal cancer: A meta-analysis of randomized controlled trials. Gastroenterol Res Pract. 2022 Jan 18;2022:6661651. 

6. Malzoni M et al. Simultaneous total laparoscopic double segmental resection with transanal natural orifice specimen extraction for deep endometriosis infiltrating the ileocaecal valve and rectum—A video vignette. Colorectal Dis 2024 Jul 25. 

7. Condous G et al. Noninvasive imaging techniques for diagnosis of pelvic deep endometriosis and endometriosis classification systems: An international consensus. J. Minim Invasive Gynecol. 2024;31(7):557-73. 

8. Malzoni M et al. Preoperative ultrasound indications determine excision technique for bowel surgery for deep infiltrating endometriosis: A single, high-volume center. J Minim Invasive Gynecol. 2020;27(5):1141-7.

What to Know About NOSE

Traditionally, a laparoscopic approach to bowel resection secondary to endometriosis means enlargement of the port site or more commonly, a Pfannenstiel incision to introduce an anvil. Both incisions raise the risk of postoperative complications including pain and incisional hernia. Moreover, recovery time is prolonged.

Natural orifice specimen extraction (NOSE) makes use of a natural orifice, the vagina or anus, to extract the specimen and introduce the anvil. Transanal extraction for the management of endometriosis-related bowel disease was first described by the late David Redwine, MD, in his 1996 publication in Fertility and Sterility.¹

The concern with use of vaginal NOSE surgery is rectovaginal fistula secondary to two incision lines in close opposition. Both transvaginal NOSE and transanal NOSE have been criticized for longer dissection of the mesorectum and thus longer resected specimen. Despite these concerns, over the past 10 years, articles have been published showing not only the feasibility of the NOSE technique, but excellent comparative outcomes, as well.^2-4

 

A recent systematic review and meta-analysis by Kar et al. comparing NOSE extraction to minilaparotomy in bowel resection due to endometriosis revealed no significant difference in complication rate, but significantly shorter operation duration, reduced length of stay, and less blood loss in the NOSE surgical arm.⁵

The most recent study to be published in the Journal of Minimally Invasive Gynecology involving total laparoscopic segmental resection with transanal NOSE for the treatment of colorectal endometriosis was written by the guest author of this edition of the Master Class in Gynecologic Surgery, Professor Mario Malzoni, Scientific Director of the Malzoni Research Hospital, the Center for Advanced Pelvic Surgery, in Avellino, Italy. In the JMIG article, and in this Master Class, Professor Malzoni, a world-renowned endometriosis specialist recognized for his extraordinary skill and multi-organ surgical work, discusses the difference between the standard bowel resection technique with that of NOSE, and reports on his experience with NOSE.⁶

It is a pleasure and honor to welcome my friend and colleague, Professor Mario Malzoni, to this edition of the Master Class in Gynecologic Surgery.

Dr. Charles E. Miller is Professor, Obstetrics & Gynecology, Department of Clinical Sciences, Rosalind Franklin University of Medicine and Science, North Chicago, and Director, Minimally Invasive Gynecologic Surgery, Advocate Lutheran General Hospital, Park Ridge, both in Illinois. Email him at obnews@mdedge.com.

References

1. Redwine DB et al. Laparoscopically assisted transvaginal segmental resection of the rectosigmoid colon for endometriosis. Fertil Steril. 1996 Jan;65(1):193-7.

2. Akladios C et al. Totally laparoscopic intracorporeal anastomosis with natural orifice specimen extraction (NOSE) techniques, particularly suitable for bowel endometriosis. J Minim Invasive Gynecol. 2014 Nov-Dec;21(6):1095-102.

3. Bokor A et al. Natural orifice specimen extraction during laparoscopic bowel resection for colorectal endometriosis: technique and outcome. J Minim Invasive Gynecol. 2018 Sep-Oct;25(6):1065-74.

4. Grigoriadis G et al. Natural orifice specimen extraction colorectal resection for deep endometriosis: A 50 case series. J Minim Invasive Gynecol. 2022 Sep;29(9):1054-62.

5. Kar E et al. Natural orifice specimen extraction as a promising alternative for minilaparotomy in bowel resection due to endometriosis: A systematic review and meta-analysis. J Minim Invasive Gynecol. 2024 Jul;31(7):574-83.e1.

6. Malzoni M et al. Total laparoscopic segmental resection with transanal natural orifice specimen extraction for treatment of colorectal endometriosis: Descriptive analysis from the TrEnd study database. J Minim Invasive Gynecol. 2024 Oct;18:S1553-4650(24)01453-5.

Laparoscopic Resection With Transanal NOSE for Deep Colorectal Endometriosis

When segmental sigmoid colon/rectal resection is indicated for treatment of deep infiltrating bowel endometriosis, a totally laparoscopic resection with intracorporeal anastomosis and transanal natural orifice specimen extraction (NOSE) can be safe, effective, and advantageous compared with an abdominal mini-laparotomy for extracorporeal anastomosis and specimen retrieval.

With advanced laparoscopic surgical skills, accurate preoperative ultrasound evaluation, and a high-quality perioperative care protocol (including high-quality bowel preparation), segmental resection with NOSE can offer better preservation of vascularization, smaller resection sizes, lower rates of postoperative pain, a shorter time for gas passage after surgery, decreased hospital stays, and lower rates of wound infection and incisional hernia.

We have seen such improved results in our high-volume center since shifting in April 2021 from our classical technique for segmental rectosigmoid resection¹ to a totally laparoscopic approach with NOSE. We first reported on this new technique in 2022 in a video article in the Journal of Minimally Invasive Gynecology,²and in October 2024, outcomes of 81 patients who underwent segmental sigmoid colon/rectal resection with intracorporeal anastomosis and transanal NOSE at our institution from April 2021 through March 2024 were reported in Journal of Minimally Invasive Gynecology.³Given our experience with this approach for deep endometriosis, I am convinced that NOSE should be preferred to transabdominal specimen extraction for segmental rectosigmoid resection. This is where the future lies for deep infiltrating endometriosis. Here, I share our outcomes and describe our technique.

Our Prior Approach With A Mini-Laparotomy

Our traditional laparoscopic approach for segmental colon/rectal resection of deep infiltrating endometriosis involved an abdominal mini-laparotomy (no more than 4 cm in length) for specimen retrieval, resection of the proximal rectum, and positioning of the head of a circular stapler for end-to-end anastomosis. (Connection of the two parts of the circular stapler for anastomosis was achieved via laparoscopy.)¹

Several factors allowed us to minimize potential complications, including standardization of our technique, the use of three-dimensional endoscopes, and indocyanine green fluorescence angiography to assess the perfusion of the bowel after the completion of anastomosis. Still, an unpublished analysis of 1050 segmental bowel resections performed over more than 17 years using our traditional technique showed that hospital stays averaged 8 days, time to first defecation averaged 7 days, and time to first passage of flatus averaged 1 day. 

Per the Clavien-Dindo classification system for surgical complications that was used at the time, 1.9% of these 1050 patients had grade 1 (minor) or grade 2 complications and 6% had grade 3 complications. Grade 2 complications were defined as needing intervention or a hospital stay more than twice the median for the procedure. Grade 3 complications were defined as leading to lasting disability or organ resection. 

In the meantime, in colorectal cancer surgery, published studies on NOSE versus conventional laparoscopy with transabdominal specimen extraction have consistently pointed to the benefits of NOSE. A 2022 review ⁴ of 19 studies involving over 3400 patients and a 2022 meta-analysis ⁵ of 21 randomized controlled trials involving more than 2000 patients both showed significantly reduced postoperative morbidity and no differences in oncologic outcomes. Among the notable differences in the 2022 meta-analysis was a relative risk of postoperative infection of 0.34 for patients treated with NOSE compared with conventional laparoscopic techniques. 

Among patients with deep rectal endometriosis, reported experience with intracorporeal anastomosis and NOSE for segmental resection is limited, with a few studies published between 2014 and 2022. Excluding anecdotal reports, only about 140 patients have been reported in the literature as having intracorporeal anastomosis and transanal NOSE for deep infiltrating bowel endometriosis. ³

Our Outcomes With A Totally Laparoscopic Approach

Our approach to evaluating our experience with totally laparoscopic resection with transanal NOSE has been to systematically collect data from consecutive patients and to analyze 1) complications of the technique, 2) conversion to the traditional technique/open surgery, and 3) endometriosis-free bowel resection margins and recurrence. Secondarily, we look at intraoperative blood loss, operative time, recovery of gastrointestinal function, hospital stay length, and reproductive outcomes.

Across 81 patients from our TrEnd study database (Surgical TReatment of women with deep ENDometriosis infiltrating the sigmoid colon and/or rectum) who received a totally laparoscopic standardized procedure involving intracorporeal anastomosis and transanal NOSE, we had no conversions even to mini-laparotomy, and no cases of protective colostomy or ileostomy. 

Complete endometriosis removal was achieved in 100% of cases, with final pathology showing endometriosis-free resection margins, and patients remained free of bowel endometriosis at a median follow-up of 21 months.³Our analysis also shows improved gastrointestinal function recovery (median time to first defecation of 4 days, compared to 7 days previously, with the same 1-day median time to first passage of flatus) and a significantly improved hospital length of stay to a median of 3 days (interquartile range, 3-4.5 days); the latter reflects in part the absence of infection.³There were no intra-operative complications. Postoperative Clavien-Dindo grade 3 complications occurred in three patients (3.7%), two of whom required reoperation (one for hemoperitoneum and one for ureteral injury) and one who experienced rectal anastomotic bleeding on postoperative day 1. (The two requiring reoperation had significant right lateral parametrial involvement and underwent nerve-sparing parametrectomy at the time of bowel resection).³Notably, 7 of the 81 patients had totally laparoscopic double segmental colorectal resection — 6 with simultaneous ileocecal valve and rectal resection, and 1 with simultaneous ileal and rectal resection. None of these seven patients had postoperative complications. (A report on the six surgeries for deep endometriosis infiltrating the ileocecal valve and rectum was also published this year in the journal Colorectal Disease.⁶) 

Median blood loss in the 81-patient cohort was 20 mL (IQR, 20-30 mL), and the median length of surgery was 160 minutes (IQR, 130-210 minutes). 

Bowel endometriotic nodules had a mean maximum diameter of 4.3 cm (3.5-5.5 cm), a mean depth of invasion of 9 mm (7-9 mm), a mean estimated stenosis of 40% (35%-50%), and a mean distance from the anal verge of 13 cm (10-15 cm).³ (The cohort in this analysis did not include patients who received concomitant hysterectomy and transvaginal NOSE.)

Specifics of the New Technique, Including Totally Intracorporeal Anastomosis

As in our previous technique, the surgical procedure starts with left and dorsal rectal mobilization. The left pelvic sidewall dissection begins with incision of the parietal peritoneum along the pelvic portions of the psoas muscle. The retroperitoneal connective tissue is dissected in order to identify the ureter, the hypogastric nerve, and the presacral parietal pelvic fascia (PPPF). Dissection is carried downward in front of the PPPF and medially to the left hypogastric nerve.

Right and ventral rectal mobilization begins with incision of the peritoneum along the gray avascular line, which is seen with upward retraction of the rectum. 

Again, for preservation of bowel and bladder function, the hypogastric nerve must be identified and preserved through dissection that displaces the nerve dorsally and laterally. 

Dissection proceeds to sharply divide the nodule into two parts (rectal and rectocervical components). The caudal boundary of ventral dissection is reached by incising the septum and opening the rectovaginal space. The lymphovascular fatty tissue surrounding the rectum is then excised and the rectal tube is denuded at the level of the distal resection margin. 

The distal and proximal resection margins are prepared and transected using a tissue-sealing device, and the resected rectal specimen is placed into a retrieval bag and pulled out through the anus (Figure 1). 

 

The totally intracorporeal side-to-end anastomosis is performed using a traditional circular stapler. Its anvil is inserted through the proximal resection line and exteriorized forward on the antimesenteric side of the sigmoid colon/rectum. The proximal and distal resection lines are closed with a 60-mm linear endo-stapler, and finally, the shaft of the circular stapler is inserted into the rectum, and the two parts of the stapler are joined. The stapler is then closed and fired (Figure 2). 

 

An air leak test is performed to check the quality of the rectal sutures. However, regardless of the results, we routinely apply interrupted stitches to the so-called “dog ears” in order to reduce tension along the anastomotic line. 

We also evaluate the microvascularization of the two parts of the bowel at the level of the reanastomosis using indocyanine green fluorescence angiography. Doing so allows us to avoid complications caused by anastomotic leakage. 

 

Patient Selection And Peri-Surgical Care

The decision to perform segmental resection as opposed to other more conservative laparoscopic excision techniques is made after skilled preoperative imaging reveals the number of lesions, the largest nodule diameter, the infiltration depth, and the circumference of bowel involvement.

A recently published international consensus statement⁷ on noninvasive imaging techniques for diagnosis of pelvic deep endometriosis and endometriosis classification systems concludes there is Level 1a evidence that preoperative imaging with transvaginal ultrasound (TVUS) can predict with good precision the size and degree of infiltration of deep endometriosis of the rectum (a Grade A statement, per the Oxford Centre for Evidence-Based Medicine levels of evidence). 

The consensus document was published across seven different journals by international and European societies, and the American Association of Gynecologic Laparoscopists (AAGL), each of which contributed to a multidisciplinary panel of gynecological surgeons, sonographers, and radiologists. 

At our center, we achieve precise preoperative evaluations with TVUS (other centers also employ MRI) and have long set clear preoperative indications for segmental resection. Based on our experience,⁸ a nodule ≥ 3 cm and infiltration of the tunica muscularis of the sigmoid colon/rectum ≥ 7 mm indicate the need for segmental resection. It is impossible to achieve surgical goals in such cases through shaving or discoid resection. 

Our perioperative care protocol for total laparoscopic segmental resection with transanal NOSE, described in our new paper,³ includes several components: antibiotic therapy (metronidazole 500 mg 12 hours before surgery; cefazolin 2 g plus metronidazole 500 mg 1 hour before skin incision; and cefazolin 1 g plus metronidazole 500 mg 12 hours after surgery); good intraoperative bowel preparation (mechanical with oral polyethylene glycol solution preoperatively, and rectal irrigation with a mixed solution of povidine-iodine and normal saline intraoperatively); and venous thromboembolism prophylaxis postoperatively for 28 days.

Moving Forward, A Word On Classification

Multicenter trials and research with longer follow-up times will be helpful in advancing the use of totally laparoscopic segmental colorectal resection for deep endometriosis. To enable better sharing of diagnostic and therapeutic results — and to advance the credibility of research — my hope is that the field will reach further agreement on endometriosis classification systems. This would also help with the development of standards for postgraduate education.

We have made significant strides in recognizing imaging as a standard for diagnosis and treatment, and I believe we currently have two very good endometriosis classification systems — the #Enzian classification system issued in 2021 and the AAGL 2021 Endometriosis Classification — that can be used in combination with imaging to reliably and consistently describe deep endometriosis.

Mario Malzoni, MD, is scientific director of the Malzoni Research Hospital, the Center for Advanced Pelvic Surgery, in Avellino, Italy. He reported having no disclosures relevant to this Master Class. 

References

1. Malzoni M et al. Surgical principles of segmental rectosigmoid resection and reanastomosis for deep infiltrating endometriosis. J Minim Invasive Gynecol. 2020;27(2):258. 

2. Malzoni M et al. Totally laparoscopic resection with transanal natural orifice specimen extraction for deep endometriosis infiltrating the rectum. J Minim Invasive Gynecol. 2022;29(1):19. 

3. Malzoni M et al. Total laparoscopic segmental resection with transanal natural orifice specimen extraction for treatment of colorectal endometriosis: Descriptive analysis from the TrEnd study database. J Minim Invasive Gynecol. 2024. (in press). 4. Brincat SD et al. Natural orifice versus transabdominal specimen extraction in laparoscopic surgery for colorectal cancer: meta-analysis. BJS Open 2022;6(3):zrac074.

5. Zhou Z et al. Laparoscopic natural orifice specimen extraction surgery versus conventional surgery in colorectal cancer: A meta-analysis of randomized controlled trials. Gastroenterol Res Pract. 2022 Jan 18;2022:6661651. 

6. Malzoni M et al. Simultaneous total laparoscopic double segmental resection with transanal natural orifice specimen extraction for deep endometriosis infiltrating the ileocaecal valve and rectum—A video vignette. Colorectal Dis 2024 Jul 25. 

7. Condous G et al. Noninvasive imaging techniques for diagnosis of pelvic deep endometriosis and endometriosis classification systems: An international consensus. J. Minim Invasive Gynecol. 2024;31(7):557-73. 

8. Malzoni M et al. Preoperative ultrasound indications determine excision technique for bowel surgery for deep infiltrating endometriosis: A single, high-volume center. J Minim Invasive Gynecol. 2020;27(5):1141-7.

A dermatophyte known as Trichophyton mentagrophytes genotype VII (TMVII) has been identified as the cause of an emerging sexually transmitted fungal infection in four adults in the United States, according to a paper published in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report.

TMVII is a sexually transmitted fungus that causes genital tinea; the fungus might be misidentified as eczema, psoriasis, or other dermatologic conditions, Jason E. Zucker, MD, an infectious disease specialist at Columbia University Irving Medical Center, New York City, and colleagues wrote.

 

“Dermatophyte infections, including TMVII, are spread through direct skin-to-skin contact,” corresponding author Avrom S. Caplan, MD, a dermatologist at New York University Grossman School of Medicine, New York City, said in an interview.

“In the United States, to our knowledge, the infection has only been in MSM [men who have sex with men], but there have been reports of TMVII in Europe in non-MSM patients, including among patients who traveled to Southeast Asia for sex tourism or partners of people who have been infected with TMVII,” he said.

The four patients were diagnosed with tinea between April 2024 and July 2024, and fungal cultures and DNA sequencing identified TMVII as the cause of the infection. All four patients were cisgender men aged 30-39 years from New York City who reported recent sexual contact with other men; one was a sex worker, two had sex with each other, and one reported recent travel to Europe.

All four patients presented with rashes on the face, buttocks, or genitals; all were successfully treated with antifungals, the authors wrote.

Individuals with genital lesions who are sexually active should be seen by a healthcare provider, and TMVII should be considered, especially in the event of scaly, itchy, or inflamed rashes elsewhere on the body, Caplan told this news organization.

Additionally, “If someone presents for a medical evaluation and has ringworm on the buttocks, face, or elsewhere, especially if they are sexually active, the question of TMVII should arise, and the patient should be asked about possible genital lesions as well,” he said. “Any patient diagnosed with an STI [sexually transmitted infection], including MSM patients, should be evaluated appropriately for other STIs including TMVII.” 

Continued surveillance and monitoring are needed to track TMVII and to better understand emerging infections, Caplan told this news organization. Clinicians can find more information and a dermatophyte registry via the American Academy of Dermatology websites on emerging diseases in general and dermatophytes in particular.

“We also need better access to testing and more rapid confirmatory testing to detect emerging dermatophyte strains and monitor antifungal resistance patterns,” Caplan added. “At this time, we do not have evidence to suggest there is antifungal resistance in TMVII, which also distinguishes it from T indotineae.” 

 

Encourage Reporting and Identify New Infections

“Emerging infections can mimic noninfectious disease processes, which can make the diagnosis challenging,” Shirin A. Mazumder, MD, associate professor and infectious disease specialist at the University of Tennessee Health Science Center, Memphis, said in an interview.

“Monitoring emerging infections can be difficult if the cases are not reported and if the disease is not widespread,” Mazumder noted. Educating clinicians with case reports and encouraging them to report unusual cases to public health helps to overcome this challenge.

In the clinical setting, skin lesions that fail to respond or worsen with the application of topical steroids could be a red flag for TMVII, Mazumder told this news organization. “Since the skin findings of TMVII can closely resemble noninfectious processes such as eczema or psoriasis, the use of topical corticosteroids may have already been tried before the diagnosis of TMVII is considered.” 

Also, location matters in making the diagnosis. TMVII lesions occur on the face, genitals, extremities, trunk, and buttocks. Obtaining a thorough sexual history is important because the fungus spreads from close contact through sexual exposure, Mazumder added.

The most effective treatment for TMVII infections remains to be determined, Mazumder said. “Treatment considerations such as combination treatment with oral and topical antifungal medications vs oral antifungal medication alone is something that needs further research along with the best treatment duration.”

“Determining the rate of transmissibility between contacts, when someone is considered to be the most infectious, how long someone is considered infectious once infected, and rates of reinfection are questions that may benefit from further study,” she added.

Although the current cases are reported in MSM, determining how TMVII affects other patient populations will be interesting as more cases are reported, said Mazumder. “Further understanding of how different degrees of immunosuppression affect TMVII disease course is another important consideration.” 

Finally, determining the rate of long-term sequelae from TMVII infection and the rate of bacterial co-infection will help better understand TMVII, she said.

The researchers had no financial conflicts to disclose. Mazumder had no financial conflicts to disclose.

A version of this article first appeared on Medscape.com.

A dermatophyte known as Trichophyton mentagrophytes genotype VII (TMVII) has been identified as the cause of an emerging sexually transmitted fungal infection in four adults in the United States, according to a paper published in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report.

TMVII is a sexually transmitted fungus that causes genital tinea; the fungus might be misidentified as eczema, psoriasis, or other dermatologic conditions, Jason E. Zucker, MD, an infectious disease specialist at Columbia University Irving Medical Center, New York City, and colleagues wrote.

 

“Dermatophyte infections, including TMVII, are spread through direct skin-to-skin contact,” corresponding author Avrom S. Caplan, MD, a dermatologist at New York University Grossman School of Medicine, New York City, said in an interview.

“In the United States, to our knowledge, the infection has only been in MSM [men who have sex with men], but there have been reports of TMVII in Europe in non-MSM patients, including among patients who traveled to Southeast Asia for sex tourism or partners of people who have been infected with TMVII,” he said.

The four patients were diagnosed with tinea between April 2024 and July 2024, and fungal cultures and DNA sequencing identified TMVII as the cause of the infection. All four patients were cisgender men aged 30-39 years from New York City who reported recent sexual contact with other men; one was a sex worker, two had sex with each other, and one reported recent travel to Europe.

All four patients presented with rashes on the face, buttocks, or genitals; all were successfully treated with antifungals, the authors wrote.

Individuals with genital lesions who are sexually active should be seen by a healthcare provider, and TMVII should be considered, especially in the event of scaly, itchy, or inflamed rashes elsewhere on the body, Caplan told this news organization.

Additionally, “If someone presents for a medical evaluation and has ringworm on the buttocks, face, or elsewhere, especially if they are sexually active, the question of TMVII should arise, and the patient should be asked about possible genital lesions as well,” he said. “Any patient diagnosed with an STI [sexually transmitted infection], including MSM patients, should be evaluated appropriately for other STIs including TMVII.” 

Continued surveillance and monitoring are needed to track TMVII and to better understand emerging infections, Caplan told this news organization. Clinicians can find more information and a dermatophyte registry via the American Academy of Dermatology websites on emerging diseases in general and dermatophytes in particular.

“We also need better access to testing and more rapid confirmatory testing to detect emerging dermatophyte strains and monitor antifungal resistance patterns,” Caplan added. “At this time, we do not have evidence to suggest there is antifungal resistance in TMVII, which also distinguishes it from T indotineae.” 

 

Encourage Reporting and Identify New Infections

“Emerging infections can mimic noninfectious disease processes, which can make the diagnosis challenging,” Shirin A. Mazumder, MD, associate professor and infectious disease specialist at the University of Tennessee Health Science Center, Memphis, said in an interview.

“Monitoring emerging infections can be difficult if the cases are not reported and if the disease is not widespread,” Mazumder noted. Educating clinicians with case reports and encouraging them to report unusual cases to public health helps to overcome this challenge.

In the clinical setting, skin lesions that fail to respond or worsen with the application of topical steroids could be a red flag for TMVII, Mazumder told this news organization. “Since the skin findings of TMVII can closely resemble noninfectious processes such as eczema or psoriasis, the use of topical corticosteroids may have already been tried before the diagnosis of TMVII is considered.” 

Also, location matters in making the diagnosis. TMVII lesions occur on the face, genitals, extremities, trunk, and buttocks. Obtaining a thorough sexual history is important because the fungus spreads from close contact through sexual exposure, Mazumder added.

The most effective treatment for TMVII infections remains to be determined, Mazumder said. “Treatment considerations such as combination treatment with oral and topical antifungal medications vs oral antifungal medication alone is something that needs further research along with the best treatment duration.”

“Determining the rate of transmissibility between contacts, when someone is considered to be the most infectious, how long someone is considered infectious once infected, and rates of reinfection are questions that may benefit from further study,” she added.

Although the current cases are reported in MSM, determining how TMVII affects other patient populations will be interesting as more cases are reported, said Mazumder. “Further understanding of how different degrees of immunosuppression affect TMVII disease course is another important consideration.” 

Finally, determining the rate of long-term sequelae from TMVII infection and the rate of bacterial co-infection will help better understand TMVII, she said.

The researchers had no financial conflicts to disclose. Mazumder had no financial conflicts to disclose.

A version of this article first appeared on Medscape.com.