ESHRE 2013

LONDON – Time-lapse imaging can help select the best embryo for implantation during fertility treatment, according to Joseph Conaghan, Ph.D., of the Pacific Fertility Center in San Francisco.

"Improved embryo selection may increase pregnancy rates following IVF [in vitro fertilization] and allow more patients to elect for single-embryo transfer [SET]," he noted at the annual meeting of the European Society of Human Reproduction and Embryology.

In recent years, there has been a move toward elective SET during IVF, but the main stumbling block has been that it is difficult to identify the best embryo to transfer.

"Historically, we have not had good pregnancy rates with frozen embryos, and it is always hard to convince patients to transfer just one embryo if they think that their chance of pregnancy is lowered," Dr. Conaghan said.

Although there are several methods available to try to select the most viable embryos, the one that Dr. Conaghan has been involved in testing in particular is time-lapse imaging. "As an embryologist, I like this technology a lot," he said. "The camera is seeing what we see, and we understand the information that we are getting."

The technology is based on identifying very early kinetic markers of embryonic development (Fertil. Steril. 2013;99:1035-43). Data show that how, and the rate at which, cells initially divide to form four-celled embryos can predict how well the blastocyst will form and later survive. Indeed, the duration of the first cytokinesis, the time between an embryo becoming three from two cells, and four from three cells, are all important stages (Nat. Biotechnol. 2010;28:1115-21).

In a recent prospective, multicenter cohort study (Fertil. Steril. 2013 [doi:10.1016/j.fertnstert.2013.04.021]), Dr. Conaghan and his associates reported on the ability of a time-lapse imaging technology to help select embryos with good morphology versus embryologists’ usual screening assessment of embryo morphology at day 3.

The technology used in the study was the Eeva (Early Embryo Viability Assessment) system developed by Auxogyn. This is one of several systems currently available; another is the EmbryoScope produced by the Danish company Unisense FertiliTech. They use computer-aided tracking to visualize the dynamic development of multiple embryos simultaneously.

While the EmbyroScopeis a self-contained system that sits on the lab bench, Eevais a microscope system that fits inside a standard incubator and an electronic touch-screen pad fits on the outside to allow the embryologist to see images taken by the microscope at 5-minute intervals.

Discussing Eeva, Dr. Conaghan explained: "The computer tracks development and tells you when an embryo has a high/low probability of making a blastocyst." Embryos that have a low probability of forming a healthy blastocyst are flagged by a yellow square whereas embryos with a high or good probability of forming a healthy blastocyst are flagged by a green square.

Five IVF clinics in the United States participated in the study, recruiting 160 women between them. Three experienced embryologists assessed patient records and morphology at day 3 for 775 embryos that had been separately evaluated using the Eeva system. There was no blinding to the Eeva results as the aim was to see if the technology could improve prediction rates for embryos that would have the best chance of implantation and a successful pregnancy.

The additional use of the time-lapse imaging technology was found to significantly improve the embryologists’ ability to identify embryos that would reach the blastocyst stage. The specificity for using day 3 morphology alone was 41.9%, 59.7%, and 79.5% for each of the three embryologists respectively. When Eeva was added into the mix, the rates increased to a respective 84.0%, 86.3%, and 86.6%.

Importantly, the additional use of Eeva was able to help embryologists to identify "good morphology" embryos, Dr. Conaghan said. These are embryos that have divided to become six or more cells, with perfect symmetry and less than 10% fragmentation.

"It’s important to point out that if an embryo does get a low score that it doesn’t mean that it is going to fail, he said. "It means that there is a high probability that the embryo is [perhaps] going to fail, but it doesn’t mean that we’re going to throw it away."

The ongoing studies – EPIC(Eeva Pregnancy Investigational Clinical Study), MERGE (Registry Study of Traditional Morphology Grading Combined With Eeva in IVF Treatment), and CCS(Correlating Time-Lapse Parameters Detected by the Eeva System With Comprehensive Chromosome Screening Results) – are assessing the use of the time-lapse imaging system, looking at aneuploidy, fragmentation, and the prospective use of Eeva to assist in embryo selection for transfer.

"I think that this is a very exciting technology," Dr. Conaghan said. "It has the potential to eliminate embryos from transfer consideration."

During a separate session, Catherine Racowksy, Ph.D., of Brigham and Women’s Hospital in Boston, made some general comments on the use of time-lapse imaging for optimizing the selection of embryos for IVF. "Time-lapse imaging really does hold a great deal of promise," she said. It is a noninvasive approach, and several teams have shown that the kinetic time points being assessed can be replicated.

"The tracking algorithms derived from retrospective cohort imaging data show that there are these key early cell cycle parameters that have value in predicting blastocyst formation and the ploidy of the embryo," Dr. Racowsky commented.

Prospective, randomized trial data are critical before this technology hits routine practice. "We cannot have these machines in the lab, hoping that they are going to help us in predicting the development potential of embryos if we haven’t proven to ourselves that they really are better than just looking down a microscope at static time points," she concluded.

Dr. Conaghan and Dr. Racowsky reported having no relevant financial disclosures.

LONDON – Time-lapse imaging can help select the best embryo for implantation during fertility treatment, according to Joseph Conaghan, Ph.D., of the Pacific Fertility Center in San Francisco.

"Improved embryo selection may increase pregnancy rates following IVF [in vitro fertilization] and allow more patients to elect for single-embryo transfer [SET]," he noted at the annual meeting of the European Society of Human Reproduction and Embryology.

In recent years, there has been a move toward elective SET during IVF, but the main stumbling block has been that it is difficult to identify the best embryo to transfer.

"Historically, we have not had good pregnancy rates with frozen embryos, and it is always hard to convince patients to transfer just one embryo if they think that their chance of pregnancy is lowered," Dr. Conaghan said.

Although there are several methods available to try to select the most viable embryos, the one that Dr. Conaghan has been involved in testing in particular is time-lapse imaging. "As an embryologist, I like this technology a lot," he said. "The camera is seeing what we see, and we understand the information that we are getting."

The technology is based on identifying very early kinetic markers of embryonic development (Fertil. Steril. 2013;99:1035-43). Data show that how, and the rate at which, cells initially divide to form four-celled embryos can predict how well the blastocyst will form and later survive. Indeed, the duration of the first cytokinesis, the time between an embryo becoming three from two cells, and four from three cells, are all important stages (Nat. Biotechnol. 2010;28:1115-21).

In a recent prospective, multicenter cohort study (Fertil. Steril. 2013 [doi:10.1016/j.fertnstert.2013.04.021]), Dr. Conaghan and his associates reported on the ability of a time-lapse imaging technology to help select embryos with good morphology versus embryologists’ usual screening assessment of embryo morphology at day 3.

The technology used in the study was the Eeva (Early Embryo Viability Assessment) system developed by Auxogyn. This is one of several systems currently available; another is the EmbryoScope produced by the Danish company Unisense FertiliTech. They use computer-aided tracking to visualize the dynamic development of multiple embryos simultaneously.

While the EmbyroScopeis a self-contained system that sits on the lab bench, Eevais a microscope system that fits inside a standard incubator and an electronic touch-screen pad fits on the outside to allow the embryologist to see images taken by the microscope at 5-minute intervals.

Discussing Eeva, Dr. Conaghan explained: "The computer tracks development and tells you when an embryo has a high/low probability of making a blastocyst." Embryos that have a low probability of forming a healthy blastocyst are flagged by a yellow square whereas embryos with a high or good probability of forming a healthy blastocyst are flagged by a green square.

Five IVF clinics in the United States participated in the study, recruiting 160 women between them. Three experienced embryologists assessed patient records and morphology at day 3 for 775 embryos that had been separately evaluated using the Eeva system. There was no blinding to the Eeva results as the aim was to see if the technology could improve prediction rates for embryos that would have the best chance of implantation and a successful pregnancy.

The additional use of the time-lapse imaging technology was found to significantly improve the embryologists’ ability to identify embryos that would reach the blastocyst stage. The specificity for using day 3 morphology alone was 41.9%, 59.7%, and 79.5% for each of the three embryologists respectively. When Eeva was added into the mix, the rates increased to a respective 84.0%, 86.3%, and 86.6%.

Importantly, the additional use of Eeva was able to help embryologists to identify "good morphology" embryos, Dr. Conaghan said. These are embryos that have divided to become six or more cells, with perfect symmetry and less than 10% fragmentation.

"It’s important to point out that if an embryo does get a low score that it doesn’t mean that it is going to fail, he said. "It means that there is a high probability that the embryo is [perhaps] going to fail, but it doesn’t mean that we’re going to throw it away."

The ongoing studies – EPIC(Eeva Pregnancy Investigational Clinical Study), MERGE (Registry Study of Traditional Morphology Grading Combined With Eeva in IVF Treatment), and CCS(Correlating Time-Lapse Parameters Detected by the Eeva System With Comprehensive Chromosome Screening Results) – are assessing the use of the time-lapse imaging system, looking at aneuploidy, fragmentation, and the prospective use of Eeva to assist in embryo selection for transfer.

"I think that this is a very exciting technology," Dr. Conaghan said. "It has the potential to eliminate embryos from transfer consideration."

During a separate session, Catherine Racowksy, Ph.D., of Brigham and Women’s Hospital in Boston, made some general comments on the use of time-lapse imaging for optimizing the selection of embryos for IVF. "Time-lapse imaging really does hold a great deal of promise," she said. It is a noninvasive approach, and several teams have shown that the kinetic time points being assessed can be replicated.

"The tracking algorithms derived from retrospective cohort imaging data show that there are these key early cell cycle parameters that have value in predicting blastocyst formation and the ploidy of the embryo," Dr. Racowsky commented.

Prospective, randomized trial data are critical before this technology hits routine practice. "We cannot have these machines in the lab, hoping that they are going to help us in predicting the development potential of embryos if we haven’t proven to ourselves that they really are better than just looking down a microscope at static time points," she concluded.

Dr. Conaghan and Dr. Racowsky reported having no relevant financial disclosures.

LONDON – Time-lapse imaging can help select the best embryo for implantation during fertility treatment, according to Joseph Conaghan, Ph.D., of the Pacific Fertility Center in San Francisco.

"Improved embryo selection may increase pregnancy rates following IVF [in vitro fertilization] and allow more patients to elect for single-embryo transfer [SET]," he noted at the annual meeting of the European Society of Human Reproduction and Embryology.

In recent years, there has been a move toward elective SET during IVF, but the main stumbling block has been that it is difficult to identify the best embryo to transfer.

"Historically, we have not had good pregnancy rates with frozen embryos, and it is always hard to convince patients to transfer just one embryo if they think that their chance of pregnancy is lowered," Dr. Conaghan said.

Although there are several methods available to try to select the most viable embryos, the one that Dr. Conaghan has been involved in testing in particular is time-lapse imaging. "As an embryologist, I like this technology a lot," he said. "The camera is seeing what we see, and we understand the information that we are getting."

The technology is based on identifying very early kinetic markers of embryonic development (Fertil. Steril. 2013;99:1035-43). Data show that how, and the rate at which, cells initially divide to form four-celled embryos can predict how well the blastocyst will form and later survive. Indeed, the duration of the first cytokinesis, the time between an embryo becoming three from two cells, and four from three cells, are all important stages (Nat. Biotechnol. 2010;28:1115-21).

In a recent prospective, multicenter cohort study (Fertil. Steril. 2013 [doi:10.1016/j.fertnstert.2013.04.021]), Dr. Conaghan and his associates reported on the ability of a time-lapse imaging technology to help select embryos with good morphology versus embryologists’ usual screening assessment of embryo morphology at day 3.

The technology used in the study was the Eeva (Early Embryo Viability Assessment) system developed by Auxogyn. This is one of several systems currently available; another is the EmbryoScope produced by the Danish company Unisense FertiliTech. They use computer-aided tracking to visualize the dynamic development of multiple embryos simultaneously.

While the EmbyroScopeis a self-contained system that sits on the lab bench, Eevais a microscope system that fits inside a standard incubator and an electronic touch-screen pad fits on the outside to allow the embryologist to see images taken by the microscope at 5-minute intervals.

Discussing Eeva, Dr. Conaghan explained: "The computer tracks development and tells you when an embryo has a high/low probability of making a blastocyst." Embryos that have a low probability of forming a healthy blastocyst are flagged by a yellow square whereas embryos with a high or good probability of forming a healthy blastocyst are flagged by a green square.

Five IVF clinics in the United States participated in the study, recruiting 160 women between them. Three experienced embryologists assessed patient records and morphology at day 3 for 775 embryos that had been separately evaluated using the Eeva system. There was no blinding to the Eeva results as the aim was to see if the technology could improve prediction rates for embryos that would have the best chance of implantation and a successful pregnancy.

The additional use of the time-lapse imaging technology was found to significantly improve the embryologists’ ability to identify embryos that would reach the blastocyst stage. The specificity for using day 3 morphology alone was 41.9%, 59.7%, and 79.5% for each of the three embryologists respectively. When Eeva was added into the mix, the rates increased to a respective 84.0%, 86.3%, and 86.6%.

Importantly, the additional use of Eeva was able to help embryologists to identify "good morphology" embryos, Dr. Conaghan said. These are embryos that have divided to become six or more cells, with perfect symmetry and less than 10% fragmentation.

"It’s important to point out that if an embryo does get a low score that it doesn’t mean that it is going to fail, he said. "It means that there is a high probability that the embryo is [perhaps] going to fail, but it doesn’t mean that we’re going to throw it away."

The ongoing studies – EPIC(Eeva Pregnancy Investigational Clinical Study), MERGE (Registry Study of Traditional Morphology Grading Combined With Eeva in IVF Treatment), and CCS(Correlating Time-Lapse Parameters Detected by the Eeva System With Comprehensive Chromosome Screening Results) – are assessing the use of the time-lapse imaging system, looking at aneuploidy, fragmentation, and the prospective use of Eeva to assist in embryo selection for transfer.

"I think that this is a very exciting technology," Dr. Conaghan said. "It has the potential to eliminate embryos from transfer consideration."

During a separate session, Catherine Racowksy, Ph.D., of Brigham and Women’s Hospital in Boston, made some general comments on the use of time-lapse imaging for optimizing the selection of embryos for IVF. "Time-lapse imaging really does hold a great deal of promise," she said. It is a noninvasive approach, and several teams have shown that the kinetic time points being assessed can be replicated.

"The tracking algorithms derived from retrospective cohort imaging data show that there are these key early cell cycle parameters that have value in predicting blastocyst formation and the ploidy of the embryo," Dr. Racowsky commented.

Prospective, randomized trial data are critical before this technology hits routine practice. "We cannot have these machines in the lab, hoping that they are going to help us in predicting the development potential of embryos if we haven’t proven to ourselves that they really are better than just looking down a microscope at static time points," she concluded.

Dr. Conaghan and Dr. Racowsky reported having no relevant financial disclosures.

LONDON – Long-standing depression may influence women’s ability to conceive, data from a large, population-based, Swedish cohort study suggest.

A significantly longer time to pregnancy was seen in women with a first diagnosis of depression occurring 6 years or more previously, with a crude odds ratio (OR) of 2.03 and an adjusted OR of 1.25.

Sara Freeman/IMNG Medical Media

"This study suggests that long-term psychological distress may lead to longer time to first pregnancy," said Carolyn Cesta, a doctoral student at the Karolinska Institute in Stockholm, where the study was performed.

The study also found that difficulty conceiving was higher in these women with long-term depression who were not treated with selective serotonin reuptake inhibitors (SSRIs), with an adjusted OR of 1.44 versus 1.37 for SSRI use.

"The effects of antidepressant treatment on fertility should be further investigated," Ms. Cesta suggested when presenting the findings at the annual meeting of the European Society of Human Reproduction and Embryology.

There are data to suggest that women with a history of depression are almost twice as likely as are those without it to report decreased fertility, but the data are conflicting. The main objective of the study presented was to investigate the controversial issue further: specifically, to look at whether psychological distress – measured as a diagnosis of depression, anxiety, or both – could predict women’s difficulties to conceive.

"Women during their childbearing years are at their greatest lifetime risk for being diagnosed with depression and anxiety," Ms. Cesta observed, "so it becomes important to know the impact of these conditions on fertility.

All together, data on 1,147,655 women who had delivered live-born infants between 1983 and 2009 were analyzed. These women were identified from several national Swedish registers: the medical birth register (1983-2009), the National Patient Register (1964-2009), the Total Population Register, and the Prescription Drug Register (2005-2009).

Women were then divided by the presence or absence of depression or anxiety reported at their first prenatal visit. There were 1,130,285 women with no such diagnoses, 7,322 with a diagnosis of depression, 7,551 with anxiety, and 2,497 with both disorders.

Involuntary childlessness, defined as the desire to conceive a child but difficulty doing so for 1 year or more, was reported by 6.7% of the overall population, with higher rates observed in women with depression (7.7%), anxiety (7.7%), or both (7.5%) than in women with no depression or anxiety (6.7%).

"We saw that there was no association between having a diagnosis of depression and/or anxiety and involuntary childlessness for more than 1 year when we compared them to women with no diagnosis," Ms. Cesta said.

Adjusted OR for a diagnosis of depression less than1.5 years, 1.5-3 years, and 3-6 years before pregnancy were 0.81, 0.92, and 1.06, respectively.

"The only significant association was seen where women diagnosed with depression had been diagnosed 6 years prior to pregnancy," Ms. Cesta said. They "had a significantly higher risk of involuntary childlessness." She noted that depression had been diagnosed before becoming pregnant in 91% of women.

Data on SSRI use in the women with depression for 6 or more years was available from 2005 onward, so this might have limited the analysis because of small patient numbers for inclusion in the analysis.

"This was a large, register-based cohort study of over 1 million women for which we have data for a large number of known confounders and the association between fertility and depression," Ms Cesta reported.

One of the main limitations, however, was that the study population includes women who have had at least one child already and not those who are perhaps infertile and remain childless.

The study was funded by the Swedish Research Council, the European Union Seventh Framework Program, and the Karolinska Institute. Ms. Cesta had no conflicts of interest to disclose.

LONDON – Long-standing depression may influence women’s ability to conceive, data from a large, population-based, Swedish cohort study suggest.

A significantly longer time to pregnancy was seen in women with a first diagnosis of depression occurring 6 years or more previously, with a crude odds ratio (OR) of 2.03 and an adjusted OR of 1.25.

Sara Freeman/IMNG Medical Media

"This study suggests that long-term psychological distress may lead to longer time to first pregnancy," said Carolyn Cesta, a doctoral student at the Karolinska Institute in Stockholm, where the study was performed.

The study also found that difficulty conceiving was higher in these women with long-term depression who were not treated with selective serotonin reuptake inhibitors (SSRIs), with an adjusted OR of 1.44 versus 1.37 for SSRI use.

"The effects of antidepressant treatment on fertility should be further investigated," Ms. Cesta suggested when presenting the findings at the annual meeting of the European Society of Human Reproduction and Embryology.

There are data to suggest that women with a history of depression are almost twice as likely as are those without it to report decreased fertility, but the data are conflicting. The main objective of the study presented was to investigate the controversial issue further: specifically, to look at whether psychological distress – measured as a diagnosis of depression, anxiety, or both – could predict women’s difficulties to conceive.

"Women during their childbearing years are at their greatest lifetime risk for being diagnosed with depression and anxiety," Ms. Cesta observed, "so it becomes important to know the impact of these conditions on fertility.

All together, data on 1,147,655 women who had delivered live-born infants between 1983 and 2009 were analyzed. These women were identified from several national Swedish registers: the medical birth register (1983-2009), the National Patient Register (1964-2009), the Total Population Register, and the Prescription Drug Register (2005-2009).

Women were then divided by the presence or absence of depression or anxiety reported at their first prenatal visit. There were 1,130,285 women with no such diagnoses, 7,322 with a diagnosis of depression, 7,551 with anxiety, and 2,497 with both disorders.

Involuntary childlessness, defined as the desire to conceive a child but difficulty doing so for 1 year or more, was reported by 6.7% of the overall population, with higher rates observed in women with depression (7.7%), anxiety (7.7%), or both (7.5%) than in women with no depression or anxiety (6.7%).

"We saw that there was no association between having a diagnosis of depression and/or anxiety and involuntary childlessness for more than 1 year when we compared them to women with no diagnosis," Ms. Cesta said.

Adjusted OR for a diagnosis of depression less than1.5 years, 1.5-3 years, and 3-6 years before pregnancy were 0.81, 0.92, and 1.06, respectively.

"The only significant association was seen where women diagnosed with depression had been diagnosed 6 years prior to pregnancy," Ms. Cesta said. They "had a significantly higher risk of involuntary childlessness." She noted that depression had been diagnosed before becoming pregnant in 91% of women.

Data on SSRI use in the women with depression for 6 or more years was available from 2005 onward, so this might have limited the analysis because of small patient numbers for inclusion in the analysis.

"This was a large, register-based cohort study of over 1 million women for which we have data for a large number of known confounders and the association between fertility and depression," Ms Cesta reported.

One of the main limitations, however, was that the study population includes women who have had at least one child already and not those who are perhaps infertile and remain childless.

The study was funded by the Swedish Research Council, the European Union Seventh Framework Program, and the Karolinska Institute. Ms. Cesta had no conflicts of interest to disclose.

LONDON – Long-standing depression may influence women’s ability to conceive, data from a large, population-based, Swedish cohort study suggest.

A significantly longer time to pregnancy was seen in women with a first diagnosis of depression occurring 6 years or more previously, with a crude odds ratio (OR) of 2.03 and an adjusted OR of 1.25.

Sara Freeman/IMNG Medical Media

"This study suggests that long-term psychological distress may lead to longer time to first pregnancy," said Carolyn Cesta, a doctoral student at the Karolinska Institute in Stockholm, where the study was performed.

The study also found that difficulty conceiving was higher in these women with long-term depression who were not treated with selective serotonin reuptake inhibitors (SSRIs), with an adjusted OR of 1.44 versus 1.37 for SSRI use.

"The effects of antidepressant treatment on fertility should be further investigated," Ms. Cesta suggested when presenting the findings at the annual meeting of the European Society of Human Reproduction and Embryology.

There are data to suggest that women with a history of depression are almost twice as likely as are those without it to report decreased fertility, but the data are conflicting. The main objective of the study presented was to investigate the controversial issue further: specifically, to look at whether psychological distress – measured as a diagnosis of depression, anxiety, or both – could predict women’s difficulties to conceive.

"Women during their childbearing years are at their greatest lifetime risk for being diagnosed with depression and anxiety," Ms. Cesta observed, "so it becomes important to know the impact of these conditions on fertility.

All together, data on 1,147,655 women who had delivered live-born infants between 1983 and 2009 were analyzed. These women were identified from several national Swedish registers: the medical birth register (1983-2009), the National Patient Register (1964-2009), the Total Population Register, and the Prescription Drug Register (2005-2009).

Women were then divided by the presence or absence of depression or anxiety reported at their first prenatal visit. There were 1,130,285 women with no such diagnoses, 7,322 with a diagnosis of depression, 7,551 with anxiety, and 2,497 with both disorders.

Involuntary childlessness, defined as the desire to conceive a child but difficulty doing so for 1 year or more, was reported by 6.7% of the overall population, with higher rates observed in women with depression (7.7%), anxiety (7.7%), or both (7.5%) than in women with no depression or anxiety (6.7%).

"We saw that there was no association between having a diagnosis of depression and/or anxiety and involuntary childlessness for more than 1 year when we compared them to women with no diagnosis," Ms. Cesta said.

Adjusted OR for a diagnosis of depression less than1.5 years, 1.5-3 years, and 3-6 years before pregnancy were 0.81, 0.92, and 1.06, respectively.

"The only significant association was seen where women diagnosed with depression had been diagnosed 6 years prior to pregnancy," Ms. Cesta said. They "had a significantly higher risk of involuntary childlessness." She noted that depression had been diagnosed before becoming pregnant in 91% of women.

Data on SSRI use in the women with depression for 6 or more years was available from 2005 onward, so this might have limited the analysis because of small patient numbers for inclusion in the analysis.

"This was a large, register-based cohort study of over 1 million women for which we have data for a large number of known confounders and the association between fertility and depression," Ms Cesta reported.

One of the main limitations, however, was that the study population includes women who have had at least one child already and not those who are perhaps infertile and remain childless.

The study was funded by the Swedish Research Council, the European Union Seventh Framework Program, and the Karolinska Institute. Ms. Cesta had no conflicts of interest to disclose.

LONDON – Low-molecular-weight heparin therapy reduced the risk for recurrent implantation failure, improved pregnancy rates, and increased the number of live births in women who had failed prior fertility treatment in a 126-patient pilot study.

As reported at the annual meeting of the European Society of Human Reproduction and Embryology, low-molecular-weight heparin (LMWH) was associated with an implantation rate of 22.2% vs. 10% for a regimen containing aspirin (P =.0136). Pregnancy (47% vs. 20.6%, P = .0026) and live birth rates (30% vs. 12%, P = .017) also were higher with the LMWH than with the aspirin-containing regimen.

Sara Freeman/IMNG Medical Media

Although larger, randomized, double blind controlled trials are needed to confirm the findings, the study’s Italian investigators are confident that LMWH has a benefit in improving fertility outcomes in this population of women who had failed two or more cycles of in vitro fertilization (IVF).

"We are convinced that low-molecular-weight heparin can enhance results in IVF procedures," said Dr. Antonio Colicchia of the Centro Fecondazione Assistita Ferticlinic, Rome, in an interview.

Strategies to improve implantation rates are needed, Dr. Colicchia explained, because there has been a plateau in live birth rates associated with assisted reproductive technology (ART). Approximately 4.2% of babies born in Europe are a consequence of ART, he said.

Women were included in the single-center study over a 2-year period starting in September 2000. For inclusion they had to have a body mass index lower than 25 mg/kg², be between 31 and 42 years old, have failed at least two cycles of IVF, and not have inherited thrombophilia.

Sixty-eight women were allocated to treatment with the LMWH dalteparin at a dose of 2,500 IU/day and 58 to treatment with aspirin at a dose of 100 mg/day and oral prednisone at a dose of 10 mg/day. Both groups of women also were given vaginal progesterone at a dose of 600 mg/day.

Treatment began at the time of embryo transfer and was continued until levels of human chorionic gonadotropin confirmed a pregnancy. If a pregnancy was confirmed, then treatment was continued until the 12th gestational week. Women administered the treatments at home.

"Heparin can potentially modulate many of the known mechanisms that underlie successful apposition, adhesion, and penetration of the developing embryo," Dr. Colicchia said.

"There is evidence that in women with repeated IVF failure, [LMWH] can improve pregnancy rates," he concluded, although further studies are needed.

The chairman of the session in which the study results were presented was critical of the findings. "This was not a randomized nor a placebo-controlled trial," Dr. Thomas D’Hooghe of Leuven (Belgium) University fertility center said in an interview. Furthermore, the control arm was flawed, as aspirin and oral prednisone are not routinely used.

Elsewhere at the annual meeting of ESHRE, a German team presented data from a 12-center trial (n = 449) on the use of LMWH in the prevention of recurrent miscarriage. The results of the ETHIG II study, in which dalteparin (5,000 IU/day) plus multivitamins were compared with vitamins alone, were not positive.

There was no difference in the primary outcome measure of the number of ongoing pregnancies at 24 complete weeks of gestation, leading the authors to conclude that "the uncontrolled use of LMWH in patients with recurrent miscarriages is not reasonable."

There was no commercial funding for the study presented by Dr. Colicchia. He reported having no relevant financial disclosures. Dr. D’Hooghe was not involved in the study and said he had no relevant conflicts of interest.

LONDON – Low-molecular-weight heparin therapy reduced the risk for recurrent implantation failure, improved pregnancy rates, and increased the number of live births in women who had failed prior fertility treatment in a 126-patient pilot study.

As reported at the annual meeting of the European Society of Human Reproduction and Embryology, low-molecular-weight heparin (LMWH) was associated with an implantation rate of 22.2% vs. 10% for a regimen containing aspirin (P =.0136). Pregnancy (47% vs. 20.6%, P = .0026) and live birth rates (30% vs. 12%, P = .017) also were higher with the LMWH than with the aspirin-containing regimen.

Sara Freeman/IMNG Medical Media

Although larger, randomized, double blind controlled trials are needed to confirm the findings, the study’s Italian investigators are confident that LMWH has a benefit in improving fertility outcomes in this population of women who had failed two or more cycles of in vitro fertilization (IVF).

"We are convinced that low-molecular-weight heparin can enhance results in IVF procedures," said Dr. Antonio Colicchia of the Centro Fecondazione Assistita Ferticlinic, Rome, in an interview.

Strategies to improve implantation rates are needed, Dr. Colicchia explained, because there has been a plateau in live birth rates associated with assisted reproductive technology (ART). Approximately 4.2% of babies born in Europe are a consequence of ART, he said.

Women were included in the single-center study over a 2-year period starting in September 2000. For inclusion they had to have a body mass index lower than 25 mg/kg², be between 31 and 42 years old, have failed at least two cycles of IVF, and not have inherited thrombophilia.

Sixty-eight women were allocated to treatment with the LMWH dalteparin at a dose of 2,500 IU/day and 58 to treatment with aspirin at a dose of 100 mg/day and oral prednisone at a dose of 10 mg/day. Both groups of women also were given vaginal progesterone at a dose of 600 mg/day.

Treatment began at the time of embryo transfer and was continued until levels of human chorionic gonadotropin confirmed a pregnancy. If a pregnancy was confirmed, then treatment was continued until the 12th gestational week. Women administered the treatments at home.

"Heparin can potentially modulate many of the known mechanisms that underlie successful apposition, adhesion, and penetration of the developing embryo," Dr. Colicchia said.

"There is evidence that in women with repeated IVF failure, [LMWH] can improve pregnancy rates," he concluded, although further studies are needed.

The chairman of the session in which the study results were presented was critical of the findings. "This was not a randomized nor a placebo-controlled trial," Dr. Thomas D’Hooghe of Leuven (Belgium) University fertility center said in an interview. Furthermore, the control arm was flawed, as aspirin and oral prednisone are not routinely used.

Elsewhere at the annual meeting of ESHRE, a German team presented data from a 12-center trial (n = 449) on the use of LMWH in the prevention of recurrent miscarriage. The results of the ETHIG II study, in which dalteparin (5,000 IU/day) plus multivitamins were compared with vitamins alone, were not positive.

There was no difference in the primary outcome measure of the number of ongoing pregnancies at 24 complete weeks of gestation, leading the authors to conclude that "the uncontrolled use of LMWH in patients with recurrent miscarriages is not reasonable."

There was no commercial funding for the study presented by Dr. Colicchia. He reported having no relevant financial disclosures. Dr. D’Hooghe was not involved in the study and said he had no relevant conflicts of interest.

LONDON – Low-molecular-weight heparin therapy reduced the risk for recurrent implantation failure, improved pregnancy rates, and increased the number of live births in women who had failed prior fertility treatment in a 126-patient pilot study.

As reported at the annual meeting of the European Society of Human Reproduction and Embryology, low-molecular-weight heparin (LMWH) was associated with an implantation rate of 22.2% vs. 10% for a regimen containing aspirin (P =.0136). Pregnancy (47% vs. 20.6%, P = .0026) and live birth rates (30% vs. 12%, P = .017) also were higher with the LMWH than with the aspirin-containing regimen.

Sara Freeman/IMNG Medical Media

Although larger, randomized, double blind controlled trials are needed to confirm the findings, the study’s Italian investigators are confident that LMWH has a benefit in improving fertility outcomes in this population of women who had failed two or more cycles of in vitro fertilization (IVF).

"We are convinced that low-molecular-weight heparin can enhance results in IVF procedures," said Dr. Antonio Colicchia of the Centro Fecondazione Assistita Ferticlinic, Rome, in an interview.

Strategies to improve implantation rates are needed, Dr. Colicchia explained, because there has been a plateau in live birth rates associated with assisted reproductive technology (ART). Approximately 4.2% of babies born in Europe are a consequence of ART, he said.

Women were included in the single-center study over a 2-year period starting in September 2000. For inclusion they had to have a body mass index lower than 25 mg/kg², be between 31 and 42 years old, have failed at least two cycles of IVF, and not have inherited thrombophilia.

Sixty-eight women were allocated to treatment with the LMWH dalteparin at a dose of 2,500 IU/day and 58 to treatment with aspirin at a dose of 100 mg/day and oral prednisone at a dose of 10 mg/day. Both groups of women also were given vaginal progesterone at a dose of 600 mg/day.

Treatment began at the time of embryo transfer and was continued until levels of human chorionic gonadotropin confirmed a pregnancy. If a pregnancy was confirmed, then treatment was continued until the 12th gestational week. Women administered the treatments at home.

"Heparin can potentially modulate many of the known mechanisms that underlie successful apposition, adhesion, and penetration of the developing embryo," Dr. Colicchia said.

"There is evidence that in women with repeated IVF failure, [LMWH] can improve pregnancy rates," he concluded, although further studies are needed.

The chairman of the session in which the study results were presented was critical of the findings. "This was not a randomized nor a placebo-controlled trial," Dr. Thomas D’Hooghe of Leuven (Belgium) University fertility center said in an interview. Furthermore, the control arm was flawed, as aspirin and oral prednisone are not routinely used.

Elsewhere at the annual meeting of ESHRE, a German team presented data from a 12-center trial (n = 449) on the use of LMWH in the prevention of recurrent miscarriage. The results of the ETHIG II study, in which dalteparin (5,000 IU/day) plus multivitamins were compared with vitamins alone, were not positive.

There was no difference in the primary outcome measure of the number of ongoing pregnancies at 24 complete weeks of gestation, leading the authors to conclude that "the uncontrolled use of LMWH in patients with recurrent miscarriages is not reasonable."

There was no commercial funding for the study presented by Dr. Colicchia. He reported having no relevant financial disclosures. Dr. D’Hooghe was not involved in the study and said he had no relevant conflicts of interest.

LONDON – Hypertensive complications are seen in more than one-third of pregnant women with Turner’s syndrome undergoing fertility treatment, according to the results of a longitudinal retrospective study performed in Finland, Denmark, and Sweden.

Of 106 women with Turner’s syndrome who conceived after oocyte donation between 1992 and 2011, 35% had hypertensive complications and 20% had preeclampsia. Although there were no maternal deaths, life-threatening complications occurred in four (3.3%) women. This included a case of aortic dissection.

"We think it’s very important to have a centralized cardiovascular assessment before pregnancy," Dr. Anna Hagman of Sahlgrenska Hospital, Gothenburg, Sweden, said on behalf of the study team at the annual meeting of the European Society of Human Reproduction and Embryology. This should include echocardiography and magnetic resonance imaging, looking for specific cardiac abnormalities known to affect women with Turner’s syndrome.

Turner’s syndrome is caused by an aberration of the X chromosome and affects around one in 2,500 women. It is associated with increased cardiovascular (CV) morbidity and mortality, which raises concern for women who may want to try to conceive either spontaneously or via assisted conception methods. Women with the condition typically are of short stature and almost all (95%–99%) are infertile. Oocyte donation may offer one of their best chances for becoming pregnant.

For the study, medical data from fertility clinics, antenatal clinics, and hospitals where women had been treated or delivered their baby between 1992 and 2011 in Finland and Denmark, or between 2003and 2011 in Sweden, were examined.

The 45,X karyotype was observed in 44% of the women and 9% had a known cardiac defect before pregnancy. Just under half (49%) of women had a CV exam within the 2 years prior to becoming pregnant, and 29% had a CV exam during their pregnancy.

Single embryo transfer was performed in 70% of the cases and the multiple birth rate was 7%; 15% of women conceived twice after two oocyte donations during the study period. The median follow-up time was 4 years, but ranged from 0.3 to 19 years.

There were 122 deliveries studied in total and 131 neonates, of which 18 were twins. Among the single births, the rate of preterm delivery, defined as before 37 weeks’ gestation, was 8%, with 9% of children having low birth weight (less than 2,500 g). Perinatal mortality was 0.8%. Congenital defects were seen in 3.8% of the children.

"Neonatal outcomes were reassuring for singletons," Dr. Hagman said at the annual meeting of the European Society of Human Reproduction and Embryology, later noting that the team "recommends single-embryo transfer."

This is because greater risks for mother and child were seen after twin births. Hypertensive complications occurred in 50% of women and around two thirds (67%) of twins were delivered prematurely. Almost three quarters (72%) had a low birth weight and perinatal mortality was approximately 11% for twin births.

Dr. Hagman suggested that pregnancy should be avoided in women with Turner’s syndrome if there is CV disease or other severe health problems exist. Thyroid, renal, and liver tests should be performed, she advised, as well as testing for diabetes.

"All pregnancies must be carefully monitored," Dr. Hagman advised. The blood pressure should be kept below 140/90 mm Hg and echocardiography, MRI, or both performed two to three times during pregnancy.

The study’s findings have recently been published (Hum. Reprod. 2013;28:1598-09).

The study was funded by a variety of sources, including: the Gothenburg Medical Society, grants from the ALF agreement at the Sahlgrenska University Hospital, Gothenburg, Sweden; Hjalmar Svensson Foundation; the Nordic Federation of Societies of Obstetrics and Gynecology Nordic Fund; Finnish Society of Paediatric and Adolescent Gynecology; Liv och hälsa Foundation in Finland; and MSD Finland, Norway, and Denmark. No conflict of interest was reported.

LONDON – Hypertensive complications are seen in more than one-third of pregnant women with Turner’s syndrome undergoing fertility treatment, according to the results of a longitudinal retrospective study performed in Finland, Denmark, and Sweden.

Of 106 women with Turner’s syndrome who conceived after oocyte donation between 1992 and 2011, 35% had hypertensive complications and 20% had preeclampsia. Although there were no maternal deaths, life-threatening complications occurred in four (3.3%) women. This included a case of aortic dissection.

"We think it’s very important to have a centralized cardiovascular assessment before pregnancy," Dr. Anna Hagman of Sahlgrenska Hospital, Gothenburg, Sweden, said on behalf of the study team at the annual meeting of the European Society of Human Reproduction and Embryology. This should include echocardiography and magnetic resonance imaging, looking for specific cardiac abnormalities known to affect women with Turner’s syndrome.

Turner’s syndrome is caused by an aberration of the X chromosome and affects around one in 2,500 women. It is associated with increased cardiovascular (CV) morbidity and mortality, which raises concern for women who may want to try to conceive either spontaneously or via assisted conception methods. Women with the condition typically are of short stature and almost all (95%–99%) are infertile. Oocyte donation may offer one of their best chances for becoming pregnant.

For the study, medical data from fertility clinics, antenatal clinics, and hospitals where women had been treated or delivered their baby between 1992 and 2011 in Finland and Denmark, or between 2003and 2011 in Sweden, were examined.

The 45,X karyotype was observed in 44% of the women and 9% had a known cardiac defect before pregnancy. Just under half (49%) of women had a CV exam within the 2 years prior to becoming pregnant, and 29% had a CV exam during their pregnancy.

Single embryo transfer was performed in 70% of the cases and the multiple birth rate was 7%; 15% of women conceived twice after two oocyte donations during the study period. The median follow-up time was 4 years, but ranged from 0.3 to 19 years.

There were 122 deliveries studied in total and 131 neonates, of which 18 were twins. Among the single births, the rate of preterm delivery, defined as before 37 weeks’ gestation, was 8%, with 9% of children having low birth weight (less than 2,500 g). Perinatal mortality was 0.8%. Congenital defects were seen in 3.8% of the children.

"Neonatal outcomes were reassuring for singletons," Dr. Hagman said at the annual meeting of the European Society of Human Reproduction and Embryology, later noting that the team "recommends single-embryo transfer."

This is because greater risks for mother and child were seen after twin births. Hypertensive complications occurred in 50% of women and around two thirds (67%) of twins were delivered prematurely. Almost three quarters (72%) had a low birth weight and perinatal mortality was approximately 11% for twin births.

Dr. Hagman suggested that pregnancy should be avoided in women with Turner’s syndrome if there is CV disease or other severe health problems exist. Thyroid, renal, and liver tests should be performed, she advised, as well as testing for diabetes.

"All pregnancies must be carefully monitored," Dr. Hagman advised. The blood pressure should be kept below 140/90 mm Hg and echocardiography, MRI, or both performed two to three times during pregnancy.

The study’s findings have recently been published (Hum. Reprod. 2013;28:1598-09).

The study was funded by a variety of sources, including: the Gothenburg Medical Society, grants from the ALF agreement at the Sahlgrenska University Hospital, Gothenburg, Sweden; Hjalmar Svensson Foundation; the Nordic Federation of Societies of Obstetrics and Gynecology Nordic Fund; Finnish Society of Paediatric and Adolescent Gynecology; Liv och hälsa Foundation in Finland; and MSD Finland, Norway, and Denmark. No conflict of interest was reported.

LONDON – Hypertensive complications are seen in more than one-third of pregnant women with Turner’s syndrome undergoing fertility treatment, according to the results of a longitudinal retrospective study performed in Finland, Denmark, and Sweden.

Of 106 women with Turner’s syndrome who conceived after oocyte donation between 1992 and 2011, 35% had hypertensive complications and 20% had preeclampsia. Although there were no maternal deaths, life-threatening complications occurred in four (3.3%) women. This included a case of aortic dissection.

"We think it’s very important to have a centralized cardiovascular assessment before pregnancy," Dr. Anna Hagman of Sahlgrenska Hospital, Gothenburg, Sweden, said on behalf of the study team at the annual meeting of the European Society of Human Reproduction and Embryology. This should include echocardiography and magnetic resonance imaging, looking for specific cardiac abnormalities known to affect women with Turner’s syndrome.

Turner’s syndrome is caused by an aberration of the X chromosome and affects around one in 2,500 women. It is associated with increased cardiovascular (CV) morbidity and mortality, which raises concern for women who may want to try to conceive either spontaneously or via assisted conception methods. Women with the condition typically are of short stature and almost all (95%–99%) are infertile. Oocyte donation may offer one of their best chances for becoming pregnant.

For the study, medical data from fertility clinics, antenatal clinics, and hospitals where women had been treated or delivered their baby between 1992 and 2011 in Finland and Denmark, or between 2003and 2011 in Sweden, were examined.

The 45,X karyotype was observed in 44% of the women and 9% had a known cardiac defect before pregnancy. Just under half (49%) of women had a CV exam within the 2 years prior to becoming pregnant, and 29% had a CV exam during their pregnancy.

Single embryo transfer was performed in 70% of the cases and the multiple birth rate was 7%; 15% of women conceived twice after two oocyte donations during the study period. The median follow-up time was 4 years, but ranged from 0.3 to 19 years.

There were 122 deliveries studied in total and 131 neonates, of which 18 were twins. Among the single births, the rate of preterm delivery, defined as before 37 weeks’ gestation, was 8%, with 9% of children having low birth weight (less than 2,500 g). Perinatal mortality was 0.8%. Congenital defects were seen in 3.8% of the children.

"Neonatal outcomes were reassuring for singletons," Dr. Hagman said at the annual meeting of the European Society of Human Reproduction and Embryology, later noting that the team "recommends single-embryo transfer."

This is because greater risks for mother and child were seen after twin births. Hypertensive complications occurred in 50% of women and around two thirds (67%) of twins were delivered prematurely. Almost three quarters (72%) had a low birth weight and perinatal mortality was approximately 11% for twin births.

Dr. Hagman suggested that pregnancy should be avoided in women with Turner’s syndrome if there is CV disease or other severe health problems exist. Thyroid, renal, and liver tests should be performed, she advised, as well as testing for diabetes.

"All pregnancies must be carefully monitored," Dr. Hagman advised. The blood pressure should be kept below 140/90 mm Hg and echocardiography, MRI, or both performed two to three times during pregnancy.

The study’s findings have recently been published (Hum. Reprod. 2013;28:1598-09).

The study was funded by a variety of sources, including: the Gothenburg Medical Society, grants from the ALF agreement at the Sahlgrenska University Hospital, Gothenburg, Sweden; Hjalmar Svensson Foundation; the Nordic Federation of Societies of Obstetrics and Gynecology Nordic Fund; Finnish Society of Paediatric and Adolescent Gynecology; Liv och hälsa Foundation in Finland; and MSD Finland, Norway, and Denmark. No conflict of interest was reported.

LONDON – Women with hypothyroidism can achieve good results following fertility treatment if they maintain low levels of thyroid-stimulating hormone before assisted conception, according to findings of a 3-year retrospective study.

"An adequate treatment maintaining serum TSH levels below the threshold value of 2.5 mIU/L seems to fully overcome the detrimental effects of hypothyroidism on the rate of success of IVF [in vitro fertilization] and ICSI [intracytoplasmic sperm injection]," Dr. Andrea Busnelli reported at the annual meeting of the European Society of Human Reproduction and Embryology.

"Therefore, women scheduled for IVF-ICSI with adequately treated hypothyroidism can be reassured regarding the success of the procedure[s]," Dr. Busnelli of IRCCS Ospedale Maggiore Policlinico Mangiagalli e Regina Elena, Milan, Italy, added.

Previous research has shown that women with hypothyroidism have less chance of becoming pregnant after assisted conception than those with normal thyroid function. Subsequent findings conflict on whether levothyroxine treatment may (Hum. Reprod. Update 2013;19:251-8) or may not (Thyroid 2012;22:631-6) improve pregnancy rates.

These studies have been performed in a small number of women and TSH levels achieved with levothyroxine therapy were higher than recently recommended (J. Clin. Endocrinol. Metab. 2012;97:2543-65).

The current study therefore looked at whether "adequate" levothyroxine treatment, meaning that which ensured the level of TSH before conception was 2.5 mIU/L or lower, would be able to compensate for the reduced fertility success reported previously.

A total of 137 women with clinical or subclinical treated hypothyroidism participated in the study. At recruitment, their baseline TSH was between 0.4 and 2.5 mIU/L. Each case was age matched to two women with normal thyroid function as a control (n = 274).

Ultrasound was used to confirm any pregnancy, defined as a vital embryo within an intrauterine gestational sac at 4-5 weeks after embryo transfer.

The average age of cases and controls was approximately 35 years, body mass index in both groups was approximately 22 kg/m², and there were no significant differences in the number of previous deliveries, serum hormone levels, or the cause of infertility leading to fertility treatment. Preconception TSH levels were approximately 1.5 mIU/L.

Looking at the number of assisted reproduction cycles, Dr. Busnelli noted that the duration of controlled ovarian hyperstimulation (COH) was longer for women with hypothyroidism than for their euthyroid counterparts: COH was 10.9 days in cases and 10.1 days in controls (P = .001).

Hyperthyroid women also had a higher chance of cancelled treatment cycles because of a poor response (3.6% vs. 0.7% in euthyroid women, P = .04). Failure to obtain viable embryos also occurred more frequently in hyperthyroid than in euthyroid women, at 17% and 7%, respectively (P = .006). Fertilization rates were also lower (75% vs. 80%; P = .017).

However, there was no difference between cases and controls in terms of the implantation (28% vs. 22%; P = .11), clinical pregnancy (36% vs. 34%; P = .93), or live delivery rates (30% vs. 25%; P = .5).

The presence of antithyroid antibodies did not influence the rates of implantation or termination. There was also no difference in the results comparing women with overt versus subclinical hypothyroidism.

Dr. Busnelli noted, however, that anti-TPO, anti-TG antibodies were not screened for in control women, so this limits the study findings as some in the control population could have had thyroid autoimmunity.

"Our observations suggest that the level of thyroxine may constitute a functional reserve in patients with positive TPO/TG antibodies which is able to compensate for the increased request typical of controlled ovarian hyperstimulation and pregnancy," Dr. Busnelli said.

The study received no commercial financial support. Dr. Busnelli reported having no relevant financial disclosures.

LONDON – Women with hypothyroidism can achieve good results following fertility treatment if they maintain low levels of thyroid-stimulating hormone before assisted conception, according to findings of a 3-year retrospective study.

"An adequate treatment maintaining serum TSH levels below the threshold value of 2.5 mIU/L seems to fully overcome the detrimental effects of hypothyroidism on the rate of success of IVF [in vitro fertilization] and ICSI [intracytoplasmic sperm injection]," Dr. Andrea Busnelli reported at the annual meeting of the European Society of Human Reproduction and Embryology.

"Therefore, women scheduled for IVF-ICSI with adequately treated hypothyroidism can be reassured regarding the success of the procedure[s]," Dr. Busnelli of IRCCS Ospedale Maggiore Policlinico Mangiagalli e Regina Elena, Milan, Italy, added.

Previous research has shown that women with hypothyroidism have less chance of becoming pregnant after assisted conception than those with normal thyroid function. Subsequent findings conflict on whether levothyroxine treatment may (Hum. Reprod. Update 2013;19:251-8) or may not (Thyroid 2012;22:631-6) improve pregnancy rates.

These studies have been performed in a small number of women and TSH levels achieved with levothyroxine therapy were higher than recently recommended (J. Clin. Endocrinol. Metab. 2012;97:2543-65).

The current study therefore looked at whether "adequate" levothyroxine treatment, meaning that which ensured the level of TSH before conception was 2.5 mIU/L or lower, would be able to compensate for the reduced fertility success reported previously.

A total of 137 women with clinical or subclinical treated hypothyroidism participated in the study. At recruitment, their baseline TSH was between 0.4 and 2.5 mIU/L. Each case was age matched to two women with normal thyroid function as a control (n = 274).

Ultrasound was used to confirm any pregnancy, defined as a vital embryo within an intrauterine gestational sac at 4-5 weeks after embryo transfer.

The average age of cases and controls was approximately 35 years, body mass index in both groups was approximately 22 kg/m², and there were no significant differences in the number of previous deliveries, serum hormone levels, or the cause of infertility leading to fertility treatment. Preconception TSH levels were approximately 1.5 mIU/L.

Looking at the number of assisted reproduction cycles, Dr. Busnelli noted that the duration of controlled ovarian hyperstimulation (COH) was longer for women with hypothyroidism than for their euthyroid counterparts: COH was 10.9 days in cases and 10.1 days in controls (P = .001).

Hyperthyroid women also had a higher chance of cancelled treatment cycles because of a poor response (3.6% vs. 0.7% in euthyroid women, P = .04). Failure to obtain viable embryos also occurred more frequently in hyperthyroid than in euthyroid women, at 17% and 7%, respectively (P = .006). Fertilization rates were also lower (75% vs. 80%; P = .017).

However, there was no difference between cases and controls in terms of the implantation (28% vs. 22%; P = .11), clinical pregnancy (36% vs. 34%; P = .93), or live delivery rates (30% vs. 25%; P = .5).

The presence of antithyroid antibodies did not influence the rates of implantation or termination. There was also no difference in the results comparing women with overt versus subclinical hypothyroidism.

Dr. Busnelli noted, however, that anti-TPO, anti-TG antibodies were not screened for in control women, so this limits the study findings as some in the control population could have had thyroid autoimmunity.

"Our observations suggest that the level of thyroxine may constitute a functional reserve in patients with positive TPO/TG antibodies which is able to compensate for the increased request typical of controlled ovarian hyperstimulation and pregnancy," Dr. Busnelli said.

The study received no commercial financial support. Dr. Busnelli reported having no relevant financial disclosures.

LONDON – Women with hypothyroidism can achieve good results following fertility treatment if they maintain low levels of thyroid-stimulating hormone before assisted conception, according to findings of a 3-year retrospective study.

"An adequate treatment maintaining serum TSH levels below the threshold value of 2.5 mIU/L seems to fully overcome the detrimental effects of hypothyroidism on the rate of success of IVF [in vitro fertilization] and ICSI [intracytoplasmic sperm injection]," Dr. Andrea Busnelli reported at the annual meeting of the European Society of Human Reproduction and Embryology.

"Therefore, women scheduled for IVF-ICSI with adequately treated hypothyroidism can be reassured regarding the success of the procedure[s]," Dr. Busnelli of IRCCS Ospedale Maggiore Policlinico Mangiagalli e Regina Elena, Milan, Italy, added.

Previous research has shown that women with hypothyroidism have less chance of becoming pregnant after assisted conception than those with normal thyroid function. Subsequent findings conflict on whether levothyroxine treatment may (Hum. Reprod. Update 2013;19:251-8) or may not (Thyroid 2012;22:631-6) improve pregnancy rates.

These studies have been performed in a small number of women and TSH levels achieved with levothyroxine therapy were higher than recently recommended (J. Clin. Endocrinol. Metab. 2012;97:2543-65).

The current study therefore looked at whether "adequate" levothyroxine treatment, meaning that which ensured the level of TSH before conception was 2.5 mIU/L or lower, would be able to compensate for the reduced fertility success reported previously.

A total of 137 women with clinical or subclinical treated hypothyroidism participated in the study. At recruitment, their baseline TSH was between 0.4 and 2.5 mIU/L. Each case was age matched to two women with normal thyroid function as a control (n = 274).

Ultrasound was used to confirm any pregnancy, defined as a vital embryo within an intrauterine gestational sac at 4-5 weeks after embryo transfer.

The average age of cases and controls was approximately 35 years, body mass index in both groups was approximately 22 kg/m², and there were no significant differences in the number of previous deliveries, serum hormone levels, or the cause of infertility leading to fertility treatment. Preconception TSH levels were approximately 1.5 mIU/L.

Looking at the number of assisted reproduction cycles, Dr. Busnelli noted that the duration of controlled ovarian hyperstimulation (COH) was longer for women with hypothyroidism than for their euthyroid counterparts: COH was 10.9 days in cases and 10.1 days in controls (P = .001).

Hyperthyroid women also had a higher chance of cancelled treatment cycles because of a poor response (3.6% vs. 0.7% in euthyroid women, P = .04). Failure to obtain viable embryos also occurred more frequently in hyperthyroid than in euthyroid women, at 17% and 7%, respectively (P = .006). Fertilization rates were also lower (75% vs. 80%; P = .017).

However, there was no difference between cases and controls in terms of the implantation (28% vs. 22%; P = .11), clinical pregnancy (36% vs. 34%; P = .93), or live delivery rates (30% vs. 25%; P = .5).

The presence of antithyroid antibodies did not influence the rates of implantation or termination. There was also no difference in the results comparing women with overt versus subclinical hypothyroidism.

Dr. Busnelli noted, however, that anti-TPO, anti-TG antibodies were not screened for in control women, so this limits the study findings as some in the control population could have had thyroid autoimmunity.

"Our observations suggest that the level of thyroxine may constitute a functional reserve in patients with positive TPO/TG antibodies which is able to compensate for the increased request typical of controlled ovarian hyperstimulation and pregnancy," Dr. Busnelli said.

The study received no commercial financial support. Dr. Busnelli reported having no relevant financial disclosures.

LONDON – Improved pregnancy rates after fertility treatment were achieved by the surgical removal of ovarian cysts in a 10-year longitudinal study of women with endometriomas.

After surgery, 63% of women became pregnant after assisted conception methods whereas before surgery only 7% conceived; overall, 46% of women became pregnant at both time points combined.

"Endometrioma itself is associated with significantly reduced reproductive performance in the long term," said study investigator Dr. Saad Amer of the Royal Derby (England) Hospital.

However, "surgery does not seem to compromise the reproductive performance any further," he said at the annual meeting of the European Society of Human Reproduction and Embryology.

Sara Freeman/IMNG Medical Media

The rates of unassisted pregnancy were about the same before (48%) and after surgery (50%), with an overall rate of 65% in the surgical groups combined versus 98% for women without endometriomas but who had endometriosis (P = .001)

The rationale for the study was that evidence suggests that ovarian reserve is reduced after excision surgery (J. Clin. Endocrinol. Metab. 2012;97:3146-54), although the long-term impact of other types of surgery remains to be seen.

Between January 1999 and December 2009, 704 women with ovarian endometriosis who had surgery, of which 153 had surgery for endometriomas, were identified from hospital records.

Women who had endometriomas were sent a questionnaire and asked to attend an interview about their reproductive history. There was a 45% response rate (n = 151), with 68 women with endometriomas actually participating; they were compared with an age- and weight-matched control group of 68 apparently healthy women.

The median ages of women in both the study group and the control group were similar, at 40 and 41 years, respectively. A similar percentage of patients had a smoking history (8% and 10%), with a little more than half of all women having regular menstruation, and 75% and 84% in each group desiring to become pregnant.

Of the 68 women with endometriomas, 33 underwent excision (n = 27) or ablation (n = 6) procedures, with 21 women having oophorectomy and 14 having the cysts drained. The median diameter of the endometriomas was 6 cm. Surgery was performed by 10 consultant gynecologists, with 53% of procedures performed laparoscopically.

If the women who conceived spontaneously and those who became pregnant following fertility treatment were grouped together, the overall rates of pregnancy before and after endometrioma surgery were 50% and 71%, respectively, with a combined overall pregnancy rate of 80%. This compares well with the 98% of women who had spontaneous pregnancy in the control group, Dr. Amer noted.

A similar percentage of patients became pregnant after single (70%, n = 23) or multiple (73%, n = 15) surgical procedures, although the number of women included in the analysis was small.

There was a trend toward a lower pregnancy rate in women who had bilateral versus unilateral surgeries, at 67% vs. 77%, although the number of patients in this analysis was again small. There also was no significant difference in pregnancy rates when the type of surgery was considered.

"These findings are reassuring for patients with endometrioma who are seeking fertility and need surgery for their disease."

Importantly, surgery was not found to alter the timing or age of menopause, Dr. Amer said. Nine (13%) women who had surgery were postmenopausal, compared with six (9%) of those in the control group. The median age of menopause was 48 years in the surgical group overall versus 49 years in the control group.

The main conclusion of the study was that surgery itself does not appear to affect women’s long-term reproductive performance.

Although the findings are limited by the retrospective design of the study and further validation is needed, the results do suggest that endometriomas per se, rather than surgery, appear to be the main reason for reduced long-term reproductive function.

"These findings are reassuring for patients with endometrioma who are seeking fertility and need surgery for their disease," Dr. Amer said.

Dr. Amer reported having no relevant financial disclosures.

LONDON – Improved pregnancy rates after fertility treatment were achieved by the surgical removal of ovarian cysts in a 10-year longitudinal study of women with endometriomas.

After surgery, 63% of women became pregnant after assisted conception methods whereas before surgery only 7% conceived; overall, 46% of women became pregnant at both time points combined.

"Endometrioma itself is associated with significantly reduced reproductive performance in the long term," said study investigator Dr. Saad Amer of the Royal Derby (England) Hospital.

However, "surgery does not seem to compromise the reproductive performance any further," he said at the annual meeting of the European Society of Human Reproduction and Embryology.

Sara Freeman/IMNG Medical Media

The rates of unassisted pregnancy were about the same before (48%) and after surgery (50%), with an overall rate of 65% in the surgical groups combined versus 98% for women without endometriomas but who had endometriosis (P = .001)

The rationale for the study was that evidence suggests that ovarian reserve is reduced after excision surgery (J. Clin. Endocrinol. Metab. 2012;97:3146-54), although the long-term impact of other types of surgery remains to be seen.

Between January 1999 and December 2009, 704 women with ovarian endometriosis who had surgery, of which 153 had surgery for endometriomas, were identified from hospital records.

Women who had endometriomas were sent a questionnaire and asked to attend an interview about their reproductive history. There was a 45% response rate (n = 151), with 68 women with endometriomas actually participating; they were compared with an age- and weight-matched control group of 68 apparently healthy women.

The median ages of women in both the study group and the control group were similar, at 40 and 41 years, respectively. A similar percentage of patients had a smoking history (8% and 10%), with a little more than half of all women having regular menstruation, and 75% and 84% in each group desiring to become pregnant.

Of the 68 women with endometriomas, 33 underwent excision (n = 27) or ablation (n = 6) procedures, with 21 women having oophorectomy and 14 having the cysts drained. The median diameter of the endometriomas was 6 cm. Surgery was performed by 10 consultant gynecologists, with 53% of procedures performed laparoscopically.

If the women who conceived spontaneously and those who became pregnant following fertility treatment were grouped together, the overall rates of pregnancy before and after endometrioma surgery were 50% and 71%, respectively, with a combined overall pregnancy rate of 80%. This compares well with the 98% of women who had spontaneous pregnancy in the control group, Dr. Amer noted.

A similar percentage of patients became pregnant after single (70%, n = 23) or multiple (73%, n = 15) surgical procedures, although the number of women included in the analysis was small.

There was a trend toward a lower pregnancy rate in women who had bilateral versus unilateral surgeries, at 67% vs. 77%, although the number of patients in this analysis was again small. There also was no significant difference in pregnancy rates when the type of surgery was considered.

"These findings are reassuring for patients with endometrioma who are seeking fertility and need surgery for their disease."

Importantly, surgery was not found to alter the timing or age of menopause, Dr. Amer said. Nine (13%) women who had surgery were postmenopausal, compared with six (9%) of those in the control group. The median age of menopause was 48 years in the surgical group overall versus 49 years in the control group.

The main conclusion of the study was that surgery itself does not appear to affect women’s long-term reproductive performance.

Although the findings are limited by the retrospective design of the study and further validation is needed, the results do suggest that endometriomas per se, rather than surgery, appear to be the main reason for reduced long-term reproductive function.

"These findings are reassuring for patients with endometrioma who are seeking fertility and need surgery for their disease," Dr. Amer said.

Dr. Amer reported having no relevant financial disclosures.

LONDON – Improved pregnancy rates after fertility treatment were achieved by the surgical removal of ovarian cysts in a 10-year longitudinal study of women with endometriomas.

After surgery, 63% of women became pregnant after assisted conception methods whereas before surgery only 7% conceived; overall, 46% of women became pregnant at both time points combined.

"Endometrioma itself is associated with significantly reduced reproductive performance in the long term," said study investigator Dr. Saad Amer of the Royal Derby (England) Hospital.

However, "surgery does not seem to compromise the reproductive performance any further," he said at the annual meeting of the European Society of Human Reproduction and Embryology.

Sara Freeman/IMNG Medical Media

The rates of unassisted pregnancy were about the same before (48%) and after surgery (50%), with an overall rate of 65% in the surgical groups combined versus 98% for women without endometriomas but who had endometriosis (P = .001)

The rationale for the study was that evidence suggests that ovarian reserve is reduced after excision surgery (J. Clin. Endocrinol. Metab. 2012;97:3146-54), although the long-term impact of other types of surgery remains to be seen.

Between January 1999 and December 2009, 704 women with ovarian endometriosis who had surgery, of which 153 had surgery for endometriomas, were identified from hospital records.

Women who had endometriomas were sent a questionnaire and asked to attend an interview about their reproductive history. There was a 45% response rate (n = 151), with 68 women with endometriomas actually participating; they were compared with an age- and weight-matched control group of 68 apparently healthy women.

The median ages of women in both the study group and the control group were similar, at 40 and 41 years, respectively. A similar percentage of patients had a smoking history (8% and 10%), with a little more than half of all women having regular menstruation, and 75% and 84% in each group desiring to become pregnant.

Of the 68 women with endometriomas, 33 underwent excision (n = 27) or ablation (n = 6) procedures, with 21 women having oophorectomy and 14 having the cysts drained. The median diameter of the endometriomas was 6 cm. Surgery was performed by 10 consultant gynecologists, with 53% of procedures performed laparoscopically.

If the women who conceived spontaneously and those who became pregnant following fertility treatment were grouped together, the overall rates of pregnancy before and after endometrioma surgery were 50% and 71%, respectively, with a combined overall pregnancy rate of 80%. This compares well with the 98% of women who had spontaneous pregnancy in the control group, Dr. Amer noted.

A similar percentage of patients became pregnant after single (70%, n = 23) or multiple (73%, n = 15) surgical procedures, although the number of women included in the analysis was small.

There was a trend toward a lower pregnancy rate in women who had bilateral versus unilateral surgeries, at 67% vs. 77%, although the number of patients in this analysis was again small. There also was no significant difference in pregnancy rates when the type of surgery was considered.

"These findings are reassuring for patients with endometrioma who are seeking fertility and need surgery for their disease."

Importantly, surgery was not found to alter the timing or age of menopause, Dr. Amer said. Nine (13%) women who had surgery were postmenopausal, compared with six (9%) of those in the control group. The median age of menopause was 48 years in the surgical group overall versus 49 years in the control group.

The main conclusion of the study was that surgery itself does not appear to affect women’s long-term reproductive performance.

Although the findings are limited by the retrospective design of the study and further validation is needed, the results do suggest that endometriomas per se, rather than surgery, appear to be the main reason for reduced long-term reproductive function.

"These findings are reassuring for patients with endometrioma who are seeking fertility and need surgery for their disease," Dr. Amer said.

Dr. Amer reported having no relevant financial disclosures.

LONDON – Children born as a result of assisted conception do not appear to be at any greater cancer risk than children born following spontaneous conception, the results of two large longitudinal studies demonstrated.

A U.K.-based study of more than 100,000 children born after assisted conception between 1992 and 2008 found a lower-than-expected number of cases of cancer, with a standardized incidence rate of 0.98.

©Monkey Business/Fotolia.com

Meanwhile the adjusted odds ratio for total cancer risk in a cohort of more than 92,000 Danish, Finnish, and Swedish children born between 1982 and 2007 was 1.15.

The findings of both studies, presented at the annual meeting of the European Society of Human Reproduction and Embryology, are "reassuring," said Dr. Carrie Williams of the Institute for Child Health at University College London.

"This is fantastic news for the 5 million children born after ART [assisted reproductive technology], their families, fertility specialists, and also for [the] wider society," Dr. Williams, who was part of the U.K. study team, added.

"The main driver for our study was parental concern," Dr. Williams explained. "In a study of several hundred families of children born after ART, over a quarter of [parents] had concerns about the health of their child as a result of their method of conception, and many of these concerns [were] related to the overall cancer risk."

Previously, Dr. Williams and her associates performed a systematic review of 11 studies and found that there was a small but significant increase in cancer risk in children born after ART, although the results of one particular study swayed the overall findings (Arch. Dis. Child. 2011;96:A6). The results of another recent meta-analysis of 25 studies also point to a possible increased risk for cancer in children following assisted conception methods (Fertil. Steril. 2013;100:150-61).

A large, population study was needed to examine the issue further, however, and the U.K. team linked data held by the Human Fertilisation and Embryology Authority (HFEA) on births due to ART with the U.K.’s National Registry of Childhood Tumours (NRCT). Over a 16-year study period, there were 106,381 children born in England, Wales, or Scotland after nondonor ART. Of these, 14,896 (14%) developed cancer before their 15th birthday or before Jan. 1, 2009.

The actual data analysis was performed on 106,013 children because the time at risk for the others could not be determined. Standardized incidence rates (SIRs) were calculated for various childhood cancers by determining the observed versus expected rates of each. Potential effect-moderating factors, such as age, sex, birth weight, multiple births, treatment type, and cause of parental infertility, among others, were considered.

The occurrence of most childhood tumors was lower than expected, with SIRs of 0.94 for renal tumors, 0.91 for leukemia, 0.88 for neuroblastoma, 0.85 for central nervous system tumors, 0.59 for retinoblastoma, and 0.56 for germ cell tumors.

"We did find an increased risk of two very rare types of cancer – hepatoblastoma and rhabdomyosarcoma," Dr. Williams reported. SIRs for these tumor types were 3.27 and 2.62, respectively. Further analysis suggested that a lower birth weight (less than 2,500 g) was associated with a 10-fold increase in the risk for hepatoblastoma. No clear explanation could be found for the increased risk for the connective tissue cancer.

"If there is a risk, then the risk is small," said Dr. Anja Pinborg who presented separate data from the Committee on Nordic ART and Safety (CoNARTaS) study, a prospective study involving all children born after assisted conception in Denmark, Finland, and Sweden (Acta. Obstet. Gynecol. Scand. 2011;90:683-91). Data from medical birth, cancer, patient, and cause of death registries were linked to help determine if ART did indeed carry an increased risk for malignancy.

"We show similar results, perhaps a little bit of an increase in the risk for cancer, but not significantly," added Dr. Pinborg of the University of Copenhagen. A total of 178 children were diagnosed with cancer in the cohort after ART, compared with 643 cancer cases in children who were not artificially conceived, giving respective incidence rates of 1.9% vs. 1.7%. Children born after ART were found to be at increased risk for CNS tumors in the Nordic cohort, but the prevalence was 0.4%.

"It’s very important to underline that the control population of parents differs from the ART population of parents because the mothers are older and they are reproductively healthy," Dr. Pinborg noted. People can be helped to conceive a child, but the underlying cause of the infertility usually cannot be resolved, she said, suggesting subfertility per se might play a role.

The increased risk for rare childhood tumors seen in the U.K. study and in the CoNARTaS study could even be down to chance as the numbers used in the analyses are relatively small.

"When we subdivide by cancer types, our numbers get smaller and smaller, and therefore the role of chance is increased," Dr. Williams commented. "The answer is to keep studying this area, perhaps do another systematic review, putting all of the results together, and then we will have more reliable findings."

Dr. Williams added: "So far, it looks like the results are really positive for the many children born after assisted conception."

Cancer Research U.K. funded the U.K. study. The U.K. National Institute of Health Research provided funding to Dr. Williams. CoNARTaS is supported by ESHRE, Sahlgrenska University Hospital, the University of Copenhagen, the Danish Agency for Science Technology and Innovation, and the Nordic Federation of Societies of Obstetrics and Gynecology. Dr. Williams and Dr. Pinborg said they had no relevant financial disclosures.

LONDON – Children born as a result of assisted conception do not appear to be at any greater cancer risk than children born following spontaneous conception, the results of two large longitudinal studies demonstrated.

A U.K.-based study of more than 100,000 children born after assisted conception between 1992 and 2008 found a lower-than-expected number of cases of cancer, with a standardized incidence rate of 0.98.

©Monkey Business/Fotolia.com

Meanwhile the adjusted odds ratio for total cancer risk in a cohort of more than 92,000 Danish, Finnish, and Swedish children born between 1982 and 2007 was 1.15.

The findings of both studies, presented at the annual meeting of the European Society of Human Reproduction and Embryology, are "reassuring," said Dr. Carrie Williams of the Institute for Child Health at University College London.

"This is fantastic news for the 5 million children born after ART [assisted reproductive technology], their families, fertility specialists, and also for [the] wider society," Dr. Williams, who was part of the U.K. study team, added.

"The main driver for our study was parental concern," Dr. Williams explained. "In a study of several hundred families of children born after ART, over a quarter of [parents] had concerns about the health of their child as a result of their method of conception, and many of these concerns [were] related to the overall cancer risk."

Previously, Dr. Williams and her associates performed a systematic review of 11 studies and found that there was a small but significant increase in cancer risk in children born after ART, although the results of one particular study swayed the overall findings (Arch. Dis. Child. 2011;96:A6). The results of another recent meta-analysis of 25 studies also point to a possible increased risk for cancer in children following assisted conception methods (Fertil. Steril. 2013;100:150-61).

A large, population study was needed to examine the issue further, however, and the U.K. team linked data held by the Human Fertilisation and Embryology Authority (HFEA) on births due to ART with the U.K.’s National Registry of Childhood Tumours (NRCT). Over a 16-year study period, there were 106,381 children born in England, Wales, or Scotland after nondonor ART. Of these, 14,896 (14%) developed cancer before their 15th birthday or before Jan. 1, 2009.

The actual data analysis was performed on 106,013 children because the time at risk for the others could not be determined. Standardized incidence rates (SIRs) were calculated for various childhood cancers by determining the observed versus expected rates of each. Potential effect-moderating factors, such as age, sex, birth weight, multiple births, treatment type, and cause of parental infertility, among others, were considered.

The occurrence of most childhood tumors was lower than expected, with SIRs of 0.94 for renal tumors, 0.91 for leukemia, 0.88 for neuroblastoma, 0.85 for central nervous system tumors, 0.59 for retinoblastoma, and 0.56 for germ cell tumors.

"We did find an increased risk of two very rare types of cancer – hepatoblastoma and rhabdomyosarcoma," Dr. Williams reported. SIRs for these tumor types were 3.27 and 2.62, respectively. Further analysis suggested that a lower birth weight (less than 2,500 g) was associated with a 10-fold increase in the risk for hepatoblastoma. No clear explanation could be found for the increased risk for the connective tissue cancer.

"If there is a risk, then the risk is small," said Dr. Anja Pinborg who presented separate data from the Committee on Nordic ART and Safety (CoNARTaS) study, a prospective study involving all children born after assisted conception in Denmark, Finland, and Sweden (Acta. Obstet. Gynecol. Scand. 2011;90:683-91). Data from medical birth, cancer, patient, and cause of death registries were linked to help determine if ART did indeed carry an increased risk for malignancy.

"We show similar results, perhaps a little bit of an increase in the risk for cancer, but not significantly," added Dr. Pinborg of the University of Copenhagen. A total of 178 children were diagnosed with cancer in the cohort after ART, compared with 643 cancer cases in children who were not artificially conceived, giving respective incidence rates of 1.9% vs. 1.7%. Children born after ART were found to be at increased risk for CNS tumors in the Nordic cohort, but the prevalence was 0.4%.

"It’s very important to underline that the control population of parents differs from the ART population of parents because the mothers are older and they are reproductively healthy," Dr. Pinborg noted. People can be helped to conceive a child, but the underlying cause of the infertility usually cannot be resolved, she said, suggesting subfertility per se might play a role.

The increased risk for rare childhood tumors seen in the U.K. study and in the CoNARTaS study could even be down to chance as the numbers used in the analyses are relatively small.

"When we subdivide by cancer types, our numbers get smaller and smaller, and therefore the role of chance is increased," Dr. Williams commented. "The answer is to keep studying this area, perhaps do another systematic review, putting all of the results together, and then we will have more reliable findings."

Dr. Williams added: "So far, it looks like the results are really positive for the many children born after assisted conception."

Cancer Research U.K. funded the U.K. study. The U.K. National Institute of Health Research provided funding to Dr. Williams. CoNARTaS is supported by ESHRE, Sahlgrenska University Hospital, the University of Copenhagen, the Danish Agency for Science Technology and Innovation, and the Nordic Federation of Societies of Obstetrics and Gynecology. Dr. Williams and Dr. Pinborg said they had no relevant financial disclosures.

LONDON – Children born as a result of assisted conception do not appear to be at any greater cancer risk than children born following spontaneous conception, the results of two large longitudinal studies demonstrated.

A U.K.-based study of more than 100,000 children born after assisted conception between 1992 and 2008 found a lower-than-expected number of cases of cancer, with a standardized incidence rate of 0.98.

©Monkey Business/Fotolia.com

Meanwhile the adjusted odds ratio for total cancer risk in a cohort of more than 92,000 Danish, Finnish, and Swedish children born between 1982 and 2007 was 1.15.

The findings of both studies, presented at the annual meeting of the European Society of Human Reproduction and Embryology, are "reassuring," said Dr. Carrie Williams of the Institute for Child Health at University College London.

"This is fantastic news for the 5 million children born after ART [assisted reproductive technology], their families, fertility specialists, and also for [the] wider society," Dr. Williams, who was part of the U.K. study team, added.

"The main driver for our study was parental concern," Dr. Williams explained. "In a study of several hundred families of children born after ART, over a quarter of [parents] had concerns about the health of their child as a result of their method of conception, and many of these concerns [were] related to the overall cancer risk."

Previously, Dr. Williams and her associates performed a systematic review of 11 studies and found that there was a small but significant increase in cancer risk in children born after ART, although the results of one particular study swayed the overall findings (Arch. Dis. Child. 2011;96:A6). The results of another recent meta-analysis of 25 studies also point to a possible increased risk for cancer in children following assisted conception methods (Fertil. Steril. 2013;100:150-61).

A large, population study was needed to examine the issue further, however, and the U.K. team linked data held by the Human Fertilisation and Embryology Authority (HFEA) on births due to ART with the U.K.’s National Registry of Childhood Tumours (NRCT). Over a 16-year study period, there were 106,381 children born in England, Wales, or Scotland after nondonor ART. Of these, 14,896 (14%) developed cancer before their 15th birthday or before Jan. 1, 2009.

The actual data analysis was performed on 106,013 children because the time at risk for the others could not be determined. Standardized incidence rates (SIRs) were calculated for various childhood cancers by determining the observed versus expected rates of each. Potential effect-moderating factors, such as age, sex, birth weight, multiple births, treatment type, and cause of parental infertility, among others, were considered.

The occurrence of most childhood tumors was lower than expected, with SIRs of 0.94 for renal tumors, 0.91 for leukemia, 0.88 for neuroblastoma, 0.85 for central nervous system tumors, 0.59 for retinoblastoma, and 0.56 for germ cell tumors.

"We did find an increased risk of two very rare types of cancer – hepatoblastoma and rhabdomyosarcoma," Dr. Williams reported. SIRs for these tumor types were 3.27 and 2.62, respectively. Further analysis suggested that a lower birth weight (less than 2,500 g) was associated with a 10-fold increase in the risk for hepatoblastoma. No clear explanation could be found for the increased risk for the connective tissue cancer.

"If there is a risk, then the risk is small," said Dr. Anja Pinborg who presented separate data from the Committee on Nordic ART and Safety (CoNARTaS) study, a prospective study involving all children born after assisted conception in Denmark, Finland, and Sweden (Acta. Obstet. Gynecol. Scand. 2011;90:683-91). Data from medical birth, cancer, patient, and cause of death registries were linked to help determine if ART did indeed carry an increased risk for malignancy.

"We show similar results, perhaps a little bit of an increase in the risk for cancer, but not significantly," added Dr. Pinborg of the University of Copenhagen. A total of 178 children were diagnosed with cancer in the cohort after ART, compared with 643 cancer cases in children who were not artificially conceived, giving respective incidence rates of 1.9% vs. 1.7%. Children born after ART were found to be at increased risk for CNS tumors in the Nordic cohort, but the prevalence was 0.4%.

"It’s very important to underline that the control population of parents differs from the ART population of parents because the mothers are older and they are reproductively healthy," Dr. Pinborg noted. People can be helped to conceive a child, but the underlying cause of the infertility usually cannot be resolved, she said, suggesting subfertility per se might play a role.

The increased risk for rare childhood tumors seen in the U.K. study and in the CoNARTaS study could even be down to chance as the numbers used in the analyses are relatively small.

"When we subdivide by cancer types, our numbers get smaller and smaller, and therefore the role of chance is increased," Dr. Williams commented. "The answer is to keep studying this area, perhaps do another systematic review, putting all of the results together, and then we will have more reliable findings."

Dr. Williams added: "So far, it looks like the results are really positive for the many children born after assisted conception."

Cancer Research U.K. funded the U.K. study. The U.K. National Institute of Health Research provided funding to Dr. Williams. CoNARTaS is supported by ESHRE, Sahlgrenska University Hospital, the University of Copenhagen, the Danish Agency for Science Technology and Innovation, and the Nordic Federation of Societies of Obstetrics and Gynecology. Dr. Williams and Dr. Pinborg said they had no relevant financial disclosures.

LONDON – A home digital pregnancy test is able to correctly estimate the likely week of conception, according to the results of a 10-month, prospective observational study of 1,505 nonpregnant U.S. women.

"There was a high [98%] level of agreement between the digital pregnancy test and standardized ultrasound," Sarah Johnson, Ph.D., said in an interview at the annual meeting of the European Society of Human Reproduction and Embryology.

The results of the digital pregnancy test were compared with ultrasound measurements performed at approximately 12 weeks after the woman had her last menstrual period (LMP).

"We received clearance from the Food and Drug Administration last December, and all being well it should be on the shelves in September," said Dr. Johnson, who is a scientific and medical affairs manager for SPD Development of Bedford, England. The digital pregnancy test is already available in the United Kingdom* based on data from a previous study (Curr. Med. Res. Opin. 2011;27:393-401).

Dr. Johnson noted that this is the first home pregnancy test to provide an accurate and early assessment of pregnancy at the time when a woman first suspects that she might be pregnant. It is also the first test to provide a digital readout, which is potentially simpler for women to understand than seeing a line in a window to indicate whether they are pregnant or not.

Similar to other home pregnancy tests, the digital pregnancy test measures levels of human chorionic gonadotrophin (hCG) excreted in the urine. Measuring hCG is a tried-and-tested method of confirming pregnancy as the hormone plays a critical role in early pregnancy, helping with the implantation of the embryo and preventing further oocyte development.

Unlike existing tests, however, the digital pregnancy test estimates the time since conception based on thresholds of hCG, which have been shown to rise rapidly after ovulation has occurred, and measurement of this hormone in the urine reflects the duration of pregnancy (Curr. Med. Res. Opin. 2009;25:741-8).

In using the digital home pregnancy test, the woman can either hold the test strip in the urine stream for 5 seconds or dip it into a urine sample collected in a clean container for 20 seconds. Results from the test are then given in a few minutes as a digital readout saying if the woman is "pregnant" or "not pregnant," with additional numbers displayed if conception was likely to be 1-2, 2-3, or 3+ weeks ago.

During the study, women were required to provide urine samples every day throughout their menstrual cycles, a random sample of which were then tested in the laboratory using the digital home pregnancy test.

A total of 250 women became pregnant during the study, with sufficient data on 153 women available for analysis. All of these women had ultrasound performed at approximately 11-13 weeks of their pregnancy to determine the gestational age according to the crown rump length measurement. More than 3,600 digital pregnancy tests were preformed in three batches, with the technicians blinded to the samples.

One of the interesting observations of the study is the inaccuracy of the LMP, Dr. Johnson said. All the women in the study planned on becoming pregnant and were carefully monitoring their menstrual cycles. Although they thought they knew exactly when their LMP was, the urine assessments suggested they were wrong by about 5 days.

"When a woman thinks she is pregnant, all she has is her last menstrual period, and that in so many cases is wrong, so this new test provides something that can provide greater accuracy," Dr. Johnson suggested.

SPD Development also has a digital ovulation test that is soon to be released in both the United States and the United Kingdom.

"Normal ovulation tests just measure luteinizing hormone [LH], so they tell you the best 2 days [to conceive]," Dr. Johnson said. The digital ovulation test still measures the LH surge, which indicates ovulation has occurred, but it also measures levels of estrone-3-glucuronide (E3G), which is a major urinary metabolite of estradiol. Levels of E3G rise a couple of days before the LH surge.

"By measuring [E3G], you are actually telling a woman about those additional fertile days during which she can also get pregnant before the 2 peak days," Dr. Johnson explained. Data presented in a poster at the annual meeting of ESHRE showed that the new digital ovulation test identified 4 or more fertile days in 80% of menstrual cycles.

The digital ovulation test will come as a kit with replaceable test strips. A woman urinates on the test strip, puts it into the reader, and the device then remembers the result and helps the woman identify her most fertile period.

The study was funded by SPD Development. Dr. Johnson is an employee of the company, which manufactures the Clearblue Digital Pregnancy Test With Conception Indicator and the Clearblue Digital Ovulation Test With Dual Hormone Indicator.

*Correction, 7/18/2013: An earlier version of this story misstated the availability of the test.

LONDON – A home digital pregnancy test is able to correctly estimate the likely week of conception, according to the results of a 10-month, prospective observational study of 1,505 nonpregnant U.S. women.

"There was a high [98%] level of agreement between the digital pregnancy test and standardized ultrasound," Sarah Johnson, Ph.D., said in an interview at the annual meeting of the European Society of Human Reproduction and Embryology.

The results of the digital pregnancy test were compared with ultrasound measurements performed at approximately 12 weeks after the woman had her last menstrual period (LMP).

"We received clearance from the Food and Drug Administration last December, and all being well it should be on the shelves in September," said Dr. Johnson, who is a scientific and medical affairs manager for SPD Development of Bedford, England. The digital pregnancy test is already available in the United Kingdom* based on data from a previous study (Curr. Med. Res. Opin. 2011;27:393-401).

Dr. Johnson noted that this is the first home pregnancy test to provide an accurate and early assessment of pregnancy at the time when a woman first suspects that she might be pregnant. It is also the first test to provide a digital readout, which is potentially simpler for women to understand than seeing a line in a window to indicate whether they are pregnant or not.

Similar to other home pregnancy tests, the digital pregnancy test measures levels of human chorionic gonadotrophin (hCG) excreted in the urine. Measuring hCG is a tried-and-tested method of confirming pregnancy as the hormone plays a critical role in early pregnancy, helping with the implantation of the embryo and preventing further oocyte development.

Unlike existing tests, however, the digital pregnancy test estimates the time since conception based on thresholds of hCG, which have been shown to rise rapidly after ovulation has occurred, and measurement of this hormone in the urine reflects the duration of pregnancy (Curr. Med. Res. Opin. 2009;25:741-8).

In using the digital home pregnancy test, the woman can either hold the test strip in the urine stream for 5 seconds or dip it into a urine sample collected in a clean container for 20 seconds. Results from the test are then given in a few minutes as a digital readout saying if the woman is "pregnant" or "not pregnant," with additional numbers displayed if conception was likely to be 1-2, 2-3, or 3+ weeks ago.

During the study, women were required to provide urine samples every day throughout their menstrual cycles, a random sample of which were then tested in the laboratory using the digital home pregnancy test.

A total of 250 women became pregnant during the study, with sufficient data on 153 women available for analysis. All of these women had ultrasound performed at approximately 11-13 weeks of their pregnancy to determine the gestational age according to the crown rump length measurement. More than 3,600 digital pregnancy tests were preformed in three batches, with the technicians blinded to the samples.

One of the interesting observations of the study is the inaccuracy of the LMP, Dr. Johnson said. All the women in the study planned on becoming pregnant and were carefully monitoring their menstrual cycles. Although they thought they knew exactly when their LMP was, the urine assessments suggested they were wrong by about 5 days.

"When a woman thinks she is pregnant, all she has is her last menstrual period, and that in so many cases is wrong, so this new test provides something that can provide greater accuracy," Dr. Johnson suggested.

SPD Development also has a digital ovulation test that is soon to be released in both the United States and the United Kingdom.

"Normal ovulation tests just measure luteinizing hormone [LH], so they tell you the best 2 days [to conceive]," Dr. Johnson said. The digital ovulation test still measures the LH surge, which indicates ovulation has occurred, but it also measures levels of estrone-3-glucuronide (E3G), which is a major urinary metabolite of estradiol. Levels of E3G rise a couple of days before the LH surge.

"By measuring [E3G], you are actually telling a woman about those additional fertile days during which she can also get pregnant before the 2 peak days," Dr. Johnson explained. Data presented in a poster at the annual meeting of ESHRE showed that the new digital ovulation test identified 4 or more fertile days in 80% of menstrual cycles.

The digital ovulation test will come as a kit with replaceable test strips. A woman urinates on the test strip, puts it into the reader, and the device then remembers the result and helps the woman identify her most fertile period.

The study was funded by SPD Development. Dr. Johnson is an employee of the company, which manufactures the Clearblue Digital Pregnancy Test With Conception Indicator and the Clearblue Digital Ovulation Test With Dual Hormone Indicator.

*Correction, 7/18/2013: An earlier version of this story misstated the availability of the test.

LONDON – A home digital pregnancy test is able to correctly estimate the likely week of conception, according to the results of a 10-month, prospective observational study of 1,505 nonpregnant U.S. women.

"There was a high [98%] level of agreement between the digital pregnancy test and standardized ultrasound," Sarah Johnson, Ph.D., said in an interview at the annual meeting of the European Society of Human Reproduction and Embryology.

The results of the digital pregnancy test were compared with ultrasound measurements performed at approximately 12 weeks after the woman had her last menstrual period (LMP).

"We received clearance from the Food and Drug Administration last December, and all being well it should be on the shelves in September," said Dr. Johnson, who is a scientific and medical affairs manager for SPD Development of Bedford, England. The digital pregnancy test is already available in the United Kingdom* based on data from a previous study (Curr. Med. Res. Opin. 2011;27:393-401).

Dr. Johnson noted that this is the first home pregnancy test to provide an accurate and early assessment of pregnancy at the time when a woman first suspects that she might be pregnant. It is also the first test to provide a digital readout, which is potentially simpler for women to understand than seeing a line in a window to indicate whether they are pregnant or not.

Similar to other home pregnancy tests, the digital pregnancy test measures levels of human chorionic gonadotrophin (hCG) excreted in the urine. Measuring hCG is a tried-and-tested method of confirming pregnancy as the hormone plays a critical role in early pregnancy, helping with the implantation of the embryo and preventing further oocyte development.

Unlike existing tests, however, the digital pregnancy test estimates the time since conception based on thresholds of hCG, which have been shown to rise rapidly after ovulation has occurred, and measurement of this hormone in the urine reflects the duration of pregnancy (Curr. Med. Res. Opin. 2009;25:741-8).

In using the digital home pregnancy test, the woman can either hold the test strip in the urine stream for 5 seconds or dip it into a urine sample collected in a clean container for 20 seconds. Results from the test are then given in a few minutes as a digital readout saying if the woman is "pregnant" or "not pregnant," with additional numbers displayed if conception was likely to be 1-2, 2-3, or 3+ weeks ago.

During the study, women were required to provide urine samples every day throughout their menstrual cycles, a random sample of which were then tested in the laboratory using the digital home pregnancy test.

A total of 250 women became pregnant during the study, with sufficient data on 153 women available for analysis. All of these women had ultrasound performed at approximately 11-13 weeks of their pregnancy to determine the gestational age according to the crown rump length measurement. More than 3,600 digital pregnancy tests were preformed in three batches, with the technicians blinded to the samples.

One of the interesting observations of the study is the inaccuracy of the LMP, Dr. Johnson said. All the women in the study planned on becoming pregnant and were carefully monitoring their menstrual cycles. Although they thought they knew exactly when their LMP was, the urine assessments suggested they were wrong by about 5 days.

"When a woman thinks she is pregnant, all she has is her last menstrual period, and that in so many cases is wrong, so this new test provides something that can provide greater accuracy," Dr. Johnson suggested.

SPD Development also has a digital ovulation test that is soon to be released in both the United States and the United Kingdom.

"Normal ovulation tests just measure luteinizing hormone [LH], so they tell you the best 2 days [to conceive]," Dr. Johnson said. The digital ovulation test still measures the LH surge, which indicates ovulation has occurred, but it also measures levels of estrone-3-glucuronide (E3G), which is a major urinary metabolite of estradiol. Levels of E3G rise a couple of days before the LH surge.

"By measuring [E3G], you are actually telling a woman about those additional fertile days during which she can also get pregnant before the 2 peak days," Dr. Johnson explained. Data presented in a poster at the annual meeting of ESHRE showed that the new digital ovulation test identified 4 or more fertile days in 80% of menstrual cycles.

The digital ovulation test will come as a kit with replaceable test strips. A woman urinates on the test strip, puts it into the reader, and the device then remembers the result and helps the woman identify her most fertile period.

The study was funded by SPD Development. Dr. Johnson is an employee of the company, which manufactures the Clearblue Digital Pregnancy Test With Conception Indicator and the Clearblue Digital Ovulation Test With Dual Hormone Indicator.

*Correction, 7/18/2013: An earlier version of this story misstated the availability of the test.

LONDON – Endometrial ovarian cysts do not reduce the rate of spontaneous ovulation and the potential ability of women to conceive, according to a prospective observational study.

Dr. Umberto Leone Roberti Maggiore of San Martino Hospital and the University of Genoa (Italy) reported the results of a study comparing the healthy and affected ovaries of 214 women with endometriosis. The overall rate of spontaneous ovulation was similar for affected and healthy ovaries over the course of six ovulatory cycles, at 50.3% vs. 49.7% (P = .919).

A total of 1,311 ovulatory cycles were examined during the study, with similar rates of ovulation observed regardless of the side, number, or size of endometriomas, he reported at the annual meeting of the European Society of Human Reproduction and Embryology.

Sara Freeman/IMNG Medical Media

"Over the last years, great attention has been given to the impact of endometriomas on ovarian physiology," Dr. Maggiore said. "Different studies have investigated whether the presence of endometriomas affect ovarian reserve and the outcome of assisted reproductive technologies."

Data from one study in particular suggested that the presence of endometriomas reduced the rate of spontaneous ovulation (Hum. Reprod. 2009;24:2183-6).

"The objective of the current study was to investigate the rate of spontaneous ovulation between the healthy and the affected ovary in women with unilateral endometriomas," Dr. Maggiore explained. Women were recruited into the study at an academic referral center between September 2009 and June 2013. For inclusion, they had to have ultrasound-confirmed endometrioma(s) of a single ovary of 20 mm or more in size, regular menstrual cycles (24-35 days), and a desire to conceive a child.

Women were excluded if they had previous adnexal surgery, had used hormonal therapies in the past 3 months, were pregnant or had breastfed their infants in the past 6 months, had a history of infertility, or had diagnoses of any of the following: hydrosalpinx, pelvic inflammatory disease, polycystic ovary syndrome, thyroid disorders, or psychiatric disturbances.

Transvaginal ultrasound was used to assess the side, number, largest diameter, and volume of the endometriomas. Ovarian reserve was assessed by measuring levels of anti-Müllerian hormone and basal follicle-stimulating hormone. The level of CA-125 was also measured.

The mean age of recruited women was 34 years; 55% of women had endometriomas of the right ovary, the majority (81.1%) had only one endometrial cyst, with 15.2% having two and 3.7% having three endometriomas. The largest diameter of the endometriomas at baseline was a mean of 4.5 cm, with 55.5% of women having a cyst equal to or greater than 4 cm and 15.1% a cyst equal to or greater than 6 cm. The total volume of endometriomas in the same ovary at baseline was a mean of 54.9 cm².

In terms of pregnancy outcomes, 43% of women conceived during the study period. Of these 63.8% were at term, 20% of patients had an ongoing pregnancy, 3.8% had been delivered preterm, 1.9% voluntarily terminated their pregnancy at the second trimester, and 10.5% had miscarriages.

No correlation was found between levels of follicle-stimulating hormone, anti-Müllerian hormone, or CA-125 and the total endometrial volume, the largest diameter of the endometrioma, or the number of endometriomas. However, the size and volume of the endometriomas by the sixth ovarian cycle were seen to increase from baseline values by a respective 3.9% and 8.1% (both P values less than .001).

Dr. Maggiore reported that 40.2% of women had a 0.1%-5% increase in the total volume of endometriomas over the course of the study, with 29.1% experiencing a volume increase of 5.1%-10%, a further 19.7% a volume increase of 10.1%-25%, and 4.7% an increase of 25.1% or more. Only 6.3% of women experienced a decrease in total endometrioma volume.

"Normal ovulatory function and the potential decrease of ovarian reserve should be considered before suggesting the surgical treatment of endometriomas," said Dr. Maggiore. While surgical removal of these cysts might not be necessary purely to improve fertility, it is too early to say if they will change practice.

"I think [the study] shows that the mere presence of endometrioma is not sufficient to operate," Dr. Thomas D’Hooghe of the Leuven (Belgium) University fertility center said in an interview.

However, Dr. D’Hooghe, who was not involved in the study, noted that an increase in endometrioma volume within 6 months of observation was not an insignificant finding. "If you extrapolate that to say 1 year or 2 years after baseline, there may be a larger increase in volume. ... The endometrioma may rupture and cause adhesions" at that point, he said.

"The fact that endometriomas appear to be progressive might suggest that women who want to conceive should perhaps undergo cystectomy as early as possible," Dr. D’Hooghe suggested. "I would think that if the endometrioma increases in size, sooner or later it may affect fertility."

Dr. Maggiore and Dr. D’Hooghe said they had no relevant financial disclosures.

LONDON – Endometrial ovarian cysts do not reduce the rate of spontaneous ovulation and the potential ability of women to conceive, according to a prospective observational study.

Dr. Umberto Leone Roberti Maggiore of San Martino Hospital and the University of Genoa (Italy) reported the results of a study comparing the healthy and affected ovaries of 214 women with endometriosis. The overall rate of spontaneous ovulation was similar for affected and healthy ovaries over the course of six ovulatory cycles, at 50.3% vs. 49.7% (P = .919).

A total of 1,311 ovulatory cycles were examined during the study, with similar rates of ovulation observed regardless of the side, number, or size of endometriomas, he reported at the annual meeting of the European Society of Human Reproduction and Embryology.

Sara Freeman/IMNG Medical Media

"Over the last years, great attention has been given to the impact of endometriomas on ovarian physiology," Dr. Maggiore said. "Different studies have investigated whether the presence of endometriomas affect ovarian reserve and the outcome of assisted reproductive technologies."

Data from one study in particular suggested that the presence of endometriomas reduced the rate of spontaneous ovulation (Hum. Reprod. 2009;24:2183-6).

"The objective of the current study was to investigate the rate of spontaneous ovulation between the healthy and the affected ovary in women with unilateral endometriomas," Dr. Maggiore explained. Women were recruited into the study at an academic referral center between September 2009 and June 2013. For inclusion, they had to have ultrasound-confirmed endometrioma(s) of a single ovary of 20 mm or more in size, regular menstrual cycles (24-35 days), and a desire to conceive a child.

Women were excluded if they had previous adnexal surgery, had used hormonal therapies in the past 3 months, were pregnant or had breastfed their infants in the past 6 months, had a history of infertility, or had diagnoses of any of the following: hydrosalpinx, pelvic inflammatory disease, polycystic ovary syndrome, thyroid disorders, or psychiatric disturbances.

Transvaginal ultrasound was used to assess the side, number, largest diameter, and volume of the endometriomas. Ovarian reserve was assessed by measuring levels of anti-Müllerian hormone and basal follicle-stimulating hormone. The level of CA-125 was also measured.

The mean age of recruited women was 34 years; 55% of women had endometriomas of the right ovary, the majority (81.1%) had only one endometrial cyst, with 15.2% having two and 3.7% having three endometriomas. The largest diameter of the endometriomas at baseline was a mean of 4.5 cm, with 55.5% of women having a cyst equal to or greater than 4 cm and 15.1% a cyst equal to or greater than 6 cm. The total volume of endometriomas in the same ovary at baseline was a mean of 54.9 cm².

In terms of pregnancy outcomes, 43% of women conceived during the study period. Of these 63.8% were at term, 20% of patients had an ongoing pregnancy, 3.8% had been delivered preterm, 1.9% voluntarily terminated their pregnancy at the second trimester, and 10.5% had miscarriages.

No correlation was found between levels of follicle-stimulating hormone, anti-Müllerian hormone, or CA-125 and the total endometrial volume, the largest diameter of the endometrioma, or the number of endometriomas. However, the size and volume of the endometriomas by the sixth ovarian cycle were seen to increase from baseline values by a respective 3.9% and 8.1% (both P values less than .001).

Dr. Maggiore reported that 40.2% of women had a 0.1%-5% increase in the total volume of endometriomas over the course of the study, with 29.1% experiencing a volume increase of 5.1%-10%, a further 19.7% a volume increase of 10.1%-25%, and 4.7% an increase of 25.1% or more. Only 6.3% of women experienced a decrease in total endometrioma volume.

"Normal ovulatory function and the potential decrease of ovarian reserve should be considered before suggesting the surgical treatment of endometriomas," said Dr. Maggiore. While surgical removal of these cysts might not be necessary purely to improve fertility, it is too early to say if they will change practice.

"I think [the study] shows that the mere presence of endometrioma is not sufficient to operate," Dr. Thomas D’Hooghe of the Leuven (Belgium) University fertility center said in an interview.

However, Dr. D’Hooghe, who was not involved in the study, noted that an increase in endometrioma volume within 6 months of observation was not an insignificant finding. "If you extrapolate that to say 1 year or 2 years after baseline, there may be a larger increase in volume. ... The endometrioma may rupture and cause adhesions" at that point, he said.

"The fact that endometriomas appear to be progressive might suggest that women who want to conceive should perhaps undergo cystectomy as early as possible," Dr. D’Hooghe suggested. "I would think that if the endometrioma increases in size, sooner or later it may affect fertility."

Dr. Maggiore and Dr. D’Hooghe said they had no relevant financial disclosures.

LONDON – Endometrial ovarian cysts do not reduce the rate of spontaneous ovulation and the potential ability of women to conceive, according to a prospective observational study.

Dr. Umberto Leone Roberti Maggiore of San Martino Hospital and the University of Genoa (Italy) reported the results of a study comparing the healthy and affected ovaries of 214 women with endometriosis. The overall rate of spontaneous ovulation was similar for affected and healthy ovaries over the course of six ovulatory cycles, at 50.3% vs. 49.7% (P = .919).

A total of 1,311 ovulatory cycles were examined during the study, with similar rates of ovulation observed regardless of the side, number, or size of endometriomas, he reported at the annual meeting of the European Society of Human Reproduction and Embryology.

Sara Freeman/IMNG Medical Media

"Over the last years, great attention has been given to the impact of endometriomas on ovarian physiology," Dr. Maggiore said. "Different studies have investigated whether the presence of endometriomas affect ovarian reserve and the outcome of assisted reproductive technologies."

Data from one study in particular suggested that the presence of endometriomas reduced the rate of spontaneous ovulation (Hum. Reprod. 2009;24:2183-6).

"The objective of the current study was to investigate the rate of spontaneous ovulation between the healthy and the affected ovary in women with unilateral endometriomas," Dr. Maggiore explained. Women were recruited into the study at an academic referral center between September 2009 and June 2013. For inclusion, they had to have ultrasound-confirmed endometrioma(s) of a single ovary of 20 mm or more in size, regular menstrual cycles (24-35 days), and a desire to conceive a child.

Women were excluded if they had previous adnexal surgery, had used hormonal therapies in the past 3 months, were pregnant or had breastfed their infants in the past 6 months, had a history of infertility, or had diagnoses of any of the following: hydrosalpinx, pelvic inflammatory disease, polycystic ovary syndrome, thyroid disorders, or psychiatric disturbances.

Transvaginal ultrasound was used to assess the side, number, largest diameter, and volume of the endometriomas. Ovarian reserve was assessed by measuring levels of anti-Müllerian hormone and basal follicle-stimulating hormone. The level of CA-125 was also measured.

The mean age of recruited women was 34 years; 55% of women had endometriomas of the right ovary, the majority (81.1%) had only one endometrial cyst, with 15.2% having two and 3.7% having three endometriomas. The largest diameter of the endometriomas at baseline was a mean of 4.5 cm, with 55.5% of women having a cyst equal to or greater than 4 cm and 15.1% a cyst equal to or greater than 6 cm. The total volume of endometriomas in the same ovary at baseline was a mean of 54.9 cm².

In terms of pregnancy outcomes, 43% of women conceived during the study period. Of these 63.8% were at term, 20% of patients had an ongoing pregnancy, 3.8% had been delivered preterm, 1.9% voluntarily terminated their pregnancy at the second trimester, and 10.5% had miscarriages.

No correlation was found between levels of follicle-stimulating hormone, anti-Müllerian hormone, or CA-125 and the total endometrial volume, the largest diameter of the endometrioma, or the number of endometriomas. However, the size and volume of the endometriomas by the sixth ovarian cycle were seen to increase from baseline values by a respective 3.9% and 8.1% (both P values less than .001).

Dr. Maggiore reported that 40.2% of women had a 0.1%-5% increase in the total volume of endometriomas over the course of the study, with 29.1% experiencing a volume increase of 5.1%-10%, a further 19.7% a volume increase of 10.1%-25%, and 4.7% an increase of 25.1% or more. Only 6.3% of women experienced a decrease in total endometrioma volume.

"Normal ovulatory function and the potential decrease of ovarian reserve should be considered before suggesting the surgical treatment of endometriomas," said Dr. Maggiore. While surgical removal of these cysts might not be necessary purely to improve fertility, it is too early to say if they will change practice.

"I think [the study] shows that the mere presence of endometrioma is not sufficient to operate," Dr. Thomas D’Hooghe of the Leuven (Belgium) University fertility center said in an interview.

However, Dr. D’Hooghe, who was not involved in the study, noted that an increase in endometrioma volume within 6 months of observation was not an insignificant finding. "If you extrapolate that to say 1 year or 2 years after baseline, there may be a larger increase in volume. ... The endometrioma may rupture and cause adhesions" at that point, he said.

"The fact that endometriomas appear to be progressive might suggest that women who want to conceive should perhaps undergo cystectomy as early as possible," Dr. D’Hooghe suggested. "I would think that if the endometrioma increases in size, sooner or later it may affect fertility."

Dr. Maggiore and Dr. D’Hooghe said they had no relevant financial disclosures.