Ob.Gyn. News

The US Preventive Services Task Force (USPSTF) has posted a draft updated statement on cervical cancer screening. The statement is open for public comment until January 13, 2025, on the task force’s website. 

Nearly all cases of cervical cancer are caused by human papilloma virus (HPV) and most occur in women who have not been regularly screened or appropriately treated, the task force stressed.
 

New Screening Option

In 2024, there will be an estimated 13,820 new cases of cervical cancer and 4360 deaths.

“Evidence shows that screening saves lives, and all women aged 21-65 need to be screened,” task force member Esa Davis, MD, MPH, FAAFP, a professor of family and community medicine and associate vice president for community health at the University of Maryland, Baltimore, said in an interview. A new feature in the 2024 draft statement endorsing self-collection of cervical samples for HPV testing may facilitate broader screening. 

“We hope the new effective option of self-collecting will expand screening and allow even more women to get screened regularly,” Davis said. “Some may feel more comfortable collecting samples themselves, and the collection can be office-based or home-based, but it’s very important that it be done under the direction of a clinician.” 

In agreement is Diego Aviles, MD, an assistant professor and a gynecologic oncologist with UTHealth Houston. “Self-collection will absolutely expand screening. I think it’s an incredible advancement in medicine that patients are able to collect in the comfort of their own homes with no need to come into the office for an uncomfortable pelvic exam,” he said in an interview. “This empowers the patient and gives her a choice.”

As to concern about potential error, he added that while this is a concern on paper, “a lot of studies have shown that self-collection is just as effective doctor collection.” 

Largely consistent with the task force’s 2018 screening recommendations, the updated suggestions also align with those of other organizations such as the American College of Obstetricians and Gynecologists (ACOG), Davis said.

Christopher M. Zahn, MD, ACOG’s chief of clinical practice and health equity and quality, stressed the importance of cervical cancer screening and said his organization will be reviewing the USPSTF recommendations. He urges ACOG members to consider them and offer their comments on the public-input platform.

Drawing on the latest evidence, the task force is also highlighting for the first time that stand-alone HPV screening gives women aged 30-65 years the best balance of benefits and harms when it comes to finding and preventing cervical cancer, while continuing to reinforce that Pap testing and co-testing are also effective screening options for these women. 

The current draft statement applies to cisgender women and those assigned female sex at birth, including transgender men and nonbinary individuals. The recommendations do not apply to women at increased risk of cervical cancer such as those with HIV infection, a compromised immune system, or a history of treatment for precancerous lesions or cervical cancer. 

Based on a review of evidence on the benefits and harms of screening, the USPSTF’s independent panel of national experts proposed the following:
 

Recommendations for Screening (Based on Grade A Evidence):

• Ages 21-65 years: All women should get screened regularly for this preventable disease.
• Ages 21-29 years: All women in this age group should undergo a Pap test every 3 years but do not need HPV testing. “In this age group most HPV infections will go away on their own because young women have strong immune systems. Older women are likely to have HPV that lasts longer and so they need testing for the virus,” Davis said.
• Ages 30-65 years: As noted, HPV screening gives women in this age category the best balance of benefits and harms in terms of preventing and finding cervical cancer. Pap testing or co-testing (Pap tests and HPV tests) are also effective screening options for this population. Ideally, these women should have an HPV test every 5 years or, alternatively, a Pap test every 3 years, or a combined HPV and Pap test every 5 years (co-testing).

Recommendations Against Screening (No Benefit or Benefit Outweighed by Harms — Grade D evidence):

• Women aged less than 21 years: Screening is not necessary.
• Other women not needing screening: Nor is screening necessary for those of any age who have had a total hysterectomy with removal of the cervix and those aged > 65 years who have had regular screenings with normal results. That means normal results from their last three Pap tests or their last two HPV tests, completed in the past 10 years, with at least one of the tests done in the past 5 years.
• Women aged 65 or more: These women should continue screening only if they have not been screened regularly or have had abnormal results in the past decade such as a high-grade precancerous lesion (cervical intraepithelial neoplasia grade 2 or 3) or cervical cancer.

Davis noted that none of the current recommendations are likely to be controversial or to spark pushback. “But,” said Aviles, “any time I see recent change in medicine, there’s always a little bit of pushback and it may take some time for everyone to be comfortable with the self-collection option. The recommendations still give doctors the grace to use the screening test they feel comfortable with, but I think eventually everyone will get on board with self-collection.”

As for the future, he added, “Over the next few years we’ll have to look at women who are on immune-weakening medications like Skyrizi [risankizumab] for skin conditions like psoriasis. These are commonly used in young people and can increase the risk of cervical cancer. I haven’t seen a lot of conversation about this, but patients should be aware of this risk and recommendations for this group should be different than for the general population.”

The USPSTF also noted a need to assess the magnitude of the incremental benefit and harms of screening and the interval of multiple rounds of HPV-primary screening in HPV-vaccinated cohorts in US populations.

Davis, Aviles, and Zahn and had no relevant competing interests to disclose.
 

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

The US Preventive Services Task Force (USPSTF) has posted a draft updated statement on cervical cancer screening. The statement is open for public comment until January 13, 2025, on the task force’s website. 

Nearly all cases of cervical cancer are caused by human papilloma virus (HPV) and most occur in women who have not been regularly screened or appropriately treated, the task force stressed.
 

New Screening Option

In 2024, there will be an estimated 13,820 new cases of cervical cancer and 4360 deaths.

“Evidence shows that screening saves lives, and all women aged 21-65 need to be screened,” task force member Esa Davis, MD, MPH, FAAFP, a professor of family and community medicine and associate vice president for community health at the University of Maryland, Baltimore, said in an interview. A new feature in the 2024 draft statement endorsing self-collection of cervical samples for HPV testing may facilitate broader screening. 

“We hope the new effective option of self-collecting will expand screening and allow even more women to get screened regularly,” Davis said. “Some may feel more comfortable collecting samples themselves, and the collection can be office-based or home-based, but it’s very important that it be done under the direction of a clinician.” 

In agreement is Diego Aviles, MD, an assistant professor and a gynecologic oncologist with UTHealth Houston. “Self-collection will absolutely expand screening. I think it’s an incredible advancement in medicine that patients are able to collect in the comfort of their own homes with no need to come into the office for an uncomfortable pelvic exam,” he said in an interview. “This empowers the patient and gives her a choice.”

As to concern about potential error, he added that while this is a concern on paper, “a lot of studies have shown that self-collection is just as effective doctor collection.” 

Largely consistent with the task force’s 2018 screening recommendations, the updated suggestions also align with those of other organizations such as the American College of Obstetricians and Gynecologists (ACOG), Davis said.

Christopher M. Zahn, MD, ACOG’s chief of clinical practice and health equity and quality, stressed the importance of cervical cancer screening and said his organization will be reviewing the USPSTF recommendations. He urges ACOG members to consider them and offer their comments on the public-input platform.

Drawing on the latest evidence, the task force is also highlighting for the first time that stand-alone HPV screening gives women aged 30-65 years the best balance of benefits and harms when it comes to finding and preventing cervical cancer, while continuing to reinforce that Pap testing and co-testing are also effective screening options for these women. 

The current draft statement applies to cisgender women and those assigned female sex at birth, including transgender men and nonbinary individuals. The recommendations do not apply to women at increased risk of cervical cancer such as those with HIV infection, a compromised immune system, or a history of treatment for precancerous lesions or cervical cancer. 

Based on a review of evidence on the benefits and harms of screening, the USPSTF’s independent panel of national experts proposed the following:
 

Recommendations for Screening (Based on Grade A Evidence):

• Ages 21-65 years: All women should get screened regularly for this preventable disease.
• Ages 21-29 years: All women in this age group should undergo a Pap test every 3 years but do not need HPV testing. “In this age group most HPV infections will go away on their own because young women have strong immune systems. Older women are likely to have HPV that lasts longer and so they need testing for the virus,” Davis said.
• Ages 30-65 years: As noted, HPV screening gives women in this age category the best balance of benefits and harms in terms of preventing and finding cervical cancer. Pap testing or co-testing (Pap tests and HPV tests) are also effective screening options for this population. Ideally, these women should have an HPV test every 5 years or, alternatively, a Pap test every 3 years, or a combined HPV and Pap test every 5 years (co-testing).

Recommendations Against Screening (No Benefit or Benefit Outweighed by Harms — Grade D evidence):

• Women aged less than 21 years: Screening is not necessary.
• Other women not needing screening: Nor is screening necessary for those of any age who have had a total hysterectomy with removal of the cervix and those aged > 65 years who have had regular screenings with normal results. That means normal results from their last three Pap tests or their last two HPV tests, completed in the past 10 years, with at least one of the tests done in the past 5 years.
• Women aged 65 or more: These women should continue screening only if they have not been screened regularly or have had abnormal results in the past decade such as a high-grade precancerous lesion (cervical intraepithelial neoplasia grade 2 or 3) or cervical cancer.

Davis noted that none of the current recommendations are likely to be controversial or to spark pushback. “But,” said Aviles, “any time I see recent change in medicine, there’s always a little bit of pushback and it may take some time for everyone to be comfortable with the self-collection option. The recommendations still give doctors the grace to use the screening test they feel comfortable with, but I think eventually everyone will get on board with self-collection.”

As for the future, he added, “Over the next few years we’ll have to look at women who are on immune-weakening medications like Skyrizi [risankizumab] for skin conditions like psoriasis. These are commonly used in young people and can increase the risk of cervical cancer. I haven’t seen a lot of conversation about this, but patients should be aware of this risk and recommendations for this group should be different than for the general population.”

The USPSTF also noted a need to assess the magnitude of the incremental benefit and harms of screening and the interval of multiple rounds of HPV-primary screening in HPV-vaccinated cohorts in US populations.

Davis, Aviles, and Zahn and had no relevant competing interests to disclose.
 

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

The US Preventive Services Task Force (USPSTF) has posted a draft updated statement on cervical cancer screening. The statement is open for public comment until January 13, 2025, on the task force’s website. 

Nearly all cases of cervical cancer are caused by human papilloma virus (HPV) and most occur in women who have not been regularly screened or appropriately treated, the task force stressed.
 

New Screening Option

In 2024, there will be an estimated 13,820 new cases of cervical cancer and 4360 deaths.

“Evidence shows that screening saves lives, and all women aged 21-65 need to be screened,” task force member Esa Davis, MD, MPH, FAAFP, a professor of family and community medicine and associate vice president for community health at the University of Maryland, Baltimore, said in an interview. A new feature in the 2024 draft statement endorsing self-collection of cervical samples for HPV testing may facilitate broader screening. 

“We hope the new effective option of self-collecting will expand screening and allow even more women to get screened regularly,” Davis said. “Some may feel more comfortable collecting samples themselves, and the collection can be office-based or home-based, but it’s very important that it be done under the direction of a clinician.” 

In agreement is Diego Aviles, MD, an assistant professor and a gynecologic oncologist with UTHealth Houston. “Self-collection will absolutely expand screening. I think it’s an incredible advancement in medicine that patients are able to collect in the comfort of their own homes with no need to come into the office for an uncomfortable pelvic exam,” he said in an interview. “This empowers the patient and gives her a choice.”

As to concern about potential error, he added that while this is a concern on paper, “a lot of studies have shown that self-collection is just as effective doctor collection.” 

Largely consistent with the task force’s 2018 screening recommendations, the updated suggestions also align with those of other organizations such as the American College of Obstetricians and Gynecologists (ACOG), Davis said.

Christopher M. Zahn, MD, ACOG’s chief of clinical practice and health equity and quality, stressed the importance of cervical cancer screening and said his organization will be reviewing the USPSTF recommendations. He urges ACOG members to consider them and offer their comments on the public-input platform.

Drawing on the latest evidence, the task force is also highlighting for the first time that stand-alone HPV screening gives women aged 30-65 years the best balance of benefits and harms when it comes to finding and preventing cervical cancer, while continuing to reinforce that Pap testing and co-testing are also effective screening options for these women. 

The current draft statement applies to cisgender women and those assigned female sex at birth, including transgender men and nonbinary individuals. The recommendations do not apply to women at increased risk of cervical cancer such as those with HIV infection, a compromised immune system, or a history of treatment for precancerous lesions or cervical cancer. 

Based on a review of evidence on the benefits and harms of screening, the USPSTF’s independent panel of national experts proposed the following:
 

Recommendations for Screening (Based on Grade A Evidence):

• Ages 21-65 years: All women should get screened regularly for this preventable disease.
• Ages 21-29 years: All women in this age group should undergo a Pap test every 3 years but do not need HPV testing. “In this age group most HPV infections will go away on their own because young women have strong immune systems. Older women are likely to have HPV that lasts longer and so they need testing for the virus,” Davis said.
• Ages 30-65 years: As noted, HPV screening gives women in this age category the best balance of benefits and harms in terms of preventing and finding cervical cancer. Pap testing or co-testing (Pap tests and HPV tests) are also effective screening options for this population. Ideally, these women should have an HPV test every 5 years or, alternatively, a Pap test every 3 years, or a combined HPV and Pap test every 5 years (co-testing).

Recommendations Against Screening (No Benefit or Benefit Outweighed by Harms — Grade D evidence):

• Women aged less than 21 years: Screening is not necessary.
• Other women not needing screening: Nor is screening necessary for those of any age who have had a total hysterectomy with removal of the cervix and those aged > 65 years who have had regular screenings with normal results. That means normal results from their last three Pap tests or their last two HPV tests, completed in the past 10 years, with at least one of the tests done in the past 5 years.
• Women aged 65 or more: These women should continue screening only if they have not been screened regularly or have had abnormal results in the past decade such as a high-grade precancerous lesion (cervical intraepithelial neoplasia grade 2 or 3) or cervical cancer.

Davis noted that none of the current recommendations are likely to be controversial or to spark pushback. “But,” said Aviles, “any time I see recent change in medicine, there’s always a little bit of pushback and it may take some time for everyone to be comfortable with the self-collection option. The recommendations still give doctors the grace to use the screening test they feel comfortable with, but I think eventually everyone will get on board with self-collection.”

As for the future, he added, “Over the next few years we’ll have to look at women who are on immune-weakening medications like Skyrizi [risankizumab] for skin conditions like psoriasis. These are commonly used in young people and can increase the risk of cervical cancer. I haven’t seen a lot of conversation about this, but patients should be aware of this risk and recommendations for this group should be different than for the general population.”

The USPSTF also noted a need to assess the magnitude of the incremental benefit and harms of screening and the interval of multiple rounds of HPV-primary screening in HPV-vaccinated cohorts in US populations.

Davis, Aviles, and Zahn and had no relevant competing interests to disclose.
 

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

SAN DIEGO — Significant complications were common in female patients with sickle cell disease (SCD) who underwent fertility preservation (FP) procedures, and 13% required multiple retrieval cycles, a five-center retrospective study found.

Of 46 patients with SCD, complications occurred in 25 of 55 controlled ovarian hyperstimulation cycles, including 29 vaso-occlusive episodes (VOEs), researchers reported at the American Society of Hematology (ASH) 2024 Annual Meeting.

Of 21 post-retrieval VOEs, 19 required emergency department care or hospitalization.

“Baseline sickle cell disease severity is most likely associated with a patient’s risk of complications from an egg retrieval cycle,” study co-author Sarah Cromack, MD, a reproductive endocrinology and infertility fellow at Northwestern University, Chicago, said in an interview.

“Both hematologists and reproductive endocrinologists can use this information to plan ahead and anticipate possible issues, check blood counts prior to and after egg retrieval to see if transfusion is needed, and plan close follow-up during stimulation and immediately after egg retrieval to evaluate and treat pain.”

 

SCD Accelerates Decline in Ovarian Reserve

Pediatric hematologist Lydia H. Pecker, MD, MS, of Johns Hopkins University School of Medicine, Baltimore, the study’s corresponding author, said in an interview that SCD is “a disease of accelerated aging” that leads to accelerated decline in ovarian reserve. “The common indication for fertility preservation in SCD is before bone marrow transplant or gene therapy,” she said, although FP can also be offered to other patients with SCD.

According to Cromack, researchers launched the study to expand information about SCD and FP in light of sparse data about outcomes.

All the 46 patients had hemoglobin SS (HbSS, 93%) and HbSβ0-thalassemia (7%) and a median age of 23.7 (18-28) years. Almost all (44 patients) underwent FP prior to curative treatments, and all had at least one SCD-related complication, mainly cerebrovascular disease (16), acute chest syndrome (23), and more than two VOEs per year (31).

Median anti-Mullerian hormone (AMH) level (2.1 ng/mL), a measurement of ovarian reserve, was lower than the expected level of 2.8-3.4 ng/mL among women in the age range of the patients, the researchers reported. “This is consistent with previous studies showing lower AMH for age in women with sickle cell disease,” Pecker said.

 

Complications in 45% of Retrieval Cycles

“In terms of success of oocyte cryopreservation, the median number of mature eggs frozen was 11,” said co-author and reproductive endocrinologist Jessica Walter, MD, of Northwestern University, in an interview. “Given the average age of 24 years in the cohort, this would give each patient about a 70% estimated probability of at least one live birth from their cohort of frozen eggs. Thus, patients hoping for more than one child may want to consider more than one cycle of egg freezing.”

The rate of complications was “fairly high” at 45% of all cycles, Walter said. “These were mostly complications from underlying sickle cell disease, including unplanned transfusions and admissions for vaso-occlusive crises. Surprisingly, there were very few cases of ovarian hyperstimulation syndrome in this young patient group, which may be due to a combination of underlying vascular disease, lower peak estradiol levels, and slightly less eggs retrieved then would be expected compared to an age-matched healthy controls.”

Any FP complication was associated with more than three VOEs in the year before controlled ovarian hyperstimulation (mean of three VOEs per patient without complications vs six per patient with complications; P = .036).

 

Higher Than Normal Need for Multiple Cycles

Reproductive endocrinologist H. Irene Su, MD, professor and co-director of the Center for OB/GYN Research Innovations at Moores Cancer Center, University of California San Diego, praised the study as “an important report” in an interview.

Su, who wasn’t involved in the research, said the percentage of patients requiring more than one cycle due to cancellation or low oocyte yield — 13% — is “higher than expected, given the young age of this cohort.”

This could reflect the hypothesis that “sickle cell crises and hypoxia adversely affect the finite number of oocytes in the ovary,” she said.

As for the study findings regarding complications, she said the rate “is very high compared to the general infertility or fertility preservation population. It would be good to learn predictors of these outcomes so that fertility and hematology clinicians can work together to stratify risk and supportive services around FP cycles. It would also be good to know if the post-retrieval VOE were unexpected given the patient’s disease activity prior to FP.”

 

Message: FP in SCD Is Feasible, Acceptable

A.D. Mishkin, MD, MPH, associate professor of psychiatry and liaison to the Blood and Marrow Transplantation Program at NewYork–Presbyterian/Columbia University Irving Medical Center, New York City, said in an interview that the study “establishes the feasibility and acceptability of oocyte harvest and preservation in a population of patients with active ongoing symptoms from SCD. It also indicates their interest in pursuing fertility preservation in the setting of frequent crises and the potential for management of ensuing complications.”

Mishkin, who didn’t take part in the research, highlighted the finding that half the patients got access to FP via public insurance or research funding. “Even in this population where most women had multiple complications in the year prior to FP, and even among patients who needed multiple retrievals, these patients wanted to go through that risk to preserve their fertility,” Mishkin said. “This is an important finding given the very limited access many individuals have to FP due to its high cost and limited insurance coverage, which is also largely state-dependent.”

There’s another factor to consider regarding SCD and FP: The potential danger of pregnancy.

Corresponding author Pecker noted that “pregnancy is high risk for people with sickle cell disease. There are very high rates of severe maternal mortality and morbidity even in high-income countries. However, some of this is modifiable with routine use of chronic transfusions during pregnancy and with high-quality and integrated expert SCD and expert maternal fetal medicine care during pregnancy.”

The National Institutes of Health supported the research. Pecker reported receiving research funding from Alexion, Novartis, and Aummune and consulting for Novo Nordisk. Other authors reported no disclosures. Su and Mishkin reported no disclosures.

 

A version of this article appeared on Medscape.com.

SAN DIEGO — Significant complications were common in female patients with sickle cell disease (SCD) who underwent fertility preservation (FP) procedures, and 13% required multiple retrieval cycles, a five-center retrospective study found.

Of 46 patients with SCD, complications occurred in 25 of 55 controlled ovarian hyperstimulation cycles, including 29 vaso-occlusive episodes (VOEs), researchers reported at the American Society of Hematology (ASH) 2024 Annual Meeting.

Of 21 post-retrieval VOEs, 19 required emergency department care or hospitalization.

“Baseline sickle cell disease severity is most likely associated with a patient’s risk of complications from an egg retrieval cycle,” study co-author Sarah Cromack, MD, a reproductive endocrinology and infertility fellow at Northwestern University, Chicago, said in an interview.

“Both hematologists and reproductive endocrinologists can use this information to plan ahead and anticipate possible issues, check blood counts prior to and after egg retrieval to see if transfusion is needed, and plan close follow-up during stimulation and immediately after egg retrieval to evaluate and treat pain.”

 

SCD Accelerates Decline in Ovarian Reserve

Pediatric hematologist Lydia H. Pecker, MD, MS, of Johns Hopkins University School of Medicine, Baltimore, the study’s corresponding author, said in an interview that SCD is “a disease of accelerated aging” that leads to accelerated decline in ovarian reserve. “The common indication for fertility preservation in SCD is before bone marrow transplant or gene therapy,” she said, although FP can also be offered to other patients with SCD.

According to Cromack, researchers launched the study to expand information about SCD and FP in light of sparse data about outcomes.

All the 46 patients had hemoglobin SS (HbSS, 93%) and HbSβ0-thalassemia (7%) and a median age of 23.7 (18-28) years. Almost all (44 patients) underwent FP prior to curative treatments, and all had at least one SCD-related complication, mainly cerebrovascular disease (16), acute chest syndrome (23), and more than two VOEs per year (31).

Median anti-Mullerian hormone (AMH) level (2.1 ng/mL), a measurement of ovarian reserve, was lower than the expected level of 2.8-3.4 ng/mL among women in the age range of the patients, the researchers reported. “This is consistent with previous studies showing lower AMH for age in women with sickle cell disease,” Pecker said.

 

Complications in 45% of Retrieval Cycles

“In terms of success of oocyte cryopreservation, the median number of mature eggs frozen was 11,” said co-author and reproductive endocrinologist Jessica Walter, MD, of Northwestern University, in an interview. “Given the average age of 24 years in the cohort, this would give each patient about a 70% estimated probability of at least one live birth from their cohort of frozen eggs. Thus, patients hoping for more than one child may want to consider more than one cycle of egg freezing.”

The rate of complications was “fairly high” at 45% of all cycles, Walter said. “These were mostly complications from underlying sickle cell disease, including unplanned transfusions and admissions for vaso-occlusive crises. Surprisingly, there were very few cases of ovarian hyperstimulation syndrome in this young patient group, which may be due to a combination of underlying vascular disease, lower peak estradiol levels, and slightly less eggs retrieved then would be expected compared to an age-matched healthy controls.”

Any FP complication was associated with more than three VOEs in the year before controlled ovarian hyperstimulation (mean of three VOEs per patient without complications vs six per patient with complications; P = .036).

 

Higher Than Normal Need for Multiple Cycles

Reproductive endocrinologist H. Irene Su, MD, professor and co-director of the Center for OB/GYN Research Innovations at Moores Cancer Center, University of California San Diego, praised the study as “an important report” in an interview.

Su, who wasn’t involved in the research, said the percentage of patients requiring more than one cycle due to cancellation or low oocyte yield — 13% — is “higher than expected, given the young age of this cohort.”

This could reflect the hypothesis that “sickle cell crises and hypoxia adversely affect the finite number of oocytes in the ovary,” she said.

As for the study findings regarding complications, she said the rate “is very high compared to the general infertility or fertility preservation population. It would be good to learn predictors of these outcomes so that fertility and hematology clinicians can work together to stratify risk and supportive services around FP cycles. It would also be good to know if the post-retrieval VOE were unexpected given the patient’s disease activity prior to FP.”

 

Message: FP in SCD Is Feasible, Acceptable

A.D. Mishkin, MD, MPH, associate professor of psychiatry and liaison to the Blood and Marrow Transplantation Program at NewYork–Presbyterian/Columbia University Irving Medical Center, New York City, said in an interview that the study “establishes the feasibility and acceptability of oocyte harvest and preservation in a population of patients with active ongoing symptoms from SCD. It also indicates their interest in pursuing fertility preservation in the setting of frequent crises and the potential for management of ensuing complications.”

Mishkin, who didn’t take part in the research, highlighted the finding that half the patients got access to FP via public insurance or research funding. “Even in this population where most women had multiple complications in the year prior to FP, and even among patients who needed multiple retrievals, these patients wanted to go through that risk to preserve their fertility,” Mishkin said. “This is an important finding given the very limited access many individuals have to FP due to its high cost and limited insurance coverage, which is also largely state-dependent.”

There’s another factor to consider regarding SCD and FP: The potential danger of pregnancy.

Corresponding author Pecker noted that “pregnancy is high risk for people with sickle cell disease. There are very high rates of severe maternal mortality and morbidity even in high-income countries. However, some of this is modifiable with routine use of chronic transfusions during pregnancy and with high-quality and integrated expert SCD and expert maternal fetal medicine care during pregnancy.”

The National Institutes of Health supported the research. Pecker reported receiving research funding from Alexion, Novartis, and Aummune and consulting for Novo Nordisk. Other authors reported no disclosures. Su and Mishkin reported no disclosures.

 

A version of this article appeared on Medscape.com.

SAN DIEGO — Significant complications were common in female patients with sickle cell disease (SCD) who underwent fertility preservation (FP) procedures, and 13% required multiple retrieval cycles, a five-center retrospective study found.

Of 46 patients with SCD, complications occurred in 25 of 55 controlled ovarian hyperstimulation cycles, including 29 vaso-occlusive episodes (VOEs), researchers reported at the American Society of Hematology (ASH) 2024 Annual Meeting.

Of 21 post-retrieval VOEs, 19 required emergency department care or hospitalization.

“Baseline sickle cell disease severity is most likely associated with a patient’s risk of complications from an egg retrieval cycle,” study co-author Sarah Cromack, MD, a reproductive endocrinology and infertility fellow at Northwestern University, Chicago, said in an interview.

“Both hematologists and reproductive endocrinologists can use this information to plan ahead and anticipate possible issues, check blood counts prior to and after egg retrieval to see if transfusion is needed, and plan close follow-up during stimulation and immediately after egg retrieval to evaluate and treat pain.”

 

SCD Accelerates Decline in Ovarian Reserve

Pediatric hematologist Lydia H. Pecker, MD, MS, of Johns Hopkins University School of Medicine, Baltimore, the study’s corresponding author, said in an interview that SCD is “a disease of accelerated aging” that leads to accelerated decline in ovarian reserve. “The common indication for fertility preservation in SCD is before bone marrow transplant or gene therapy,” she said, although FP can also be offered to other patients with SCD.

According to Cromack, researchers launched the study to expand information about SCD and FP in light of sparse data about outcomes.

All the 46 patients had hemoglobin SS (HbSS, 93%) and HbSβ0-thalassemia (7%) and a median age of 23.7 (18-28) years. Almost all (44 patients) underwent FP prior to curative treatments, and all had at least one SCD-related complication, mainly cerebrovascular disease (16), acute chest syndrome (23), and more than two VOEs per year (31).

Median anti-Mullerian hormone (AMH) level (2.1 ng/mL), a measurement of ovarian reserve, was lower than the expected level of 2.8-3.4 ng/mL among women in the age range of the patients, the researchers reported. “This is consistent with previous studies showing lower AMH for age in women with sickle cell disease,” Pecker said.

 

Complications in 45% of Retrieval Cycles

“In terms of success of oocyte cryopreservation, the median number of mature eggs frozen was 11,” said co-author and reproductive endocrinologist Jessica Walter, MD, of Northwestern University, in an interview. “Given the average age of 24 years in the cohort, this would give each patient about a 70% estimated probability of at least one live birth from their cohort of frozen eggs. Thus, patients hoping for more than one child may want to consider more than one cycle of egg freezing.”

The rate of complications was “fairly high” at 45% of all cycles, Walter said. “These were mostly complications from underlying sickle cell disease, including unplanned transfusions and admissions for vaso-occlusive crises. Surprisingly, there were very few cases of ovarian hyperstimulation syndrome in this young patient group, which may be due to a combination of underlying vascular disease, lower peak estradiol levels, and slightly less eggs retrieved then would be expected compared to an age-matched healthy controls.”

Any FP complication was associated with more than three VOEs in the year before controlled ovarian hyperstimulation (mean of three VOEs per patient without complications vs six per patient with complications; P = .036).

 

Higher Than Normal Need for Multiple Cycles

Reproductive endocrinologist H. Irene Su, MD, professor and co-director of the Center for OB/GYN Research Innovations at Moores Cancer Center, University of California San Diego, praised the study as “an important report” in an interview.

Su, who wasn’t involved in the research, said the percentage of patients requiring more than one cycle due to cancellation or low oocyte yield — 13% — is “higher than expected, given the young age of this cohort.”

This could reflect the hypothesis that “sickle cell crises and hypoxia adversely affect the finite number of oocytes in the ovary,” she said.

As for the study findings regarding complications, she said the rate “is very high compared to the general infertility or fertility preservation population. It would be good to learn predictors of these outcomes so that fertility and hematology clinicians can work together to stratify risk and supportive services around FP cycles. It would also be good to know if the post-retrieval VOE were unexpected given the patient’s disease activity prior to FP.”

 

Message: FP in SCD Is Feasible, Acceptable

A.D. Mishkin, MD, MPH, associate professor of psychiatry and liaison to the Blood and Marrow Transplantation Program at NewYork–Presbyterian/Columbia University Irving Medical Center, New York City, said in an interview that the study “establishes the feasibility and acceptability of oocyte harvest and preservation in a population of patients with active ongoing symptoms from SCD. It also indicates their interest in pursuing fertility preservation in the setting of frequent crises and the potential for management of ensuing complications.”

Mishkin, who didn’t take part in the research, highlighted the finding that half the patients got access to FP via public insurance or research funding. “Even in this population where most women had multiple complications in the year prior to FP, and even among patients who needed multiple retrievals, these patients wanted to go through that risk to preserve their fertility,” Mishkin said. “This is an important finding given the very limited access many individuals have to FP due to its high cost and limited insurance coverage, which is also largely state-dependent.”

There’s another factor to consider regarding SCD and FP: The potential danger of pregnancy.

Corresponding author Pecker noted that “pregnancy is high risk for people with sickle cell disease. There are very high rates of severe maternal mortality and morbidity even in high-income countries. However, some of this is modifiable with routine use of chronic transfusions during pregnancy and with high-quality and integrated expert SCD and expert maternal fetal medicine care during pregnancy.”

The National Institutes of Health supported the research. Pecker reported receiving research funding from Alexion, Novartis, and Aummune and consulting for Novo Nordisk. Other authors reported no disclosures. Su and Mishkin reported no disclosures.

 

A version of this article appeared on Medscape.com.

TOPLINE:

The association persists even after accounting for adverse pregnancy outcomes. Women who have experienced infertility without fertility treatment show a 25% higher risk for systemic autoimmune rheumatic disease (SARD) up to 9 years after delivery, compared with those without infertility.

METHODOLOGY:

• Population-based cohort study analyzed 568,053 singleton births among 465,078 women aged 18-50 years without pre-existing SARD in Ontario, Canada, from 2012 to 2021.
• Participants were categorized into four groups: No infertility with unassisted conception (88.0%), infertility without fertility treatment (9.2%), infertility with noninvasive fertility treatment (1.4%), and infertility with invasive fertility treatment (1.4%).
• Researchers used marginal structural Cox proportional hazards models to generate hazard ratios and 95% CIs, adjusting for sociodemographic characteristics, comorbidities, smoking, and adverse pregnancy outcomes.
• Analysis included a median follow-up duration of 6.5 years (interquartile range: 4-9 years) from delivery date until SARD diagnosis, death, loss of health insurance, or study end.

TAKEAWAY:

• The incidence rate of SARD was 12.5 per 10,000 person-years in women with untreated infertility, compared with 9.3 per 10,000 person-years in women without infertility.
• Women with untreated infertility showed an elevated risk for SARD (controlled direct effect hazard ratio [HR], 1.25; 95% CI, 1.12-1.40) even after accounting for adverse pregnancy outcomes.
• Neither noninvasive fertility treatment (total effect HR, 1.06; 95% CI, 0.79-1.42) nor invasive fertility treatment (total effect HR, 0.97; 95% CI, 0.69-1.36) were associated with increased SARD risk.
• The association between untreated infertility and SARD persisted in analyses restricted to women aged < 38 years and in those without endometriosis or other autoimmune diseases.

IN PRACTICE:

“Future research efforts should seek to corroborate this association by infertility cause, with a focus on possible mechanisms related to ovulatory, ovarian, and sexual dysfunction. Greater health provider awareness of SARD symptoms and related gynecological issues that may present in women with infertility could facilitate earlier detection and treatment of SARD during the reproductive years,” wrote the authors of the study.

SOURCE:

The study was led by Natalie V. Scime of the Department of Health and Society, University of Toronto Scarborough in Ontario, Canada. It was published online in Human Reproduction.

LIMITATIONS:

Exposure and outcome misclassification was possible due to the use of published algorithms in health administrative data with unknown or imperfect sensitivity and specificity. The researchers noted that individual-level social and lifestyle factors and underlying causes of infertility were not available, and thus, were not included in the analysis.

DISCLOSURES:

This research received funding through a Banting Postdoctoral Fellowship to Scime and Canada Research Chair to Hilary K. Brown (2019-00158), with support from ICES, funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care. One coauthor disclosed consulting for Celltrion, Werfen, Organon, MitogenDx, AstraZeneca, Mallinckrodt Canada, and GlaxoSmithKline. All other authors reported no conflicts of interest.

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:

The association persists even after accounting for adverse pregnancy outcomes. Women who have experienced infertility without fertility treatment show a 25% higher risk for systemic autoimmune rheumatic disease (SARD) up to 9 years after delivery, compared with those without infertility.

METHODOLOGY:

• Population-based cohort study analyzed 568,053 singleton births among 465,078 women aged 18-50 years without pre-existing SARD in Ontario, Canada, from 2012 to 2021.
• Participants were categorized into four groups: No infertility with unassisted conception (88.0%), infertility without fertility treatment (9.2%), infertility with noninvasive fertility treatment (1.4%), and infertility with invasive fertility treatment (1.4%).
• Researchers used marginal structural Cox proportional hazards models to generate hazard ratios and 95% CIs, adjusting for sociodemographic characteristics, comorbidities, smoking, and adverse pregnancy outcomes.
• Analysis included a median follow-up duration of 6.5 years (interquartile range: 4-9 years) from delivery date until SARD diagnosis, death, loss of health insurance, or study end.

TAKEAWAY:

• The incidence rate of SARD was 12.5 per 10,000 person-years in women with untreated infertility, compared with 9.3 per 10,000 person-years in women without infertility.
• Women with untreated infertility showed an elevated risk for SARD (controlled direct effect hazard ratio [HR], 1.25; 95% CI, 1.12-1.40) even after accounting for adverse pregnancy outcomes.
• Neither noninvasive fertility treatment (total effect HR, 1.06; 95% CI, 0.79-1.42) nor invasive fertility treatment (total effect HR, 0.97; 95% CI, 0.69-1.36) were associated with increased SARD risk.
• The association between untreated infertility and SARD persisted in analyses restricted to women aged < 38 years and in those without endometriosis or other autoimmune diseases.

IN PRACTICE:

“Future research efforts should seek to corroborate this association by infertility cause, with a focus on possible mechanisms related to ovulatory, ovarian, and sexual dysfunction. Greater health provider awareness of SARD symptoms and related gynecological issues that may present in women with infertility could facilitate earlier detection and treatment of SARD during the reproductive years,” wrote the authors of the study.

SOURCE:

The study was led by Natalie V. Scime of the Department of Health and Society, University of Toronto Scarborough in Ontario, Canada. It was published online in Human Reproduction.

LIMITATIONS:

Exposure and outcome misclassification was possible due to the use of published algorithms in health administrative data with unknown or imperfect sensitivity and specificity. The researchers noted that individual-level social and lifestyle factors and underlying causes of infertility were not available, and thus, were not included in the analysis.

DISCLOSURES:

This research received funding through a Banting Postdoctoral Fellowship to Scime and Canada Research Chair to Hilary K. Brown (2019-00158), with support from ICES, funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care. One coauthor disclosed consulting for Celltrion, Werfen, Organon, MitogenDx, AstraZeneca, Mallinckrodt Canada, and GlaxoSmithKline. All other authors reported no conflicts of interest.

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:

The association persists even after accounting for adverse pregnancy outcomes. Women who have experienced infertility without fertility treatment show a 25% higher risk for systemic autoimmune rheumatic disease (SARD) up to 9 years after delivery, compared with those without infertility.

METHODOLOGY:

• Population-based cohort study analyzed 568,053 singleton births among 465,078 women aged 18-50 years without pre-existing SARD in Ontario, Canada, from 2012 to 2021.
• Participants were categorized into four groups: No infertility with unassisted conception (88.0%), infertility without fertility treatment (9.2%), infertility with noninvasive fertility treatment (1.4%), and infertility with invasive fertility treatment (1.4%).
• Researchers used marginal structural Cox proportional hazards models to generate hazard ratios and 95% CIs, adjusting for sociodemographic characteristics, comorbidities, smoking, and adverse pregnancy outcomes.
• Analysis included a median follow-up duration of 6.5 years (interquartile range: 4-9 years) from delivery date until SARD diagnosis, death, loss of health insurance, or study end.

TAKEAWAY:

• The incidence rate of SARD was 12.5 per 10,000 person-years in women with untreated infertility, compared with 9.3 per 10,000 person-years in women without infertility.
• Women with untreated infertility showed an elevated risk for SARD (controlled direct effect hazard ratio [HR], 1.25; 95% CI, 1.12-1.40) even after accounting for adverse pregnancy outcomes.
• Neither noninvasive fertility treatment (total effect HR, 1.06; 95% CI, 0.79-1.42) nor invasive fertility treatment (total effect HR, 0.97; 95% CI, 0.69-1.36) were associated with increased SARD risk.
• The association between untreated infertility and SARD persisted in analyses restricted to women aged < 38 years and in those without endometriosis or other autoimmune diseases.

IN PRACTICE:

“Future research efforts should seek to corroborate this association by infertility cause, with a focus on possible mechanisms related to ovulatory, ovarian, and sexual dysfunction. Greater health provider awareness of SARD symptoms and related gynecological issues that may present in women with infertility could facilitate earlier detection and treatment of SARD during the reproductive years,” wrote the authors of the study.

SOURCE:

The study was led by Natalie V. Scime of the Department of Health and Society, University of Toronto Scarborough in Ontario, Canada. It was published online in Human Reproduction.

LIMITATIONS:

Exposure and outcome misclassification was possible due to the use of published algorithms in health administrative data with unknown or imperfect sensitivity and specificity. The researchers noted that individual-level social and lifestyle factors and underlying causes of infertility were not available, and thus, were not included in the analysis.

DISCLOSURES:

This research received funding through a Banting Postdoctoral Fellowship to Scime and Canada Research Chair to Hilary K. Brown (2019-00158), with support from ICES, funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care. One coauthor disclosed consulting for Celltrion, Werfen, Organon, MitogenDx, AstraZeneca, Mallinckrodt Canada, and GlaxoSmithKline. All other authors reported no conflicts of interest.

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:

Among pregnant patients with chronic hypertension, delivery at 39 weeks of gestation provides an optimal balance between stillbirth risk and neonatal outcomes. Analysis of 227,977 term singleton deliveries shows consistent findings across different patient subgroups.

METHODOLOGY:

• A population-based retrospective cohort study analyzed 227,977 nonanomalous singleton term births in the United States from 2014 to 2018 among patients with chronic hypertension.
• Researchers excluded pregnancies with superimposed preeclampsia, eclampsia, pregestational diabetes, and deliveries occurring before 37 weeks or at 43 or more weeks of gestation.
• Analysis compared rates of stillbirth, infant death within 1 year of life, and neonatal morbidity at each week of term pregnancy.
• Neonatal morbidity was defined as a composite of neonatal intensive care unit admission, ventilation for 6 hours or longer, a low 5-minute Apgar score (≤ 3), and seizures.

TAKEAWAY:

• The rate of stillbirth per 10,000 ongoing pregnancies increased with gestational age and was lowest at 38 weeks (6.5; 95% CI, 5.4-7.7).
• Rates of infant death and neonatal morbidity were lowest at 40 weeks (18.0/10,000 live births; 95% CI, 13.7-23.6) and 39 weeks (637/10,000 live births; 95% CI, 619-654), respectively.
• At 39 weeks of gestation, the risk for delivery was lower (651/10,000; 95% CI, 633-670) than the composite risk for expectant management (750/10,000; 95% CI, 720-781).
• According to the authors, findings were consistent for non-Hispanic Black patients and pregnancies complicated by fetal growth restriction.

IN PRACTICE:

“To prevent one case of stillbirth, infant death, or neonatal morbidity, an estimated 101 patients with chronic hypertension would need to deliver at 39 weeks of gestation as opposed to 40 weeks. Given the approximately 45,000 patients with chronic hypertension who deliver at term each year in the United States, a policy of delivery at 39 weeks of gestation theoretically would prevent 450 adverse perinatal events per year,” wrote the authors of the study.

SOURCE:

The study was led by Ira Hamilton, James Liu, Labeena Wajahat, and Robert Rossi, University of Cincinnati College of Medicine in Cincinnati. It was published online in O&G Open.

LIMITATIONS:

According to the authors, the study could not stratify chronic hypertension based on medication use, number of medications, or degree of control. The researchers note that exact timing of delivery in weeks and days was not reported, limiting precise understanding of optimal delivery timing. Additionally, the study could not examine rates of neonatal morbidity and mortality in patients who developed superimposed preeclampsia during expectant management.

DISCLOSURES:

The authors did not report any potential conflicts of interest.

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:

Among pregnant patients with chronic hypertension, delivery at 39 weeks of gestation provides an optimal balance between stillbirth risk and neonatal outcomes. Analysis of 227,977 term singleton deliveries shows consistent findings across different patient subgroups.

METHODOLOGY:

• A population-based retrospective cohort study analyzed 227,977 nonanomalous singleton term births in the United States from 2014 to 2018 among patients with chronic hypertension.
• Researchers excluded pregnancies with superimposed preeclampsia, eclampsia, pregestational diabetes, and deliveries occurring before 37 weeks or at 43 or more weeks of gestation.
• Analysis compared rates of stillbirth, infant death within 1 year of life, and neonatal morbidity at each week of term pregnancy.
• Neonatal morbidity was defined as a composite of neonatal intensive care unit admission, ventilation for 6 hours or longer, a low 5-minute Apgar score (≤ 3), and seizures.

TAKEAWAY:

• The rate of stillbirth per 10,000 ongoing pregnancies increased with gestational age and was lowest at 38 weeks (6.5; 95% CI, 5.4-7.7).
• Rates of infant death and neonatal morbidity were lowest at 40 weeks (18.0/10,000 live births; 95% CI, 13.7-23.6) and 39 weeks (637/10,000 live births; 95% CI, 619-654), respectively.
• At 39 weeks of gestation, the risk for delivery was lower (651/10,000; 95% CI, 633-670) than the composite risk for expectant management (750/10,000; 95% CI, 720-781).
• According to the authors, findings were consistent for non-Hispanic Black patients and pregnancies complicated by fetal growth restriction.

IN PRACTICE:

“To prevent one case of stillbirth, infant death, or neonatal morbidity, an estimated 101 patients with chronic hypertension would need to deliver at 39 weeks of gestation as opposed to 40 weeks. Given the approximately 45,000 patients with chronic hypertension who deliver at term each year in the United States, a policy of delivery at 39 weeks of gestation theoretically would prevent 450 adverse perinatal events per year,” wrote the authors of the study.

SOURCE:

The study was led by Ira Hamilton, James Liu, Labeena Wajahat, and Robert Rossi, University of Cincinnati College of Medicine in Cincinnati. It was published online in O&G Open.

LIMITATIONS:

According to the authors, the study could not stratify chronic hypertension based on medication use, number of medications, or degree of control. The researchers note that exact timing of delivery in weeks and days was not reported, limiting precise understanding of optimal delivery timing. Additionally, the study could not examine rates of neonatal morbidity and mortality in patients who developed superimposed preeclampsia during expectant management.

DISCLOSURES:

The authors did not report any potential conflicts of interest.

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:

Among pregnant patients with chronic hypertension, delivery at 39 weeks of gestation provides an optimal balance between stillbirth risk and neonatal outcomes. Analysis of 227,977 term singleton deliveries shows consistent findings across different patient subgroups.

METHODOLOGY:

• A population-based retrospective cohort study analyzed 227,977 nonanomalous singleton term births in the United States from 2014 to 2018 among patients with chronic hypertension.
• Researchers excluded pregnancies with superimposed preeclampsia, eclampsia, pregestational diabetes, and deliveries occurring before 37 weeks or at 43 or more weeks of gestation.
• Analysis compared rates of stillbirth, infant death within 1 year of life, and neonatal morbidity at each week of term pregnancy.
• Neonatal morbidity was defined as a composite of neonatal intensive care unit admission, ventilation for 6 hours or longer, a low 5-minute Apgar score (≤ 3), and seizures.

TAKEAWAY:

• The rate of stillbirth per 10,000 ongoing pregnancies increased with gestational age and was lowest at 38 weeks (6.5; 95% CI, 5.4-7.7).
• Rates of infant death and neonatal morbidity were lowest at 40 weeks (18.0/10,000 live births; 95% CI, 13.7-23.6) and 39 weeks (637/10,000 live births; 95% CI, 619-654), respectively.
• At 39 weeks of gestation, the risk for delivery was lower (651/10,000; 95% CI, 633-670) than the composite risk for expectant management (750/10,000; 95% CI, 720-781).
• According to the authors, findings were consistent for non-Hispanic Black patients and pregnancies complicated by fetal growth restriction.

IN PRACTICE:

“To prevent one case of stillbirth, infant death, or neonatal morbidity, an estimated 101 patients with chronic hypertension would need to deliver at 39 weeks of gestation as opposed to 40 weeks. Given the approximately 45,000 patients with chronic hypertension who deliver at term each year in the United States, a policy of delivery at 39 weeks of gestation theoretically would prevent 450 adverse perinatal events per year,” wrote the authors of the study.

SOURCE:

The study was led by Ira Hamilton, James Liu, Labeena Wajahat, and Robert Rossi, University of Cincinnati College of Medicine in Cincinnati. It was published online in O&G Open.

LIMITATIONS:

According to the authors, the study could not stratify chronic hypertension based on medication use, number of medications, or degree of control. The researchers note that exact timing of delivery in weeks and days was not reported, limiting precise understanding of optimal delivery timing. Additionally, the study could not examine rates of neonatal morbidity and mortality in patients who developed superimposed preeclampsia during expectant management.

DISCLOSURES:

The authors did not report any potential conflicts of interest.

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.

I’d like to talk with you about a recent report in the British Medical Journal (BMJ) on different forms of contemporary menopausal hormone therapy and risks for cardiovascular disease (CVD). 

This is a very large-scale and comprehensive study from Sweden that looked at more than 900,000 women, including more than 77,000 users of hormone therapy. The women were aged 50-58 years and the study leveraged the nationwide register system, where they have information on prescription medications as well as health outcomes that can be linked. 

This study looked at the different forms of hormone therapy: oral vs transdermal, estrogen with and without a progestogen, and also tibolone (which is not available in the United States). The endpoints included myocardial infarction (MI), total ischemic heart disease, stroke, a composite of CVD, as well as venous thromboembolism (VTE). 

They found that tibolone was associated with the greatest increased risk for CVD; there was actually an increase in both ischemic heart disease and stroke as well as composite CVD. They did not see an increased risk for VTE. This may be related to the unique pharmacologic profile of tibolone, which has estrogenic, progestogenic, and androgenic properties. 

The estrogens tested in the estrogen plus progestin and estrogen alone formulations were not conjugated equine estrogen as tested in the Women’s Health Initiative (WHI) and HERS trials, but mostly oral or transdermal estradiol. With combination estrogen plus progestin, they saw a small (about 20%) increase in ischemic heart disease, similar to what was seen in the WHI. And they saw about a doubling in the risk for VTE, also similar to what was seen in the WHI. With estrogen alone there was no increase in ischemic heart disease or MI, but there was about a 50% increase in VTE — again, similar to the WHI findings. 

With transdermal estradiol (transdermal forms of estrogen), in contrast, there was no clear increase in any of these CVD outcomes. In fact, there was a borderline reduction in both MI and composite CVD. 

So overall, this study suggests greater cardiovascular safety with transdermal compared with oral estrogen. This would be expected, given the first-pass metabolism and increased clotting associated with oral estrogens. 

On the basis of a large body of evidence, we know that for women in early menopause who have bothersome vasomotor symptoms, if they’re healthy, oral or transdermal estrogen could be used according to the preference of the woman. But this study suggests that, especially in women who do have cardiovascular risk factors, it may be very reasonable to lean toward the use of transdermal over oral estrogen among those who are choosing to use hormone therapy. 

We certainly need more research on transdermal estradiol, micronized progesterone, and these contemporary formulations that are being used. But in the meantime, this study in the BMJ does provide very useful information for women and their clinicians.

Dr Manson, Professor of Medicine and the Michael and Lee Bell Professor of Women’s Health, Harvard Medical School; Chief, Division of Preventive Medicine, Brigham and Women’s Hospital, both in Boston, Massachusetts; Past President, North American Menopause Society, 2011-2012, has disclosed receiving study pill donation and infrastructure support from Mars Symbioscience (for the COSMOS trial).

A version of this article appeared on Medscape.com.

I’d like to talk with you about a recent report in the British Medical Journal (BMJ) on different forms of contemporary menopausal hormone therapy and risks for cardiovascular disease (CVD). 

This is a very large-scale and comprehensive study from Sweden that looked at more than 900,000 women, including more than 77,000 users of hormone therapy. The women were aged 50-58 years and the study leveraged the nationwide register system, where they have information on prescription medications as well as health outcomes that can be linked. 

This study looked at the different forms of hormone therapy: oral vs transdermal, estrogen with and without a progestogen, and also tibolone (which is not available in the United States). The endpoints included myocardial infarction (MI), total ischemic heart disease, stroke, a composite of CVD, as well as venous thromboembolism (VTE). 

They found that tibolone was associated with the greatest increased risk for CVD; there was actually an increase in both ischemic heart disease and stroke as well as composite CVD. They did not see an increased risk for VTE. This may be related to the unique pharmacologic profile of tibolone, which has estrogenic, progestogenic, and androgenic properties. 

The estrogens tested in the estrogen plus progestin and estrogen alone formulations were not conjugated equine estrogen as tested in the Women’s Health Initiative (WHI) and HERS trials, but mostly oral or transdermal estradiol. With combination estrogen plus progestin, they saw a small (about 20%) increase in ischemic heart disease, similar to what was seen in the WHI. And they saw about a doubling in the risk for VTE, also similar to what was seen in the WHI. With estrogen alone there was no increase in ischemic heart disease or MI, but there was about a 50% increase in VTE — again, similar to the WHI findings. 

With transdermal estradiol (transdermal forms of estrogen), in contrast, there was no clear increase in any of these CVD outcomes. In fact, there was a borderline reduction in both MI and composite CVD. 

So overall, this study suggests greater cardiovascular safety with transdermal compared with oral estrogen. This would be expected, given the first-pass metabolism and increased clotting associated with oral estrogens. 

On the basis of a large body of evidence, we know that for women in early menopause who have bothersome vasomotor symptoms, if they’re healthy, oral or transdermal estrogen could be used according to the preference of the woman. But this study suggests that, especially in women who do have cardiovascular risk factors, it may be very reasonable to lean toward the use of transdermal over oral estrogen among those who are choosing to use hormone therapy. 

We certainly need more research on transdermal estradiol, micronized progesterone, and these contemporary formulations that are being used. But in the meantime, this study in the BMJ does provide very useful information for women and their clinicians.

Dr Manson, Professor of Medicine and the Michael and Lee Bell Professor of Women’s Health, Harvard Medical School; Chief, Division of Preventive Medicine, Brigham and Women’s Hospital, both in Boston, Massachusetts; Past President, North American Menopause Society, 2011-2012, has disclosed receiving study pill donation and infrastructure support from Mars Symbioscience (for the COSMOS trial).

A version of this article appeared on Medscape.com.

I’d like to talk with you about a recent report in the British Medical Journal (BMJ) on different forms of contemporary menopausal hormone therapy and risks for cardiovascular disease (CVD). 

This is a very large-scale and comprehensive study from Sweden that looked at more than 900,000 women, including more than 77,000 users of hormone therapy. The women were aged 50-58 years and the study leveraged the nationwide register system, where they have information on prescription medications as well as health outcomes that can be linked. 

This study looked at the different forms of hormone therapy: oral vs transdermal, estrogen with and without a progestogen, and also tibolone (which is not available in the United States). The endpoints included myocardial infarction (MI), total ischemic heart disease, stroke, a composite of CVD, as well as venous thromboembolism (VTE). 

They found that tibolone was associated with the greatest increased risk for CVD; there was actually an increase in both ischemic heart disease and stroke as well as composite CVD. They did not see an increased risk for VTE. This may be related to the unique pharmacologic profile of tibolone, which has estrogenic, progestogenic, and androgenic properties. 

The estrogens tested in the estrogen plus progestin and estrogen alone formulations were not conjugated equine estrogen as tested in the Women’s Health Initiative (WHI) and HERS trials, but mostly oral or transdermal estradiol. With combination estrogen plus progestin, they saw a small (about 20%) increase in ischemic heart disease, similar to what was seen in the WHI. And they saw about a doubling in the risk for VTE, also similar to what was seen in the WHI. With estrogen alone there was no increase in ischemic heart disease or MI, but there was about a 50% increase in VTE — again, similar to the WHI findings. 

With transdermal estradiol (transdermal forms of estrogen), in contrast, there was no clear increase in any of these CVD outcomes. In fact, there was a borderline reduction in both MI and composite CVD. 

So overall, this study suggests greater cardiovascular safety with transdermal compared with oral estrogen. This would be expected, given the first-pass metabolism and increased clotting associated with oral estrogens. 

On the basis of a large body of evidence, we know that for women in early menopause who have bothersome vasomotor symptoms, if they’re healthy, oral or transdermal estrogen could be used according to the preference of the woman. But this study suggests that, especially in women who do have cardiovascular risk factors, it may be very reasonable to lean toward the use of transdermal over oral estrogen among those who are choosing to use hormone therapy. 

We certainly need more research on transdermal estradiol, micronized progesterone, and these contemporary formulations that are being used. But in the meantime, this study in the BMJ does provide very useful information for women and their clinicians.

Dr Manson, Professor of Medicine and the Michael and Lee Bell Professor of Women’s Health, Harvard Medical School; Chief, Division of Preventive Medicine, Brigham and Women’s Hospital, both in Boston, Massachusetts; Past President, North American Menopause Society, 2011-2012, has disclosed receiving study pill donation and infrastructure support from Mars Symbioscience (for the COSMOS trial).

A version of this article appeared on Medscape.com.

Vitamin E may be best known for boosting skin and eye health as well as immune function. In recent years, researchers have explored the potential benefits of vitamin E on bone loss, especially in women with menopause-related osteoporosis. While data are beginning to roll in from these studies, evidence supporting a positive impact of vitamin E on osteoporosis and hip fracture risk in perimenopausal women remains elusive.

For osteoporosis, the rationale for using vitamin E is based on its antioxidant activity, which can scavenge potentially damaging free radicals. Researchers have asked whether vitamin E can help maintain the integrity of bone matrix and stimulate bone formation while minimizing bone resorption, particularly in trabecular (spongy) bone, the bone compartment preferentially affected in perimenopausal bone loss. 

Vitamin E mostly consists of two isomers: alpha-tocopherol and gamma-tocopherol. Alpha-tocopherol has higher antioxidant activity and is found in nuts, seeds, vegetable oils, green leafy vegetables, fortified cereals, and vitamin E supplements. Gamma-tocopherol is known for its superior anti-inflammatory properties and accounts for about 70% of the total vitamin E intake in a typical American diet, largely sourced from soybean and other vegetable oils. 

 

Benefits and Risks in Bone Loss Studies

Perimenopausal bone loss is caused, to a great extent, by the decrease in sex hormones. Studies of vitamin E in ovariectomized rats have yielded mixed results. This animal model lacks sex hormones and has similar bone changes to those of postmenopausal women. Some animal studies have suggested a positive effect of vitamin E on bone while others have reported no effect. 

Studies in humans also have produced conflicting reports of positive, neutral, and negative associations of vitamin E with bone health. For example, the Women’s Health Initiative examined the relationship between vitamin and mineral antioxidants and bone health in postmenopausal women and found no significant association between antioxidants and bone mineral density. 

Another study examining data from children and adolescents enrolled in the National Health and Nutrition Examination Survey (NHANES) database found an inverse association between alpha-tocopherol and lumbar spine bone density, suggesting a deleterious effect on bone. Inverse associations also have been reported in certain studies of postmenopausal women.

High doses of alpha-tocopherol have been linked to a risk for impaired bone health through a variety of mechanisms, such as interference with vitamin K metabolism; competitive binding for alpha-tocopherol transfer protein, inhibiting the entry of beneficial vitamin E isomers, including gamma-tocopherol; and pro-oxidant effects that harm bone. Thus, postmenopausal women taking vitamin E supplements primarily as high doses of alpha-tocopherol might be hindering their bone health. 

Data for gamma-tocopherol are more promising. Some studies hypothesize that gamma-tocopherol might uncouple bone turnover, leading to increased bone formation without affecting bone resorption. Further, a randomized controlled study of mixed tocopherols (rather than alpha-tocopherol) vs placebo reported a protective effect of this preparation on bone outcomes by suppressing bone resorption. This raises the importance of considering the specific forms of vitamin E when evaluating its role in bone health.

 

Limitations of Current Studies

Researchers acknowledge several limitations in studies to date. For example, there are very few randomized controlled trials assessing the impact of vitamin E on bone health. Most studies are cross-sectional or observational, even when longitudinal. Cross-sectional and observational designs prevent us from establishing a causal relationship between vitamin E and bone endpoints. 

Such designs also run the risk of additional confounders that may affect associations between vitamin E and bone, or the lack thereof. These could include both known and unknown confounders. Of note, gamma-tocopherol intake data were not available for certain NHANES studies. 

Further, people often consume multiple nutrients and supplements, complicating the identification of specific nutrient-disease associations. Most human studies estimate tocopherol intake by dietary questionnaires or measure serum tocopherol levels, which reflect short-term dietary intake, while bone mineral density is probably influenced by long-term dietary patterns.

 

Too Soon to Prescribe Vitamin E for Bone Health

Some nutrition experts advocate for vitamin E supplements containing mixed tocopherols, specifically suggesting a ratio of 50-100 IU of gamma-tocopherol per 400 IU of D-alpha-tocopherol. Additional research is essential to confirm and further clarify the role of gamma-tocopherol in bone formation and resorption. In fact, it is also important to explore the influence of other compounds in the vitamin E family on skeletal health.

Until more data are available, we would recommend following the Institute of Medicine’s guidelines for the recommended daily allowance (RDA) of vitamin E. This is age dependent, ranging from 4 to 11 mg/d between the ages of 0 and 13 years, and 15 mg/d thereafter. 

Overall, evidence of vitamin E’s impact on osteoporosis and hip fracture risk in perimenopausal women remains inconclusive. Although some observational and interventional studies suggest potential benefits, more interventional studies, particularly randomized controlled trials, are necessary to explore the risks and benefits of vitamin E supplementation and serum vitamin E levels on bone density and fracture risk more thoroughly.

Dr. Pani, Assistant Professor, Department of Internal Medicine, UVA School of Medicine; Medical Director, Department of General Medicine, Same Day Care Clinic, both in Charlottesville, has disclosed no relevant financial relationships. Dr. Misra, Professor, Chair, Physician-in-Chief, Department of Pediatrics, University of Virginia, and UVA Health Children’s, Charlottesville, has disclosed being a key opinion leader for Lumos Pharma.

A version of this article appeared on Medscape.com.

Vitamin E may be best known for boosting skin and eye health as well as immune function. In recent years, researchers have explored the potential benefits of vitamin E on bone loss, especially in women with menopause-related osteoporosis. While data are beginning to roll in from these studies, evidence supporting a positive impact of vitamin E on osteoporosis and hip fracture risk in perimenopausal women remains elusive.

For osteoporosis, the rationale for using vitamin E is based on its antioxidant activity, which can scavenge potentially damaging free radicals. Researchers have asked whether vitamin E can help maintain the integrity of bone matrix and stimulate bone formation while minimizing bone resorption, particularly in trabecular (spongy) bone, the bone compartment preferentially affected in perimenopausal bone loss. 

Vitamin E mostly consists of two isomers: alpha-tocopherol and gamma-tocopherol. Alpha-tocopherol has higher antioxidant activity and is found in nuts, seeds, vegetable oils, green leafy vegetables, fortified cereals, and vitamin E supplements. Gamma-tocopherol is known for its superior anti-inflammatory properties and accounts for about 70% of the total vitamin E intake in a typical American diet, largely sourced from soybean and other vegetable oils. 

 

Benefits and Risks in Bone Loss Studies

Perimenopausal bone loss is caused, to a great extent, by the decrease in sex hormones. Studies of vitamin E in ovariectomized rats have yielded mixed results. This animal model lacks sex hormones and has similar bone changes to those of postmenopausal women. Some animal studies have suggested a positive effect of vitamin E on bone while others have reported no effect. 

Studies in humans also have produced conflicting reports of positive, neutral, and negative associations of vitamin E with bone health. For example, the Women’s Health Initiative examined the relationship between vitamin and mineral antioxidants and bone health in postmenopausal women and found no significant association between antioxidants and bone mineral density. 

Another study examining data from children and adolescents enrolled in the National Health and Nutrition Examination Survey (NHANES) database found an inverse association between alpha-tocopherol and lumbar spine bone density, suggesting a deleterious effect on bone. Inverse associations also have been reported in certain studies of postmenopausal women.

High doses of alpha-tocopherol have been linked to a risk for impaired bone health through a variety of mechanisms, such as interference with vitamin K metabolism; competitive binding for alpha-tocopherol transfer protein, inhibiting the entry of beneficial vitamin E isomers, including gamma-tocopherol; and pro-oxidant effects that harm bone. Thus, postmenopausal women taking vitamin E supplements primarily as high doses of alpha-tocopherol might be hindering their bone health. 

Data for gamma-tocopherol are more promising. Some studies hypothesize that gamma-tocopherol might uncouple bone turnover, leading to increased bone formation without affecting bone resorption. Further, a randomized controlled study of mixed tocopherols (rather than alpha-tocopherol) vs placebo reported a protective effect of this preparation on bone outcomes by suppressing bone resorption. This raises the importance of considering the specific forms of vitamin E when evaluating its role in bone health.

 

Limitations of Current Studies

Researchers acknowledge several limitations in studies to date. For example, there are very few randomized controlled trials assessing the impact of vitamin E on bone health. Most studies are cross-sectional or observational, even when longitudinal. Cross-sectional and observational designs prevent us from establishing a causal relationship between vitamin E and bone endpoints. 

Such designs also run the risk of additional confounders that may affect associations between vitamin E and bone, or the lack thereof. These could include both known and unknown confounders. Of note, gamma-tocopherol intake data were not available for certain NHANES studies. 

Further, people often consume multiple nutrients and supplements, complicating the identification of specific nutrient-disease associations. Most human studies estimate tocopherol intake by dietary questionnaires or measure serum tocopherol levels, which reflect short-term dietary intake, while bone mineral density is probably influenced by long-term dietary patterns.

 

Too Soon to Prescribe Vitamin E for Bone Health

Some nutrition experts advocate for vitamin E supplements containing mixed tocopherols, specifically suggesting a ratio of 50-100 IU of gamma-tocopherol per 400 IU of D-alpha-tocopherol. Additional research is essential to confirm and further clarify the role of gamma-tocopherol in bone formation and resorption. In fact, it is also important to explore the influence of other compounds in the vitamin E family on skeletal health.

Until more data are available, we would recommend following the Institute of Medicine’s guidelines for the recommended daily allowance (RDA) of vitamin E. This is age dependent, ranging from 4 to 11 mg/d between the ages of 0 and 13 years, and 15 mg/d thereafter. 

Overall, evidence of vitamin E’s impact on osteoporosis and hip fracture risk in perimenopausal women remains inconclusive. Although some observational and interventional studies suggest potential benefits, more interventional studies, particularly randomized controlled trials, are necessary to explore the risks and benefits of vitamin E supplementation and serum vitamin E levels on bone density and fracture risk more thoroughly.

Dr. Pani, Assistant Professor, Department of Internal Medicine, UVA School of Medicine; Medical Director, Department of General Medicine, Same Day Care Clinic, both in Charlottesville, has disclosed no relevant financial relationships. Dr. Misra, Professor, Chair, Physician-in-Chief, Department of Pediatrics, University of Virginia, and UVA Health Children’s, Charlottesville, has disclosed being a key opinion leader for Lumos Pharma.

A version of this article appeared on Medscape.com.

Vitamin E may be best known for boosting skin and eye health as well as immune function. In recent years, researchers have explored the potential benefits of vitamin E on bone loss, especially in women with menopause-related osteoporosis. While data are beginning to roll in from these studies, evidence supporting a positive impact of vitamin E on osteoporosis and hip fracture risk in perimenopausal women remains elusive.

For osteoporosis, the rationale for using vitamin E is based on its antioxidant activity, which can scavenge potentially damaging free radicals. Researchers have asked whether vitamin E can help maintain the integrity of bone matrix and stimulate bone formation while minimizing bone resorption, particularly in trabecular (spongy) bone, the bone compartment preferentially affected in perimenopausal bone loss. 

Vitamin E mostly consists of two isomers: alpha-tocopherol and gamma-tocopherol. Alpha-tocopherol has higher antioxidant activity and is found in nuts, seeds, vegetable oils, green leafy vegetables, fortified cereals, and vitamin E supplements. Gamma-tocopherol is known for its superior anti-inflammatory properties and accounts for about 70% of the total vitamin E intake in a typical American diet, largely sourced from soybean and other vegetable oils. 

 

Benefits and Risks in Bone Loss Studies

Perimenopausal bone loss is caused, to a great extent, by the decrease in sex hormones. Studies of vitamin E in ovariectomized rats have yielded mixed results. This animal model lacks sex hormones and has similar bone changes to those of postmenopausal women. Some animal studies have suggested a positive effect of vitamin E on bone while others have reported no effect. 

Studies in humans also have produced conflicting reports of positive, neutral, and negative associations of vitamin E with bone health. For example, the Women’s Health Initiative examined the relationship between vitamin and mineral antioxidants and bone health in postmenopausal women and found no significant association between antioxidants and bone mineral density. 

Another study examining data from children and adolescents enrolled in the National Health and Nutrition Examination Survey (NHANES) database found an inverse association between alpha-tocopherol and lumbar spine bone density, suggesting a deleterious effect on bone. Inverse associations also have been reported in certain studies of postmenopausal women.

High doses of alpha-tocopherol have been linked to a risk for impaired bone health through a variety of mechanisms, such as interference with vitamin K metabolism; competitive binding for alpha-tocopherol transfer protein, inhibiting the entry of beneficial vitamin E isomers, including gamma-tocopherol; and pro-oxidant effects that harm bone. Thus, postmenopausal women taking vitamin E supplements primarily as high doses of alpha-tocopherol might be hindering their bone health. 

Data for gamma-tocopherol are more promising. Some studies hypothesize that gamma-tocopherol might uncouple bone turnover, leading to increased bone formation without affecting bone resorption. Further, a randomized controlled study of mixed tocopherols (rather than alpha-tocopherol) vs placebo reported a protective effect of this preparation on bone outcomes by suppressing bone resorption. This raises the importance of considering the specific forms of vitamin E when evaluating its role in bone health.

 

Limitations of Current Studies

Researchers acknowledge several limitations in studies to date. For example, there are very few randomized controlled trials assessing the impact of vitamin E on bone health. Most studies are cross-sectional or observational, even when longitudinal. Cross-sectional and observational designs prevent us from establishing a causal relationship between vitamin E and bone endpoints. 

Such designs also run the risk of additional confounders that may affect associations between vitamin E and bone, or the lack thereof. These could include both known and unknown confounders. Of note, gamma-tocopherol intake data were not available for certain NHANES studies. 

Further, people often consume multiple nutrients and supplements, complicating the identification of specific nutrient-disease associations. Most human studies estimate tocopherol intake by dietary questionnaires or measure serum tocopherol levels, which reflect short-term dietary intake, while bone mineral density is probably influenced by long-term dietary patterns.

 

Too Soon to Prescribe Vitamin E for Bone Health

Some nutrition experts advocate for vitamin E supplements containing mixed tocopherols, specifically suggesting a ratio of 50-100 IU of gamma-tocopherol per 400 IU of D-alpha-tocopherol. Additional research is essential to confirm and further clarify the role of gamma-tocopherol in bone formation and resorption. In fact, it is also important to explore the influence of other compounds in the vitamin E family on skeletal health.

Until more data are available, we would recommend following the Institute of Medicine’s guidelines for the recommended daily allowance (RDA) of vitamin E. This is age dependent, ranging from 4 to 11 mg/d between the ages of 0 and 13 years, and 15 mg/d thereafter. 

Overall, evidence of vitamin E’s impact on osteoporosis and hip fracture risk in perimenopausal women remains inconclusive. Although some observational and interventional studies suggest potential benefits, more interventional studies, particularly randomized controlled trials, are necessary to explore the risks and benefits of vitamin E supplementation and serum vitamin E levels on bone density and fracture risk more thoroughly.

Dr. Pani, Assistant Professor, Department of Internal Medicine, UVA School of Medicine; Medical Director, Department of General Medicine, Same Day Care Clinic, both in Charlottesville, has disclosed no relevant financial relationships. Dr. Misra, Professor, Chair, Physician-in-Chief, Department of Pediatrics, University of Virginia, and UVA Health Children’s, Charlottesville, has disclosed being a key opinion leader for Lumos Pharma.

A version of this article appeared on Medscape.com.

TOPLINE:

For patients with early-stage ERBB2 (formerly HER2)–positive breast cancer, injections of increasing doses of autologous conventional type 1 dendritic cells (cDC1) combined with ERBB2-targeted antibodies demonstrate safety and effectiveness in enhancing immune response. The higher dose (100 million cells) shows enhanced immune effector recruitment and significant tumor regression before chemotherapy initiation.

METHODOLOGY:

• ERBB2-positive breast cancer survival has improved with anti-ERBB2 antibodies trastuzumab and pertuzumab, but for a pathologic complete response, chemotherapy remains necessary, which comes with significant toxic effects.
• A phase 1, nonrandomized clinical trial enrolled 12 patients with early-stage ERBB2-positive breast cancer in Tampa, Florida, from October 2021 to October 2022.
• Participants received intratumoral (IT) cDC1 injections weekly for 6 weeks at two dose levels (50 million cells for dose level 1 and 100 million cells for dose level 2), with six patients in each group.
• Starting from day 1 of the cDC1 injections, treatment included trastuzumab (8-mg/kg loading dose, then 6 mg/kg) and pertuzumab (840-mg loading dose, then 420 mg) administered intravenously every 3 weeks for six cycles, followed by paclitaxel (80 mg/m²) weekly for 12 weeks and surgery with lumpectomy or mastectomy.
• Primary outcomes measured safety and immune response of increasing doses of cDC1 combined with anti-ERBB2 antibodies before neoadjuvant chemotherapy; secondary outcomes assessed antitumor efficacy through breast MRI and residual cancer burden at surgery.

TAKEAWAY:

• IT delivery of ERBB2 cDC1 was safe and not associated with any dose-limiting toxic effects. The most frequent adverse events attributed to cDC1 were grade 1-2 chills (50%), fatigue (41.7%), headache (33%), and injection-site reactions (33%).
• Dose level 2 showed enhanced recruitment of adaptive CD3, CD4, and CD8 T cells and B cells within the tumor microenvironment (TME), along with increased innate gamma delta T cells and natural killer T cells.
• Breast MRI revealed nine objective responses, including six partial responses and three complete responses, with three cases of stable disease.
• Following surgery, 7 of 12 patients (58%) achieved a pathologic complete response, including all 3 hormone receptor–negative patients and 4 of the 9 hormone receptor–positive patients.

IN PRACTICE:

“Overall, the clinical data shown here demonstrate the effects of combining ERBB2 antibodies with IT [intratumoral] delivery of targeted cDC1 to enhance immune cell infiltration within the TME [tumor microenvironment] and subsequently induce tumor regression before chemotherapy,” wrote the authors, who noted they will be testing the higher dose for an ongoing phase 2 trial with an additional 41 patients.

SOURCE:

The study was led by Hyo S. Han, MD, of H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida. It was published online on December 5, 2024, in JAMA Oncology.

LIMITATIONS:

Because only two dose levels of cDC1 were tested, it remains unclear whether higher doses or different administration schedules could further enhance immune response. Additionally, the nonrandomized design prevents definitive conclusions about whether the clinical benefits were solely from the anti-ERBB2 antibodies. The small sample size also makes it difficult to determine if the pathologic complete responses were primarily due to the 12 weeks of trastuzumab/pertuzumab/paclitaxel treatment.

DISCLOSURES:

This study was funded by the Moffitt Breast Cancer Research Fund, Shula Fund, and Pennies in Action. Several authors reported research support and personal and consulting fees from US funding agencies and multiple pharmaceutical companies outside of the submitted work, as well as related intellectual property and patents.

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:

For patients with early-stage ERBB2 (formerly HER2)–positive breast cancer, injections of increasing doses of autologous conventional type 1 dendritic cells (cDC1) combined with ERBB2-targeted antibodies demonstrate safety and effectiveness in enhancing immune response. The higher dose (100 million cells) shows enhanced immune effector recruitment and significant tumor regression before chemotherapy initiation.

METHODOLOGY:

• ERBB2-positive breast cancer survival has improved with anti-ERBB2 antibodies trastuzumab and pertuzumab, but for a pathologic complete response, chemotherapy remains necessary, which comes with significant toxic effects.
• A phase 1, nonrandomized clinical trial enrolled 12 patients with early-stage ERBB2-positive breast cancer in Tampa, Florida, from October 2021 to October 2022.
• Participants received intratumoral (IT) cDC1 injections weekly for 6 weeks at two dose levels (50 million cells for dose level 1 and 100 million cells for dose level 2), with six patients in each group.
• Starting from day 1 of the cDC1 injections, treatment included trastuzumab (8-mg/kg loading dose, then 6 mg/kg) and pertuzumab (840-mg loading dose, then 420 mg) administered intravenously every 3 weeks for six cycles, followed by paclitaxel (80 mg/m²) weekly for 12 weeks and surgery with lumpectomy or mastectomy.
• Primary outcomes measured safety and immune response of increasing doses of cDC1 combined with anti-ERBB2 antibodies before neoadjuvant chemotherapy; secondary outcomes assessed antitumor efficacy through breast MRI and residual cancer burden at surgery.

TAKEAWAY:

• IT delivery of ERBB2 cDC1 was safe and not associated with any dose-limiting toxic effects. The most frequent adverse events attributed to cDC1 were grade 1-2 chills (50%), fatigue (41.7%), headache (33%), and injection-site reactions (33%).
• Dose level 2 showed enhanced recruitment of adaptive CD3, CD4, and CD8 T cells and B cells within the tumor microenvironment (TME), along with increased innate gamma delta T cells and natural killer T cells.
• Breast MRI revealed nine objective responses, including six partial responses and three complete responses, with three cases of stable disease.
• Following surgery, 7 of 12 patients (58%) achieved a pathologic complete response, including all 3 hormone receptor–negative patients and 4 of the 9 hormone receptor–positive patients.

IN PRACTICE:

“Overall, the clinical data shown here demonstrate the effects of combining ERBB2 antibodies with IT [intratumoral] delivery of targeted cDC1 to enhance immune cell infiltration within the TME [tumor microenvironment] and subsequently induce tumor regression before chemotherapy,” wrote the authors, who noted they will be testing the higher dose for an ongoing phase 2 trial with an additional 41 patients.

SOURCE:

The study was led by Hyo S. Han, MD, of H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida. It was published online on December 5, 2024, in JAMA Oncology.

LIMITATIONS:

Because only two dose levels of cDC1 were tested, it remains unclear whether higher doses or different administration schedules could further enhance immune response. Additionally, the nonrandomized design prevents definitive conclusions about whether the clinical benefits were solely from the anti-ERBB2 antibodies. The small sample size also makes it difficult to determine if the pathologic complete responses were primarily due to the 12 weeks of trastuzumab/pertuzumab/paclitaxel treatment.

DISCLOSURES:

This study was funded by the Moffitt Breast Cancer Research Fund, Shula Fund, and Pennies in Action. Several authors reported research support and personal and consulting fees from US funding agencies and multiple pharmaceutical companies outside of the submitted work, as well as related intellectual property and patents.

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:

For patients with early-stage ERBB2 (formerly HER2)–positive breast cancer, injections of increasing doses of autologous conventional type 1 dendritic cells (cDC1) combined with ERBB2-targeted antibodies demonstrate safety and effectiveness in enhancing immune response. The higher dose (100 million cells) shows enhanced immune effector recruitment and significant tumor regression before chemotherapy initiation.

METHODOLOGY:

• ERBB2-positive breast cancer survival has improved with anti-ERBB2 antibodies trastuzumab and pertuzumab, but for a pathologic complete response, chemotherapy remains necessary, which comes with significant toxic effects.
• A phase 1, nonrandomized clinical trial enrolled 12 patients with early-stage ERBB2-positive breast cancer in Tampa, Florida, from October 2021 to October 2022.
• Participants received intratumoral (IT) cDC1 injections weekly for 6 weeks at two dose levels (50 million cells for dose level 1 and 100 million cells for dose level 2), with six patients in each group.
• Starting from day 1 of the cDC1 injections, treatment included trastuzumab (8-mg/kg loading dose, then 6 mg/kg) and pertuzumab (840-mg loading dose, then 420 mg) administered intravenously every 3 weeks for six cycles, followed by paclitaxel (80 mg/m²) weekly for 12 weeks and surgery with lumpectomy or mastectomy.
• Primary outcomes measured safety and immune response of increasing doses of cDC1 combined with anti-ERBB2 antibodies before neoadjuvant chemotherapy; secondary outcomes assessed antitumor efficacy through breast MRI and residual cancer burden at surgery.

TAKEAWAY:

• IT delivery of ERBB2 cDC1 was safe and not associated with any dose-limiting toxic effects. The most frequent adverse events attributed to cDC1 were grade 1-2 chills (50%), fatigue (41.7%), headache (33%), and injection-site reactions (33%).
• Dose level 2 showed enhanced recruitment of adaptive CD3, CD4, and CD8 T cells and B cells within the tumor microenvironment (TME), along with increased innate gamma delta T cells and natural killer T cells.
• Breast MRI revealed nine objective responses, including six partial responses and three complete responses, with three cases of stable disease.
• Following surgery, 7 of 12 patients (58%) achieved a pathologic complete response, including all 3 hormone receptor–negative patients and 4 of the 9 hormone receptor–positive patients.

IN PRACTICE:

“Overall, the clinical data shown here demonstrate the effects of combining ERBB2 antibodies with IT [intratumoral] delivery of targeted cDC1 to enhance immune cell infiltration within the TME [tumor microenvironment] and subsequently induce tumor regression before chemotherapy,” wrote the authors, who noted they will be testing the higher dose for an ongoing phase 2 trial with an additional 41 patients.

SOURCE:

The study was led by Hyo S. Han, MD, of H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida. It was published online on December 5, 2024, in JAMA Oncology.

LIMITATIONS:

Because only two dose levels of cDC1 were tested, it remains unclear whether higher doses or different administration schedules could further enhance immune response. Additionally, the nonrandomized design prevents definitive conclusions about whether the clinical benefits were solely from the anti-ERBB2 antibodies. The small sample size also makes it difficult to determine if the pathologic complete responses were primarily due to the 12 weeks of trastuzumab/pertuzumab/paclitaxel treatment.

DISCLOSURES:

This study was funded by the Moffitt Breast Cancer Research Fund, Shula Fund, and Pennies in Action. Several authors reported research support and personal and consulting fees from US funding agencies and multiple pharmaceutical companies outside of the submitted work, as well as related intellectual property and patents.

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.

Vaccines for treating and preventing cancer have long been considered a holy grail in oncology.

But aside from a few notable exceptions — including the human papillomavirus (HPV) vaccine, which has dramatically reduced the incidence of HPV-related cancers, and a Bacillus Calmette-Guerin vaccine, which helps prevent early-stage bladder cancer recurrence — most have failed to deliver.

Following a string of disappointments over the past decade, recent advances in the immunotherapy space are bringing renewed hope for progress.

In an American Association for Cancer Research (AACR) series earlier in 2024, Catherine J. Wu, MD, predicted big strides for cancer vaccines, especially for personalized vaccines that target patient-specific neoantigens — the proteins that form on cancer cells — as well as vaccines that can treat diverse tumor types.

“A focus on neoantigens that arise from driver mutations in different tumor types could allow us to make progress in creating off-the-shelf vaccines,” said Wu, the Lavine Family Chair of Preventative Cancer Therapies at Dana-Farber Cancer Institute and a professor of medicine at Harvard Medical School, both in Boston, Massachusetts.

A prime example is a personalized, messenger RNA (mRNA)–based vaccine designed to prevent melanoma recurrence. The mRNA-4157 vaccine encodes up to 34 different patient-specific neoantigens.

“This is one of the most exciting developments in modern cancer therapy,” said Lawrence Young, a virologist and professor of molecular oncology at the University of Warwick, Coventry, England, who commented on the investigational vaccine via the UK-based Science Media Centre.

Other promising options are on the horizon as well. In August, BioNTech announced a phase 1 global trial to study BNT116 — a vaccine to treat non–small cell lung cancer (NSCLC). BNT116, like mRNA-4157, targets specific antigens in the lung cancer cells.

“This technology is the next big phase of cancer treatment,” Siow Ming Lee, MD, a consultant medical oncologist at University College London Hospitals in England, which is leading the UK trial for the lung cancer and melanoma vaccines, told The Guardian. “We are now entering this very exciting new era of mRNA-based immunotherapy clinical trials to investigate the treatment of lung cancer.”

Still, these predictions have a familiar ring. While the prospects are exciting, delivering on them is another story. There are simply no guarantees these strategies will work as hoped.

 

Then: Where We Were

Cancer vaccine research began to ramp up in the 2000s, and in 2006, the first-generation HPV vaccine, Gardasil, was approved. Gardasil prevents infection from four strains of HPV that cause about 80% of cervical cancer cases.

In 2010, the Food and Drug Administration approved sipuleucel-T, the first therapeutic cancer vaccine, which improved overall survival in patients with hormone-refractory prostate cancer.

Researchers predicted this approval would “pave the way for developing innovative, next generation of vaccines with enhanced antitumor potency.”

In a 2015 AACR research forecast report, Drew Pardoll, MD, PhD, co-director of the Cancer Immunology and Hematopoiesis Program at Johns Hopkins University, Baltimore, Maryland, said that “we can expect to see encouraging results from studies using cancer vaccines.”

Despite the excitement surrounding cancer vaccines alongside a few successes, the next decade brought a longer string of late-phase disappointments.

In 2016, the phase 3 ACT IV trial of a therapeutic vaccine to treat glioblastoma multiforme (CDX-110) was terminated after it failed to demonstrate improved survival.

In 2017, a phase 3 trial of the therapeutic pancreatic cancer vaccine, GVAX, was stopped early for lack of efficacy.

That year, an attenuated Listeria monocytogenes vaccine to treat pancreatic cancer and mesothelioma also failed to come to fruition. In late 2017, concerns over listeria infections prompted Aduro Biotech to cancel its listeria-based cancer treatment program.

In 2018, a phase 3 trial of belagenpumatucel-L, a therapeutic NSCLC vaccine, failed to demonstrate a significant improvement in survival and further study was discontinued.

And in 2019, a vaccine targeting MAGE-A3, a cancer-testis antigen present in multiple tumor types, failed to meet endpoints for improved survival in a phase 3 trial, leading to discontinuation of the vaccine program.

But these disappointments and failures are normal parts of medical research and drug development and have allowed for incremental advances that helped fuel renewed interest and hope for cancer vaccines, when the timing was right, explained vaccine pioneer Larry W. Kwak, MD, PhD, deputy director of the Comprehensive Cancer Center at City of Hope, Duarte, California.

When it comes to vaccine progress, timing makes a difference. In 2011, Kwak and colleagues published promising phase 3 trial results on a personalized vaccine. The vaccine was a patient-specific tumor-derived antigen for patients with follicular lymphoma in their first remission following chemotherapy. Patients who received the vaccine demonstrated significantly longer disease-free survival.

But, at the time, personalized vaccines faced strong headwinds due, largely, to high costs, and commercial interest failed to materialize. “That’s been the major hurdle for a long time,” said Kwak.

Now, however, interest has returned alongside advances in technology and research. The big shift has been the emergence of lower-cost rapid-production mRNA and DNA platforms and a better understanding of how vaccines and potent immune stimulants, like checkpoint inhibitors, can work together to improve outcomes, he explained.

“The timing wasn’t right” back then, Kwak noted. “Now, it’s a different environment and a different time.”

 

A Turning Point?

Indeed, a decade later, cancer vaccine development appears to be headed in a more promising direction.

Among key cancer vaccines to watch is the mRNA-4157 vaccine, developed by Merck and Moderna, designed to prevent melanoma recurrence. In a recent phase 2 study, patients receiving the mRNA-4157 vaccine alongside pembrolizumab had nearly half the risk for melanoma recurrence or death at 3 years compared with those receiving pembrolizumab alone. Investigators are now evaluating the vaccine in a global phase 3 study in patients with high-risk, stage IIB to IV melanoma following surgery.

Another one to watch is the BNT116 NSCLC vaccine from BioNTech. This vaccine presents the immune system with NSCLC tumor markers to encourage the body to fight cancer cells expressing those markers while ignoring healthy cells. BioNTech also launched a global clinical trial for its vaccine this year.

Other notables include a pancreatic cancer mRNA vaccine, which has shown promising early results in a small trial of 16 patients. Of 16 patients who received the vaccine alongside chemotherapy and after surgery and immunotherapy, 8 responded. Of these eight, six remained recurrence free at 3 years. Investigators noted that the vaccine appeared to stimulate a durable T-cell response in patients who responded.

Kwak has also continued his work on lymphoma vaccines. In August, his team published promising first-in-human data on the use of personalized neoantigen vaccines as an early intervention in untreated patients with lymphoplasmacytic lymphoma. Among nine asymptomatic patients who received the vaccine, all achieved stable disease or better, with no dose-limiting toxicities. One patient had a minor response, and the median time to progression was greater than 72 months.

“The current setting is more for advanced disease,” Kwak explained. “It’s a tougher task, but combined with checkpoint blockade, it may be potent enough to work.” 

Still, caution is important. Despite early promise, it’s too soon to tell which, if any, of these investigational vaccines will pan out in the long run. Like investigational drugs, cancer vaccines may show big promising initially but then fail in larger trials.

One key to success, according to Kwak, is to design trials so that even negative results will inform next steps.

But, he noted, failures in large clinical trials will “put a chilling effect on cancer vaccine research again.”

“That’s what keeps me up at night,” he said. “We know the science is fundamentally sound and we have seen glimpses over decades of research that cancer vaccines can work, so it’s really just a matter of tweaking things to optimize trial design.”

Companies tend to design trials to test if a vaccine works or not, without trying to understand why, he said.

“What we need to do is design those so that we can learn from negative results,” he said. That’s what he and his colleagues attempted to do in their recent trial. “We didn’t just look at clinical results; we’re interrogating the actual tumor environment to understand what worked and didn’t and how to tweak that for the next trial.”

Kwak and his colleagues found, for instance, that the vaccine had a greater effect on B cell–derived tumor cells than on cells of plasma origin, so “the most rational design for the next iteration is to combine the vaccine with agents that work directly against plasma cells,” he explained.

As for what’s next, Kwak said: “We’re just focused on trying to do good science and understand. We’ve seen glimpses of success. That’s where we are.”

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

Vaccines for treating and preventing cancer have long been considered a holy grail in oncology.

But aside from a few notable exceptions — including the human papillomavirus (HPV) vaccine, which has dramatically reduced the incidence of HPV-related cancers, and a Bacillus Calmette-Guerin vaccine, which helps prevent early-stage bladder cancer recurrence — most have failed to deliver.

Following a string of disappointments over the past decade, recent advances in the immunotherapy space are bringing renewed hope for progress.

In an American Association for Cancer Research (AACR) series earlier in 2024, Catherine J. Wu, MD, predicted big strides for cancer vaccines, especially for personalized vaccines that target patient-specific neoantigens — the proteins that form on cancer cells — as well as vaccines that can treat diverse tumor types.

“A focus on neoantigens that arise from driver mutations in different tumor types could allow us to make progress in creating off-the-shelf vaccines,” said Wu, the Lavine Family Chair of Preventative Cancer Therapies at Dana-Farber Cancer Institute and a professor of medicine at Harvard Medical School, both in Boston, Massachusetts.

A prime example is a personalized, messenger RNA (mRNA)–based vaccine designed to prevent melanoma recurrence. The mRNA-4157 vaccine encodes up to 34 different patient-specific neoantigens.

“This is one of the most exciting developments in modern cancer therapy,” said Lawrence Young, a virologist and professor of molecular oncology at the University of Warwick, Coventry, England, who commented on the investigational vaccine via the UK-based Science Media Centre.

Other promising options are on the horizon as well. In August, BioNTech announced a phase 1 global trial to study BNT116 — a vaccine to treat non–small cell lung cancer (NSCLC). BNT116, like mRNA-4157, targets specific antigens in the lung cancer cells.

“This technology is the next big phase of cancer treatment,” Siow Ming Lee, MD, a consultant medical oncologist at University College London Hospitals in England, which is leading the UK trial for the lung cancer and melanoma vaccines, told The Guardian. “We are now entering this very exciting new era of mRNA-based immunotherapy clinical trials to investigate the treatment of lung cancer.”

Still, these predictions have a familiar ring. While the prospects are exciting, delivering on them is another story. There are simply no guarantees these strategies will work as hoped.

 

Then: Where We Were

Cancer vaccine research began to ramp up in the 2000s, and in 2006, the first-generation HPV vaccine, Gardasil, was approved. Gardasil prevents infection from four strains of HPV that cause about 80% of cervical cancer cases.

In 2010, the Food and Drug Administration approved sipuleucel-T, the first therapeutic cancer vaccine, which improved overall survival in patients with hormone-refractory prostate cancer.

Researchers predicted this approval would “pave the way for developing innovative, next generation of vaccines with enhanced antitumor potency.”

In a 2015 AACR research forecast report, Drew Pardoll, MD, PhD, co-director of the Cancer Immunology and Hematopoiesis Program at Johns Hopkins University, Baltimore, Maryland, said that “we can expect to see encouraging results from studies using cancer vaccines.”

Despite the excitement surrounding cancer vaccines alongside a few successes, the next decade brought a longer string of late-phase disappointments.

In 2016, the phase 3 ACT IV trial of a therapeutic vaccine to treat glioblastoma multiforme (CDX-110) was terminated after it failed to demonstrate improved survival.

In 2017, a phase 3 trial of the therapeutic pancreatic cancer vaccine, GVAX, was stopped early for lack of efficacy.

That year, an attenuated Listeria monocytogenes vaccine to treat pancreatic cancer and mesothelioma also failed to come to fruition. In late 2017, concerns over listeria infections prompted Aduro Biotech to cancel its listeria-based cancer treatment program.

In 2018, a phase 3 trial of belagenpumatucel-L, a therapeutic NSCLC vaccine, failed to demonstrate a significant improvement in survival and further study was discontinued.

And in 2019, a vaccine targeting MAGE-A3, a cancer-testis antigen present in multiple tumor types, failed to meet endpoints for improved survival in a phase 3 trial, leading to discontinuation of the vaccine program.

But these disappointments and failures are normal parts of medical research and drug development and have allowed for incremental advances that helped fuel renewed interest and hope for cancer vaccines, when the timing was right, explained vaccine pioneer Larry W. Kwak, MD, PhD, deputy director of the Comprehensive Cancer Center at City of Hope, Duarte, California.

When it comes to vaccine progress, timing makes a difference. In 2011, Kwak and colleagues published promising phase 3 trial results on a personalized vaccine. The vaccine was a patient-specific tumor-derived antigen for patients with follicular lymphoma in their first remission following chemotherapy. Patients who received the vaccine demonstrated significantly longer disease-free survival.

But, at the time, personalized vaccines faced strong headwinds due, largely, to high costs, and commercial interest failed to materialize. “That’s been the major hurdle for a long time,” said Kwak.

Now, however, interest has returned alongside advances in technology and research. The big shift has been the emergence of lower-cost rapid-production mRNA and DNA platforms and a better understanding of how vaccines and potent immune stimulants, like checkpoint inhibitors, can work together to improve outcomes, he explained.

“The timing wasn’t right” back then, Kwak noted. “Now, it’s a different environment and a different time.”

 

A Turning Point?

Indeed, a decade later, cancer vaccine development appears to be headed in a more promising direction.

Among key cancer vaccines to watch is the mRNA-4157 vaccine, developed by Merck and Moderna, designed to prevent melanoma recurrence. In a recent phase 2 study, patients receiving the mRNA-4157 vaccine alongside pembrolizumab had nearly half the risk for melanoma recurrence or death at 3 years compared with those receiving pembrolizumab alone. Investigators are now evaluating the vaccine in a global phase 3 study in patients with high-risk, stage IIB to IV melanoma following surgery.

Another one to watch is the BNT116 NSCLC vaccine from BioNTech. This vaccine presents the immune system with NSCLC tumor markers to encourage the body to fight cancer cells expressing those markers while ignoring healthy cells. BioNTech also launched a global clinical trial for its vaccine this year.

Other notables include a pancreatic cancer mRNA vaccine, which has shown promising early results in a small trial of 16 patients. Of 16 patients who received the vaccine alongside chemotherapy and after surgery and immunotherapy, 8 responded. Of these eight, six remained recurrence free at 3 years. Investigators noted that the vaccine appeared to stimulate a durable T-cell response in patients who responded.

Kwak has also continued his work on lymphoma vaccines. In August, his team published promising first-in-human data on the use of personalized neoantigen vaccines as an early intervention in untreated patients with lymphoplasmacytic lymphoma. Among nine asymptomatic patients who received the vaccine, all achieved stable disease or better, with no dose-limiting toxicities. One patient had a minor response, and the median time to progression was greater than 72 months.

“The current setting is more for advanced disease,” Kwak explained. “It’s a tougher task, but combined with checkpoint blockade, it may be potent enough to work.” 

Still, caution is important. Despite early promise, it’s too soon to tell which, if any, of these investigational vaccines will pan out in the long run. Like investigational drugs, cancer vaccines may show big promising initially but then fail in larger trials.

One key to success, according to Kwak, is to design trials so that even negative results will inform next steps.

But, he noted, failures in large clinical trials will “put a chilling effect on cancer vaccine research again.”

“That’s what keeps me up at night,” he said. “We know the science is fundamentally sound and we have seen glimpses over decades of research that cancer vaccines can work, so it’s really just a matter of tweaking things to optimize trial design.”

Companies tend to design trials to test if a vaccine works or not, without trying to understand why, he said.

“What we need to do is design those so that we can learn from negative results,” he said. That’s what he and his colleagues attempted to do in their recent trial. “We didn’t just look at clinical results; we’re interrogating the actual tumor environment to understand what worked and didn’t and how to tweak that for the next trial.”

Kwak and his colleagues found, for instance, that the vaccine had a greater effect on B cell–derived tumor cells than on cells of plasma origin, so “the most rational design for the next iteration is to combine the vaccine with agents that work directly against plasma cells,” he explained.

As for what’s next, Kwak said: “We’re just focused on trying to do good science and understand. We’ve seen glimpses of success. That’s where we are.”

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

Vaccines for treating and preventing cancer have long been considered a holy grail in oncology.

But aside from a few notable exceptions — including the human papillomavirus (HPV) vaccine, which has dramatically reduced the incidence of HPV-related cancers, and a Bacillus Calmette-Guerin vaccine, which helps prevent early-stage bladder cancer recurrence — most have failed to deliver.

Following a string of disappointments over the past decade, recent advances in the immunotherapy space are bringing renewed hope for progress.

In an American Association for Cancer Research (AACR) series earlier in 2024, Catherine J. Wu, MD, predicted big strides for cancer vaccines, especially for personalized vaccines that target patient-specific neoantigens — the proteins that form on cancer cells — as well as vaccines that can treat diverse tumor types.

“A focus on neoantigens that arise from driver mutations in different tumor types could allow us to make progress in creating off-the-shelf vaccines,” said Wu, the Lavine Family Chair of Preventative Cancer Therapies at Dana-Farber Cancer Institute and a professor of medicine at Harvard Medical School, both in Boston, Massachusetts.

A prime example is a personalized, messenger RNA (mRNA)–based vaccine designed to prevent melanoma recurrence. The mRNA-4157 vaccine encodes up to 34 different patient-specific neoantigens.

“This is one of the most exciting developments in modern cancer therapy,” said Lawrence Young, a virologist and professor of molecular oncology at the University of Warwick, Coventry, England, who commented on the investigational vaccine via the UK-based Science Media Centre.

Other promising options are on the horizon as well. In August, BioNTech announced a phase 1 global trial to study BNT116 — a vaccine to treat non–small cell lung cancer (NSCLC). BNT116, like mRNA-4157, targets specific antigens in the lung cancer cells.

“This technology is the next big phase of cancer treatment,” Siow Ming Lee, MD, a consultant medical oncologist at University College London Hospitals in England, which is leading the UK trial for the lung cancer and melanoma vaccines, told The Guardian. “We are now entering this very exciting new era of mRNA-based immunotherapy clinical trials to investigate the treatment of lung cancer.”

Still, these predictions have a familiar ring. While the prospects are exciting, delivering on them is another story. There are simply no guarantees these strategies will work as hoped.

 

Then: Where We Were

Cancer vaccine research began to ramp up in the 2000s, and in 2006, the first-generation HPV vaccine, Gardasil, was approved. Gardasil prevents infection from four strains of HPV that cause about 80% of cervical cancer cases.

In 2010, the Food and Drug Administration approved sipuleucel-T, the first therapeutic cancer vaccine, which improved overall survival in patients with hormone-refractory prostate cancer.

Researchers predicted this approval would “pave the way for developing innovative, next generation of vaccines with enhanced antitumor potency.”

In a 2015 AACR research forecast report, Drew Pardoll, MD, PhD, co-director of the Cancer Immunology and Hematopoiesis Program at Johns Hopkins University, Baltimore, Maryland, said that “we can expect to see encouraging results from studies using cancer vaccines.”

Despite the excitement surrounding cancer vaccines alongside a few successes, the next decade brought a longer string of late-phase disappointments.

In 2016, the phase 3 ACT IV trial of a therapeutic vaccine to treat glioblastoma multiforme (CDX-110) was terminated after it failed to demonstrate improved survival.

In 2017, a phase 3 trial of the therapeutic pancreatic cancer vaccine, GVAX, was stopped early for lack of efficacy.

That year, an attenuated Listeria monocytogenes vaccine to treat pancreatic cancer and mesothelioma also failed to come to fruition. In late 2017, concerns over listeria infections prompted Aduro Biotech to cancel its listeria-based cancer treatment program.

In 2018, a phase 3 trial of belagenpumatucel-L, a therapeutic NSCLC vaccine, failed to demonstrate a significant improvement in survival and further study was discontinued.

And in 2019, a vaccine targeting MAGE-A3, a cancer-testis antigen present in multiple tumor types, failed to meet endpoints for improved survival in a phase 3 trial, leading to discontinuation of the vaccine program.

But these disappointments and failures are normal parts of medical research and drug development and have allowed for incremental advances that helped fuel renewed interest and hope for cancer vaccines, when the timing was right, explained vaccine pioneer Larry W. Kwak, MD, PhD, deputy director of the Comprehensive Cancer Center at City of Hope, Duarte, California.

When it comes to vaccine progress, timing makes a difference. In 2011, Kwak and colleagues published promising phase 3 trial results on a personalized vaccine. The vaccine was a patient-specific tumor-derived antigen for patients with follicular lymphoma in their first remission following chemotherapy. Patients who received the vaccine demonstrated significantly longer disease-free survival.

But, at the time, personalized vaccines faced strong headwinds due, largely, to high costs, and commercial interest failed to materialize. “That’s been the major hurdle for a long time,” said Kwak.

Now, however, interest has returned alongside advances in technology and research. The big shift has been the emergence of lower-cost rapid-production mRNA and DNA platforms and a better understanding of how vaccines and potent immune stimulants, like checkpoint inhibitors, can work together to improve outcomes, he explained.

“The timing wasn’t right” back then, Kwak noted. “Now, it’s a different environment and a different time.”

 

A Turning Point?

Indeed, a decade later, cancer vaccine development appears to be headed in a more promising direction.

Among key cancer vaccines to watch is the mRNA-4157 vaccine, developed by Merck and Moderna, designed to prevent melanoma recurrence. In a recent phase 2 study, patients receiving the mRNA-4157 vaccine alongside pembrolizumab had nearly half the risk for melanoma recurrence or death at 3 years compared with those receiving pembrolizumab alone. Investigators are now evaluating the vaccine in a global phase 3 study in patients with high-risk, stage IIB to IV melanoma following surgery.

Another one to watch is the BNT116 NSCLC vaccine from BioNTech. This vaccine presents the immune system with NSCLC tumor markers to encourage the body to fight cancer cells expressing those markers while ignoring healthy cells. BioNTech also launched a global clinical trial for its vaccine this year.

Other notables include a pancreatic cancer mRNA vaccine, which has shown promising early results in a small trial of 16 patients. Of 16 patients who received the vaccine alongside chemotherapy and after surgery and immunotherapy, 8 responded. Of these eight, six remained recurrence free at 3 years. Investigators noted that the vaccine appeared to stimulate a durable T-cell response in patients who responded.

Kwak has also continued his work on lymphoma vaccines. In August, his team published promising first-in-human data on the use of personalized neoantigen vaccines as an early intervention in untreated patients with lymphoplasmacytic lymphoma. Among nine asymptomatic patients who received the vaccine, all achieved stable disease or better, with no dose-limiting toxicities. One patient had a minor response, and the median time to progression was greater than 72 months.

“The current setting is more for advanced disease,” Kwak explained. “It’s a tougher task, but combined with checkpoint blockade, it may be potent enough to work.” 

Still, caution is important. Despite early promise, it’s too soon to tell which, if any, of these investigational vaccines will pan out in the long run. Like investigational drugs, cancer vaccines may show big promising initially but then fail in larger trials.

One key to success, according to Kwak, is to design trials so that even negative results will inform next steps.

But, he noted, failures in large clinical trials will “put a chilling effect on cancer vaccine research again.”

“That’s what keeps me up at night,” he said. “We know the science is fundamentally sound and we have seen glimpses over decades of research that cancer vaccines can work, so it’s really just a matter of tweaking things to optimize trial design.”

Companies tend to design trials to test if a vaccine works or not, without trying to understand why, he said.

“What we need to do is design those so that we can learn from negative results,” he said. That’s what he and his colleagues attempted to do in their recent trial. “We didn’t just look at clinical results; we’re interrogating the actual tumor environment to understand what worked and didn’t and how to tweak that for the next trial.”

Kwak and his colleagues found, for instance, that the vaccine had a greater effect on B cell–derived tumor cells than on cells of plasma origin, so “the most rational design for the next iteration is to combine the vaccine with agents that work directly against plasma cells,” he explained.

As for what’s next, Kwak said: “We’re just focused on trying to do good science and understand. We’ve seen glimpses of success. That’s where we are.”

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

TOPLINE:

Between 2010 and 2022, hospital-based obstetric care declined significantly across the United States, with 52.4% of rural hospitals and 35.7% of urban hospitals not offering obstetric services by 2022. Rural hospitals experienced a steeper increase in the percentage of facilities without obstetrics than urban counterparts, despite several national maternity care access initiatives.

METHODOLOGY:

• Researchers conducted a retrospective cohort study of 4964 United States short-term acute care hospitals, including 1982 in rural counties and 2982 in urban counties, analyzing data from 2010 to 2022.
• Analysis utilized American Hospital Association annual surveys and Centers for Medicare & Medicaid Services Provider of Services files, applying an enhanced algorithm to identify hospital-based obstetric services availability.
• Hospital rurality classification followed Office of Management and Budget definitions, with urban hospitals located in metropolitan statistical areas having > 250,000 inhabitants and rural hospitals in nonmetropolitan areas with < 50,000 inhabitants.

TAKEAWAY:

• A total of 537 hospitals lost obstetric services between 2010 and 2022, with 238 rural hospitals and 299 urban hospitals affected, while only 138 hospitals gained obstetric services during this period.
• The percentage of hospitals without obstetrics increased steadily from 35.2% to 42.4% of all hospitals between 2010 and 2022, with rural hospitals consistently showing higher rates than urban facilities.
• By 2022, more than half (52.4%) of rural hospitals and over one third (35.7%) of urban hospitals did not offer obstetric care, representing a significant decline in access to maternal healthcare services.
• Urban areas showed greater potential for service recovery with 112 hospitals gaining obstetric services than only 26 rural hospitals during the study period.

IN PRACTICE:

“Access to obstetric care is an important determinant of maternal and infant health outcomes, and amidst a maternal health crisis in the US, hospital-based obstetric care has declined in both rural and urban communities,” wrote the authors of the study.

SOURCE:

The study was led by Katy B. Kozhimannil, PhD, MPA, Division of Health Policy and Management, University of Minnesota School of Public Health in Minneapolis. It was published online on December 4 in JAMA.

LIMITATIONS: 

The study was limited by the lack of data on births outside hospital settings, which represent less than 2% of United States births. Additionally, the denominator for the study outcome declined each year because of hospital closures, particularly affecting rural hospitals. The researchers also noted that while rurality exists on a continuum, they applied a dichotomous county–based measure of hospital location. Furthermore, the hospital-level data did not contain patient-level information, making it impossible to analyze how changes in obstetric status affected patient outcomes. 

DISCLOSURES:

This study was supported by the Federal Office of Rural Health Policy, Health Resources and Services Administration, Department of Health & Human Services under Public Health Service Cooperative Agreement. One coauthor disclosed receiving grants from the Laura and John Arnold Foundation, Ballad Health, and the Commonwealth Fund outside the submitted work. A coauthor reported receiving personal fees from the American Institute of Biological Sciences on behalf of March of Dimes as a grant reviewer. Another coauthor reported receiving grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development outside the submitted work. 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:

Between 2010 and 2022, hospital-based obstetric care declined significantly across the United States, with 52.4% of rural hospitals and 35.7% of urban hospitals not offering obstetric services by 2022. Rural hospitals experienced a steeper increase in the percentage of facilities without obstetrics than urban counterparts, despite several national maternity care access initiatives.

METHODOLOGY:

• Researchers conducted a retrospective cohort study of 4964 United States short-term acute care hospitals, including 1982 in rural counties and 2982 in urban counties, analyzing data from 2010 to 2022.
• Analysis utilized American Hospital Association annual surveys and Centers for Medicare & Medicaid Services Provider of Services files, applying an enhanced algorithm to identify hospital-based obstetric services availability.
• Hospital rurality classification followed Office of Management and Budget definitions, with urban hospitals located in metropolitan statistical areas having > 250,000 inhabitants and rural hospitals in nonmetropolitan areas with < 50,000 inhabitants.

TAKEAWAY:

• A total of 537 hospitals lost obstetric services between 2010 and 2022, with 238 rural hospitals and 299 urban hospitals affected, while only 138 hospitals gained obstetric services during this period.
• The percentage of hospitals without obstetrics increased steadily from 35.2% to 42.4% of all hospitals between 2010 and 2022, with rural hospitals consistently showing higher rates than urban facilities.
• By 2022, more than half (52.4%) of rural hospitals and over one third (35.7%) of urban hospitals did not offer obstetric care, representing a significant decline in access to maternal healthcare services.
• Urban areas showed greater potential for service recovery with 112 hospitals gaining obstetric services than only 26 rural hospitals during the study period.

IN PRACTICE:

“Access to obstetric care is an important determinant of maternal and infant health outcomes, and amidst a maternal health crisis in the US, hospital-based obstetric care has declined in both rural and urban communities,” wrote the authors of the study.

SOURCE:

The study was led by Katy B. Kozhimannil, PhD, MPA, Division of Health Policy and Management, University of Minnesota School of Public Health in Minneapolis. It was published online on December 4 in JAMA.

LIMITATIONS: 

The study was limited by the lack of data on births outside hospital settings, which represent less than 2% of United States births. Additionally, the denominator for the study outcome declined each year because of hospital closures, particularly affecting rural hospitals. The researchers also noted that while rurality exists on a continuum, they applied a dichotomous county–based measure of hospital location. Furthermore, the hospital-level data did not contain patient-level information, making it impossible to analyze how changes in obstetric status affected patient outcomes. 

DISCLOSURES:

This study was supported by the Federal Office of Rural Health Policy, Health Resources and Services Administration, Department of Health & Human Services under Public Health Service Cooperative Agreement. One coauthor disclosed receiving grants from the Laura and John Arnold Foundation, Ballad Health, and the Commonwealth Fund outside the submitted work. A coauthor reported receiving personal fees from the American Institute of Biological Sciences on behalf of March of Dimes as a grant reviewer. Another coauthor reported receiving grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development outside the submitted work. 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:

Between 2010 and 2022, hospital-based obstetric care declined significantly across the United States, with 52.4% of rural hospitals and 35.7% of urban hospitals not offering obstetric services by 2022. Rural hospitals experienced a steeper increase in the percentage of facilities without obstetrics than urban counterparts, despite several national maternity care access initiatives.

METHODOLOGY:

• Researchers conducted a retrospective cohort study of 4964 United States short-term acute care hospitals, including 1982 in rural counties and 2982 in urban counties, analyzing data from 2010 to 2022.
• Analysis utilized American Hospital Association annual surveys and Centers for Medicare & Medicaid Services Provider of Services files, applying an enhanced algorithm to identify hospital-based obstetric services availability.
• Hospital rurality classification followed Office of Management and Budget definitions, with urban hospitals located in metropolitan statistical areas having > 250,000 inhabitants and rural hospitals in nonmetropolitan areas with < 50,000 inhabitants.

TAKEAWAY:

• A total of 537 hospitals lost obstetric services between 2010 and 2022, with 238 rural hospitals and 299 urban hospitals affected, while only 138 hospitals gained obstetric services during this period.
• The percentage of hospitals without obstetrics increased steadily from 35.2% to 42.4% of all hospitals between 2010 and 2022, with rural hospitals consistently showing higher rates than urban facilities.
• By 2022, more than half (52.4%) of rural hospitals and over one third (35.7%) of urban hospitals did not offer obstetric care, representing a significant decline in access to maternal healthcare services.
• Urban areas showed greater potential for service recovery with 112 hospitals gaining obstetric services than only 26 rural hospitals during the study period.

IN PRACTICE:

“Access to obstetric care is an important determinant of maternal and infant health outcomes, and amidst a maternal health crisis in the US, hospital-based obstetric care has declined in both rural and urban communities,” wrote the authors of the study.

SOURCE:

The study was led by Katy B. Kozhimannil, PhD, MPA, Division of Health Policy and Management, University of Minnesota School of Public Health in Minneapolis. It was published online on December 4 in JAMA.

LIMITATIONS: 

The study was limited by the lack of data on births outside hospital settings, which represent less than 2% of United States births. Additionally, the denominator for the study outcome declined each year because of hospital closures, particularly affecting rural hospitals. The researchers also noted that while rurality exists on a continuum, they applied a dichotomous county–based measure of hospital location. Furthermore, the hospital-level data did not contain patient-level information, making it impossible to analyze how changes in obstetric status affected patient outcomes. 

DISCLOSURES:

This study was supported by the Federal Office of Rural Health Policy, Health Resources and Services Administration, Department of Health & Human Services under Public Health Service Cooperative Agreement. One coauthor disclosed receiving grants from the Laura and John Arnold Foundation, Ballad Health, and the Commonwealth Fund outside the submitted work. A coauthor reported receiving personal fees from the American Institute of Biological Sciences on behalf of March of Dimes as a grant reviewer. Another coauthor reported receiving grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development outside the submitted work. 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:

Digital lifestyle coaching through the Smarter Pregnancy program reduces maternal blood pressure (BP) by approximately 2 mm Hg during the first trimester of pregnancy. The program enhances lifestyle behaviors through personalized coaching on vegetable and fruit intake, smoking cessation, and alcohol abstinence.

METHODOLOGY:

• Researchers analyzed data from the Rotterdam Periconception Cohort between 2010 and 2019, including 132 pregnant women who used Smarter Pregnancy for 6-24 weeks in the intervention group and 1091 pregnant women in the control group.
• Participants’ outcomes included changes in systolic, diastolic, and mean arterial BPs between baseline and first trimester measurements, with median gestational age of 7 weeks at inclusion.
• Analysis tracked lifestyle behaviors in the intervention group at 12 and 24 weeks using risk scores for vegetables, fruits, smoking, and alcohol consumption.
• Multivariable analysis adjusted for baseline BP measurements, age, gestational age, geographic origin, parity, and conception mode to evaluate program effectiveness.

TAKEAWAY:

• The intervention group demonstrated significant reductions in systolic (beta, −2.34 mm Hg; 95% CI, −4.67 to −0.01; P = .049), diastolic (beta, −2.00 mm Hg; 95% CI, −3.57 to −0.45; P = .012), and mean arterial BP (beta, −2.22 mm Hg; 95% CI, −3.81 to −0.52; P = .011) compared with controls.
• Among women who underwent assisted reproductive technology (ART), significant reductions were observed in diastolic (beta, −2.38 mm Hg; 95% CI, −4.20 to −0.56) and mean arterial BP (beta, −2.63 mm Hg; 95% CI, −4.61 to −0.56).
• Program usage was associated with decreased lifestyle risk scores at 12 weeks (beta, −0.84; 95% CI, −1.19 to −0.49) and 24 weeks (beta, −1.07; 95% CI, −1.44 to −0.69), indicating improved lifestyle behaviors.
• Lifestyle risk scores significantly decreased in both ART and natural pregnancy subgroups after program completion.

IN PRACTICE:

“The findings suggest that Smarter Pregnancy can be used to coach women on healthy lifestyle behaviors commencing from the preconception period onwards to improve BP outcomes. Of note, although implementing the program during [the] first trimester seems easier, initiating lifestyle coaching as early as preconceptional period can act as preventive measure against adverse health outcomes,” wrote the authors of the study.

SOURCE:

The study was led by Batoul Hojeij, PhD, Erasmus University Medical Center in Rotterdam, the Netherlands. It was published online in the American Journal of Preventive Medicine.

LIMITATIONS:

According to the authors, participants in the intervention group might have had healthier lifestyles due to their motivation to use a digital coaching program. The sample size of naturally conceived pregnancies in the intervention group was small (n = 41), reducing statistical power for subgroup analysis. The high percentage of missing data for baseline BP measurements (64%) could have affected statistical power and led to potential bias, though multiple imputations were used to address this limitation.

DISCLOSURES:

This study was supported by the European Union’s Horizon 2020 research and innovation program (DohART-NET) and the Department of Obstetrics and Gynaecology of the Erasmus MC. Kevin D Sinclair, PhD, DSc, received funding from the Biotechnology and Biological Sciences Research Council.

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:

Digital lifestyle coaching through the Smarter Pregnancy program reduces maternal blood pressure (BP) by approximately 2 mm Hg during the first trimester of pregnancy. The program enhances lifestyle behaviors through personalized coaching on vegetable and fruit intake, smoking cessation, and alcohol abstinence.

METHODOLOGY:

• Researchers analyzed data from the Rotterdam Periconception Cohort between 2010 and 2019, including 132 pregnant women who used Smarter Pregnancy for 6-24 weeks in the intervention group and 1091 pregnant women in the control group.
• Participants’ outcomes included changes in systolic, diastolic, and mean arterial BPs between baseline and first trimester measurements, with median gestational age of 7 weeks at inclusion.
• Analysis tracked lifestyle behaviors in the intervention group at 12 and 24 weeks using risk scores for vegetables, fruits, smoking, and alcohol consumption.
• Multivariable analysis adjusted for baseline BP measurements, age, gestational age, geographic origin, parity, and conception mode to evaluate program effectiveness.

TAKEAWAY:

• The intervention group demonstrated significant reductions in systolic (beta, −2.34 mm Hg; 95% CI, −4.67 to −0.01; P = .049), diastolic (beta, −2.00 mm Hg; 95% CI, −3.57 to −0.45; P = .012), and mean arterial BP (beta, −2.22 mm Hg; 95% CI, −3.81 to −0.52; P = .011) compared with controls.
• Among women who underwent assisted reproductive technology (ART), significant reductions were observed in diastolic (beta, −2.38 mm Hg; 95% CI, −4.20 to −0.56) and mean arterial BP (beta, −2.63 mm Hg; 95% CI, −4.61 to −0.56).
• Program usage was associated with decreased lifestyle risk scores at 12 weeks (beta, −0.84; 95% CI, −1.19 to −0.49) and 24 weeks (beta, −1.07; 95% CI, −1.44 to −0.69), indicating improved lifestyle behaviors.
• Lifestyle risk scores significantly decreased in both ART and natural pregnancy subgroups after program completion.

IN PRACTICE:

“The findings suggest that Smarter Pregnancy can be used to coach women on healthy lifestyle behaviors commencing from the preconception period onwards to improve BP outcomes. Of note, although implementing the program during [the] first trimester seems easier, initiating lifestyle coaching as early as preconceptional period can act as preventive measure against adverse health outcomes,” wrote the authors of the study.

SOURCE:

The study was led by Batoul Hojeij, PhD, Erasmus University Medical Center in Rotterdam, the Netherlands. It was published online in the American Journal of Preventive Medicine.

LIMITATIONS:

According to the authors, participants in the intervention group might have had healthier lifestyles due to their motivation to use a digital coaching program. The sample size of naturally conceived pregnancies in the intervention group was small (n = 41), reducing statistical power for subgroup analysis. The high percentage of missing data for baseline BP measurements (64%) could have affected statistical power and led to potential bias, though multiple imputations were used to address this limitation.

DISCLOSURES:

This study was supported by the European Union’s Horizon 2020 research and innovation program (DohART-NET) and the Department of Obstetrics and Gynaecology of the Erasmus MC. Kevin D Sinclair, PhD, DSc, received funding from the Biotechnology and Biological Sciences Research Council.

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:

Digital lifestyle coaching through the Smarter Pregnancy program reduces maternal blood pressure (BP) by approximately 2 mm Hg during the first trimester of pregnancy. The program enhances lifestyle behaviors through personalized coaching on vegetable and fruit intake, smoking cessation, and alcohol abstinence.

METHODOLOGY:

• Researchers analyzed data from the Rotterdam Periconception Cohort between 2010 and 2019, including 132 pregnant women who used Smarter Pregnancy for 6-24 weeks in the intervention group and 1091 pregnant women in the control group.
• Participants’ outcomes included changes in systolic, diastolic, and mean arterial BPs between baseline and first trimester measurements, with median gestational age of 7 weeks at inclusion.
• Analysis tracked lifestyle behaviors in the intervention group at 12 and 24 weeks using risk scores for vegetables, fruits, smoking, and alcohol consumption.
• Multivariable analysis adjusted for baseline BP measurements, age, gestational age, geographic origin, parity, and conception mode to evaluate program effectiveness.

TAKEAWAY:

• The intervention group demonstrated significant reductions in systolic (beta, −2.34 mm Hg; 95% CI, −4.67 to −0.01; P = .049), diastolic (beta, −2.00 mm Hg; 95% CI, −3.57 to −0.45; P = .012), and mean arterial BP (beta, −2.22 mm Hg; 95% CI, −3.81 to −0.52; P = .011) compared with controls.
• Among women who underwent assisted reproductive technology (ART), significant reductions were observed in diastolic (beta, −2.38 mm Hg; 95% CI, −4.20 to −0.56) and mean arterial BP (beta, −2.63 mm Hg; 95% CI, −4.61 to −0.56).
• Program usage was associated with decreased lifestyle risk scores at 12 weeks (beta, −0.84; 95% CI, −1.19 to −0.49) and 24 weeks (beta, −1.07; 95% CI, −1.44 to −0.69), indicating improved lifestyle behaviors.
• Lifestyle risk scores significantly decreased in both ART and natural pregnancy subgroups after program completion.

IN PRACTICE:

“The findings suggest that Smarter Pregnancy can be used to coach women on healthy lifestyle behaviors commencing from the preconception period onwards to improve BP outcomes. Of note, although implementing the program during [the] first trimester seems easier, initiating lifestyle coaching as early as preconceptional period can act as preventive measure against adverse health outcomes,” wrote the authors of the study.

SOURCE:

The study was led by Batoul Hojeij, PhD, Erasmus University Medical Center in Rotterdam, the Netherlands. It was published online in the American Journal of Preventive Medicine.

LIMITATIONS:

According to the authors, participants in the intervention group might have had healthier lifestyles due to their motivation to use a digital coaching program. The sample size of naturally conceived pregnancies in the intervention group was small (n = 41), reducing statistical power for subgroup analysis. The high percentage of missing data for baseline BP measurements (64%) could have affected statistical power and led to potential bias, though multiple imputations were used to address this limitation.

DISCLOSURES:

This study was supported by the European Union’s Horizon 2020 research and innovation program (DohART-NET) and the Department of Obstetrics and Gynaecology of the Erasmus MC. Kevin D Sinclair, PhD, DSc, received funding from the Biotechnology and Biological Sciences Research Council.

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.