ESHRE 2015

LISBON – Melatonin supplementation during ovarian stimulation improved oocyte and embryo quality but not clinical pregnancy rates in older women undergoing in vitro fertilization in a double-blind, randomized trial.

© Wjeger/Thinkstockphotos.com

“In clinical pregnancy, we did not find a statistical difference, even if we can see a higher proportion of pregnant patients,”said Dr. Arianna Pacchiarotti, director of the IVF Center Praxi Provita, Rome.

Melatonin is secreted by the pineal gland and declines in middle age after peaking in early childhood. The powerful free-radical scavenger and antioxidant has been shown to protect the testis and ovary from oxidative stress, stimulates the secretion of progesterone, and inhibits the synthesis of prostaglandins, she said.

In a recent study, fertilization rates nearly doubled, and the rate of good quality embryos increased from 48% to 65.6% following at least 2 weeks of oral melatonin 3 mg/day in all women undergoing in vitro fertilization (Gynecol. Endocrinol. 2014;30:359-62).

The current study involved 358 women, aged 38-42 years, who were undergoing their first IVF treatment comprised of a short down regulation protocol with a gonadotropin-releasing hormone analogue and combined stimulation with urinary and recombinant follicle stimulating hormone. Patients were randomly assigned in a double-blind fashion to 4 mg of melatonin 1 month before starting stimulation or no pretreatment.

The 165 evaluable patients treated with melatonin and the 166 evaluable controls were similar in age, body mass index, cycle length, duration of sterility, or primary and secondary sterility.

Following supplementation, the melatonin group had significantly higher progesterone concentration in follicular fluid than did controls (10.4 ng/mL vs. 4.3 ng/mL; P = .001), more mature oocytes (48.2% vs. 35%; P = .008), and more grade 1 embryos (45.7% vs. 30.4%; P = .0045), Dr. Pacchiarotti reported at the annual meeting of the European Society of Human Reproduction and Embryology.

The study also demonstrated a significant reduction of oxygen free radicals in the melatonin group (190 Carratelli units vs. 388 CARR U; P = .014) and therefore higher concentrations of intrafollicular melatonin (213 pg/mL vs. 69 pg/mL; P = .0013), she said.

Antioxidative capacity was also significantly higher with melatonin supplementation (1.76 vs. 0.89; P = 018).

“This hypothesizes an important scavenger role of melatonin, which results in better oocyte and embryo quality in aged women and IVF outcome,” Dr. Pacchiarotti concluded.

No significant differences were observed between the melatonin group and controls in endometrial thickness on the day of human chorionic gonadotropin administration (10.8 mm vs. 11.2 mm), total oocytes retrieved (5.1 vs. 5.2), implantation rates (13.8% vs. 12.2%), abortion rates (10.8% vs. 8.6%), and twin pregnancies (20.8% vs. 20%).

Audience members questioned how the investigators arrived at the melatonin dose and whether the study was underpowered to identify an effect of melatonin on pregnancy. A prior study evaluating melatonin 2 mg showed no difference in outcomes, while a 5-mg dose has been shown to be effective in cancer prevention, Dr. Pacchiarotti said. The study had 80% power to detect a 20% difference with 50 evaluable patients per group.

[email protected]

LISBON – Melatonin supplementation during ovarian stimulation improved oocyte and embryo quality but not clinical pregnancy rates in older women undergoing in vitro fertilization in a double-blind, randomized trial.

© Wjeger/Thinkstockphotos.com

“In clinical pregnancy, we did not find a statistical difference, even if we can see a higher proportion of pregnant patients,”said Dr. Arianna Pacchiarotti, director of the IVF Center Praxi Provita, Rome.

Melatonin is secreted by the pineal gland and declines in middle age after peaking in early childhood. The powerful free-radical scavenger and antioxidant has been shown to protect the testis and ovary from oxidative stress, stimulates the secretion of progesterone, and inhibits the synthesis of prostaglandins, she said.

In a recent study, fertilization rates nearly doubled, and the rate of good quality embryos increased from 48% to 65.6% following at least 2 weeks of oral melatonin 3 mg/day in all women undergoing in vitro fertilization (Gynecol. Endocrinol. 2014;30:359-62).

The current study involved 358 women, aged 38-42 years, who were undergoing their first IVF treatment comprised of a short down regulation protocol with a gonadotropin-releasing hormone analogue and combined stimulation with urinary and recombinant follicle stimulating hormone. Patients were randomly assigned in a double-blind fashion to 4 mg of melatonin 1 month before starting stimulation or no pretreatment.

The 165 evaluable patients treated with melatonin and the 166 evaluable controls were similar in age, body mass index, cycle length, duration of sterility, or primary and secondary sterility.

Following supplementation, the melatonin group had significantly higher progesterone concentration in follicular fluid than did controls (10.4 ng/mL vs. 4.3 ng/mL; P = .001), more mature oocytes (48.2% vs. 35%; P = .008), and more grade 1 embryos (45.7% vs. 30.4%; P = .0045), Dr. Pacchiarotti reported at the annual meeting of the European Society of Human Reproduction and Embryology.

The study also demonstrated a significant reduction of oxygen free radicals in the melatonin group (190 Carratelli units vs. 388 CARR U; P = .014) and therefore higher concentrations of intrafollicular melatonin (213 pg/mL vs. 69 pg/mL; P = .0013), she said.

Antioxidative capacity was also significantly higher with melatonin supplementation (1.76 vs. 0.89; P = 018).

“This hypothesizes an important scavenger role of melatonin, which results in better oocyte and embryo quality in aged women and IVF outcome,” Dr. Pacchiarotti concluded.

No significant differences were observed between the melatonin group and controls in endometrial thickness on the day of human chorionic gonadotropin administration (10.8 mm vs. 11.2 mm), total oocytes retrieved (5.1 vs. 5.2), implantation rates (13.8% vs. 12.2%), abortion rates (10.8% vs. 8.6%), and twin pregnancies (20.8% vs. 20%).

Audience members questioned how the investigators arrived at the melatonin dose and whether the study was underpowered to identify an effect of melatonin on pregnancy. A prior study evaluating melatonin 2 mg showed no difference in outcomes, while a 5-mg dose has been shown to be effective in cancer prevention, Dr. Pacchiarotti said. The study had 80% power to detect a 20% difference with 50 evaluable patients per group.

[email protected]

LISBON – Melatonin supplementation during ovarian stimulation improved oocyte and embryo quality but not clinical pregnancy rates in older women undergoing in vitro fertilization in a double-blind, randomized trial.

© Wjeger/Thinkstockphotos.com

“In clinical pregnancy, we did not find a statistical difference, even if we can see a higher proportion of pregnant patients,”said Dr. Arianna Pacchiarotti, director of the IVF Center Praxi Provita, Rome.

Melatonin is secreted by the pineal gland and declines in middle age after peaking in early childhood. The powerful free-radical scavenger and antioxidant has been shown to protect the testis and ovary from oxidative stress, stimulates the secretion of progesterone, and inhibits the synthesis of prostaglandins, she said.

In a recent study, fertilization rates nearly doubled, and the rate of good quality embryos increased from 48% to 65.6% following at least 2 weeks of oral melatonin 3 mg/day in all women undergoing in vitro fertilization (Gynecol. Endocrinol. 2014;30:359-62).

The current study involved 358 women, aged 38-42 years, who were undergoing their first IVF treatment comprised of a short down regulation protocol with a gonadotropin-releasing hormone analogue and combined stimulation with urinary and recombinant follicle stimulating hormone. Patients were randomly assigned in a double-blind fashion to 4 mg of melatonin 1 month before starting stimulation or no pretreatment.

The 165 evaluable patients treated with melatonin and the 166 evaluable controls were similar in age, body mass index, cycle length, duration of sterility, or primary and secondary sterility.

Following supplementation, the melatonin group had significantly higher progesterone concentration in follicular fluid than did controls (10.4 ng/mL vs. 4.3 ng/mL; P = .001), more mature oocytes (48.2% vs. 35%; P = .008), and more grade 1 embryos (45.7% vs. 30.4%; P = .0045), Dr. Pacchiarotti reported at the annual meeting of the European Society of Human Reproduction and Embryology.

The study also demonstrated a significant reduction of oxygen free radicals in the melatonin group (190 Carratelli units vs. 388 CARR U; P = .014) and therefore higher concentrations of intrafollicular melatonin (213 pg/mL vs. 69 pg/mL; P = .0013), she said.

Antioxidative capacity was also significantly higher with melatonin supplementation (1.76 vs. 0.89; P = 018).

“This hypothesizes an important scavenger role of melatonin, which results in better oocyte and embryo quality in aged women and IVF outcome,” Dr. Pacchiarotti concluded.

No significant differences were observed between the melatonin group and controls in endometrial thickness on the day of human chorionic gonadotropin administration (10.8 mm vs. 11.2 mm), total oocytes retrieved (5.1 vs. 5.2), implantation rates (13.8% vs. 12.2%), abortion rates (10.8% vs. 8.6%), and twin pregnancies (20.8% vs. 20%).

Audience members questioned how the investigators arrived at the melatonin dose and whether the study was underpowered to identify an effect of melatonin on pregnancy. A prior study evaluating melatonin 2 mg showed no difference in outcomes, while a 5-mg dose has been shown to be effective in cancer prevention, Dr. Pacchiarotti said. The study had 80% power to detect a 20% difference with 50 evaluable patients per group.

[email protected]

LISBON – Singletons born after frozen embryo transfer are at significantly increased risk for being born large for gestational age, results of a retrospective, case-matched cohort study confirm.

Frozen embryo transfer (FET) was found to be a significant independent risk factor for LGA among FET singletons (odds ratio, 1.697; P = .032) on par with multiparity (OR, 1.615; P = .039) and maternal body mass index (BMI) between 25 kg/m² and 30 kg/m² (OR, 1.85; P = .026).

BMI greater than 30 kg/m² tripled LGA risk (OR, 3.12; P = .002).Fresh embryo transfer (ET) and intra-cytoplasmic sperm injection had no effect on LGA occurrence, whereas double embryo transfer insignificantly reduced the LGA risk, study author Sara Korosec, Ph.D., of University Medical Centre Ljubljana (Slovenia), reported.

The logistic regression model included smoking, hypertension, multiparity, BMI^, gestational diabetes, and in vitro fertilization (IVF)/intra-cytoplasmic sperm injection.

“It appears we are running out of the most obvious maternal and IVF reasons for this phenomenon,” Dr. Korosec said at the annual meeting of the European Society of Human Reproduction and Embryology.

The findings are consistent with prior research demonstrating an increased risk for LGA in FET singletons, suggesting that the freezing and thawing procedures per se are partly to blame.

A recent Danish national cohort study (Hum. Reprod. 2014;29:618-27) reported adjusted odds ratios of 1.34 and 1.91 for LGA and macrosomia in FET singletons vs. singletons conceived after fresh ET. This increased risk was confirmed in a sibling cohort, where one singleton was born after FET and the next after fresh ET, or vice versa.

Danish study author Dr. Anja Pinborg of the University of Copenhagen rose from the audience to acknowledge that adjustment for BMI as a possible confounder was not possible in their study and applauded the inclusion of BMI and diabetes in the current analysis.

“I really congratulate you on your findings and it’s nice to see that after controlling for these factors, it’s still there,” she said.

Several audience members agreed with the investigators that further research is needed to identify possible reasons for higher LGA rates in FET babies now that the “low-hanging fruit,” including maternal diabetes and BMI, are being excluded. Other factors to consider include placental differences between fresh and frozen embryo pregnancies, embryo selection using vitrification vs. slow freezing, and “the thing we are all most afraid of, underlying epigenetic disturbances,” Dr. Korosec said.

Dr. Korosec and her associates identified 4,508 singleton pregnancies and births (211 after FET and 916 after fresh ET) conceived as a result of IVF at the university between 2004 and 2011 and 3,381 naturally conceived controls in the National Perinatal Data System. There were 3 controls for each IVF pregnancy, matched by maternal age, parity, and maternity hospital.

LGA, defined as a birth weight above the 90th percentile, occurred in 14.7% of FET singletons vs. 8.7% of FET controls (P = .017) and in 9.4% of fresh ET singletons vs. 9.1% of fresh controls (P = .791), Dr. Korosec reported.

LGA above the 95th percentile was reported in 10% of FET singletons vs. 4.9% of FET controls (P = .012) and in 4.9% of fresh ET vs. 5.1% of fresh controls (P = .862).

Significant LGA risk factors among fresh ET singletons were multiparity (OR, 1.61; P = .001), BMI 25-30 kg/m² (OR 1.70; P = .000), and BMI greater than 30 kg/m² (OR, 1.93; P = .0001), she said.

Dr. Korosec reported no conflicting interests.

[email protected]

LISBON – Singletons born after frozen embryo transfer are at significantly increased risk for being born large for gestational age, results of a retrospective, case-matched cohort study confirm.

Frozen embryo transfer (FET) was found to be a significant independent risk factor for LGA among FET singletons (odds ratio, 1.697; P = .032) on par with multiparity (OR, 1.615; P = .039) and maternal body mass index (BMI) between 25 kg/m² and 30 kg/m² (OR, 1.85; P = .026).

BMI greater than 30 kg/m² tripled LGA risk (OR, 3.12; P = .002).Fresh embryo transfer (ET) and intra-cytoplasmic sperm injection had no effect on LGA occurrence, whereas double embryo transfer insignificantly reduced the LGA risk, study author Sara Korosec, Ph.D., of University Medical Centre Ljubljana (Slovenia), reported.

The logistic regression model included smoking, hypertension, multiparity, BMI^, gestational diabetes, and in vitro fertilization (IVF)/intra-cytoplasmic sperm injection.

“It appears we are running out of the most obvious maternal and IVF reasons for this phenomenon,” Dr. Korosec said at the annual meeting of the European Society of Human Reproduction and Embryology.

The findings are consistent with prior research demonstrating an increased risk for LGA in FET singletons, suggesting that the freezing and thawing procedures per se are partly to blame.

A recent Danish national cohort study (Hum. Reprod. 2014;29:618-27) reported adjusted odds ratios of 1.34 and 1.91 for LGA and macrosomia in FET singletons vs. singletons conceived after fresh ET. This increased risk was confirmed in a sibling cohort, where one singleton was born after FET and the next after fresh ET, or vice versa.

Danish study author Dr. Anja Pinborg of the University of Copenhagen rose from the audience to acknowledge that adjustment for BMI as a possible confounder was not possible in their study and applauded the inclusion of BMI and diabetes in the current analysis.

“I really congratulate you on your findings and it’s nice to see that after controlling for these factors, it’s still there,” she said.

Several audience members agreed with the investigators that further research is needed to identify possible reasons for higher LGA rates in FET babies now that the “low-hanging fruit,” including maternal diabetes and BMI, are being excluded. Other factors to consider include placental differences between fresh and frozen embryo pregnancies, embryo selection using vitrification vs. slow freezing, and “the thing we are all most afraid of, underlying epigenetic disturbances,” Dr. Korosec said.

Dr. Korosec and her associates identified 4,508 singleton pregnancies and births (211 after FET and 916 after fresh ET) conceived as a result of IVF at the university between 2004 and 2011 and 3,381 naturally conceived controls in the National Perinatal Data System. There were 3 controls for each IVF pregnancy, matched by maternal age, parity, and maternity hospital.

LGA, defined as a birth weight above the 90th percentile, occurred in 14.7% of FET singletons vs. 8.7% of FET controls (P = .017) and in 9.4% of fresh ET singletons vs. 9.1% of fresh controls (P = .791), Dr. Korosec reported.

LGA above the 95th percentile was reported in 10% of FET singletons vs. 4.9% of FET controls (P = .012) and in 4.9% of fresh ET vs. 5.1% of fresh controls (P = .862).

Significant LGA risk factors among fresh ET singletons were multiparity (OR, 1.61; P = .001), BMI 25-30 kg/m² (OR 1.70; P = .000), and BMI greater than 30 kg/m² (OR, 1.93; P = .0001), she said.

Dr. Korosec reported no conflicting interests.

[email protected]

LISBON – Singletons born after frozen embryo transfer are at significantly increased risk for being born large for gestational age, results of a retrospective, case-matched cohort study confirm.

Frozen embryo transfer (FET) was found to be a significant independent risk factor for LGA among FET singletons (odds ratio, 1.697; P = .032) on par with multiparity (OR, 1.615; P = .039) and maternal body mass index (BMI) between 25 kg/m² and 30 kg/m² (OR, 1.85; P = .026).

BMI greater than 30 kg/m² tripled LGA risk (OR, 3.12; P = .002).Fresh embryo transfer (ET) and intra-cytoplasmic sperm injection had no effect on LGA occurrence, whereas double embryo transfer insignificantly reduced the LGA risk, study author Sara Korosec, Ph.D., of University Medical Centre Ljubljana (Slovenia), reported.

The logistic regression model included smoking, hypertension, multiparity, BMI^, gestational diabetes, and in vitro fertilization (IVF)/intra-cytoplasmic sperm injection.

“It appears we are running out of the most obvious maternal and IVF reasons for this phenomenon,” Dr. Korosec said at the annual meeting of the European Society of Human Reproduction and Embryology.

The findings are consistent with prior research demonstrating an increased risk for LGA in FET singletons, suggesting that the freezing and thawing procedures per se are partly to blame.

A recent Danish national cohort study (Hum. Reprod. 2014;29:618-27) reported adjusted odds ratios of 1.34 and 1.91 for LGA and macrosomia in FET singletons vs. singletons conceived after fresh ET. This increased risk was confirmed in a sibling cohort, where one singleton was born after FET and the next after fresh ET, or vice versa.

Danish study author Dr. Anja Pinborg of the University of Copenhagen rose from the audience to acknowledge that adjustment for BMI as a possible confounder was not possible in their study and applauded the inclusion of BMI and diabetes in the current analysis.

“I really congratulate you on your findings and it’s nice to see that after controlling for these factors, it’s still there,” she said.

Several audience members agreed with the investigators that further research is needed to identify possible reasons for higher LGA rates in FET babies now that the “low-hanging fruit,” including maternal diabetes and BMI, are being excluded. Other factors to consider include placental differences between fresh and frozen embryo pregnancies, embryo selection using vitrification vs. slow freezing, and “the thing we are all most afraid of, underlying epigenetic disturbances,” Dr. Korosec said.

Dr. Korosec and her associates identified 4,508 singleton pregnancies and births (211 after FET and 916 after fresh ET) conceived as a result of IVF at the university between 2004 and 2011 and 3,381 naturally conceived controls in the National Perinatal Data System. There were 3 controls for each IVF pregnancy, matched by maternal age, parity, and maternity hospital.

LGA, defined as a birth weight above the 90th percentile, occurred in 14.7% of FET singletons vs. 8.7% of FET controls (P = .017) and in 9.4% of fresh ET singletons vs. 9.1% of fresh controls (P = .791), Dr. Korosec reported.

LGA above the 95th percentile was reported in 10% of FET singletons vs. 4.9% of FET controls (P = .012) and in 4.9% of fresh ET vs. 5.1% of fresh controls (P = .862).

Significant LGA risk factors among fresh ET singletons were multiparity (OR, 1.61; P = .001), BMI 25-30 kg/m² (OR 1.70; P = .000), and BMI greater than 30 kg/m² (OR, 1.93; P = .0001), she said.

Dr. Korosec reported no conflicting interests.

[email protected]

LISBON – Dehydroepiandrosterone supplementation was no match for the powerful effects of ovarian aging in women with diminished ovarian reserve in the DITTO trial.

Women who received oral dehydroepiandrosterone (DHEA) for at least 12 weeks prior to ovarian stimulation had a median of four oocytes retrieved, the same number as those given placebo.

Adjunct DHEA was also no better than placebo with regard to clinical pregnancy (28.6% vs. 36.0%; relative risk, 0.79) and live birth (25% vs. 32%; RR, 0.78) rates.

There were three miscarriages in each group, Dr. Kanna Jayaprakasan reported to an overflow crowd at the annual meeting of the European Society of Human Reproduction and Embryology.

The double-blind, randomized pilot trial was designed to test whether DHEA supplementation would improve in vitro fertilization (IVF) outcomes in women predicted to have poor ovarian response and to evaluate the feasibility of conducting a large multicenter DHEA trial.

“Successful recruitment for this pilot trial suggests a large definitive trial is feasible, but the lack of effect on IVF outcome – not even a trend – suggests it is a low priority,” Dr. Jayaprakasan of Royal Derby (England) Hospital and the University of Nottingham (England), said.

An animal study by the same investigators suggested that DHEA, a weak androgenic steroid secreted by the adrenal glands as well as the ovaries, might be a useful therapy to delay the effects of ovarian aging (Hum. Reprod. 2014;29:146-54).

Data from randomized controlled trials (RCTs) supporting its efficacy in humans, however, are limited, he said.

DHEA supplementation was associated with fewer miscarriages and significantly more live births in infertile women with normal ovarian reserve in a recent blinded RCT (Reprod. Biol. Endocrinol. 2015;13:18.).

Results were mixed, however, in a nonblinded RCT involving poor responders (Hum. Reprod. 2010;25:2496-500) in which DHEA 75 mg daily for at least 6 weeks (mean, 13.5 weeks) before ovulation induction had no impact on the number of oocytes retrieved, but more than quadrupled the live birth rate, compared with no pretreatment after two cycles (23% vs. 4%; P = .05).

The DITTO (Dehydroepiandrosterone Intervention to Treat Ovarian Aging) study used the same 75-mg daily dose of DHEA for up to 16 weeks (median, 12 weeks) before egg collection in 60 women, aged 23-43 years, with diminished ovarian reserve (antral follicle count <10 or serum Mullerian hormone level <5 pmol/L).All patients underwent a standard long downregulation protocol using human gonadotropin 300 IU/day. Seven women did not start the trial medication, leaving 28 DHEA patients and 25 patients allocated to matched placebo capsules evaluable for analysis.

DHEA levels were similar at baseline in the DHEA and control groups (9.4 vs. 7.5 ng/mL). Compliance was good, with DHEA levels significantly higher at the prestimulation stage in the study group than in controls (16.3 vs. 11.1 ng/mL; P <.01), Dr. Jayaprakasan said.Meeting attendees questioned whether longer DHEA supplementation might improve IVF outcomes, perhaps by affecting the gonadotropin-responsive follicle pool. While it is difficult to know whether prolonged DHEA would result in an improved outcome, it is less likely, he said.

As for whether the DITTO results nix further DHEA supplementation in poor responders, but leave the door open in normal responders, Dr. Jayaprakasan said, “I think there is no evidence to support its routine use in predicted poor or normal responders currently, and its use should be restricted to randomized controlled studies rather than a blanket approach.” The University of Nottingham supported the research. The authors reported having no relevant financial disclosures.

[email protected]

LISBON – Dehydroepiandrosterone supplementation was no match for the powerful effects of ovarian aging in women with diminished ovarian reserve in the DITTO trial.

Women who received oral dehydroepiandrosterone (DHEA) for at least 12 weeks prior to ovarian stimulation had a median of four oocytes retrieved, the same number as those given placebo.

Adjunct DHEA was also no better than placebo with regard to clinical pregnancy (28.6% vs. 36.0%; relative risk, 0.79) and live birth (25% vs. 32%; RR, 0.78) rates.

There were three miscarriages in each group, Dr. Kanna Jayaprakasan reported to an overflow crowd at the annual meeting of the European Society of Human Reproduction and Embryology.

The double-blind, randomized pilot trial was designed to test whether DHEA supplementation would improve in vitro fertilization (IVF) outcomes in women predicted to have poor ovarian response and to evaluate the feasibility of conducting a large multicenter DHEA trial.

“Successful recruitment for this pilot trial suggests a large definitive trial is feasible, but the lack of effect on IVF outcome – not even a trend – suggests it is a low priority,” Dr. Jayaprakasan of Royal Derby (England) Hospital and the University of Nottingham (England), said.

An animal study by the same investigators suggested that DHEA, a weak androgenic steroid secreted by the adrenal glands as well as the ovaries, might be a useful therapy to delay the effects of ovarian aging (Hum. Reprod. 2014;29:146-54).

Data from randomized controlled trials (RCTs) supporting its efficacy in humans, however, are limited, he said.

DHEA supplementation was associated with fewer miscarriages and significantly more live births in infertile women with normal ovarian reserve in a recent blinded RCT (Reprod. Biol. Endocrinol. 2015;13:18.).

Results were mixed, however, in a nonblinded RCT involving poor responders (Hum. Reprod. 2010;25:2496-500) in which DHEA 75 mg daily for at least 6 weeks (mean, 13.5 weeks) before ovulation induction had no impact on the number of oocytes retrieved, but more than quadrupled the live birth rate, compared with no pretreatment after two cycles (23% vs. 4%; P = .05).

The DITTO (Dehydroepiandrosterone Intervention to Treat Ovarian Aging) study used the same 75-mg daily dose of DHEA for up to 16 weeks (median, 12 weeks) before egg collection in 60 women, aged 23-43 years, with diminished ovarian reserve (antral follicle count <10 or serum Mullerian hormone level <5 pmol/L).All patients underwent a standard long downregulation protocol using human gonadotropin 300 IU/day. Seven women did not start the trial medication, leaving 28 DHEA patients and 25 patients allocated to matched placebo capsules evaluable for analysis.

DHEA levels were similar at baseline in the DHEA and control groups (9.4 vs. 7.5 ng/mL). Compliance was good, with DHEA levels significantly higher at the prestimulation stage in the study group than in controls (16.3 vs. 11.1 ng/mL; P <.01), Dr. Jayaprakasan said.Meeting attendees questioned whether longer DHEA supplementation might improve IVF outcomes, perhaps by affecting the gonadotropin-responsive follicle pool. While it is difficult to know whether prolonged DHEA would result in an improved outcome, it is less likely, he said.

As for whether the DITTO results nix further DHEA supplementation in poor responders, but leave the door open in normal responders, Dr. Jayaprakasan said, “I think there is no evidence to support its routine use in predicted poor or normal responders currently, and its use should be restricted to randomized controlled studies rather than a blanket approach.” The University of Nottingham supported the research. The authors reported having no relevant financial disclosures.

[email protected]

LISBON – Dehydroepiandrosterone supplementation was no match for the powerful effects of ovarian aging in women with diminished ovarian reserve in the DITTO trial.

Women who received oral dehydroepiandrosterone (DHEA) for at least 12 weeks prior to ovarian stimulation had a median of four oocytes retrieved, the same number as those given placebo.

Adjunct DHEA was also no better than placebo with regard to clinical pregnancy (28.6% vs. 36.0%; relative risk, 0.79) and live birth (25% vs. 32%; RR, 0.78) rates.

There were three miscarriages in each group, Dr. Kanna Jayaprakasan reported to an overflow crowd at the annual meeting of the European Society of Human Reproduction and Embryology.

The double-blind, randomized pilot trial was designed to test whether DHEA supplementation would improve in vitro fertilization (IVF) outcomes in women predicted to have poor ovarian response and to evaluate the feasibility of conducting a large multicenter DHEA trial.

“Successful recruitment for this pilot trial suggests a large definitive trial is feasible, but the lack of effect on IVF outcome – not even a trend – suggests it is a low priority,” Dr. Jayaprakasan of Royal Derby (England) Hospital and the University of Nottingham (England), said.

An animal study by the same investigators suggested that DHEA, a weak androgenic steroid secreted by the adrenal glands as well as the ovaries, might be a useful therapy to delay the effects of ovarian aging (Hum. Reprod. 2014;29:146-54).

Data from randomized controlled trials (RCTs) supporting its efficacy in humans, however, are limited, he said.

DHEA supplementation was associated with fewer miscarriages and significantly more live births in infertile women with normal ovarian reserve in a recent blinded RCT (Reprod. Biol. Endocrinol. 2015;13:18.).

Results were mixed, however, in a nonblinded RCT involving poor responders (Hum. Reprod. 2010;25:2496-500) in which DHEA 75 mg daily for at least 6 weeks (mean, 13.5 weeks) before ovulation induction had no impact on the number of oocytes retrieved, but more than quadrupled the live birth rate, compared with no pretreatment after two cycles (23% vs. 4%; P = .05).

The DITTO (Dehydroepiandrosterone Intervention to Treat Ovarian Aging) study used the same 75-mg daily dose of DHEA for up to 16 weeks (median, 12 weeks) before egg collection in 60 women, aged 23-43 years, with diminished ovarian reserve (antral follicle count <10 or serum Mullerian hormone level <5 pmol/L).All patients underwent a standard long downregulation protocol using human gonadotropin 300 IU/day. Seven women did not start the trial medication, leaving 28 DHEA patients and 25 patients allocated to matched placebo capsules evaluable for analysis.

DHEA levels were similar at baseline in the DHEA and control groups (9.4 vs. 7.5 ng/mL). Compliance was good, with DHEA levels significantly higher at the prestimulation stage in the study group than in controls (16.3 vs. 11.1 ng/mL; P <.01), Dr. Jayaprakasan said.Meeting attendees questioned whether longer DHEA supplementation might improve IVF outcomes, perhaps by affecting the gonadotropin-responsive follicle pool. While it is difficult to know whether prolonged DHEA would result in an improved outcome, it is less likely, he said.

As for whether the DITTO results nix further DHEA supplementation in poor responders, but leave the door open in normal responders, Dr. Jayaprakasan said, “I think there is no evidence to support its routine use in predicted poor or normal responders currently, and its use should be restricted to randomized controlled studies rather than a blanket approach.” The University of Nottingham supported the research. The authors reported having no relevant financial disclosures.

[email protected]

LISBON – Depression and emotional stress did not lead to poorer pregnancy outcomes 1 year after referral for recurrent pregnancy loss in a prospective, longitudinal study.

Among 287 women with recurrent pregnancy loss (RPL), 132 had a live birth or an ongoing pregnancy after 12 weeks gestation 1 year after referral to a tertiary RPL unit.

High scores on the PSS (Cohen Perceived Stress Scale) at referral were not associated with the chance of a subsequent live birth or ongoing pregnancy in unadjusted analysis (odds ratio, 1.012 ; 95% confidence interval 0.98-1.045) or after adjustment for maternal age and number of pregnancy losses prior to referral (OR, 1.015; CI 0.98-1.050).

Moderate to severe depression on the Major Depression Inventory (MDI) also was not associated with the chance of either outcome in unadjusted (OR, 2.12; CI 0.91-4.93) or adjusted (OR, 1.86; CI 0.78-4.42) analyses.

Patrice Wendling/Frontline Medical News

“We did not find an association between emotional distress at referral and the chance for a positive pregnancy outcome,” study author Dr. Astrid Marie Kolte said at the annual meeting of the European Society of Human Reproduction and Embryology.

It is well-known that pregnancy loss is a significant major life event that can invoke grief similar to that after a neonatal death. Studies have also shown that depression and stress are highly prominent among women with RPL.

In a recent study by Dr. Kolte and her associates, moderate to severe depression was identified in 8.6% and high stress levels in 41.2% of 301 women with three or more pregnancy losses before 12 weeks gestation, compared with rates of 2.2% and 23.2%, respectively, among 1,813 women without RPL (Hum. Reprod. 2015;30:777-782).Other groups have found significantly higher prevalence rates of moderate to severe depression in RPL patients, in the range of 15% to 33%, Dr. Kolte of the RPL Unit, Copenhagen University Hospital Rigshospitalet, said.

Data are scarce and results mixed, however, on the impact of depression and stress on subsequent live birth rates, prompting the investigators to examine pregnancy outcomes among the 301 previously studied women.

A total of 185 participants completed a follow-up questionnaire at 1 year containing the same PSS and MDI filled out a referral, along with questions about their pregnancy. Reliable data was available for 102 pregnancies among the 116 nonrespondents, resulting in 287 patients in the current analysis.

Among these women, 82 had given birth to a live child within the first year after referral, 50 had an ongoing pregnancy after 12 weeks’ gestation, and 11 were pregnant at less than 12 weeks’ gestation.

Interestingly, women with a live birth or ongoing pregnancy after 12 weeks’ gestation had significantly lower MDI (13.59 vs. 10.12) and PSS (16.94 vs. 12.47) scores on follow-up. This was not the case for patients without a positive pregnancy outcome for either the MDI (12.65 vs. 12.92) or PSS (16.86 vs. 15.49), Dr. Kolte said.

She noted that the study may have been insufficiently powered because of the low prevalence (8.6%) of major depression at referral and remarkably similar perceived stress among patients with and without live births. However, the study used validated psychometric scales, had good obstetrical follow-up, and is by far the largest study of emotional stress and live birth/ongoing pregnancy to date, she said.

Dr. Kolte expressed frustration at providing the best care for these patients, observing that there is a severe lack of understanding of the pathophysiology of recurrent pregnancy loss and no evidence-based treatment for the majority of RPL patients.

“You can indeed discuss whether a cumulative live birth rate of 70% on average is a good prognosis, but this is still a distressing event for these patients and their partners,” she said.

All newly referred patients and their partners are now being screened for major depression and perceived stress in the Danish RPL Unit, but providers do not have the means to treat those patients with psychological morbidities and must refer them back to their general physician.

“In my opinion, this is an understudied and underprioritized area in early pregnancy management, at least in Denmark,” Dr. Kolte said.

Several attendees echoed this frustration and asked Dr. Kolte for advice. While not all women will need psychological medication, having a psychologist associated with a RPL program is essential, as is a good working relationship with a psychiatrist, she replied.

University Hospital Copenhagen Rigshospitalet funded the study. Dr. Kolte reported having no financial disclosures.

[email protected]

LISBON – Depression and emotional stress did not lead to poorer pregnancy outcomes 1 year after referral for recurrent pregnancy loss in a prospective, longitudinal study.

Among 287 women with recurrent pregnancy loss (RPL), 132 had a live birth or an ongoing pregnancy after 12 weeks gestation 1 year after referral to a tertiary RPL unit.

High scores on the PSS (Cohen Perceived Stress Scale) at referral were not associated with the chance of a subsequent live birth or ongoing pregnancy in unadjusted analysis (odds ratio, 1.012 ; 95% confidence interval 0.98-1.045) or after adjustment for maternal age and number of pregnancy losses prior to referral (OR, 1.015; CI 0.98-1.050).

Moderate to severe depression on the Major Depression Inventory (MDI) also was not associated with the chance of either outcome in unadjusted (OR, 2.12; CI 0.91-4.93) or adjusted (OR, 1.86; CI 0.78-4.42) analyses.

Patrice Wendling/Frontline Medical News

“We did not find an association between emotional distress at referral and the chance for a positive pregnancy outcome,” study author Dr. Astrid Marie Kolte said at the annual meeting of the European Society of Human Reproduction and Embryology.

It is well-known that pregnancy loss is a significant major life event that can invoke grief similar to that after a neonatal death. Studies have also shown that depression and stress are highly prominent among women with RPL.

In a recent study by Dr. Kolte and her associates, moderate to severe depression was identified in 8.6% and high stress levels in 41.2% of 301 women with three or more pregnancy losses before 12 weeks gestation, compared with rates of 2.2% and 23.2%, respectively, among 1,813 women without RPL (Hum. Reprod. 2015;30:777-782).Other groups have found significantly higher prevalence rates of moderate to severe depression in RPL patients, in the range of 15% to 33%, Dr. Kolte of the RPL Unit, Copenhagen University Hospital Rigshospitalet, said.

Data are scarce and results mixed, however, on the impact of depression and stress on subsequent live birth rates, prompting the investigators to examine pregnancy outcomes among the 301 previously studied women.

A total of 185 participants completed a follow-up questionnaire at 1 year containing the same PSS and MDI filled out a referral, along with questions about their pregnancy. Reliable data was available for 102 pregnancies among the 116 nonrespondents, resulting in 287 patients in the current analysis.

Among these women, 82 had given birth to a live child within the first year after referral, 50 had an ongoing pregnancy after 12 weeks’ gestation, and 11 were pregnant at less than 12 weeks’ gestation.

Interestingly, women with a live birth or ongoing pregnancy after 12 weeks’ gestation had significantly lower MDI (13.59 vs. 10.12) and PSS (16.94 vs. 12.47) scores on follow-up. This was not the case for patients without a positive pregnancy outcome for either the MDI (12.65 vs. 12.92) or PSS (16.86 vs. 15.49), Dr. Kolte said.

She noted that the study may have been insufficiently powered because of the low prevalence (8.6%) of major depression at referral and remarkably similar perceived stress among patients with and without live births. However, the study used validated psychometric scales, had good obstetrical follow-up, and is by far the largest study of emotional stress and live birth/ongoing pregnancy to date, she said.

Dr. Kolte expressed frustration at providing the best care for these patients, observing that there is a severe lack of understanding of the pathophysiology of recurrent pregnancy loss and no evidence-based treatment for the majority of RPL patients.

“You can indeed discuss whether a cumulative live birth rate of 70% on average is a good prognosis, but this is still a distressing event for these patients and their partners,” she said.

All newly referred patients and their partners are now being screened for major depression and perceived stress in the Danish RPL Unit, but providers do not have the means to treat those patients with psychological morbidities and must refer them back to their general physician.

“In my opinion, this is an understudied and underprioritized area in early pregnancy management, at least in Denmark,” Dr. Kolte said.

Several attendees echoed this frustration and asked Dr. Kolte for advice. While not all women will need psychological medication, having a psychologist associated with a RPL program is essential, as is a good working relationship with a psychiatrist, she replied.

University Hospital Copenhagen Rigshospitalet funded the study. Dr. Kolte reported having no financial disclosures.

[email protected]

LISBON – Depression and emotional stress did not lead to poorer pregnancy outcomes 1 year after referral for recurrent pregnancy loss in a prospective, longitudinal study.

Among 287 women with recurrent pregnancy loss (RPL), 132 had a live birth or an ongoing pregnancy after 12 weeks gestation 1 year after referral to a tertiary RPL unit.

High scores on the PSS (Cohen Perceived Stress Scale) at referral were not associated with the chance of a subsequent live birth or ongoing pregnancy in unadjusted analysis (odds ratio, 1.012 ; 95% confidence interval 0.98-1.045) or after adjustment for maternal age and number of pregnancy losses prior to referral (OR, 1.015; CI 0.98-1.050).

Moderate to severe depression on the Major Depression Inventory (MDI) also was not associated with the chance of either outcome in unadjusted (OR, 2.12; CI 0.91-4.93) or adjusted (OR, 1.86; CI 0.78-4.42) analyses.

Patrice Wendling/Frontline Medical News

“We did not find an association between emotional distress at referral and the chance for a positive pregnancy outcome,” study author Dr. Astrid Marie Kolte said at the annual meeting of the European Society of Human Reproduction and Embryology.

It is well-known that pregnancy loss is a significant major life event that can invoke grief similar to that after a neonatal death. Studies have also shown that depression and stress are highly prominent among women with RPL.

In a recent study by Dr. Kolte and her associates, moderate to severe depression was identified in 8.6% and high stress levels in 41.2% of 301 women with three or more pregnancy losses before 12 weeks gestation, compared with rates of 2.2% and 23.2%, respectively, among 1,813 women without RPL (Hum. Reprod. 2015;30:777-782).Other groups have found significantly higher prevalence rates of moderate to severe depression in RPL patients, in the range of 15% to 33%, Dr. Kolte of the RPL Unit, Copenhagen University Hospital Rigshospitalet, said.

Data are scarce and results mixed, however, on the impact of depression and stress on subsequent live birth rates, prompting the investigators to examine pregnancy outcomes among the 301 previously studied women.

A total of 185 participants completed a follow-up questionnaire at 1 year containing the same PSS and MDI filled out a referral, along with questions about their pregnancy. Reliable data was available for 102 pregnancies among the 116 nonrespondents, resulting in 287 patients in the current analysis.

Among these women, 82 had given birth to a live child within the first year after referral, 50 had an ongoing pregnancy after 12 weeks’ gestation, and 11 were pregnant at less than 12 weeks’ gestation.

Interestingly, women with a live birth or ongoing pregnancy after 12 weeks’ gestation had significantly lower MDI (13.59 vs. 10.12) and PSS (16.94 vs. 12.47) scores on follow-up. This was not the case for patients without a positive pregnancy outcome for either the MDI (12.65 vs. 12.92) or PSS (16.86 vs. 15.49), Dr. Kolte said.

She noted that the study may have been insufficiently powered because of the low prevalence (8.6%) of major depression at referral and remarkably similar perceived stress among patients with and without live births. However, the study used validated psychometric scales, had good obstetrical follow-up, and is by far the largest study of emotional stress and live birth/ongoing pregnancy to date, she said.

Dr. Kolte expressed frustration at providing the best care for these patients, observing that there is a severe lack of understanding of the pathophysiology of recurrent pregnancy loss and no evidence-based treatment for the majority of RPL patients.

“You can indeed discuss whether a cumulative live birth rate of 70% on average is a good prognosis, but this is still a distressing event for these patients and their partners,” she said.

All newly referred patients and their partners are now being screened for major depression and perceived stress in the Danish RPL Unit, but providers do not have the means to treat those patients with psychological morbidities and must refer them back to their general physician.

“In my opinion, this is an understudied and underprioritized area in early pregnancy management, at least in Denmark,” Dr. Kolte said.

Several attendees echoed this frustration and asked Dr. Kolte for advice. While not all women will need psychological medication, having a psychologist associated with a RPL program is essential, as is a good working relationship with a psychiatrist, she replied.

University Hospital Copenhagen Rigshospitalet funded the study. Dr. Kolte reported having no financial disclosures.

[email protected]

LISBON – A large observational study found no increased risk of preterm birth or low birth weight following in vitro fertilization within acceptable limits of ovarian stimulation compared with unstimulated IVF.

“These findings support that ovarian stimulation is safe for maximizing live birth rates when you use acceptable limits of ovarian stimulation such as less than 20 oocytes,” Dr. Sesh Kamal Sunkara said at the annual meeting of the European Society of Human Reproduction and Embryology.

Epigenetic modifications resulting from ovarian stimulation or embryo culture are under increasing scrutiny as possible contributory factors to adverse perinatal outcomes.

A recent analysis of almost 66,000 singleton births by Dr. Sunkara and her associates showed a significantly higher risk of preterm birth (PTB) and low birth weight (LBW) in women with an excessive response (> 20 oocytes) to ovarian stimulation versus those with a normal response (10-15 oocytes) (Hum. Reprod. 2015; 30:1473-80).

A 2013 systematic review and meta-analysis also identified a higher risk of PTB and early PTB among singletons born after blastocyst- versus cleavage-stage embryo transfer in IVF (Fertil. Steril. 2013; 100: 1615-21.e10).

Both of these confounding factors were taken into account in the current analysis, reported Dr. Sunkara, of Aberdeen Fertility Centre, Aberdeen Maternity Hospital, University of Aberdeen, Scotland.

Using the Human Fertilisation and Embryology Authority database, which includes data for all IVF cycles performed in the United Kingdom from 1991 to 2012, the investigators examined 719,220 fresh IVF stimulated cycles and 135,570 fresh IVF unstimulated cycles, resulting in 105,374 and 10,668 singleton live births, respectively. Surprisingly, most women in either group were aged 18-34 years at the time of treatment, Dr. Sunkara said.

A large proportion of the unstimulated cycles did not have any oocytes retrieved compared with the stimulated group (41.7% vs. ~7%).

The overall birth rate per cycle was significantly higher with stimulation than without stimulation (19.4% vs. 8%), as was the multiple birth rate (24.4% vs. 2.1%), she said.

In the unadjusted analyses, the stimulated versus unstimulated group had significantly higher rates of PTB (9.2% vs. 5.5%; odds ratio, 1.72; 95% confidence interval 1.58-1.88), early PTB (1.7% vs. 0.7%; OR, 2.36; CI, 1.88-2.96), LBW (9.3% vs. 5.1%; OR, 1.91; CI, 1.75-2.09), and very LBW (1.8% vs. 0.8%; OR, 2.23; CI, 1.80-2.77).

No significant differences were observed, however, for each outcome between stimulated and unstimulated cycles following logistic regression and adjustment for maternal age, year of treatment, previous IVF cycles, previous live birth, number of oocytes retrieved (≤ 20 or > 20), and day of embryo transfer (cleavage or blastocyst stage), Dr. Sunkara said.

The adjusted odds ratios were: PTB (aOR, 1.04; C.I. 0.60-1.80), early PTB (aOR, 1.60; C.I. 0.51-5.01), LBW (aOR, 1.93; C.I. 0.95-3.94), and very LBW (aOR, 1.01; C.I. 0.55-4.22).

“The results demonstrated that safe stimulation within acceptable limits does not increase the risk of PTB and LBW,” she said.

Dr. Sunkara reported no having no financial conflicts.

[email protected]

LISBON – A large observational study found no increased risk of preterm birth or low birth weight following in vitro fertilization within acceptable limits of ovarian stimulation compared with unstimulated IVF.

“These findings support that ovarian stimulation is safe for maximizing live birth rates when you use acceptable limits of ovarian stimulation such as less than 20 oocytes,” Dr. Sesh Kamal Sunkara said at the annual meeting of the European Society of Human Reproduction and Embryology.

Epigenetic modifications resulting from ovarian stimulation or embryo culture are under increasing scrutiny as possible contributory factors to adverse perinatal outcomes.

A recent analysis of almost 66,000 singleton births by Dr. Sunkara and her associates showed a significantly higher risk of preterm birth (PTB) and low birth weight (LBW) in women with an excessive response (> 20 oocytes) to ovarian stimulation versus those with a normal response (10-15 oocytes) (Hum. Reprod. 2015; 30:1473-80).

A 2013 systematic review and meta-analysis also identified a higher risk of PTB and early PTB among singletons born after blastocyst- versus cleavage-stage embryo transfer in IVF (Fertil. Steril. 2013; 100: 1615-21.e10).

Both of these confounding factors were taken into account in the current analysis, reported Dr. Sunkara, of Aberdeen Fertility Centre, Aberdeen Maternity Hospital, University of Aberdeen, Scotland.

Using the Human Fertilisation and Embryology Authority database, which includes data for all IVF cycles performed in the United Kingdom from 1991 to 2012, the investigators examined 719,220 fresh IVF stimulated cycles and 135,570 fresh IVF unstimulated cycles, resulting in 105,374 and 10,668 singleton live births, respectively. Surprisingly, most women in either group were aged 18-34 years at the time of treatment, Dr. Sunkara said.

A large proportion of the unstimulated cycles did not have any oocytes retrieved compared with the stimulated group (41.7% vs. ~7%).

The overall birth rate per cycle was significantly higher with stimulation than without stimulation (19.4% vs. 8%), as was the multiple birth rate (24.4% vs. 2.1%), she said.

In the unadjusted analyses, the stimulated versus unstimulated group had significantly higher rates of PTB (9.2% vs. 5.5%; odds ratio, 1.72; 95% confidence interval 1.58-1.88), early PTB (1.7% vs. 0.7%; OR, 2.36; CI, 1.88-2.96), LBW (9.3% vs. 5.1%; OR, 1.91; CI, 1.75-2.09), and very LBW (1.8% vs. 0.8%; OR, 2.23; CI, 1.80-2.77).

No significant differences were observed, however, for each outcome between stimulated and unstimulated cycles following logistic regression and adjustment for maternal age, year of treatment, previous IVF cycles, previous live birth, number of oocytes retrieved (≤ 20 or > 20), and day of embryo transfer (cleavage or blastocyst stage), Dr. Sunkara said.

The adjusted odds ratios were: PTB (aOR, 1.04; C.I. 0.60-1.80), early PTB (aOR, 1.60; C.I. 0.51-5.01), LBW (aOR, 1.93; C.I. 0.95-3.94), and very LBW (aOR, 1.01; C.I. 0.55-4.22).

“The results demonstrated that safe stimulation within acceptable limits does not increase the risk of PTB and LBW,” she said.

Dr. Sunkara reported no having no financial conflicts.

[email protected]

LISBON – A large observational study found no increased risk of preterm birth or low birth weight following in vitro fertilization within acceptable limits of ovarian stimulation compared with unstimulated IVF.

“These findings support that ovarian stimulation is safe for maximizing live birth rates when you use acceptable limits of ovarian stimulation such as less than 20 oocytes,” Dr. Sesh Kamal Sunkara said at the annual meeting of the European Society of Human Reproduction and Embryology.

Epigenetic modifications resulting from ovarian stimulation or embryo culture are under increasing scrutiny as possible contributory factors to adverse perinatal outcomes.

A recent analysis of almost 66,000 singleton births by Dr. Sunkara and her associates showed a significantly higher risk of preterm birth (PTB) and low birth weight (LBW) in women with an excessive response (> 20 oocytes) to ovarian stimulation versus those with a normal response (10-15 oocytes) (Hum. Reprod. 2015; 30:1473-80).

A 2013 systematic review and meta-analysis also identified a higher risk of PTB and early PTB among singletons born after blastocyst- versus cleavage-stage embryo transfer in IVF (Fertil. Steril. 2013; 100: 1615-21.e10).

Both of these confounding factors were taken into account in the current analysis, reported Dr. Sunkara, of Aberdeen Fertility Centre, Aberdeen Maternity Hospital, University of Aberdeen, Scotland.

Using the Human Fertilisation and Embryology Authority database, which includes data for all IVF cycles performed in the United Kingdom from 1991 to 2012, the investigators examined 719,220 fresh IVF stimulated cycles and 135,570 fresh IVF unstimulated cycles, resulting in 105,374 and 10,668 singleton live births, respectively. Surprisingly, most women in either group were aged 18-34 years at the time of treatment, Dr. Sunkara said.

A large proportion of the unstimulated cycles did not have any oocytes retrieved compared with the stimulated group (41.7% vs. ~7%).

The overall birth rate per cycle was significantly higher with stimulation than without stimulation (19.4% vs. 8%), as was the multiple birth rate (24.4% vs. 2.1%), she said.

In the unadjusted analyses, the stimulated versus unstimulated group had significantly higher rates of PTB (9.2% vs. 5.5%; odds ratio, 1.72; 95% confidence interval 1.58-1.88), early PTB (1.7% vs. 0.7%; OR, 2.36; CI, 1.88-2.96), LBW (9.3% vs. 5.1%; OR, 1.91; CI, 1.75-2.09), and very LBW (1.8% vs. 0.8%; OR, 2.23; CI, 1.80-2.77).

No significant differences were observed, however, for each outcome between stimulated and unstimulated cycles following logistic regression and adjustment for maternal age, year of treatment, previous IVF cycles, previous live birth, number of oocytes retrieved (≤ 20 or > 20), and day of embryo transfer (cleavage or blastocyst stage), Dr. Sunkara said.

The adjusted odds ratios were: PTB (aOR, 1.04; C.I. 0.60-1.80), early PTB (aOR, 1.60; C.I. 0.51-5.01), LBW (aOR, 1.93; C.I. 0.95-3.94), and very LBW (aOR, 1.01; C.I. 0.55-4.22).

“The results demonstrated that safe stimulation within acceptable limits does not increase the risk of PTB and LBW,” she said.

Dr. Sunkara reported no having no financial conflicts.

[email protected]

LISBON – Dilation and curettage increases the risk for prematurity in subsequent pregnancy, according to a systematic review and meta-analysis of nearly 2 million women.

Overall, D&C for first-trimester miscarriage or pregnancy termination increased the risk for preterm birth (< 37 weeks) by 29% (Odds ratio, 1.29; 95% confidence interval 1.17-1.42).

Subgroup and sensitivity analyses performed to test the robustness of the finding showed D&C upped the risk for very preterm birth (< 32 weeks) by 69% (OR, 1.69; C.I. 1.20-2.38) and critical preterm birth (< 28 weeks) by 68% (OR, 1.68; C.I. 1.47-1.92).

Patrice Wendling/Frontline Medical News

A dose-response relationship was also identified, with multiple D&C procedures raising the risk of preterm birth even higher (OR, 1.74; C.I. 1.10-2.76), Dr. Marike Lemmers reported at the annual meeting of the European Society of Human Reproduction and Embryology.

“This really questions the use of dilation and curettage as first-line treatment for women with a miscarriage or termination of pregnancy since other treatment options are non-invasive, safe, well-tolerated, cheap, and accessible,” Dr. Lemmers, of the Academic Medical Center, Amsterdam, the Netherlands, said.

The increasing popularity of misoprostol as an alternative to D&C or for cervical priming prior to curettage would suggest that D&C use is declining. Still, gynecologists in the Netherlands treat half of all miscarriages with D&C, a figure that likely reflects practice elsewhere, Dr. Willem Ankum, the principal investigator, said during a press briefing.

The authors hypothesize that the mechanism behind the increased risk from D&C is that dilation may damage the cervix and affect cervical tightness or may damage the endometrial lining, leading to a malpresentation.

The systematic review and meta-analysis included 21 studies (7 prospective cohort studies, 11 retrospective cohort studies, and 3 case-control studies) involving 66,003 women with a history of D&C for first trimester miscarriage or termination, and 1,781,786 controls with a medically managed miscarriage or termination or no such events. The quality of the studies varied from 7 to 29 based on the Strobe score.

The primary outcome of risk of preterm birth was significantly increased with D&C regardless of whether the analysis relied only on the prospective studies (OR, 1.28; C.I. 1.01-1.60), retrospective studies (OR, 1.27; C.I. 1.12-1.45), or case-control studies (OR, 1.44; C.I. 1.18-1.77), Dr. Lemmers said.

Several audience members questioned the inclusion of older trials dating back to the late 1970s before prostoglandins had been introduced for cycle priming. One attendee cited a recent Scottish cohort study showing a declining preterm birth rate in women with previous miscarriage, possibly attributable to the increasing use of misoprostol (Cytotec) for miscarriage or termination and cervical priming before D&C (PLoS. Med. 2013; 10: e1001481 [doi:10.1371/journal.pmed.1001481]).

Dr. Lemmers was aware of the Scottish study and said a funnel plot they performed showed “the exact same results” between older and newer studies. Further, a subgroup analysis of 38,905 women from studies dating from 1999 forward also showed an increased risk of preterm birth with D&C versus medical treatment (OR, 1.19; C.I. 1.10-1.28).

She added that it’s unlikely that the use of hysteroscopy with minimal dilation before in-vitro fertilization impacted results, but that outcomes may differ between women with a miscarriage versus termination of an attached pregnancy, although this calculation wasn’t possible based on the available data.

ZonMw, a Dutch organization for health research and development, funded the study. Dr. Lemmers and Dr. Ankum reported having no financial conflicts.

[email protected]

On Twitter @pwendl

LISBON – Dilation and curettage increases the risk for prematurity in subsequent pregnancy, according to a systematic review and meta-analysis of nearly 2 million women.

Overall, D&C for first-trimester miscarriage or pregnancy termination increased the risk for preterm birth (< 37 weeks) by 29% (Odds ratio, 1.29; 95% confidence interval 1.17-1.42).

Subgroup and sensitivity analyses performed to test the robustness of the finding showed D&C upped the risk for very preterm birth (< 32 weeks) by 69% (OR, 1.69; C.I. 1.20-2.38) and critical preterm birth (< 28 weeks) by 68% (OR, 1.68; C.I. 1.47-1.92).

Patrice Wendling/Frontline Medical News

A dose-response relationship was also identified, with multiple D&C procedures raising the risk of preterm birth even higher (OR, 1.74; C.I. 1.10-2.76), Dr. Marike Lemmers reported at the annual meeting of the European Society of Human Reproduction and Embryology.

“This really questions the use of dilation and curettage as first-line treatment for women with a miscarriage or termination of pregnancy since other treatment options are non-invasive, safe, well-tolerated, cheap, and accessible,” Dr. Lemmers, of the Academic Medical Center, Amsterdam, the Netherlands, said.

The increasing popularity of misoprostol as an alternative to D&C or for cervical priming prior to curettage would suggest that D&C use is declining. Still, gynecologists in the Netherlands treat half of all miscarriages with D&C, a figure that likely reflects practice elsewhere, Dr. Willem Ankum, the principal investigator, said during a press briefing.

The authors hypothesize that the mechanism behind the increased risk from D&C is that dilation may damage the cervix and affect cervical tightness or may damage the endometrial lining, leading to a malpresentation.

The systematic review and meta-analysis included 21 studies (7 prospective cohort studies, 11 retrospective cohort studies, and 3 case-control studies) involving 66,003 women with a history of D&C for first trimester miscarriage or termination, and 1,781,786 controls with a medically managed miscarriage or termination or no such events. The quality of the studies varied from 7 to 29 based on the Strobe score.

The primary outcome of risk of preterm birth was significantly increased with D&C regardless of whether the analysis relied only on the prospective studies (OR, 1.28; C.I. 1.01-1.60), retrospective studies (OR, 1.27; C.I. 1.12-1.45), or case-control studies (OR, 1.44; C.I. 1.18-1.77), Dr. Lemmers said.

Several audience members questioned the inclusion of older trials dating back to the late 1970s before prostoglandins had been introduced for cycle priming. One attendee cited a recent Scottish cohort study showing a declining preterm birth rate in women with previous miscarriage, possibly attributable to the increasing use of misoprostol (Cytotec) for miscarriage or termination and cervical priming before D&C (PLoS. Med. 2013; 10: e1001481 [doi:10.1371/journal.pmed.1001481]).

Dr. Lemmers was aware of the Scottish study and said a funnel plot they performed showed “the exact same results” between older and newer studies. Further, a subgroup analysis of 38,905 women from studies dating from 1999 forward also showed an increased risk of preterm birth with D&C versus medical treatment (OR, 1.19; C.I. 1.10-1.28).

She added that it’s unlikely that the use of hysteroscopy with minimal dilation before in-vitro fertilization impacted results, but that outcomes may differ between women with a miscarriage versus termination of an attached pregnancy, although this calculation wasn’t possible based on the available data.

ZonMw, a Dutch organization for health research and development, funded the study. Dr. Lemmers and Dr. Ankum reported having no financial conflicts.

[email protected]

On Twitter @pwendl

LISBON – Dilation and curettage increases the risk for prematurity in subsequent pregnancy, according to a systematic review and meta-analysis of nearly 2 million women.

Overall, D&C for first-trimester miscarriage or pregnancy termination increased the risk for preterm birth (< 37 weeks) by 29% (Odds ratio, 1.29; 95% confidence interval 1.17-1.42).

Subgroup and sensitivity analyses performed to test the robustness of the finding showed D&C upped the risk for very preterm birth (< 32 weeks) by 69% (OR, 1.69; C.I. 1.20-2.38) and critical preterm birth (< 28 weeks) by 68% (OR, 1.68; C.I. 1.47-1.92).

Patrice Wendling/Frontline Medical News

A dose-response relationship was also identified, with multiple D&C procedures raising the risk of preterm birth even higher (OR, 1.74; C.I. 1.10-2.76), Dr. Marike Lemmers reported at the annual meeting of the European Society of Human Reproduction and Embryology.

“This really questions the use of dilation and curettage as first-line treatment for women with a miscarriage or termination of pregnancy since other treatment options are non-invasive, safe, well-tolerated, cheap, and accessible,” Dr. Lemmers, of the Academic Medical Center, Amsterdam, the Netherlands, said.

The increasing popularity of misoprostol as an alternative to D&C or for cervical priming prior to curettage would suggest that D&C use is declining. Still, gynecologists in the Netherlands treat half of all miscarriages with D&C, a figure that likely reflects practice elsewhere, Dr. Willem Ankum, the principal investigator, said during a press briefing.

The authors hypothesize that the mechanism behind the increased risk from D&C is that dilation may damage the cervix and affect cervical tightness or may damage the endometrial lining, leading to a malpresentation.

The systematic review and meta-analysis included 21 studies (7 prospective cohort studies, 11 retrospective cohort studies, and 3 case-control studies) involving 66,003 women with a history of D&C for first trimester miscarriage or termination, and 1,781,786 controls with a medically managed miscarriage or termination or no such events. The quality of the studies varied from 7 to 29 based on the Strobe score.

The primary outcome of risk of preterm birth was significantly increased with D&C regardless of whether the analysis relied only on the prospective studies (OR, 1.28; C.I. 1.01-1.60), retrospective studies (OR, 1.27; C.I. 1.12-1.45), or case-control studies (OR, 1.44; C.I. 1.18-1.77), Dr. Lemmers said.

Several audience members questioned the inclusion of older trials dating back to the late 1970s before prostoglandins had been introduced for cycle priming. One attendee cited a recent Scottish cohort study showing a declining preterm birth rate in women with previous miscarriage, possibly attributable to the increasing use of misoprostol (Cytotec) for miscarriage or termination and cervical priming before D&C (PLoS. Med. 2013; 10: e1001481 [doi:10.1371/journal.pmed.1001481]).

Dr. Lemmers was aware of the Scottish study and said a funnel plot they performed showed “the exact same results” between older and newer studies. Further, a subgroup analysis of 38,905 women from studies dating from 1999 forward also showed an increased risk of preterm birth with D&C versus medical treatment (OR, 1.19; C.I. 1.10-1.28).

She added that it’s unlikely that the use of hysteroscopy with minimal dilation before in-vitro fertilization impacted results, but that outcomes may differ between women with a miscarriage versus termination of an attached pregnancy, although this calculation wasn’t possible based on the available data.

ZonMw, a Dutch organization for health research and development, funded the study. Dr. Lemmers and Dr. Ankum reported having no financial conflicts.

[email protected]

On Twitter @pwendl

LISBON – Expectant management is a safe and effective treatment for incomplete miscarriage after misoprostol, results of the MisoREST trial show.

“Because it is non-invasive, we think it should be considered as first-line treatment and to reserve curettage only for specific patients,” Dr. Marianne Verschoor said at the annual meeting of the European Society of Human Reproduction and Embryology.

Patrice Wendling/Frontline Medical News

Misoprostol (Cytotec) is an inexpensive and effective treatment for miscarriage, but about 30% of women are left with an incomplete evacuation of the uterus. Curettage is often performed in these typically asymptomatic women, but carries both short- and long-term risks, said Dr. Verschoor of the Academic Medical Center, Amsterdam.

No study had directly compared the effectiveness of curettage and expectant management, she said. To fill this void, the researchers performed a randomized controlled trial (RCT) and parallel observational cohort study at 27 community and academic hospitals. Women who had sonographic findings of intrauterine remnants and/or a thick endometrium (> 10 mm) 1-2 weeks after misoprostol treatment for first-trimester miscarriage were randomly assigned to curettage within 3 days of diagnosis or expectant management. Women who declined randomization were prospectively followed.

The primary outcome was sonographic evidence of an empty uterine cavity at 6 weeks or an uneventful clinical course at 3 months in the absence of sonography.

Because of strong preferences for expectant management (EM), 59 women were randomized in the RCT (30 curettage, 29 EM) and 197 women were followed prospectively (65 curettage, 132 EM). All groups were comparable at baseline with regard to age, gestational age, and previous miscarriage or curettage.

In the RCT, 93% of women had an empty cavity or uneventful clinical course with curettage vs. 76% with EM. This difference was not statistically significant (relative risk, 1.23; 95% confidence interval, 0.098-1.54), Dr. Verschoor said.

In the observational cohort, 95% of patients choosing curettage had a successful outcome vs. 83% choosing EM. This difference was statistically significant (RR, 1.14; CI, 1.04-1.26).

When the two populations were pooled, 95% of patients (90/95) treated with curettage reached the primary end point vs. 82% of patients (132/161) with EM, which was statistically different (RR, 1.16; CI, 1.06-1.26), she said.

There were no significant differences in secondary outcomes in the RCT between the curettage and EM groups, including intrauterine infection (each 1 patient), excessive blood loss defined as > 500 mL (1 patient vs. 2 patients), or duration of bleeding (mean 5.4 days vs. 5.5 days).

However, one patient had already developed Asherman syndrome in the curettage group within 3 months of follow-up, Dr. Verschoor said. Two patients in each arm underwent reintervention with hysteroscopy and 5 EM patients underwent curettage.

Secondary outcomes in the observational cohort were also comparable between the curettage and EM groups for intrauterine infection (3 vs. 2), excessive blood loss (0 vs. 1), and duration of bleeding (mean 5.7 days vs. 7.1 days). One patient who underwent curettage developed Asherman syndrome vs. none in the EM group, she said. There were 11 reinterventions in the curettage group (7 hysteroscopy, 4 recurettage), compared with 30 in the EM group (12 hysteroscopy, 18 curettage).

A closer look at the EM patients who underwent reintervention revealed that “the interventions were primarily elective,” Dr. Vershcoor said. “Only in 26% of cases was there a medical reason for performing the intervention like bleeding, fever, or excessive abdominal pain.” Histology performed in these patients found no pregnancy tissue in 46%.

A separate quality of life analysis of the MisoREST participants found no statistical differences at baseline, 2, 4, and 12 weeks for the Short Form 36 Health Survey mental and physical score in all four treatment arms. Anxiety and depression measured with the Hospital Anxiety and Depression Scale were also not statistically different at any time, study coauthor Dr. Marike Lemmers, also of the Academic Medical Center, Amsterdam, reported in a poster at the meeting.

ZonMw, a Dutch organization for health research and development, funded the study. Dr. Verschoor reported having no financial conflicts.

[email protected]

On Twitter @pwendl

LISBON – Expectant management is a safe and effective treatment for incomplete miscarriage after misoprostol, results of the MisoREST trial show.

“Because it is non-invasive, we think it should be considered as first-line treatment and to reserve curettage only for specific patients,” Dr. Marianne Verschoor said at the annual meeting of the European Society of Human Reproduction and Embryology.

Patrice Wendling/Frontline Medical News

Misoprostol (Cytotec) is an inexpensive and effective treatment for miscarriage, but about 30% of women are left with an incomplete evacuation of the uterus. Curettage is often performed in these typically asymptomatic women, but carries both short- and long-term risks, said Dr. Verschoor of the Academic Medical Center, Amsterdam.

No study had directly compared the effectiveness of curettage and expectant management, she said. To fill this void, the researchers performed a randomized controlled trial (RCT) and parallel observational cohort study at 27 community and academic hospitals. Women who had sonographic findings of intrauterine remnants and/or a thick endometrium (> 10 mm) 1-2 weeks after misoprostol treatment for first-trimester miscarriage were randomly assigned to curettage within 3 days of diagnosis or expectant management. Women who declined randomization were prospectively followed.

The primary outcome was sonographic evidence of an empty uterine cavity at 6 weeks or an uneventful clinical course at 3 months in the absence of sonography.

Because of strong preferences for expectant management (EM), 59 women were randomized in the RCT (30 curettage, 29 EM) and 197 women were followed prospectively (65 curettage, 132 EM). All groups were comparable at baseline with regard to age, gestational age, and previous miscarriage or curettage.

In the RCT, 93% of women had an empty cavity or uneventful clinical course with curettage vs. 76% with EM. This difference was not statistically significant (relative risk, 1.23; 95% confidence interval, 0.098-1.54), Dr. Verschoor said.

In the observational cohort, 95% of patients choosing curettage had a successful outcome vs. 83% choosing EM. This difference was statistically significant (RR, 1.14; CI, 1.04-1.26).

When the two populations were pooled, 95% of patients (90/95) treated with curettage reached the primary end point vs. 82% of patients (132/161) with EM, which was statistically different (RR, 1.16; CI, 1.06-1.26), she said.

There were no significant differences in secondary outcomes in the RCT between the curettage and EM groups, including intrauterine infection (each 1 patient), excessive blood loss defined as > 500 mL (1 patient vs. 2 patients), or duration of bleeding (mean 5.4 days vs. 5.5 days).

However, one patient had already developed Asherman syndrome in the curettage group within 3 months of follow-up, Dr. Verschoor said. Two patients in each arm underwent reintervention with hysteroscopy and 5 EM patients underwent curettage.

Secondary outcomes in the observational cohort were also comparable between the curettage and EM groups for intrauterine infection (3 vs. 2), excessive blood loss (0 vs. 1), and duration of bleeding (mean 5.7 days vs. 7.1 days). One patient who underwent curettage developed Asherman syndrome vs. none in the EM group, she said. There were 11 reinterventions in the curettage group (7 hysteroscopy, 4 recurettage), compared with 30 in the EM group (12 hysteroscopy, 18 curettage).

A closer look at the EM patients who underwent reintervention revealed that “the interventions were primarily elective,” Dr. Vershcoor said. “Only in 26% of cases was there a medical reason for performing the intervention like bleeding, fever, or excessive abdominal pain.” Histology performed in these patients found no pregnancy tissue in 46%.

A separate quality of life analysis of the MisoREST participants found no statistical differences at baseline, 2, 4, and 12 weeks for the Short Form 36 Health Survey mental and physical score in all four treatment arms. Anxiety and depression measured with the Hospital Anxiety and Depression Scale were also not statistically different at any time, study coauthor Dr. Marike Lemmers, also of the Academic Medical Center, Amsterdam, reported in a poster at the meeting.

ZonMw, a Dutch organization for health research and development, funded the study. Dr. Verschoor reported having no financial conflicts.

[email protected]

On Twitter @pwendl

LISBON – Expectant management is a safe and effective treatment for incomplete miscarriage after misoprostol, results of the MisoREST trial show.

“Because it is non-invasive, we think it should be considered as first-line treatment and to reserve curettage only for specific patients,” Dr. Marianne Verschoor said at the annual meeting of the European Society of Human Reproduction and Embryology.

Patrice Wendling/Frontline Medical News

Misoprostol (Cytotec) is an inexpensive and effective treatment for miscarriage, but about 30% of women are left with an incomplete evacuation of the uterus. Curettage is often performed in these typically asymptomatic women, but carries both short- and long-term risks, said Dr. Verschoor of the Academic Medical Center, Amsterdam.

No study had directly compared the effectiveness of curettage and expectant management, she said. To fill this void, the researchers performed a randomized controlled trial (RCT) and parallel observational cohort study at 27 community and academic hospitals. Women who had sonographic findings of intrauterine remnants and/or a thick endometrium (> 10 mm) 1-2 weeks after misoprostol treatment for first-trimester miscarriage were randomly assigned to curettage within 3 days of diagnosis or expectant management. Women who declined randomization were prospectively followed.

The primary outcome was sonographic evidence of an empty uterine cavity at 6 weeks or an uneventful clinical course at 3 months in the absence of sonography.

Because of strong preferences for expectant management (EM), 59 women were randomized in the RCT (30 curettage, 29 EM) and 197 women were followed prospectively (65 curettage, 132 EM). All groups were comparable at baseline with regard to age, gestational age, and previous miscarriage or curettage.

In the RCT, 93% of women had an empty cavity or uneventful clinical course with curettage vs. 76% with EM. This difference was not statistically significant (relative risk, 1.23; 95% confidence interval, 0.098-1.54), Dr. Verschoor said.

In the observational cohort, 95% of patients choosing curettage had a successful outcome vs. 83% choosing EM. This difference was statistically significant (RR, 1.14; CI, 1.04-1.26).

When the two populations were pooled, 95% of patients (90/95) treated with curettage reached the primary end point vs. 82% of patients (132/161) with EM, which was statistically different (RR, 1.16; CI, 1.06-1.26), she said.

There were no significant differences in secondary outcomes in the RCT between the curettage and EM groups, including intrauterine infection (each 1 patient), excessive blood loss defined as > 500 mL (1 patient vs. 2 patients), or duration of bleeding (mean 5.4 days vs. 5.5 days).

However, one patient had already developed Asherman syndrome in the curettage group within 3 months of follow-up, Dr. Verschoor said. Two patients in each arm underwent reintervention with hysteroscopy and 5 EM patients underwent curettage.

Secondary outcomes in the observational cohort were also comparable between the curettage and EM groups for intrauterine infection (3 vs. 2), excessive blood loss (0 vs. 1), and duration of bleeding (mean 5.7 days vs. 7.1 days). One patient who underwent curettage developed Asherman syndrome vs. none in the EM group, she said. There were 11 reinterventions in the curettage group (7 hysteroscopy, 4 recurettage), compared with 30 in the EM group (12 hysteroscopy, 18 curettage).

A closer look at the EM patients who underwent reintervention revealed that “the interventions were primarily elective,” Dr. Vershcoor said. “Only in 26% of cases was there a medical reason for performing the intervention like bleeding, fever, or excessive abdominal pain.” Histology performed in these patients found no pregnancy tissue in 46%.

A separate quality of life analysis of the MisoREST participants found no statistical differences at baseline, 2, 4, and 12 weeks for the Short Form 36 Health Survey mental and physical score in all four treatment arms. Anxiety and depression measured with the Hospital Anxiety and Depression Scale were also not statistically different at any time, study coauthor Dr. Marike Lemmers, also of the Academic Medical Center, Amsterdam, reported in a poster at the meeting.

ZonMw, a Dutch organization for health research and development, funded the study. Dr. Verschoor reported having no financial conflicts.

[email protected]

On Twitter @pwendl

LISBON – Advanced age appears to trump disease activity or antirheumatic drug treatment as the driving force behind miscarriage in women with rheumatoid arthritis.

“The risk for miscarriage in rheumatoid arthritis is age dependent,” Dr. Jenny Brouwer said at the annual meeting of the European Society of Human Reproduction and Embryology.

Patrice Wendling/Frontline Medical News

She reported on 162 evaluable pregnancies in 239 Dutch women enrolled during 2002-2010 in the nationwide Pregnancy-Induced Amelioration of Rheumatoid Arthritis (PARA) study, the world’s largest prospective cohort of pregnant RA patients. They had a mean age of 32.3 years and a mean RA duration of 4.9 years. Overall, 49.4% were nulliparous and 13.6% had suffered a previous miscarriage.

Prednisone (37%), sulfasalazine (33%), and NSAIDs (29%) were most commonly used in the periconceptional period. Women eligible for PARA had to have stopped methotrexate for at least 3 months prior to attempting to conceive, a parameter included because it is an indicator for more severe disease.

Varying reports have shown no increased miscarriage rate in women with RA, while others have reported a significantly higher risk. These studies, however, were cross-sectional or retrospective in nature and lacked detailed information on preconception disease activity and antirheumatic drug use, observed Dr. Brouwer of Erasmus Medical Center, Rotterdam, the Netherlands.

Among the 162 pregnancies, 28 miscarriages occurred (17.3%), roughly half in weeks 5-9.

Reassuringly, the miscarriage rate is comparable with that in the general population, she said. Indeed, a recent study from the Nurses Health Study II also reported a miscarriage rate of 17.3%.

Disease Activity Score based on 28 joints (DAS28) was higher 6 and 12 weeks after miscarriage than before pregnancy, with 33% of women having a disease flare after miscarriage.

“This can be a sign that women who have more active disease have a higher risk for miscarriage and should be monitored more closely when their disease activity in the preconceptional period increases,” Dr. Brouwer said.

Women who miscarried were significantly older than were women with an ongoing pregnancy (mean 33.9 years vs. 32 years; P = .022). They also were more likely to be positive for anti-citrullinated protein antibodies (ACPA) (82% vs. 60%; P = .058), have higher DAS28 scores (3.92 vs. 3.59; P = .166), and have used methotrexate in the past (82% vs. 68%; P = .174).

No significant association was observed between miscarriage and corticosteroids, anti-inflammatories, or biological therapies, she said.

Because of the low frequency of miscarriages in the study, logistic regression showed only a trend toward higher miscarriage risk in association with increasing age (OR, 1.12; P = .065 per year of age increase) and ACPA positivity (OR, 2.47; P = .092), Dr. Brouwer said.

“Since the confidence interval is 0.99-1.25, there clearly seems to be a trend toward a higher risk for occurrence of miscarriage with increasing age, which is only logical since in the general population we also see an increase in miscarriage rate with increasing age,” she said in an interview. “My expectation is that, in a larger RA cohort, with a larger absolute number of miscarriages, the association will be significant.”

Follow-up revealed that, within 1 year of miscarriage, 68% of women became pregnant again, 14% stopped trying to conceive, and 11% were lost to follow-up. The live birth rate in the subsequent pregnancy was 90%. A follow-up study of these children did not find an increased rate of congenital malformations, despite the use of RA medications during pregnancy, Dr. Brouwer said.

The audience questioned whether the investigators are suggesting that rheumatoid arthritis has no role in miscarriage, observing that the study outcomes look very similar to patients without RA. Dr. Brouwer responded that there seems to be a higher sensitivity in patients with ACPA using methotrexate in the past but that this failed to reach significance.

“The results found in this study: some association with more severe disease – ACPA positivity and past methotrexate use – although not significant are a confirmation to us that extra care should be given to suppressing active disease already before actively trying to achieve a pregnancy,” she told this publication.

For more details, the full manuscript has been published (Arthritis Rheumatol. 2015;67:1738-43).

Reumafond, the Dutch Arthritis Foundation, funded the study. Dr. Brouwer reported no financial conflicts.

[email protected]

LISBON – Advanced age appears to trump disease activity or antirheumatic drug treatment as the driving force behind miscarriage in women with rheumatoid arthritis.

“The risk for miscarriage in rheumatoid arthritis is age dependent,” Dr. Jenny Brouwer said at the annual meeting of the European Society of Human Reproduction and Embryology.

Patrice Wendling/Frontline Medical News

She reported on 162 evaluable pregnancies in 239 Dutch women enrolled during 2002-2010 in the nationwide Pregnancy-Induced Amelioration of Rheumatoid Arthritis (PARA) study, the world’s largest prospective cohort of pregnant RA patients. They had a mean age of 32.3 years and a mean RA duration of 4.9 years. Overall, 49.4% were nulliparous and 13.6% had suffered a previous miscarriage.

Prednisone (37%), sulfasalazine (33%), and NSAIDs (29%) were most commonly used in the periconceptional period. Women eligible for PARA had to have stopped methotrexate for at least 3 months prior to attempting to conceive, a parameter included because it is an indicator for more severe disease.

Varying reports have shown no increased miscarriage rate in women with RA, while others have reported a significantly higher risk. These studies, however, were cross-sectional or retrospective in nature and lacked detailed information on preconception disease activity and antirheumatic drug use, observed Dr. Brouwer of Erasmus Medical Center, Rotterdam, the Netherlands.

Among the 162 pregnancies, 28 miscarriages occurred (17.3%), roughly half in weeks 5-9.

Reassuringly, the miscarriage rate is comparable with that in the general population, she said. Indeed, a recent study from the Nurses Health Study II also reported a miscarriage rate of 17.3%.

Disease Activity Score based on 28 joints (DAS28) was higher 6 and 12 weeks after miscarriage than before pregnancy, with 33% of women having a disease flare after miscarriage.

“This can be a sign that women who have more active disease have a higher risk for miscarriage and should be monitored more closely when their disease activity in the preconceptional period increases,” Dr. Brouwer said.

Women who miscarried were significantly older than were women with an ongoing pregnancy (mean 33.9 years vs. 32 years; P = .022). They also were more likely to be positive for anti-citrullinated protein antibodies (ACPA) (82% vs. 60%; P = .058), have higher DAS28 scores (3.92 vs. 3.59; P = .166), and have used methotrexate in the past (82% vs. 68%; P = .174).

No significant association was observed between miscarriage and corticosteroids, anti-inflammatories, or biological therapies, she said.

Because of the low frequency of miscarriages in the study, logistic regression showed only a trend toward higher miscarriage risk in association with increasing age (OR, 1.12; P = .065 per year of age increase) and ACPA positivity (OR, 2.47; P = .092), Dr. Brouwer said.

“Since the confidence interval is 0.99-1.25, there clearly seems to be a trend toward a higher risk for occurrence of miscarriage with increasing age, which is only logical since in the general population we also see an increase in miscarriage rate with increasing age,” she said in an interview. “My expectation is that, in a larger RA cohort, with a larger absolute number of miscarriages, the association will be significant.”

Follow-up revealed that, within 1 year of miscarriage, 68% of women became pregnant again, 14% stopped trying to conceive, and 11% were lost to follow-up. The live birth rate in the subsequent pregnancy was 90%. A follow-up study of these children did not find an increased rate of congenital malformations, despite the use of RA medications during pregnancy, Dr. Brouwer said.

The audience questioned whether the investigators are suggesting that rheumatoid arthritis has no role in miscarriage, observing that the study outcomes look very similar to patients without RA. Dr. Brouwer responded that there seems to be a higher sensitivity in patients with ACPA using methotrexate in the past but that this failed to reach significance.

“The results found in this study: some association with more severe disease – ACPA positivity and past methotrexate use – although not significant are a confirmation to us that extra care should be given to suppressing active disease already before actively trying to achieve a pregnancy,” she told this publication.

For more details, the full manuscript has been published (Arthritis Rheumatol. 2015;67:1738-43).

Reumafond, the Dutch Arthritis Foundation, funded the study. Dr. Brouwer reported no financial conflicts.

[email protected]

LISBON – Advanced age appears to trump disease activity or antirheumatic drug treatment as the driving force behind miscarriage in women with rheumatoid arthritis.

“The risk for miscarriage in rheumatoid arthritis is age dependent,” Dr. Jenny Brouwer said at the annual meeting of the European Society of Human Reproduction and Embryology.

Patrice Wendling/Frontline Medical News

She reported on 162 evaluable pregnancies in 239 Dutch women enrolled during 2002-2010 in the nationwide Pregnancy-Induced Amelioration of Rheumatoid Arthritis (PARA) study, the world’s largest prospective cohort of pregnant RA patients. They had a mean age of 32.3 years and a mean RA duration of 4.9 years. Overall, 49.4% were nulliparous and 13.6% had suffered a previous miscarriage.

Prednisone (37%), sulfasalazine (33%), and NSAIDs (29%) were most commonly used in the periconceptional period. Women eligible for PARA had to have stopped methotrexate for at least 3 months prior to attempting to conceive, a parameter included because it is an indicator for more severe disease.

Varying reports have shown no increased miscarriage rate in women with RA, while others have reported a significantly higher risk. These studies, however, were cross-sectional or retrospective in nature and lacked detailed information on preconception disease activity and antirheumatic drug use, observed Dr. Brouwer of Erasmus Medical Center, Rotterdam, the Netherlands.

Among the 162 pregnancies, 28 miscarriages occurred (17.3%), roughly half in weeks 5-9.

Reassuringly, the miscarriage rate is comparable with that in the general population, she said. Indeed, a recent study from the Nurses Health Study II also reported a miscarriage rate of 17.3%.

Disease Activity Score based on 28 joints (DAS28) was higher 6 and 12 weeks after miscarriage than before pregnancy, with 33% of women having a disease flare after miscarriage.

“This can be a sign that women who have more active disease have a higher risk for miscarriage and should be monitored more closely when their disease activity in the preconceptional period increases,” Dr. Brouwer said.

Women who miscarried were significantly older than were women with an ongoing pregnancy (mean 33.9 years vs. 32 years; P = .022). They also were more likely to be positive for anti-citrullinated protein antibodies (ACPA) (82% vs. 60%; P = .058), have higher DAS28 scores (3.92 vs. 3.59; P = .166), and have used methotrexate in the past (82% vs. 68%; P = .174).

No significant association was observed between miscarriage and corticosteroids, anti-inflammatories, or biological therapies, she said.

Because of the low frequency of miscarriages in the study, logistic regression showed only a trend toward higher miscarriage risk in association with increasing age (OR, 1.12; P = .065 per year of age increase) and ACPA positivity (OR, 2.47; P = .092), Dr. Brouwer said.

“Since the confidence interval is 0.99-1.25, there clearly seems to be a trend toward a higher risk for occurrence of miscarriage with increasing age, which is only logical since in the general population we also see an increase in miscarriage rate with increasing age,” she said in an interview. “My expectation is that, in a larger RA cohort, with a larger absolute number of miscarriages, the association will be significant.”

Follow-up revealed that, within 1 year of miscarriage, 68% of women became pregnant again, 14% stopped trying to conceive, and 11% were lost to follow-up. The live birth rate in the subsequent pregnancy was 90%. A follow-up study of these children did not find an increased rate of congenital malformations, despite the use of RA medications during pregnancy, Dr. Brouwer said.

The audience questioned whether the investigators are suggesting that rheumatoid arthritis has no role in miscarriage, observing that the study outcomes look very similar to patients without RA. Dr. Brouwer responded that there seems to be a higher sensitivity in patients with ACPA using methotrexate in the past but that this failed to reach significance.

“The results found in this study: some association with more severe disease – ACPA positivity and past methotrexate use – although not significant are a confirmation to us that extra care should be given to suppressing active disease already before actively trying to achieve a pregnancy,” she told this publication.

For more details, the full manuscript has been published (Arthritis Rheumatol. 2015;67:1738-43).

Reumafond, the Dutch Arthritis Foundation, funded the study. Dr. Brouwer reported no financial conflicts.

[email protected]

LISBON – Women undergoing assisted reproduction had similar pregnancy rates with gonadotropin-releasing hormone agonist and antagonist protocols, but less ovarian hyperstimulation syndrome with the GnRH-antagonist protocol in a large randomized trial.

Severe ovarian hyperstimulation syndrome (OHSS) was roughly halved with the GnRH-antagonist vs. the GnRH-agonist protocol (3.2% vs. 6.1%; P = .03), as were ascites punctures (0 vs. 2%: P = .001) and treatment changes due to risk of OHSS (5.7% vs. 10.3%; P = .006).

Patrice Wendling/Frontline Medical News

Hospital admissions for OHSS also favored the GnRH antagonist protocol (1.7% vs. 3.6%; P = .06), Dr. Mette Toftager reported at the annual meeting of the European Society of Human Reproduction and Embryology.

The exact impact of these protocols has been controversial following early reports that GnRH antagonists were associated with lower pregnancy rates.

Two 2006 meta-analyses yielded conflicting results, but were based on small heterogeneous trials that were not powered for OHSS nor pregnancy rates and were conducted in selected populations, said Dr. Toftager of Fertility Clinic, Hvidovre Hospital, Denmark.

The current noninferiority trial used few inclusion criteria – just age 18-40 years and first in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycle – to prospectively enroll 1,099 women and evenly randomize them to a classic short GnRH-antagonist protocol or a classic long GnRH-agonist protocol.

Women received a fixed dose of either recombinant follicle stimulating hormone 150 IU or 225 IU based on age (≤ 36 years vs. > 36 years) and were given the option to adjust the rFSH dose based on ovarian response at stimulation day 6.

The trial was designed to detect a 2.5% difference in moderate/severe OHSS per Golan OHSS criteria between the two groups, stratified by age, IVF center, and IVF/ICSI.

At baseline, the two groups were comparable in age (mean 32 years), cycle length (mean 28.9 days), and nulliparity (92.3%). The study included women with irregular cycles and polycystic ovary syndrome, who represented about 13% of each group.

Regarding stimulation, significant differences were found between the GnRH-antagonist and GnRH-agonist groups in total rFSH dose (mean 1,522 IU vs. 1,999 IU), days of stimulation (mean 9 vs. 11), and the number of aspirated oocytes (mean 8.5 vs. 10; P < .0001 for all), Dr. Toftager reported.

The GnRH-antagonist and GnRH-agonist groups had the same number of embryos transferred (mean 1.1 vs. 1.2), use of embryo freezing (50% vs. 53%), and number of frozen embryos (mean 3.2 vs. 3.4).

By all measures used, pregnancy outcomes were similar between protocols, she said.

The GnRH-antagonist and GnRH-agonist groups had similar clinical pregnancy rates (35% vs. 35.7%) and clinical pregnancies per embryo transfer (42.6% vs. 41%). There were similar results for ongoing pregnancy rates analyzed per randomization (25.5% vs. 26.4%), if patient started stimulation (24.8% vs. 24.0%), and per embryo transfer (30.7% vs. 29%).

During a discussion of the results, an audience member questioned the high FSH starting doses and suggested they may be the cause of OHSS. Dr. Toftager said the trial was designed in 2007 and that they now use lower FSH doses, but that starting doses were the same in both groups.

Another attendee asked whether OHSS rates remained statistically significant after controlling for the number of oocytes collected and the gonadotropin dose, which were significantly lower in the GnRH-antagonist group and hence, so was OHSS. That analysis will likely be conducted, but the data were just received days before the presentation, Dr. Toftager said.

Merck Sharp & Dohme sponsored the study. Dr. Toftager reported having no financial conflicts.

[email protected]

On Twitter @pwendl

LISBON – Women undergoing assisted reproduction had similar pregnancy rates with gonadotropin-releasing hormone agonist and antagonist protocols, but less ovarian hyperstimulation syndrome with the GnRH-antagonist protocol in a large randomized trial.

Severe ovarian hyperstimulation syndrome (OHSS) was roughly halved with the GnRH-antagonist vs. the GnRH-agonist protocol (3.2% vs. 6.1%; P = .03), as were ascites punctures (0 vs. 2%: P = .001) and treatment changes due to risk of OHSS (5.7% vs. 10.3%; P = .006).

Patrice Wendling/Frontline Medical News

Hospital admissions for OHSS also favored the GnRH antagonist protocol (1.7% vs. 3.6%; P = .06), Dr. Mette Toftager reported at the annual meeting of the European Society of Human Reproduction and Embryology.

The exact impact of these protocols has been controversial following early reports that GnRH antagonists were associated with lower pregnancy rates.

Two 2006 meta-analyses yielded conflicting results, but were based on small heterogeneous trials that were not powered for OHSS nor pregnancy rates and were conducted in selected populations, said Dr. Toftager of Fertility Clinic, Hvidovre Hospital, Denmark.

The current noninferiority trial used few inclusion criteria – just age 18-40 years and first in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycle – to prospectively enroll 1,099 women and evenly randomize them to a classic short GnRH-antagonist protocol or a classic long GnRH-agonist protocol.

Women received a fixed dose of either recombinant follicle stimulating hormone 150 IU or 225 IU based on age (≤ 36 years vs. > 36 years) and were given the option to adjust the rFSH dose based on ovarian response at stimulation day 6.

The trial was designed to detect a 2.5% difference in moderate/severe OHSS per Golan OHSS criteria between the two groups, stratified by age, IVF center, and IVF/ICSI.

At baseline, the two groups were comparable in age (mean 32 years), cycle length (mean 28.9 days), and nulliparity (92.3%). The study included women with irregular cycles and polycystic ovary syndrome, who represented about 13% of each group.

Regarding stimulation, significant differences were found between the GnRH-antagonist and GnRH-agonist groups in total rFSH dose (mean 1,522 IU vs. 1,999 IU), days of stimulation (mean 9 vs. 11), and the number of aspirated oocytes (mean 8.5 vs. 10; P < .0001 for all), Dr. Toftager reported.

The GnRH-antagonist and GnRH-agonist groups had the same number of embryos transferred (mean 1.1 vs. 1.2), use of embryo freezing (50% vs. 53%), and number of frozen embryos (mean 3.2 vs. 3.4).

By all measures used, pregnancy outcomes were similar between protocols, she said.

The GnRH-antagonist and GnRH-agonist groups had similar clinical pregnancy rates (35% vs. 35.7%) and clinical pregnancies per embryo transfer (42.6% vs. 41%). There were similar results for ongoing pregnancy rates analyzed per randomization (25.5% vs. 26.4%), if patient started stimulation (24.8% vs. 24.0%), and per embryo transfer (30.7% vs. 29%).

During a discussion of the results, an audience member questioned the high FSH starting doses and suggested they may be the cause of OHSS. Dr. Toftager said the trial was designed in 2007 and that they now use lower FSH doses, but that starting doses were the same in both groups.

Another attendee asked whether OHSS rates remained statistically significant after controlling for the number of oocytes collected and the gonadotropin dose, which were significantly lower in the GnRH-antagonist group and hence, so was OHSS. That analysis will likely be conducted, but the data were just received days before the presentation, Dr. Toftager said.

Merck Sharp & Dohme sponsored the study. Dr. Toftager reported having no financial conflicts.

[email protected]

On Twitter @pwendl

LISBON – Women undergoing assisted reproduction had similar pregnancy rates with gonadotropin-releasing hormone agonist and antagonist protocols, but less ovarian hyperstimulation syndrome with the GnRH-antagonist protocol in a large randomized trial.

Severe ovarian hyperstimulation syndrome (OHSS) was roughly halved with the GnRH-antagonist vs. the GnRH-agonist protocol (3.2% vs. 6.1%; P = .03), as were ascites punctures (0 vs. 2%: P = .001) and treatment changes due to risk of OHSS (5.7% vs. 10.3%; P = .006).

Patrice Wendling/Frontline Medical News

Hospital admissions for OHSS also favored the GnRH antagonist protocol (1.7% vs. 3.6%; P = .06), Dr. Mette Toftager reported at the annual meeting of the European Society of Human Reproduction and Embryology.

The exact impact of these protocols has been controversial following early reports that GnRH antagonists were associated with lower pregnancy rates.

Two 2006 meta-analyses yielded conflicting results, but were based on small heterogeneous trials that were not powered for OHSS nor pregnancy rates and were conducted in selected populations, said Dr. Toftager of Fertility Clinic, Hvidovre Hospital, Denmark.

The current noninferiority trial used few inclusion criteria – just age 18-40 years and first in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycle – to prospectively enroll 1,099 women and evenly randomize them to a classic short GnRH-antagonist protocol or a classic long GnRH-agonist protocol.

Women received a fixed dose of either recombinant follicle stimulating hormone 150 IU or 225 IU based on age (≤ 36 years vs. > 36 years) and were given the option to adjust the rFSH dose based on ovarian response at stimulation day 6.

The trial was designed to detect a 2.5% difference in moderate/severe OHSS per Golan OHSS criteria between the two groups, stratified by age, IVF center, and IVF/ICSI.

At baseline, the two groups were comparable in age (mean 32 years), cycle length (mean 28.9 days), and nulliparity (92.3%). The study included women with irregular cycles and polycystic ovary syndrome, who represented about 13% of each group.

Regarding stimulation, significant differences were found between the GnRH-antagonist and GnRH-agonist groups in total rFSH dose (mean 1,522 IU vs. 1,999 IU), days of stimulation (mean 9 vs. 11), and the number of aspirated oocytes (mean 8.5 vs. 10; P < .0001 for all), Dr. Toftager reported.

The GnRH-antagonist and GnRH-agonist groups had the same number of embryos transferred (mean 1.1 vs. 1.2), use of embryo freezing (50% vs. 53%), and number of frozen embryos (mean 3.2 vs. 3.4).

By all measures used, pregnancy outcomes were similar between protocols, she said.

The GnRH-antagonist and GnRH-agonist groups had similar clinical pregnancy rates (35% vs. 35.7%) and clinical pregnancies per embryo transfer (42.6% vs. 41%). There were similar results for ongoing pregnancy rates analyzed per randomization (25.5% vs. 26.4%), if patient started stimulation (24.8% vs. 24.0%), and per embryo transfer (30.7% vs. 29%).

During a discussion of the results, an audience member questioned the high FSH starting doses and suggested they may be the cause of OHSS. Dr. Toftager said the trial was designed in 2007 and that they now use lower FSH doses, but that starting doses were the same in both groups.

Another attendee asked whether OHSS rates remained statistically significant after controlling for the number of oocytes collected and the gonadotropin dose, which were significantly lower in the GnRH-antagonist group and hence, so was OHSS. That analysis will likely be conducted, but the data were just received days before the presentation, Dr. Toftager said.

Merck Sharp & Dohme sponsored the study. Dr. Toftager reported having no financial conflicts.

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LISBON – Pretreatment with transdermal testosterone failed to improve outcomes in women with poor ovarian response who were undergoing intra-cytoplasmic sperm injection in a randomized clinical study.

The primary endpoint, number of cumulus-oocyte complexes (COCs) retrieved, was not significantly different with testosterone gel 10 mg applied to the thigh for 21 days before ovarian stimulation versus no pretreatment (median, 3.5 vs. 3.0; P = .91).

Further, no differences were observed in fertilization rates (66.7% vs. 66.7%; P = .97) or live birth rates per intention-to-treat analysis (7.7% vs. 8.3%; 95% confidence interval, –19.0 to +16.9).

Patrice Wendling/Frontline Medical News

“An improvement in {in vitro fertilization] outcome cannot be excluded using a larger dose of testosterone more than 10 mg or a pretreatment period longer than 21 days,” study author Dr. Julia Bosdou said at the annual meeting of the European Society of Human Reproduction and Embryology.

Because of sample size restrictions, no conclusions can be drawn regarding the probability of live birth, she added.

The study was designed to detect a difference of 1.5 COCs retrieved with a sample size of 42 patients. In all, 50 women who fulfilled the Bologna criteria for poor ovarian response were allocated to the testosterone group (n = 26) or control group (n = 24). All patients underwent a long follicular gonadotropin-releasing hormone agonist (GnRHa) protocol. Recombinant follicle-stimulating hormone (FSH) 300 IU daily was started on day 22 following GnRHa initiation.

The testosterone dose was based on published data showing a beneficial effect with a 21-day duration, said Dr. Bosdou of the Aristotle University of Thessaloniki (Greece).

Androgens have been suggested to play a critical role in early follicular development by enhancing ovarian sensitivity to FSH. A recent meta-analysis by the investigators of the current study also showed that pretreatment with transdermal testosterone increased clinical pregnancy and live birth rates in poor responders, but it was based on only two randomized trials (Hum. Reprod. Update 2012;18:127-45), she observed.

As expected, testosterone levels in the current study were significantly higher in the testosterone group than the control group on day 22 (median, 114 ng/dL vs. 20 ng/dL; P < .001). Duration of FSH stimulation was comparable between groups (12.5 days vs. 12 days; P = .48), Dr. Bosdou said.

Endometrial thickness on the day of human chorionic gonadotropin administration was significantly greater with testosterone pretreatment (median, 10.7 mm vs. 9 mm; P = .03).

No adverse events were reported in either group, she said.

The study was partially funded by a scholarship award to Dr. Bosdou from the Academy of Athens. Dr. Bosdou reported having no conflicts of interest.

[email protected]

On Twitter @pwendl

LISBON – Pretreatment with transdermal testosterone failed to improve outcomes in women with poor ovarian response who were undergoing intra-cytoplasmic sperm injection in a randomized clinical study.

The primary endpoint, number of cumulus-oocyte complexes (COCs) retrieved, was not significantly different with testosterone gel 10 mg applied to the thigh for 21 days before ovarian stimulation versus no pretreatment (median, 3.5 vs. 3.0; P = .91).

Further, no differences were observed in fertilization rates (66.7% vs. 66.7%; P = .97) or live birth rates per intention-to-treat analysis (7.7% vs. 8.3%; 95% confidence interval, –19.0 to +16.9).

Patrice Wendling/Frontline Medical News

“An improvement in {in vitro fertilization] outcome cannot be excluded using a larger dose of testosterone more than 10 mg or a pretreatment period longer than 21 days,” study author Dr. Julia Bosdou said at the annual meeting of the European Society of Human Reproduction and Embryology.

Because of sample size restrictions, no conclusions can be drawn regarding the probability of live birth, she added.

The study was designed to detect a difference of 1.5 COCs retrieved with a sample size of 42 patients. In all, 50 women who fulfilled the Bologna criteria for poor ovarian response were allocated to the testosterone group (n = 26) or control group (n = 24). All patients underwent a long follicular gonadotropin-releasing hormone agonist (GnRHa) protocol. Recombinant follicle-stimulating hormone (FSH) 300 IU daily was started on day 22 following GnRHa initiation.

The testosterone dose was based on published data showing a beneficial effect with a 21-day duration, said Dr. Bosdou of the Aristotle University of Thessaloniki (Greece).

Androgens have been suggested to play a critical role in early follicular development by enhancing ovarian sensitivity to FSH. A recent meta-analysis by the investigators of the current study also showed that pretreatment with transdermal testosterone increased clinical pregnancy and live birth rates in poor responders, but it was based on only two randomized trials (Hum. Reprod. Update 2012;18:127-45), she observed.

As expected, testosterone levels in the current study were significantly higher in the testosterone group than the control group on day 22 (median, 114 ng/dL vs. 20 ng/dL; P < .001). Duration of FSH stimulation was comparable between groups (12.5 days vs. 12 days; P = .48), Dr. Bosdou said.

Endometrial thickness on the day of human chorionic gonadotropin administration was significantly greater with testosterone pretreatment (median, 10.7 mm vs. 9 mm; P = .03).

No adverse events were reported in either group, she said.

The study was partially funded by a scholarship award to Dr. Bosdou from the Academy of Athens. Dr. Bosdou reported having no conflicts of interest.

[email protected]

On Twitter @pwendl

LISBON – Pretreatment with transdermal testosterone failed to improve outcomes in women with poor ovarian response who were undergoing intra-cytoplasmic sperm injection in a randomized clinical study.

The primary endpoint, number of cumulus-oocyte complexes (COCs) retrieved, was not significantly different with testosterone gel 10 mg applied to the thigh for 21 days before ovarian stimulation versus no pretreatment (median, 3.5 vs. 3.0; P = .91).

Further, no differences were observed in fertilization rates (66.7% vs. 66.7%; P = .97) or live birth rates per intention-to-treat analysis (7.7% vs. 8.3%; 95% confidence interval, –19.0 to +16.9).

Patrice Wendling/Frontline Medical News

“An improvement in {in vitro fertilization] outcome cannot be excluded using a larger dose of testosterone more than 10 mg or a pretreatment period longer than 21 days,” study author Dr. Julia Bosdou said at the annual meeting of the European Society of Human Reproduction and Embryology.

Because of sample size restrictions, no conclusions can be drawn regarding the probability of live birth, she added.

The study was designed to detect a difference of 1.5 COCs retrieved with a sample size of 42 patients. In all, 50 women who fulfilled the Bologna criteria for poor ovarian response were allocated to the testosterone group (n = 26) or control group (n = 24). All patients underwent a long follicular gonadotropin-releasing hormone agonist (GnRHa) protocol. Recombinant follicle-stimulating hormone (FSH) 300 IU daily was started on day 22 following GnRHa initiation.

The testosterone dose was based on published data showing a beneficial effect with a 21-day duration, said Dr. Bosdou of the Aristotle University of Thessaloniki (Greece).

Androgens have been suggested to play a critical role in early follicular development by enhancing ovarian sensitivity to FSH. A recent meta-analysis by the investigators of the current study also showed that pretreatment with transdermal testosterone increased clinical pregnancy and live birth rates in poor responders, but it was based on only two randomized trials (Hum. Reprod. Update 2012;18:127-45), she observed.

As expected, testosterone levels in the current study were significantly higher in the testosterone group than the control group on day 22 (median, 114 ng/dL vs. 20 ng/dL; P < .001). Duration of FSH stimulation was comparable between groups (12.5 days vs. 12 days; P = .48), Dr. Bosdou said.

Endometrial thickness on the day of human chorionic gonadotropin administration was significantly greater with testosterone pretreatment (median, 10.7 mm vs. 9 mm; P = .03).

No adverse events were reported in either group, she said.

The study was partially funded by a scholarship award to Dr. Bosdou from the Academy of Athens. Dr. Bosdou reported having no conflicts of interest.

[email protected]

On Twitter @pwendl