European Society for Human Reproduction and Embryology (ESHRE): Annual Meeting

Children conceived by frozen embryo transfer are significantly more likely to be large for gestational age at birth than those conceived naturally or by fresh embryo transfer.

Population-based studies from both France and Denmark have come to the same conclusion: Compared with fresh embryos, frozen embryos are up to 60% more likely to develop into large for gestational age (LGA) infants.

No one can yet be sure of the mechanism behind this finding, which also has been observed in Asian studies, Dr. Anja Pinborg said at the annual meeting of the European Society of Human Reproduction and Embryology. It may be related to the oocyte transfer, to keeping the embryo an extra day in the culture media, or even to something in the culture media itself.

"It may also be [an] example of epigenetic changes in the very early embryos caused by freezing and thawing," said Dr. Pinborg of Rigshospitalet, Copenhagen. "At this point all we have are theories. We need much more data to understand this. But I think it is important that we do understand more."

Dr. Pinborg presented the results of the Danish study, which included data on 910 singleton pregnancies conceived by frozen embryo transfer, 9,603 from fresh embryo transfer, and 4,656 conceived naturally.

The rate of LGA infants was 17% in the frozen embryo group – significantly higher than the 10% rate in the fresh embryo group and 11% rate in the natural conception group.

After adjusting for maternal age and parity, and the babies’ gender and birth year, frozen embryo infants were 60% more likely to be LGA than fresh embryo infants.

The number of infants with a birth weight of more than 4,500 g also was significantly higher in the frozen embryo group (6%) than in the fresh embryo and naturally conceived group (3% each).

"When we look at it from the other end – babies who are small for gestational age (SGA) – we see the reverse pattern," Dr. Pinborg said. The rate of SGA infants was 9% in the frozen embryo group, 15% in the fresh embryo group, and 11% in the naturally conceived group. After adjusting for the confounding factors, frozen embryo infants were 40% less likely to be SGA than fresh embryo infants.

The group also looked at the incidence of placenta previa – a factor associated with SGA infants. The incidence was 0.5% in the frozen embryo group, 1.5% in the fresh embryo group, and 0.3% in the naturally conceived group. The adjusted odds ratio of placenta previa was 2.8 for the frozen versus natural conception group and 5.0 for the fresh versus natural conception group.

Dr. Pinborg said the study has three key messages. "The first is a positive message: Children born after frozen embryo transfer have obstetrical outcomes similar to naturally conceived children. But our study also shows that these children are at a significantly increased risk of being large for gestational age and having a birth weight of more than 4,500 g. At this point, we don’t know the implications of this message. But in general, all children born by assisted reproductive technology do very well and have no problems."

The French study, presented by Dr. Sylvie Epelboin of the Bichat-Claude Bernard Hospital, Paris, came to similar conclusions about birth weight.

The French cohort consisted of 16,002 singleton pregnancies conceived by assisted reproductive technology (ART); 2,140 (13%) were frozen embryo transfer. The control group consisted of the 13,862 fresh embryo transfer pregnancies.

The gestational age at birth was slightly, but not significantly, younger in the frozen embryo group (39.1 vs. 39.3 weeks). The rate of preterm birth was also similar (8.6% in the frozen group and 8.3% in the fresh group). Neonatal mortality was less than 0.25% in each group.

Measures of weight were the only statistically significant between-group differences, Dr. Epelboin said.

The mean birth weight was 102 g higher in the frozen embryo group than in the fresh embryo group, while the incidence of low birth weight (less than 2,500 g) was significantly lower in the frozen embryo group.

Using the 90th percentile, the incidence of LGA births was significantly higher in the frozen embryo than the fresh embryo group (13% vs. 9%). The difference was also significant when comparing the 95th percentile (7% vs. 5%).

The good news, Dr. Epelboin said, is that embryo freezing does not adversely affect neonatal outcome, particularly in the risk of giving birth to a SGA infant.

Again, she said, there are only theories about the mechanism behind larger babies from frozen embryos. The finding may be related to the process of freezing and thawing, or perhaps to differences in the hormonal environment and its effect on the endometrium.

The study was sponsored by the ART Follow-Up Scientific Board. Dr. Epelboin said she had no relevant financial disclosures. Dr. Pinborg also reported no relevant financial disclosures.

Children conceived by frozen embryo transfer are significantly more likely to be large for gestational age at birth than those conceived naturally or by fresh embryo transfer.

Population-based studies from both France and Denmark have come to the same conclusion: Compared with fresh embryos, frozen embryos are up to 60% more likely to develop into large for gestational age (LGA) infants.

No one can yet be sure of the mechanism behind this finding, which also has been observed in Asian studies, Dr. Anja Pinborg said at the annual meeting of the European Society of Human Reproduction and Embryology. It may be related to the oocyte transfer, to keeping the embryo an extra day in the culture media, or even to something in the culture media itself.

"It may also be [an] example of epigenetic changes in the very early embryos caused by freezing and thawing," said Dr. Pinborg of Rigshospitalet, Copenhagen. "At this point all we have are theories. We need much more data to understand this. But I think it is important that we do understand more."

Dr. Pinborg presented the results of the Danish study, which included data on 910 singleton pregnancies conceived by frozen embryo transfer, 9,603 from fresh embryo transfer, and 4,656 conceived naturally.

The rate of LGA infants was 17% in the frozen embryo group – significantly higher than the 10% rate in the fresh embryo group and 11% rate in the natural conception group.

After adjusting for maternal age and parity, and the babies’ gender and birth year, frozen embryo infants were 60% more likely to be LGA than fresh embryo infants.

The number of infants with a birth weight of more than 4,500 g also was significantly higher in the frozen embryo group (6%) than in the fresh embryo and naturally conceived group (3% each).

"When we look at it from the other end – babies who are small for gestational age (SGA) – we see the reverse pattern," Dr. Pinborg said. The rate of SGA infants was 9% in the frozen embryo group, 15% in the fresh embryo group, and 11% in the naturally conceived group. After adjusting for the confounding factors, frozen embryo infants were 40% less likely to be SGA than fresh embryo infants.

The group also looked at the incidence of placenta previa – a factor associated with SGA infants. The incidence was 0.5% in the frozen embryo group, 1.5% in the fresh embryo group, and 0.3% in the naturally conceived group. The adjusted odds ratio of placenta previa was 2.8 for the frozen versus natural conception group and 5.0 for the fresh versus natural conception group.

Dr. Pinborg said the study has three key messages. "The first is a positive message: Children born after frozen embryo transfer have obstetrical outcomes similar to naturally conceived children. But our study also shows that these children are at a significantly increased risk of being large for gestational age and having a birth weight of more than 4,500 g. At this point, we don’t know the implications of this message. But in general, all children born by assisted reproductive technology do very well and have no problems."

The French study, presented by Dr. Sylvie Epelboin of the Bichat-Claude Bernard Hospital, Paris, came to similar conclusions about birth weight.

The French cohort consisted of 16,002 singleton pregnancies conceived by assisted reproductive technology (ART); 2,140 (13%) were frozen embryo transfer. The control group consisted of the 13,862 fresh embryo transfer pregnancies.

The gestational age at birth was slightly, but not significantly, younger in the frozen embryo group (39.1 vs. 39.3 weeks). The rate of preterm birth was also similar (8.6% in the frozen group and 8.3% in the fresh group). Neonatal mortality was less than 0.25% in each group.

Measures of weight were the only statistically significant between-group differences, Dr. Epelboin said.

The mean birth weight was 102 g higher in the frozen embryo group than in the fresh embryo group, while the incidence of low birth weight (less than 2,500 g) was significantly lower in the frozen embryo group.

Using the 90th percentile, the incidence of LGA births was significantly higher in the frozen embryo than the fresh embryo group (13% vs. 9%). The difference was also significant when comparing the 95th percentile (7% vs. 5%).

The good news, Dr. Epelboin said, is that embryo freezing does not adversely affect neonatal outcome, particularly in the risk of giving birth to a SGA infant.

Again, she said, there are only theories about the mechanism behind larger babies from frozen embryos. The finding may be related to the process of freezing and thawing, or perhaps to differences in the hormonal environment and its effect on the endometrium.

The study was sponsored by the ART Follow-Up Scientific Board. Dr. Epelboin said she had no relevant financial disclosures. Dr. Pinborg also reported no relevant financial disclosures.

Children conceived by frozen embryo transfer are significantly more likely to be large for gestational age at birth than those conceived naturally or by fresh embryo transfer.

Population-based studies from both France and Denmark have come to the same conclusion: Compared with fresh embryos, frozen embryos are up to 60% more likely to develop into large for gestational age (LGA) infants.

No one can yet be sure of the mechanism behind this finding, which also has been observed in Asian studies, Dr. Anja Pinborg said at the annual meeting of the European Society of Human Reproduction and Embryology. It may be related to the oocyte transfer, to keeping the embryo an extra day in the culture media, or even to something in the culture media itself.

"It may also be [an] example of epigenetic changes in the very early embryos caused by freezing and thawing," said Dr. Pinborg of Rigshospitalet, Copenhagen. "At this point all we have are theories. We need much more data to understand this. But I think it is important that we do understand more."

Dr. Pinborg presented the results of the Danish study, which included data on 910 singleton pregnancies conceived by frozen embryo transfer, 9,603 from fresh embryo transfer, and 4,656 conceived naturally.

The rate of LGA infants was 17% in the frozen embryo group – significantly higher than the 10% rate in the fresh embryo group and 11% rate in the natural conception group.

After adjusting for maternal age and parity, and the babies’ gender and birth year, frozen embryo infants were 60% more likely to be LGA than fresh embryo infants.

The number of infants with a birth weight of more than 4,500 g also was significantly higher in the frozen embryo group (6%) than in the fresh embryo and naturally conceived group (3% each).

"When we look at it from the other end – babies who are small for gestational age (SGA) – we see the reverse pattern," Dr. Pinborg said. The rate of SGA infants was 9% in the frozen embryo group, 15% in the fresh embryo group, and 11% in the naturally conceived group. After adjusting for the confounding factors, frozen embryo infants were 40% less likely to be SGA than fresh embryo infants.

The group also looked at the incidence of placenta previa – a factor associated with SGA infants. The incidence was 0.5% in the frozen embryo group, 1.5% in the fresh embryo group, and 0.3% in the naturally conceived group. The adjusted odds ratio of placenta previa was 2.8 for the frozen versus natural conception group and 5.0 for the fresh versus natural conception group.

Dr. Pinborg said the study has three key messages. "The first is a positive message: Children born after frozen embryo transfer have obstetrical outcomes similar to naturally conceived children. But our study also shows that these children are at a significantly increased risk of being large for gestational age and having a birth weight of more than 4,500 g. At this point, we don’t know the implications of this message. But in general, all children born by assisted reproductive technology do very well and have no problems."

The French study, presented by Dr. Sylvie Epelboin of the Bichat-Claude Bernard Hospital, Paris, came to similar conclusions about birth weight.

The French cohort consisted of 16,002 singleton pregnancies conceived by assisted reproductive technology (ART); 2,140 (13%) were frozen embryo transfer. The control group consisted of the 13,862 fresh embryo transfer pregnancies.

The gestational age at birth was slightly, but not significantly, younger in the frozen embryo group (39.1 vs. 39.3 weeks). The rate of preterm birth was also similar (8.6% in the frozen group and 8.3% in the fresh group). Neonatal mortality was less than 0.25% in each group.

Measures of weight were the only statistically significant between-group differences, Dr. Epelboin said.

The mean birth weight was 102 g higher in the frozen embryo group than in the fresh embryo group, while the incidence of low birth weight (less than 2,500 g) was significantly lower in the frozen embryo group.

Using the 90th percentile, the incidence of LGA births was significantly higher in the frozen embryo than the fresh embryo group (13% vs. 9%). The difference was also significant when comparing the 95th percentile (7% vs. 5%).

The good news, Dr. Epelboin said, is that embryo freezing does not adversely affect neonatal outcome, particularly in the risk of giving birth to a SGA infant.

Again, she said, there are only theories about the mechanism behind larger babies from frozen embryos. The finding may be related to the process of freezing and thawing, or perhaps to differences in the hormonal environment and its effect on the endometrium.

The study was sponsored by the ART Follow-Up Scientific Board. Dr. Epelboin said she had no relevant financial disclosures. Dr. Pinborg also reported no relevant financial disclosures.

It’s never too late for a pregnant woman to stop smoking.

After reviewing the records of more than 50,000 pregnancies, Dr. Nick Macklon concluded that every day a pregnant woman doesn’t smoke is a good day for her developing baby.

"The more a woman smokes during pregnancy, the worse the effect on the baby," Dr. Macklon said during a press briefing at the annual meeting of the European Society of Human Reproduction and Embryology. "But stopping – even at the time a woman discovers she’s pregnant – can completely ameliorate the effects of smoking" on the fetal outcomes of gestational age and birth weight. "For the baby, a mom stopping in the periconceptional phase is as good as her never having smoked at all."

Smoking among pregnant women affects more than the health of mother and child, said Dr. Macklon of the University of Southampton, England.

"We all know that smoking is bad for babies, increasing the rates of stillbirth, neonatal death, congenital malformations, preterm birth, and low birth weight – causing hardship to both parents and child. But it is also a significant public health issue in terms of cost."

Dr. Macklon and his associates reviewed the records of 50,000 women who gave birth at Southampton hospitals from 2002 to 2010. Women were divided into seven groups, depending on how much they smoked: never, stopped in the last year, stopped more than 1 year ago, stopped at confirmation of pregnancy, and current smokers of up to 10 cigarettes each day, 10-20 each day, and more than 20. About 12,000 women decided to stop smoking when they discovered their pregnancy.

For nonsmokers, the mean gestational age at birth was 280 days – significantly longer than for those who smoked up to 10 cigarettes/day (279 days), 10-20/day (277 days), and 20 or more/day (276 days).

The gestational age of infants whose mothers ceased smoking a year or longer before birth was the same as those of never-smoking mothers. The surprise, Dr. Macklon said, was that the gestational age of infants whose mothers who gave up cigarettes only when they became pregnant was exactly the same as the infants of never-smokers. This relationship remained significant even after the researchers corrected for other factors that affect gestational age, including education and socioeconomic status.

Birth weight also showed a similar relationship with smoking. The infants of current smokers were significantly smaller were than those of nonsmokers, as well as those who had quit a year or more before giving birth.

Mothers who smoked up to 10 cigarettes/day had infants with a mean birth weight of 3.25 kg; mothers who smoked 10-20 cigarettes/day had infants weighing a mean 3.2 kg; and the infants of women who smoked more than 20 cigarettes/day weighed in at a mean 3.1 kg.

"This effect is quite substantial, with a difference of more than 300 grams," Dr. Macklon noted.

Again, however, mothers who quit smoking as soon as they became pregnant conferred a significant benefit on their infants; these infants weighed a mean 3.4 kg – the same as those of women who had never smoked.

The findings shouldn’t be construed as a free license to smoke until conception, he warned. "Many women don’t plan their pregnancies and if they come in smoking and pregnant and we tell them it’s too late to do anything, this sends a negative, and unnecessary, message. What we can now say is ‘If you stop smoking now, you and your baby will get a major health benefit.’ "

Smoking directly affects transplacental oxygen and nutrient flow, contributing to low birth weight and premature delivery. But couples who want to conceive should stop smoking for other reasons as well, Dr. Macklon advised.

"Smoking is a contraceptive. It’s been shown to reduce the success of in vitro fertilization by at least 50%. Smoking affects the male partner as well, lowering fertility by impairing the DNA of sperm. Couples who want to conceive quickly and healthily should both stop smoking."

Cigarette smoke contains about 4,000 known chemicals, Dr. Macklon said. "It’s reasonable to assume that at least some of these have effects on fertility, miscarriage, and the health of babies."

For women who want to quit before or during pregnancy, nicotine replacement therapy is a good choice. "It’s far less toxic than smoking, and even if we can’t get a patient to stop completely I would support its use."

Dr. Macklon said he had no relevant financial disclosures.

It’s never too late for a pregnant woman to stop smoking.

After reviewing the records of more than 50,000 pregnancies, Dr. Nick Macklon concluded that every day a pregnant woman doesn’t smoke is a good day for her developing baby.

"The more a woman smokes during pregnancy, the worse the effect on the baby," Dr. Macklon said during a press briefing at the annual meeting of the European Society of Human Reproduction and Embryology. "But stopping – even at the time a woman discovers she’s pregnant – can completely ameliorate the effects of smoking" on the fetal outcomes of gestational age and birth weight. "For the baby, a mom stopping in the periconceptional phase is as good as her never having smoked at all."

Smoking among pregnant women affects more than the health of mother and child, said Dr. Macklon of the University of Southampton, England.

"We all know that smoking is bad for babies, increasing the rates of stillbirth, neonatal death, congenital malformations, preterm birth, and low birth weight – causing hardship to both parents and child. But it is also a significant public health issue in terms of cost."

Dr. Macklon and his associates reviewed the records of 50,000 women who gave birth at Southampton hospitals from 2002 to 2010. Women were divided into seven groups, depending on how much they smoked: never, stopped in the last year, stopped more than 1 year ago, stopped at confirmation of pregnancy, and current smokers of up to 10 cigarettes each day, 10-20 each day, and more than 20. About 12,000 women decided to stop smoking when they discovered their pregnancy.

For nonsmokers, the mean gestational age at birth was 280 days – significantly longer than for those who smoked up to 10 cigarettes/day (279 days), 10-20/day (277 days), and 20 or more/day (276 days).

The gestational age of infants whose mothers ceased smoking a year or longer before birth was the same as those of never-smoking mothers. The surprise, Dr. Macklon said, was that the gestational age of infants whose mothers who gave up cigarettes only when they became pregnant was exactly the same as the infants of never-smokers. This relationship remained significant even after the researchers corrected for other factors that affect gestational age, including education and socioeconomic status.

Birth weight also showed a similar relationship with smoking. The infants of current smokers were significantly smaller were than those of nonsmokers, as well as those who had quit a year or more before giving birth.

Mothers who smoked up to 10 cigarettes/day had infants with a mean birth weight of 3.25 kg; mothers who smoked 10-20 cigarettes/day had infants weighing a mean 3.2 kg; and the infants of women who smoked more than 20 cigarettes/day weighed in at a mean 3.1 kg.

"This effect is quite substantial, with a difference of more than 300 grams," Dr. Macklon noted.

Again, however, mothers who quit smoking as soon as they became pregnant conferred a significant benefit on their infants; these infants weighed a mean 3.4 kg – the same as those of women who had never smoked.

The findings shouldn’t be construed as a free license to smoke until conception, he warned. "Many women don’t plan their pregnancies and if they come in smoking and pregnant and we tell them it’s too late to do anything, this sends a negative, and unnecessary, message. What we can now say is ‘If you stop smoking now, you and your baby will get a major health benefit.’ "

Smoking directly affects transplacental oxygen and nutrient flow, contributing to low birth weight and premature delivery. But couples who want to conceive should stop smoking for other reasons as well, Dr. Macklon advised.

"Smoking is a contraceptive. It’s been shown to reduce the success of in vitro fertilization by at least 50%. Smoking affects the male partner as well, lowering fertility by impairing the DNA of sperm. Couples who want to conceive quickly and healthily should both stop smoking."

Cigarette smoke contains about 4,000 known chemicals, Dr. Macklon said. "It’s reasonable to assume that at least some of these have effects on fertility, miscarriage, and the health of babies."

For women who want to quit before or during pregnancy, nicotine replacement therapy is a good choice. "It’s far less toxic than smoking, and even if we can’t get a patient to stop completely I would support its use."

Dr. Macklon said he had no relevant financial disclosures.

It’s never too late for a pregnant woman to stop smoking.

After reviewing the records of more than 50,000 pregnancies, Dr. Nick Macklon concluded that every day a pregnant woman doesn’t smoke is a good day for her developing baby.

"The more a woman smokes during pregnancy, the worse the effect on the baby," Dr. Macklon said during a press briefing at the annual meeting of the European Society of Human Reproduction and Embryology. "But stopping – even at the time a woman discovers she’s pregnant – can completely ameliorate the effects of smoking" on the fetal outcomes of gestational age and birth weight. "For the baby, a mom stopping in the periconceptional phase is as good as her never having smoked at all."

Smoking among pregnant women affects more than the health of mother and child, said Dr. Macklon of the University of Southampton, England.

"We all know that smoking is bad for babies, increasing the rates of stillbirth, neonatal death, congenital malformations, preterm birth, and low birth weight – causing hardship to both parents and child. But it is also a significant public health issue in terms of cost."

Dr. Macklon and his associates reviewed the records of 50,000 women who gave birth at Southampton hospitals from 2002 to 2010. Women were divided into seven groups, depending on how much they smoked: never, stopped in the last year, stopped more than 1 year ago, stopped at confirmation of pregnancy, and current smokers of up to 10 cigarettes each day, 10-20 each day, and more than 20. About 12,000 women decided to stop smoking when they discovered their pregnancy.

For nonsmokers, the mean gestational age at birth was 280 days – significantly longer than for those who smoked up to 10 cigarettes/day (279 days), 10-20/day (277 days), and 20 or more/day (276 days).

The gestational age of infants whose mothers ceased smoking a year or longer before birth was the same as those of never-smoking mothers. The surprise, Dr. Macklon said, was that the gestational age of infants whose mothers who gave up cigarettes only when they became pregnant was exactly the same as the infants of never-smokers. This relationship remained significant even after the researchers corrected for other factors that affect gestational age, including education and socioeconomic status.

Birth weight also showed a similar relationship with smoking. The infants of current smokers were significantly smaller were than those of nonsmokers, as well as those who had quit a year or more before giving birth.

Mothers who smoked up to 10 cigarettes/day had infants with a mean birth weight of 3.25 kg; mothers who smoked 10-20 cigarettes/day had infants weighing a mean 3.2 kg; and the infants of women who smoked more than 20 cigarettes/day weighed in at a mean 3.1 kg.

"This effect is quite substantial, with a difference of more than 300 grams," Dr. Macklon noted.

Again, however, mothers who quit smoking as soon as they became pregnant conferred a significant benefit on their infants; these infants weighed a mean 3.4 kg – the same as those of women who had never smoked.

The findings shouldn’t be construed as a free license to smoke until conception, he warned. "Many women don’t plan their pregnancies and if they come in smoking and pregnant and we tell them it’s too late to do anything, this sends a negative, and unnecessary, message. What we can now say is ‘If you stop smoking now, you and your baby will get a major health benefit.’ "

Smoking directly affects transplacental oxygen and nutrient flow, contributing to low birth weight and premature delivery. But couples who want to conceive should stop smoking for other reasons as well, Dr. Macklon advised.

"Smoking is a contraceptive. It’s been shown to reduce the success of in vitro fertilization by at least 50%. Smoking affects the male partner as well, lowering fertility by impairing the DNA of sperm. Couples who want to conceive quickly and healthily should both stop smoking."

Cigarette smoke contains about 4,000 known chemicals, Dr. Macklon said. "It’s reasonable to assume that at least some of these have effects on fertility, miscarriage, and the health of babies."

For women who want to quit before or during pregnancy, nicotine replacement therapy is a good choice. "It’s far less toxic than smoking, and even if we can’t get a patient to stop completely I would support its use."

Dr. Macklon said he had no relevant financial disclosures.

A combination of vaginal bleeding score and human chorionic gonadotropin levels may predict the possibility of miscarriage by up to 77%, and the possibility of ongoing pregnancy by 94%.

The "pregnancy viability index" could help physicians reassure women who present with threatened miscarriage that the pregnancy is likely to continue and prepare those who may face miscarriage. Additionally, the score might help channel medical interventions more appropriately, Dr. Kaltum Adam said at the annual meeting of the European Society of Human Reproduction and Embryology.

"It will enable us to provide targeted management and counseling for the affected women and reassure those who are likely to achieve a live birth," said Dr. Adam, an honorary clinical research fellow at St. Mary’s Hospital in Manchester, England.

Her prospective longitudinal study included 112 women who presented with threatened miscarriage at 6-10 weeks’ gestation and with a confirmed intrauterine pregnancy. They were followed for 5 weeks, during which time they completed daily charts of pain and vaginal bleeding; had a weekly ultrasound and physical exam; and contributed weekly blood samples that were analyzed for progesterone, human chorionic gonadotropin (hCG), hemoglobin, and other standard blood chemistry factors. Baseline screening also included maternal demographics, educational, and socioeconomic status. At the final visit, there was an ultrasound exam to confirm the pregnancy’s outcome.

Of the 112 women, 22 (20%) miscarried. Time of first vaginal bleeding to miscarriage was available for 20 women: 11 miscarried in the first 7 days, 15 within 14 days, and 18 within 21 days. All of the miscarriages occurred within 28 days of the first bleed.

Dr. Adam determined that six baseline biomarkers were significantly associated with miscarriage at the 20th percentile: history of subfertility, bleeding score of two on a five-point scale, gestational age of the fetus, fetal crown-rump length of 4 mm, and serum levels of progesterone and hCG (32 nmol/L and 1,500 iU/L, respectively).

"All of these had good positive predictive values, indicating that a pregnancy had a good chance of surviving," Dr. Adam said, "but the negative predictive values were not useful for clinical practice or research."

A multivariate regression analysis, however, did identify that a combination of baseline bleeding score (two on a five-point scale) and baseline hCG level (1,500 iU/L) exhibited excellent positive and negative predictive values (94% and 77%, respectively). The equation used for computing the pregnancy viability index was hCG level/bleeding score × 1.87 × 10, where the bleeding score odds ratio for miscarriage is 1.87.

"This research has, for the first time, offered us a tool to begin to attempt to rescue pregnancies threatening to miscarry when, currently, all we can do is fold our hands and hope for the best," Dr. Adam said.

Dr. Adam plans to carry out a validation study on at least 1,000 women in the near future.

The study was funded by the Central Manchester Foundation Trust Biomedical Research Center. Dr. Adam said she had no relevant financial disclosures.

A combination of vaginal bleeding score and human chorionic gonadotropin levels may predict the possibility of miscarriage by up to 77%, and the possibility of ongoing pregnancy by 94%.

The "pregnancy viability index" could help physicians reassure women who present with threatened miscarriage that the pregnancy is likely to continue and prepare those who may face miscarriage. Additionally, the score might help channel medical interventions more appropriately, Dr. Kaltum Adam said at the annual meeting of the European Society of Human Reproduction and Embryology.

"It will enable us to provide targeted management and counseling for the affected women and reassure those who are likely to achieve a live birth," said Dr. Adam, an honorary clinical research fellow at St. Mary’s Hospital in Manchester, England.

Her prospective longitudinal study included 112 women who presented with threatened miscarriage at 6-10 weeks’ gestation and with a confirmed intrauterine pregnancy. They were followed for 5 weeks, during which time they completed daily charts of pain and vaginal bleeding; had a weekly ultrasound and physical exam; and contributed weekly blood samples that were analyzed for progesterone, human chorionic gonadotropin (hCG), hemoglobin, and other standard blood chemistry factors. Baseline screening also included maternal demographics, educational, and socioeconomic status. At the final visit, there was an ultrasound exam to confirm the pregnancy’s outcome.

Of the 112 women, 22 (20%) miscarried. Time of first vaginal bleeding to miscarriage was available for 20 women: 11 miscarried in the first 7 days, 15 within 14 days, and 18 within 21 days. All of the miscarriages occurred within 28 days of the first bleed.

Dr. Adam determined that six baseline biomarkers were significantly associated with miscarriage at the 20th percentile: history of subfertility, bleeding score of two on a five-point scale, gestational age of the fetus, fetal crown-rump length of 4 mm, and serum levels of progesterone and hCG (32 nmol/L and 1,500 iU/L, respectively).

"All of these had good positive predictive values, indicating that a pregnancy had a good chance of surviving," Dr. Adam said, "but the negative predictive values were not useful for clinical practice or research."

A multivariate regression analysis, however, did identify that a combination of baseline bleeding score (two on a five-point scale) and baseline hCG level (1,500 iU/L) exhibited excellent positive and negative predictive values (94% and 77%, respectively). The equation used for computing the pregnancy viability index was hCG level/bleeding score × 1.87 × 10, where the bleeding score odds ratio for miscarriage is 1.87.

"This research has, for the first time, offered us a tool to begin to attempt to rescue pregnancies threatening to miscarry when, currently, all we can do is fold our hands and hope for the best," Dr. Adam said.

Dr. Adam plans to carry out a validation study on at least 1,000 women in the near future.

The study was funded by the Central Manchester Foundation Trust Biomedical Research Center. Dr. Adam said she had no relevant financial disclosures.

A combination of vaginal bleeding score and human chorionic gonadotropin levels may predict the possibility of miscarriage by up to 77%, and the possibility of ongoing pregnancy by 94%.

The "pregnancy viability index" could help physicians reassure women who present with threatened miscarriage that the pregnancy is likely to continue and prepare those who may face miscarriage. Additionally, the score might help channel medical interventions more appropriately, Dr. Kaltum Adam said at the annual meeting of the European Society of Human Reproduction and Embryology.

"It will enable us to provide targeted management and counseling for the affected women and reassure those who are likely to achieve a live birth," said Dr. Adam, an honorary clinical research fellow at St. Mary’s Hospital in Manchester, England.

Her prospective longitudinal study included 112 women who presented with threatened miscarriage at 6-10 weeks’ gestation and with a confirmed intrauterine pregnancy. They were followed for 5 weeks, during which time they completed daily charts of pain and vaginal bleeding; had a weekly ultrasound and physical exam; and contributed weekly blood samples that were analyzed for progesterone, human chorionic gonadotropin (hCG), hemoglobin, and other standard blood chemistry factors. Baseline screening also included maternal demographics, educational, and socioeconomic status. At the final visit, there was an ultrasound exam to confirm the pregnancy’s outcome.

Of the 112 women, 22 (20%) miscarried. Time of first vaginal bleeding to miscarriage was available for 20 women: 11 miscarried in the first 7 days, 15 within 14 days, and 18 within 21 days. All of the miscarriages occurred within 28 days of the first bleed.

Dr. Adam determined that six baseline biomarkers were significantly associated with miscarriage at the 20th percentile: history of subfertility, bleeding score of two on a five-point scale, gestational age of the fetus, fetal crown-rump length of 4 mm, and serum levels of progesterone and hCG (32 nmol/L and 1,500 iU/L, respectively).

"All of these had good positive predictive values, indicating that a pregnancy had a good chance of surviving," Dr. Adam said, "but the negative predictive values were not useful for clinical practice or research."

A multivariate regression analysis, however, did identify that a combination of baseline bleeding score (two on a five-point scale) and baseline hCG level (1,500 iU/L) exhibited excellent positive and negative predictive values (94% and 77%, respectively). The equation used for computing the pregnancy viability index was hCG level/bleeding score × 1.87 × 10, where the bleeding score odds ratio for miscarriage is 1.87.

"This research has, for the first time, offered us a tool to begin to attempt to rescue pregnancies threatening to miscarry when, currently, all we can do is fold our hands and hope for the best," Dr. Adam said.

Dr. Adam plans to carry out a validation study on at least 1,000 women in the near future.

The study was funded by the Central Manchester Foundation Trust Biomedical Research Center. Dr. Adam said she had no relevant financial disclosures.

After a double embryo transfer, women who are 5’7" or taller are twice as likely to carry dizygotic twins as are shorter women.

The incidence of twinning also significantly increased with an increasing number of retrieved oocytes, according to a retrospective database review.

The findings may help reproductive specialists develop a "tailor-made, personalized in vitro fertilization treatment," Dr. Marieke Lambers said during a press briefing at the annual meeting of the European Society of Human Reproduction and Embryology.

Dr. Lambers of Vrije Universiteit Medisch Centrum, Amsterdam, used information from the OMEGA database, a Dutch cohort study of ovarian stimulation for in vitro fertilization (IVF) and subsequent gynecologic diseases. The study comprised 19,840 women who underwent IVF or intracytoplasmic sperm injection from 1983 to 1995. Women received health questionnaires from 1997 to 1999, which were combined with data from their medical records.

Dr. Lambers’s analysis included 2,357 women who completed a first fresh – not cryopreserved – IVF cycle with a double embryo transfer. These resulted in 371 singleton pregnancies and 125 twin pregnancies.

The investigators conducted a multifactorial regression analysis to determine what factors, if any, influenced twinning in the mothers. These included body mass index, weight and height, maternal age, number of retrieved oocytes, alcohol use, education, and parity.

Two factors – maternal height and the number of eggs retrieved – were significantly associated with twinning, Dr. Lambers said. Women taller than 174 cm (5’7") were twice as likely to have twins as were shorter women. Those who had more than 11 oocytes retrieved were 2.4 times more likely to have twins than were those with fewer eggs retrieved.

Since the data were observational, it’s not possible to draw any causal relationships, but Dr. Lambers suggested that the higher number of oocytes could be an indication of egg quality. "The positive relationship between a higher number of oocytes retrieved and a twin pregnancy probably reflects the fact that these women would have had a larger choice of good quality embryos," she said.

However, "the association between increased height and pregnancy is more difficult to explain." Vascular endothelial growth factor (VEG-F) could play a part, she suggested. "Previous studies have shown that women who are prone to conceive twins after IVF had a higher level of [the growth factor], which promotes the growth of blood vessels at the site of implantation. Perhaps there is also an association between tall stature and increased VEG-F levels."

Theory aside, the findings could help refine IVF strategies for both doctors and patients.

"Doctors working in IVF are faced with a constant balancing act between giving the best chance of achieving a pregnancy without incurring all the problems associated with multiple births. We hope this work could be used in the future as a basis for predictive models that assist in the choice between single and double embryo transfer. This is important, because multiple pregnancies involved a higher risk of problems for the mother, such as preeclampsia, and also for the baby, [because of] preterm or immature delivery."

Dr. Lambers did not have any relevant financial disclosures.

After a double embryo transfer, women who are 5’7" or taller are twice as likely to carry dizygotic twins as are shorter women.

The incidence of twinning also significantly increased with an increasing number of retrieved oocytes, according to a retrospective database review.

The findings may help reproductive specialists develop a "tailor-made, personalized in vitro fertilization treatment," Dr. Marieke Lambers said during a press briefing at the annual meeting of the European Society of Human Reproduction and Embryology.

Dr. Lambers of Vrije Universiteit Medisch Centrum, Amsterdam, used information from the OMEGA database, a Dutch cohort study of ovarian stimulation for in vitro fertilization (IVF) and subsequent gynecologic diseases. The study comprised 19,840 women who underwent IVF or intracytoplasmic sperm injection from 1983 to 1995. Women received health questionnaires from 1997 to 1999, which were combined with data from their medical records.

Dr. Lambers’s analysis included 2,357 women who completed a first fresh – not cryopreserved – IVF cycle with a double embryo transfer. These resulted in 371 singleton pregnancies and 125 twin pregnancies.

The investigators conducted a multifactorial regression analysis to determine what factors, if any, influenced twinning in the mothers. These included body mass index, weight and height, maternal age, number of retrieved oocytes, alcohol use, education, and parity.

Two factors – maternal height and the number of eggs retrieved – were significantly associated with twinning, Dr. Lambers said. Women taller than 174 cm (5’7") were twice as likely to have twins as were shorter women. Those who had more than 11 oocytes retrieved were 2.4 times more likely to have twins than were those with fewer eggs retrieved.

Since the data were observational, it’s not possible to draw any causal relationships, but Dr. Lambers suggested that the higher number of oocytes could be an indication of egg quality. "The positive relationship between a higher number of oocytes retrieved and a twin pregnancy probably reflects the fact that these women would have had a larger choice of good quality embryos," she said.

However, "the association between increased height and pregnancy is more difficult to explain." Vascular endothelial growth factor (VEG-F) could play a part, she suggested. "Previous studies have shown that women who are prone to conceive twins after IVF had a higher level of [the growth factor], which promotes the growth of blood vessels at the site of implantation. Perhaps there is also an association between tall stature and increased VEG-F levels."

Theory aside, the findings could help refine IVF strategies for both doctors and patients.

"Doctors working in IVF are faced with a constant balancing act between giving the best chance of achieving a pregnancy without incurring all the problems associated with multiple births. We hope this work could be used in the future as a basis for predictive models that assist in the choice between single and double embryo transfer. This is important, because multiple pregnancies involved a higher risk of problems for the mother, such as preeclampsia, and also for the baby, [because of] preterm or immature delivery."

Dr. Lambers did not have any relevant financial disclosures.

After a double embryo transfer, women who are 5’7" or taller are twice as likely to carry dizygotic twins as are shorter women.

The incidence of twinning also significantly increased with an increasing number of retrieved oocytes, according to a retrospective database review.

The findings may help reproductive specialists develop a "tailor-made, personalized in vitro fertilization treatment," Dr. Marieke Lambers said during a press briefing at the annual meeting of the European Society of Human Reproduction and Embryology.

Dr. Lambers of Vrije Universiteit Medisch Centrum, Amsterdam, used information from the OMEGA database, a Dutch cohort study of ovarian stimulation for in vitro fertilization (IVF) and subsequent gynecologic diseases. The study comprised 19,840 women who underwent IVF or intracytoplasmic sperm injection from 1983 to 1995. Women received health questionnaires from 1997 to 1999, which were combined with data from their medical records.

Dr. Lambers’s analysis included 2,357 women who completed a first fresh – not cryopreserved – IVF cycle with a double embryo transfer. These resulted in 371 singleton pregnancies and 125 twin pregnancies.

The investigators conducted a multifactorial regression analysis to determine what factors, if any, influenced twinning in the mothers. These included body mass index, weight and height, maternal age, number of retrieved oocytes, alcohol use, education, and parity.

Two factors – maternal height and the number of eggs retrieved – were significantly associated with twinning, Dr. Lambers said. Women taller than 174 cm (5’7") were twice as likely to have twins as were shorter women. Those who had more than 11 oocytes retrieved were 2.4 times more likely to have twins than were those with fewer eggs retrieved.

Since the data were observational, it’s not possible to draw any causal relationships, but Dr. Lambers suggested that the higher number of oocytes could be an indication of egg quality. "The positive relationship between a higher number of oocytes retrieved and a twin pregnancy probably reflects the fact that these women would have had a larger choice of good quality embryos," she said.

However, "the association between increased height and pregnancy is more difficult to explain." Vascular endothelial growth factor (VEG-F) could play a part, she suggested. "Previous studies have shown that women who are prone to conceive twins after IVF had a higher level of [the growth factor], which promotes the growth of blood vessels at the site of implantation. Perhaps there is also an association between tall stature and increased VEG-F levels."

Theory aside, the findings could help refine IVF strategies for both doctors and patients.

"Doctors working in IVF are faced with a constant balancing act between giving the best chance of achieving a pregnancy without incurring all the problems associated with multiple births. We hope this work could be used in the future as a basis for predictive models that assist in the choice between single and double embryo transfer. This is important, because multiple pregnancies involved a higher risk of problems for the mother, such as preeclampsia, and also for the baby, [because of] preterm or immature delivery."

Dr. Lambers did not have any relevant financial disclosures.

Women who experience two or even more unexplained miscarriages are still likely to conceive and carry a child, with about 65% giving birth to a live infant, results of two new studies show.

Most of the successful pregnancies seem to occur within a year or so after a woman sees a fertility specialist, Dr. Ole Christiansen said during a press briefing at the annual meeting of the European Society of Reproduction and Embryology. Success is not related to treatment, since none exists for unexplained miscarriage. Instead, said Dr. Christiansen of Rigshospitalet, Copenhagen, the declining incidence of birth over 5 years is probably related to increasing maternal age with each attempt, or to the decision to give up efforts to conceive.

Dr. Stef P. Kaandorp, whose study came to a similar conclusion, said the results of both are encouraging.

"Women with recurrent miscarriage can be reassured that their time to a subsequent conception is not significantly longer that that for fertile women without a history of miscarriage," said Dr. Kaandorp, a research fellow at the University of Amsterdam. "Recurrent miscarriage is extremely stressful for these women, and we hope that our study will give them hope and encourage them to keep trying for the baby they want so much."

Prof. Christiansen presented a population-based retrospective study conducted in Denmark. Data were extracted from the National Danish Birth registry and identified 987 women who had at least three consecutive miscarriages and had been referred to a specialist clinic between 1986 and 2008. All of these women were aged 20-46 years at the time of referral. About one-third had some prior fertility treatments, including hormones, anticoagulants, and intravenous immunoglobulin.

Overall, 66% of the women (651) achieved a live birth after the consultation, Dr. Christiansen said. The highest rate occurred within the first 15 months of the consultation (71%). "The curve declines very rapidly after the first year after the consultation, then after 5 years it really flattens out," he said. "Only 2%-3% are likely to have a child after that."

Subgroup analyses found that increasing maternal age and the number of prior miscarriages were significantly associated with a continued rate of unsuccessful pregnancy. Nor were prior infertility treatments related to a later live birth, he said.

However, the new data should allow researchers to create a risk estimate graph that can predict the chance of a live birth much more precisely. "Instead of giving these women an uncertain risk estimate [for future live birth], we can now combine their age and number of miscarriages to give them a closer estimate of a live birth, and that is what matters to these women," he said.

Future research on this same cohort may look at what factors the male partner brings to the picture of recurrent miscarriage – if any.

In the second study, Dr. Kaandorp conducted a subanalysis of the ALIFE trial – a randomized, placebo-controlled study that showed neither aspirin combined with nadroparin nor aspirin alone improved the live-birth rate among women with unexplained recurrent miscarriage; the study ran from 2004-2008 (N. Engl. J. Med. 2010;362:1586-96).

Of the 364 women enrolled in that trial, Dr. Kaandorp identified 251 who had at least two miscarriages with a gestational age of 20 weeks or less and examined their subsequent rates of conception and live birth.

Of the cohort, 213 became naturally pregnant during by 2009. The median time to conception, regardless of outcome, was 21 weeks, although the range was 8-55 weeks. The cumulative pregnancy rate was 56% after 6 months, 74% after 12 months, and 86% after 24 months.

Of those who did conceive, 139 gave birth to a living child; 69 experienced another miscarriage; 2 had an ectopic pregnancy; 2 terminated the pregnancy; and 1 had an intrauterine death.

The presence of the Factor V Leiden genetic condition was the only factor significantly related to a shorter time to pregnancy; it increased by 91% the chance of conception by 11 weeks, compared with noncarriers.

"We should be cautious with this finding, because it only occurred in 11 women," Dr. Kaandorp noted. "At this point, I think we can only see it as hypothesis generating."

Neither Dr. Christiansen nor Dr. Kaandorp had any financial disclosures.

Women who experience two or even more unexplained miscarriages are still likely to conceive and carry a child, with about 65% giving birth to a live infant, results of two new studies show.

Most of the successful pregnancies seem to occur within a year or so after a woman sees a fertility specialist, Dr. Ole Christiansen said during a press briefing at the annual meeting of the European Society of Reproduction and Embryology. Success is not related to treatment, since none exists for unexplained miscarriage. Instead, said Dr. Christiansen of Rigshospitalet, Copenhagen, the declining incidence of birth over 5 years is probably related to increasing maternal age with each attempt, or to the decision to give up efforts to conceive.

Dr. Stef P. Kaandorp, whose study came to a similar conclusion, said the results of both are encouraging.

"Women with recurrent miscarriage can be reassured that their time to a subsequent conception is not significantly longer that that for fertile women without a history of miscarriage," said Dr. Kaandorp, a research fellow at the University of Amsterdam. "Recurrent miscarriage is extremely stressful for these women, and we hope that our study will give them hope and encourage them to keep trying for the baby they want so much."

Prof. Christiansen presented a population-based retrospective study conducted in Denmark. Data were extracted from the National Danish Birth registry and identified 987 women who had at least three consecutive miscarriages and had been referred to a specialist clinic between 1986 and 2008. All of these women were aged 20-46 years at the time of referral. About one-third had some prior fertility treatments, including hormones, anticoagulants, and intravenous immunoglobulin.

Overall, 66% of the women (651) achieved a live birth after the consultation, Dr. Christiansen said. The highest rate occurred within the first 15 months of the consultation (71%). "The curve declines very rapidly after the first year after the consultation, then after 5 years it really flattens out," he said. "Only 2%-3% are likely to have a child after that."

Subgroup analyses found that increasing maternal age and the number of prior miscarriages were significantly associated with a continued rate of unsuccessful pregnancy. Nor were prior infertility treatments related to a later live birth, he said.

However, the new data should allow researchers to create a risk estimate graph that can predict the chance of a live birth much more precisely. "Instead of giving these women an uncertain risk estimate [for future live birth], we can now combine their age and number of miscarriages to give them a closer estimate of a live birth, and that is what matters to these women," he said.

Future research on this same cohort may look at what factors the male partner brings to the picture of recurrent miscarriage – if any.

In the second study, Dr. Kaandorp conducted a subanalysis of the ALIFE trial – a randomized, placebo-controlled study that showed neither aspirin combined with nadroparin nor aspirin alone improved the live-birth rate among women with unexplained recurrent miscarriage; the study ran from 2004-2008 (N. Engl. J. Med. 2010;362:1586-96).

Of the 364 women enrolled in that trial, Dr. Kaandorp identified 251 who had at least two miscarriages with a gestational age of 20 weeks or less and examined their subsequent rates of conception and live birth.

Of the cohort, 213 became naturally pregnant during by 2009. The median time to conception, regardless of outcome, was 21 weeks, although the range was 8-55 weeks. The cumulative pregnancy rate was 56% after 6 months, 74% after 12 months, and 86% after 24 months.

Of those who did conceive, 139 gave birth to a living child; 69 experienced another miscarriage; 2 had an ectopic pregnancy; 2 terminated the pregnancy; and 1 had an intrauterine death.

The presence of the Factor V Leiden genetic condition was the only factor significantly related to a shorter time to pregnancy; it increased by 91% the chance of conception by 11 weeks, compared with noncarriers.

"We should be cautious with this finding, because it only occurred in 11 women," Dr. Kaandorp noted. "At this point, I think we can only see it as hypothesis generating."

Neither Dr. Christiansen nor Dr. Kaandorp had any financial disclosures.

Women who experience two or even more unexplained miscarriages are still likely to conceive and carry a child, with about 65% giving birth to a live infant, results of two new studies show.

Most of the successful pregnancies seem to occur within a year or so after a woman sees a fertility specialist, Dr. Ole Christiansen said during a press briefing at the annual meeting of the European Society of Reproduction and Embryology. Success is not related to treatment, since none exists for unexplained miscarriage. Instead, said Dr. Christiansen of Rigshospitalet, Copenhagen, the declining incidence of birth over 5 years is probably related to increasing maternal age with each attempt, or to the decision to give up efforts to conceive.

Dr. Stef P. Kaandorp, whose study came to a similar conclusion, said the results of both are encouraging.

"Women with recurrent miscarriage can be reassured that their time to a subsequent conception is not significantly longer that that for fertile women without a history of miscarriage," said Dr. Kaandorp, a research fellow at the University of Amsterdam. "Recurrent miscarriage is extremely stressful for these women, and we hope that our study will give them hope and encourage them to keep trying for the baby they want so much."

Prof. Christiansen presented a population-based retrospective study conducted in Denmark. Data were extracted from the National Danish Birth registry and identified 987 women who had at least three consecutive miscarriages and had been referred to a specialist clinic between 1986 and 2008. All of these women were aged 20-46 years at the time of referral. About one-third had some prior fertility treatments, including hormones, anticoagulants, and intravenous immunoglobulin.

Overall, 66% of the women (651) achieved a live birth after the consultation, Dr. Christiansen said. The highest rate occurred within the first 15 months of the consultation (71%). "The curve declines very rapidly after the first year after the consultation, then after 5 years it really flattens out," he said. "Only 2%-3% are likely to have a child after that."

Subgroup analyses found that increasing maternal age and the number of prior miscarriages were significantly associated with a continued rate of unsuccessful pregnancy. Nor were prior infertility treatments related to a later live birth, he said.

However, the new data should allow researchers to create a risk estimate graph that can predict the chance of a live birth much more precisely. "Instead of giving these women an uncertain risk estimate [for future live birth], we can now combine their age and number of miscarriages to give them a closer estimate of a live birth, and that is what matters to these women," he said.

Future research on this same cohort may look at what factors the male partner brings to the picture of recurrent miscarriage – if any.

In the second study, Dr. Kaandorp conducted a subanalysis of the ALIFE trial – a randomized, placebo-controlled study that showed neither aspirin combined with nadroparin nor aspirin alone improved the live-birth rate among women with unexplained recurrent miscarriage; the study ran from 2004-2008 (N. Engl. J. Med. 2010;362:1586-96).

Of the 364 women enrolled in that trial, Dr. Kaandorp identified 251 who had at least two miscarriages with a gestational age of 20 weeks or less and examined their subsequent rates of conception and live birth.

Of the cohort, 213 became naturally pregnant during by 2009. The median time to conception, regardless of outcome, was 21 weeks, although the range was 8-55 weeks. The cumulative pregnancy rate was 56% after 6 months, 74% after 12 months, and 86% after 24 months.

Of those who did conceive, 139 gave birth to a living child; 69 experienced another miscarriage; 2 had an ectopic pregnancy; 2 terminated the pregnancy; and 1 had an intrauterine death.

The presence of the Factor V Leiden genetic condition was the only factor significantly related to a shorter time to pregnancy; it increased by 91% the chance of conception by 11 weeks, compared with noncarriers.

"We should be cautious with this finding, because it only occurred in 11 women," Dr. Kaandorp noted. "At this point, I think we can only see it as hypothesis generating."

Neither Dr. Christiansen nor Dr. Kaandorp had any financial disclosures.