User login
Oocyte donation may up risk of preterm birth
HELSINKI – The risk of preterm birth and low birth weight is higher following oocyte donation for in vitro fertilization, compared with autologous IVF, according to a review of more than 100,000 singleton live births.
The findings could help in counseling women and when managing pregnancies resulting from oocyte donation IVF, Mohan S. Kamath, MBBS, reported at the annual meeting of the European Society of Human Reproduction and Embryology.
In a review of 100,092 singleton live births among women who underwent either fresh donor oocyte or autologous IVF, the rates of several outcomes were increased among the donor recipients. For example, preterm birth, defined as live birth before 37 weeks’ gestation, occurred in 14.8% vs. 9.4% of patients in the groups, respectively (odds ratio, 1.68), early preterm birth (live birth before 32 weeks’ gestation) occurred in 2.1% and 1.8% of patients (OR, 1.77), low birth weight (less than 2,500 g), occurred in 13.8% vs. 9.5% of patients (OR, 1.53), and very low birth weight (less than 1,500 g) occurred in 2.65% vs. 1.9% of patients (OR, 1.42).
The differences between the groups were statistically significant, said Dr. Kamath of Christian Medical College and Hospital, Vellore, India.
After adjusting for potential confounders, including female age, treatment duration, previous live birth, number of embryos transferred, single vs. multiple pregnancies resulting in singleton birth, and day of embryo transfer (before 5 days vs. 5 days or later), the increase in the risk of adverse perinatal outcomes of preterm birth, early preterm birth, and low birth weight remained significant (adjusted OR, 1.56, 1.41, and 1.43, respectively), he said.
The findings are important because the burden of poor ovarian response following IVF has been increasing, likely as a result of delayed childbearing and thus advanced age among those seeking IVF, Dr. Kamath said. However, little information is available regarding maternal or infant outcomes following oocyte donation, and the data that do exist have been conflicting, he said.
The increased risk of pregnancy complications following assisted reproductive technology, compared with spontaneously conceived pregnancies, has been largely attributed to the underlying infertility itself or to embryo-specific epigenetic modifications because of the in vitro fertilization techniques. The current study was conducted to determine whether use of donor oocytes affects obstetric and perinatal outcomes when compared with pregnancies that follow autologous IVF.
Anonymous data were obtained from the Human Fertilisation & Embryology Authority of the United Kingdom, which has collected data on all assisted reproductive treatment in the United Kingdom since 1991. For the current analysis, data from 1991 to 2011, including all singleton live births following fresh oocyte donor and autologous IVF cycles, were evaluated.
Although the dataset did not include information on potential confounders, such as smoking, body mass index, and medical history during pregnancy, the findings provide important insight into potential outcomes, Dr. Kamath said.
Dr. Kamath reported having no financial disclosures.
HELSINKI – The risk of preterm birth and low birth weight is higher following oocyte donation for in vitro fertilization, compared with autologous IVF, according to a review of more than 100,000 singleton live births.
The findings could help in counseling women and when managing pregnancies resulting from oocyte donation IVF, Mohan S. Kamath, MBBS, reported at the annual meeting of the European Society of Human Reproduction and Embryology.
In a review of 100,092 singleton live births among women who underwent either fresh donor oocyte or autologous IVF, the rates of several outcomes were increased among the donor recipients. For example, preterm birth, defined as live birth before 37 weeks’ gestation, occurred in 14.8% vs. 9.4% of patients in the groups, respectively (odds ratio, 1.68), early preterm birth (live birth before 32 weeks’ gestation) occurred in 2.1% and 1.8% of patients (OR, 1.77), low birth weight (less than 2,500 g), occurred in 13.8% vs. 9.5% of patients (OR, 1.53), and very low birth weight (less than 1,500 g) occurred in 2.65% vs. 1.9% of patients (OR, 1.42).
The differences between the groups were statistically significant, said Dr. Kamath of Christian Medical College and Hospital, Vellore, India.
After adjusting for potential confounders, including female age, treatment duration, previous live birth, number of embryos transferred, single vs. multiple pregnancies resulting in singleton birth, and day of embryo transfer (before 5 days vs. 5 days or later), the increase in the risk of adverse perinatal outcomes of preterm birth, early preterm birth, and low birth weight remained significant (adjusted OR, 1.56, 1.41, and 1.43, respectively), he said.
The findings are important because the burden of poor ovarian response following IVF has been increasing, likely as a result of delayed childbearing and thus advanced age among those seeking IVF, Dr. Kamath said. However, little information is available regarding maternal or infant outcomes following oocyte donation, and the data that do exist have been conflicting, he said.
The increased risk of pregnancy complications following assisted reproductive technology, compared with spontaneously conceived pregnancies, has been largely attributed to the underlying infertility itself or to embryo-specific epigenetic modifications because of the in vitro fertilization techniques. The current study was conducted to determine whether use of donor oocytes affects obstetric and perinatal outcomes when compared with pregnancies that follow autologous IVF.
Anonymous data were obtained from the Human Fertilisation & Embryology Authority of the United Kingdom, which has collected data on all assisted reproductive treatment in the United Kingdom since 1991. For the current analysis, data from 1991 to 2011, including all singleton live births following fresh oocyte donor and autologous IVF cycles, were evaluated.
Although the dataset did not include information on potential confounders, such as smoking, body mass index, and medical history during pregnancy, the findings provide important insight into potential outcomes, Dr. Kamath said.
Dr. Kamath reported having no financial disclosures.
HELSINKI – The risk of preterm birth and low birth weight is higher following oocyte donation for in vitro fertilization, compared with autologous IVF, according to a review of more than 100,000 singleton live births.
The findings could help in counseling women and when managing pregnancies resulting from oocyte donation IVF, Mohan S. Kamath, MBBS, reported at the annual meeting of the European Society of Human Reproduction and Embryology.
In a review of 100,092 singleton live births among women who underwent either fresh donor oocyte or autologous IVF, the rates of several outcomes were increased among the donor recipients. For example, preterm birth, defined as live birth before 37 weeks’ gestation, occurred in 14.8% vs. 9.4% of patients in the groups, respectively (odds ratio, 1.68), early preterm birth (live birth before 32 weeks’ gestation) occurred in 2.1% and 1.8% of patients (OR, 1.77), low birth weight (less than 2,500 g), occurred in 13.8% vs. 9.5% of patients (OR, 1.53), and very low birth weight (less than 1,500 g) occurred in 2.65% vs. 1.9% of patients (OR, 1.42).
The differences between the groups were statistically significant, said Dr. Kamath of Christian Medical College and Hospital, Vellore, India.
After adjusting for potential confounders, including female age, treatment duration, previous live birth, number of embryos transferred, single vs. multiple pregnancies resulting in singleton birth, and day of embryo transfer (before 5 days vs. 5 days or later), the increase in the risk of adverse perinatal outcomes of preterm birth, early preterm birth, and low birth weight remained significant (adjusted OR, 1.56, 1.41, and 1.43, respectively), he said.
The findings are important because the burden of poor ovarian response following IVF has been increasing, likely as a result of delayed childbearing and thus advanced age among those seeking IVF, Dr. Kamath said. However, little information is available regarding maternal or infant outcomes following oocyte donation, and the data that do exist have been conflicting, he said.
The increased risk of pregnancy complications following assisted reproductive technology, compared with spontaneously conceived pregnancies, has been largely attributed to the underlying infertility itself or to embryo-specific epigenetic modifications because of the in vitro fertilization techniques. The current study was conducted to determine whether use of donor oocytes affects obstetric and perinatal outcomes when compared with pregnancies that follow autologous IVF.
Anonymous data were obtained from the Human Fertilisation & Embryology Authority of the United Kingdom, which has collected data on all assisted reproductive treatment in the United Kingdom since 1991. For the current analysis, data from 1991 to 2011, including all singleton live births following fresh oocyte donor and autologous IVF cycles, were evaluated.
Although the dataset did not include information on potential confounders, such as smoking, body mass index, and medical history during pregnancy, the findings provide important insight into potential outcomes, Dr. Kamath said.
Dr. Kamath reported having no financial disclosures.
AT ESHRE 2016
Key clinical point: Risk for preterm birth and low birth weight was increased with oocyte donation, compared with autologous IVF.
Major finding: With oocyte donation, the risk of preterm birth, early preterm birth, and low birth weight were significantly increased (adjusted OR, 1.56, 1.41, and 1.43, respectively), compared with autologous IVF.
Data source: A review of data on 100,092 singleton live births.
Disclosures: Dr. Kamath reported having no financial disclosures.
IVF freeze-all strategy shows promise for improving pregnancy rates
HELSINKI – A freeze-all strategy in women of advanced maternal age who are undergoing in vitro fertilization appears to increase the likelihood of pregnancy, according to findings from two retrospective cohort studies.
In one matched cohort study comparing the outcomes of 1,636 freeze-all cycles and 1,636 fresh cycles, the ongoing pregnancy rates were 50% for freeze-all cycles and 44% for fresh cycles. After controlling for hormone levels, number of embryos transferred, diagnosis, age, and preimplantation genetic screening utilization, the investigators found that the difference was largely attributable to an effect in older women; the ongoing pregnancy rate was significantly higher in freeze-all cycles, compared with fresh cycles, among patients over age 35 years (46% vs. 33%; odds ratio, 1.6), Karen Hunter Cohn, PhD, reported at the annual meeting of the European Society of Human Reproduction and Embryology.
A benefit of frozen vs. fresh cycles also was seen among women with elevated progesterone levels prior to egg retrieval, and this was true regardless of age; the pregnancy rates for freeze-all vs. fresh cycles in those over age 35 years with progesterone levels over 1.3 ng/ml were 54% and 45%, respectively (OR, 1.4), and for those under age 35 with elevated progesterone, they were 44% and 30%, respectively (OR, 1.4), said Dr. Cohn, of Celmatix in New York.
However, a diagnosis of polycystic ovarian syndrome, endometriosis, tubal disease, or unexplained infertility had no significant impact on outcomes.
In another study comparing outcomes of 1,180 fresh embryo transfers and 517 frozen transfers after a freeze-all strategy in 1,469 women, the clinical pregnancy rates were higher for frozen transfers both in women under age 39 years (44.5% vs. 38.2%) and in those aged 39 years and older (34.9% vs. 22.7%), Sara Lopez, MD, reported during an abstract session.
Multivariate analysis showed a significantly positive effect of performing frozen transfers in both age groups, but the effect was greater in the older age group (OR, 1.60 vs. 1.39), said Dr. Lopez, of Clinica CIRH in Barcelona.
No difference was seen in miscarriage rates in either group, she noted.
Dr. Cohn’s study included patients from 12 fertility treatment centers in the United States who underwent IVF cycles from 2009 to 2015. Dr. Lopez and her colleagues studied women who underwent IVF between January 2014 and December 2015.
Both authors noted that IVF with frozen embryo transfer has become more common, and that freeze-all protocols in which all embryos are frozen and transferred in a later cycle have emerged to reduce the risk for ovarian hyperstimulation syndrome (OHSS), and to address concerns about endometrial receptivity in women undergoing controlled ovarian stimulation and/or experiencing a premature elevation of progesterone.
However, randomized controlled studies comparing the two approaches have focused only on good prognosis patients, and thus have not addressed which patients might benefit most from a freeze-all protocol, Dr. Cohn said.
Dr. Lopez further noted that “older IVF patients usually present with a diminished ovarian reserve and suboptimal oocyte quality.”
“These women are not normally at risk for ovarian hyperstimulation syndrome, so they usually have the best embryos transferred during a fresh cycle and are therefore exposed to embryo-endometrium asynchrony,” she explained, adding that since suboptimal embryo quality cannot be amended, efforts should be directed toward providing the best endometrial environment for embryo transfer.
Though both studies are limited by their retrospective design, the authors each concluded that a freeze-all strategy appears to be the best approach to achieving that environment in older women.
Eric A. Widra, MD, of Shady Grove Fertility in Washington, and one of Dr. Cohn’s coauthors, noted in a press statement that interest in a freeze-all approach is growing but is not used broadly.
“There are several reasons clinics do freeze-all cycles. These include patients at high risk for OHSS, patients having preimplantation genetic diagnosis prior to embryo transfer, and, importantly, those patients who have a premature rise in the concentration of progesterone hormone prior to egg retrieval. Several studies have shown that this rise in progesterone is associated with a lower pregnancy rate after fresh embryo transfer,” he said, concluding that while the evidence is intriguing, a prospective randomized study will be necessary to conclude whether a freeze-all strategy is effective for any group of patients.
Dr. Cohn is an employee of Celmatix. Dr. Widra and Dr. Lopez reported having no disclosures.
HELSINKI – A freeze-all strategy in women of advanced maternal age who are undergoing in vitro fertilization appears to increase the likelihood of pregnancy, according to findings from two retrospective cohort studies.
In one matched cohort study comparing the outcomes of 1,636 freeze-all cycles and 1,636 fresh cycles, the ongoing pregnancy rates were 50% for freeze-all cycles and 44% for fresh cycles. After controlling for hormone levels, number of embryos transferred, diagnosis, age, and preimplantation genetic screening utilization, the investigators found that the difference was largely attributable to an effect in older women; the ongoing pregnancy rate was significantly higher in freeze-all cycles, compared with fresh cycles, among patients over age 35 years (46% vs. 33%; odds ratio, 1.6), Karen Hunter Cohn, PhD, reported at the annual meeting of the European Society of Human Reproduction and Embryology.
A benefit of frozen vs. fresh cycles also was seen among women with elevated progesterone levels prior to egg retrieval, and this was true regardless of age; the pregnancy rates for freeze-all vs. fresh cycles in those over age 35 years with progesterone levels over 1.3 ng/ml were 54% and 45%, respectively (OR, 1.4), and for those under age 35 with elevated progesterone, they were 44% and 30%, respectively (OR, 1.4), said Dr. Cohn, of Celmatix in New York.
However, a diagnosis of polycystic ovarian syndrome, endometriosis, tubal disease, or unexplained infertility had no significant impact on outcomes.
In another study comparing outcomes of 1,180 fresh embryo transfers and 517 frozen transfers after a freeze-all strategy in 1,469 women, the clinical pregnancy rates were higher for frozen transfers both in women under age 39 years (44.5% vs. 38.2%) and in those aged 39 years and older (34.9% vs. 22.7%), Sara Lopez, MD, reported during an abstract session.
Multivariate analysis showed a significantly positive effect of performing frozen transfers in both age groups, but the effect was greater in the older age group (OR, 1.60 vs. 1.39), said Dr. Lopez, of Clinica CIRH in Barcelona.
No difference was seen in miscarriage rates in either group, she noted.
Dr. Cohn’s study included patients from 12 fertility treatment centers in the United States who underwent IVF cycles from 2009 to 2015. Dr. Lopez and her colleagues studied women who underwent IVF between January 2014 and December 2015.
Both authors noted that IVF with frozen embryo transfer has become more common, and that freeze-all protocols in which all embryos are frozen and transferred in a later cycle have emerged to reduce the risk for ovarian hyperstimulation syndrome (OHSS), and to address concerns about endometrial receptivity in women undergoing controlled ovarian stimulation and/or experiencing a premature elevation of progesterone.
However, randomized controlled studies comparing the two approaches have focused only on good prognosis patients, and thus have not addressed which patients might benefit most from a freeze-all protocol, Dr. Cohn said.
Dr. Lopez further noted that “older IVF patients usually present with a diminished ovarian reserve and suboptimal oocyte quality.”
“These women are not normally at risk for ovarian hyperstimulation syndrome, so they usually have the best embryos transferred during a fresh cycle and are therefore exposed to embryo-endometrium asynchrony,” she explained, adding that since suboptimal embryo quality cannot be amended, efforts should be directed toward providing the best endometrial environment for embryo transfer.
Though both studies are limited by their retrospective design, the authors each concluded that a freeze-all strategy appears to be the best approach to achieving that environment in older women.
Eric A. Widra, MD, of Shady Grove Fertility in Washington, and one of Dr. Cohn’s coauthors, noted in a press statement that interest in a freeze-all approach is growing but is not used broadly.
“There are several reasons clinics do freeze-all cycles. These include patients at high risk for OHSS, patients having preimplantation genetic diagnosis prior to embryo transfer, and, importantly, those patients who have a premature rise in the concentration of progesterone hormone prior to egg retrieval. Several studies have shown that this rise in progesterone is associated with a lower pregnancy rate after fresh embryo transfer,” he said, concluding that while the evidence is intriguing, a prospective randomized study will be necessary to conclude whether a freeze-all strategy is effective for any group of patients.
Dr. Cohn is an employee of Celmatix. Dr. Widra and Dr. Lopez reported having no disclosures.
HELSINKI – A freeze-all strategy in women of advanced maternal age who are undergoing in vitro fertilization appears to increase the likelihood of pregnancy, according to findings from two retrospective cohort studies.
In one matched cohort study comparing the outcomes of 1,636 freeze-all cycles and 1,636 fresh cycles, the ongoing pregnancy rates were 50% for freeze-all cycles and 44% for fresh cycles. After controlling for hormone levels, number of embryos transferred, diagnosis, age, and preimplantation genetic screening utilization, the investigators found that the difference was largely attributable to an effect in older women; the ongoing pregnancy rate was significantly higher in freeze-all cycles, compared with fresh cycles, among patients over age 35 years (46% vs. 33%; odds ratio, 1.6), Karen Hunter Cohn, PhD, reported at the annual meeting of the European Society of Human Reproduction and Embryology.
A benefit of frozen vs. fresh cycles also was seen among women with elevated progesterone levels prior to egg retrieval, and this was true regardless of age; the pregnancy rates for freeze-all vs. fresh cycles in those over age 35 years with progesterone levels over 1.3 ng/ml were 54% and 45%, respectively (OR, 1.4), and for those under age 35 with elevated progesterone, they were 44% and 30%, respectively (OR, 1.4), said Dr. Cohn, of Celmatix in New York.
However, a diagnosis of polycystic ovarian syndrome, endometriosis, tubal disease, or unexplained infertility had no significant impact on outcomes.
In another study comparing outcomes of 1,180 fresh embryo transfers and 517 frozen transfers after a freeze-all strategy in 1,469 women, the clinical pregnancy rates were higher for frozen transfers both in women under age 39 years (44.5% vs. 38.2%) and in those aged 39 years and older (34.9% vs. 22.7%), Sara Lopez, MD, reported during an abstract session.
Multivariate analysis showed a significantly positive effect of performing frozen transfers in both age groups, but the effect was greater in the older age group (OR, 1.60 vs. 1.39), said Dr. Lopez, of Clinica CIRH in Barcelona.
No difference was seen in miscarriage rates in either group, she noted.
Dr. Cohn’s study included patients from 12 fertility treatment centers in the United States who underwent IVF cycles from 2009 to 2015. Dr. Lopez and her colleagues studied women who underwent IVF between January 2014 and December 2015.
Both authors noted that IVF with frozen embryo transfer has become more common, and that freeze-all protocols in which all embryos are frozen and transferred in a later cycle have emerged to reduce the risk for ovarian hyperstimulation syndrome (OHSS), and to address concerns about endometrial receptivity in women undergoing controlled ovarian stimulation and/or experiencing a premature elevation of progesterone.
However, randomized controlled studies comparing the two approaches have focused only on good prognosis patients, and thus have not addressed which patients might benefit most from a freeze-all protocol, Dr. Cohn said.
Dr. Lopez further noted that “older IVF patients usually present with a diminished ovarian reserve and suboptimal oocyte quality.”
“These women are not normally at risk for ovarian hyperstimulation syndrome, so they usually have the best embryos transferred during a fresh cycle and are therefore exposed to embryo-endometrium asynchrony,” she explained, adding that since suboptimal embryo quality cannot be amended, efforts should be directed toward providing the best endometrial environment for embryo transfer.
Though both studies are limited by their retrospective design, the authors each concluded that a freeze-all strategy appears to be the best approach to achieving that environment in older women.
Eric A. Widra, MD, of Shady Grove Fertility in Washington, and one of Dr. Cohn’s coauthors, noted in a press statement that interest in a freeze-all approach is growing but is not used broadly.
“There are several reasons clinics do freeze-all cycles. These include patients at high risk for OHSS, patients having preimplantation genetic diagnosis prior to embryo transfer, and, importantly, those patients who have a premature rise in the concentration of progesterone hormone prior to egg retrieval. Several studies have shown that this rise in progesterone is associated with a lower pregnancy rate after fresh embryo transfer,” he said, concluding that while the evidence is intriguing, a prospective randomized study will be necessary to conclude whether a freeze-all strategy is effective for any group of patients.
Dr. Cohn is an employee of Celmatix. Dr. Widra and Dr. Lopez reported having no disclosures.
At ESHRE 2016
Weight loss may improve fertility in anovulatory obese women
HELSINKI – A 6-month lifestyle intervention was associated with an increased natural conception rate in infertile anovulatory obese women, compared with infertile ovulatory obese women, although the rate of vaginal births of healthy singletons did not differ between the groups, according to subgroup analyses of the Lifestyle randomized controlled trial.
The findings, which confirm those in the overall study population and are likely explained by the beneficial effects of weight loss on the resumption of ovulation, have implications for managing obese women who are experiencing infertility, according to Anne van Oers, MD, of the University of Groningen (the Netherlands).
The Lifestyle trial – a multicenter study conducted in the Netherlands and published in 2016 – involved a 6-month lifestyle intervention preceding fertility treatment in obese infertile women. The intervention had no effect on the rate of vaginal births of healthy term singletons within 24 months versus immediate fertility treatment (relative risk, 0.77), although natural conceptions with an ongoing pregnancy did occur more often in the lifestyle intervention group (relative risk, 1.6).
For that study, conducted from 2009 to 2012, the investigators randomized 577 obese infertile women to either the 6-month lifestyle intervention followed by 18 months of infertility treatment or to immediate fertility treatment. Weight loss was 4.4 kg in the intervention group and 1.1 kg in the control group, Dr. van Oers said at the annual meeting of the European Society of Human Reproduction and Embryology.
For the subgroup analyses, the investigators focused on six groups based on age (those 36 years and older and those under age 36), ovulation status (those who were anovulatory and those who were ovulatory), and body mass index (those with a body-mass index (BMI) of 35 kg/m2 or greater and those with BMI under 35).
In the 564 women who completed follow-up, only the rate of natural conception was improved by the preconception lifestyle intervention: This was true in most of the subgroups, but was most pronounced among anovulatory women (28% vs. 11.4% in ovulatory women who received the intervention), she said.
Obese women are known to be at increased risk of infertility and are less likely than nonobese women to conceive after fertility treatment. In one prior study, ovulating subfertile women with a BMI of 29 kg/m2 or higher had a 4% lower pregnancy rate per kg/m2 increase per year, compared with ovulatory subfertile women with a BMI below 29, Dr. van Oers noted.
Although the current findings are limited by the nature of the subgroup analyses – the main study was not powered on analyses of subgroups or interaction tests – the findings do suggest a benefit of lifestyle intervention in some women, she noted.
“Our findings that lifestyle intervention in obese women more often leads to natural conception, specifically in anovulatory women, should be used in their counseling before fertility treatment and could reasonably be offered as first-line treatment for anovulation in obese women,” she said in a written statement.
Of note, 22% of the women in the main study were unable to adhere to the lifestyle intervention despite intensive coaching, according to the study’s project leader, Annemieke Hoek, MD, PhD, also from the University of Groningen.
The women who did not complete the program were significantly less likely to become pregnant, and those who did complete the program were more likely to conceive naturally, compared with the women in the control group who received immediate fertility treatment, Dr. Hoek said, noting that, again, this effect was most pronounced in anovulatory women.
Dr. van Oers and Dr. Hoek reported having no financial disclosures.
HELSINKI – A 6-month lifestyle intervention was associated with an increased natural conception rate in infertile anovulatory obese women, compared with infertile ovulatory obese women, although the rate of vaginal births of healthy singletons did not differ between the groups, according to subgroup analyses of the Lifestyle randomized controlled trial.
The findings, which confirm those in the overall study population and are likely explained by the beneficial effects of weight loss on the resumption of ovulation, have implications for managing obese women who are experiencing infertility, according to Anne van Oers, MD, of the University of Groningen (the Netherlands).
The Lifestyle trial – a multicenter study conducted in the Netherlands and published in 2016 – involved a 6-month lifestyle intervention preceding fertility treatment in obese infertile women. The intervention had no effect on the rate of vaginal births of healthy term singletons within 24 months versus immediate fertility treatment (relative risk, 0.77), although natural conceptions with an ongoing pregnancy did occur more often in the lifestyle intervention group (relative risk, 1.6).
For that study, conducted from 2009 to 2012, the investigators randomized 577 obese infertile women to either the 6-month lifestyle intervention followed by 18 months of infertility treatment or to immediate fertility treatment. Weight loss was 4.4 kg in the intervention group and 1.1 kg in the control group, Dr. van Oers said at the annual meeting of the European Society of Human Reproduction and Embryology.
For the subgroup analyses, the investigators focused on six groups based on age (those 36 years and older and those under age 36), ovulation status (those who were anovulatory and those who were ovulatory), and body mass index (those with a body-mass index (BMI) of 35 kg/m2 or greater and those with BMI under 35).
In the 564 women who completed follow-up, only the rate of natural conception was improved by the preconception lifestyle intervention: This was true in most of the subgroups, but was most pronounced among anovulatory women (28% vs. 11.4% in ovulatory women who received the intervention), she said.
Obese women are known to be at increased risk of infertility and are less likely than nonobese women to conceive after fertility treatment. In one prior study, ovulating subfertile women with a BMI of 29 kg/m2 or higher had a 4% lower pregnancy rate per kg/m2 increase per year, compared with ovulatory subfertile women with a BMI below 29, Dr. van Oers noted.
Although the current findings are limited by the nature of the subgroup analyses – the main study was not powered on analyses of subgroups or interaction tests – the findings do suggest a benefit of lifestyle intervention in some women, she noted.
“Our findings that lifestyle intervention in obese women more often leads to natural conception, specifically in anovulatory women, should be used in their counseling before fertility treatment and could reasonably be offered as first-line treatment for anovulation in obese women,” she said in a written statement.
Of note, 22% of the women in the main study were unable to adhere to the lifestyle intervention despite intensive coaching, according to the study’s project leader, Annemieke Hoek, MD, PhD, also from the University of Groningen.
The women who did not complete the program were significantly less likely to become pregnant, and those who did complete the program were more likely to conceive naturally, compared with the women in the control group who received immediate fertility treatment, Dr. Hoek said, noting that, again, this effect was most pronounced in anovulatory women.
Dr. van Oers and Dr. Hoek reported having no financial disclosures.
HELSINKI – A 6-month lifestyle intervention was associated with an increased natural conception rate in infertile anovulatory obese women, compared with infertile ovulatory obese women, although the rate of vaginal births of healthy singletons did not differ between the groups, according to subgroup analyses of the Lifestyle randomized controlled trial.
The findings, which confirm those in the overall study population and are likely explained by the beneficial effects of weight loss on the resumption of ovulation, have implications for managing obese women who are experiencing infertility, according to Anne van Oers, MD, of the University of Groningen (the Netherlands).
The Lifestyle trial – a multicenter study conducted in the Netherlands and published in 2016 – involved a 6-month lifestyle intervention preceding fertility treatment in obese infertile women. The intervention had no effect on the rate of vaginal births of healthy term singletons within 24 months versus immediate fertility treatment (relative risk, 0.77), although natural conceptions with an ongoing pregnancy did occur more often in the lifestyle intervention group (relative risk, 1.6).
For that study, conducted from 2009 to 2012, the investigators randomized 577 obese infertile women to either the 6-month lifestyle intervention followed by 18 months of infertility treatment or to immediate fertility treatment. Weight loss was 4.4 kg in the intervention group and 1.1 kg in the control group, Dr. van Oers said at the annual meeting of the European Society of Human Reproduction and Embryology.
For the subgroup analyses, the investigators focused on six groups based on age (those 36 years and older and those under age 36), ovulation status (those who were anovulatory and those who were ovulatory), and body mass index (those with a body-mass index (BMI) of 35 kg/m2 or greater and those with BMI under 35).
In the 564 women who completed follow-up, only the rate of natural conception was improved by the preconception lifestyle intervention: This was true in most of the subgroups, but was most pronounced among anovulatory women (28% vs. 11.4% in ovulatory women who received the intervention), she said.
Obese women are known to be at increased risk of infertility and are less likely than nonobese women to conceive after fertility treatment. In one prior study, ovulating subfertile women with a BMI of 29 kg/m2 or higher had a 4% lower pregnancy rate per kg/m2 increase per year, compared with ovulatory subfertile women with a BMI below 29, Dr. van Oers noted.
Although the current findings are limited by the nature of the subgroup analyses – the main study was not powered on analyses of subgroups or interaction tests – the findings do suggest a benefit of lifestyle intervention in some women, she noted.
“Our findings that lifestyle intervention in obese women more often leads to natural conception, specifically in anovulatory women, should be used in their counseling before fertility treatment and could reasonably be offered as first-line treatment for anovulation in obese women,” she said in a written statement.
Of note, 22% of the women in the main study were unable to adhere to the lifestyle intervention despite intensive coaching, according to the study’s project leader, Annemieke Hoek, MD, PhD, also from the University of Groningen.
The women who did not complete the program were significantly less likely to become pregnant, and those who did complete the program were more likely to conceive naturally, compared with the women in the control group who received immediate fertility treatment, Dr. Hoek said, noting that, again, this effect was most pronounced in anovulatory women.
Dr. van Oers and Dr. Hoek reported having no financial disclosures.
AT ESHRE 2016
Key clinical point: A lifestyle intervention involving weight loss was associated with an increased natural conception rate in infertile anovulatory obese women, compared with infertile ovulatory obese women.
Major finding: The postintervention natural conception rate was 28% in anovulatory obese women, compared with 11.4% in ovulatory obese women.
Data source: Subgroup analyses in 564 infertile obese women from a randomized controlled trial.
Disclosures: Dr. van Oers and Dr. Hoek reported having no financial disclosures.
Threatened miscarriage diagnosis increases risk for other poor outcomes
HELSINKI, FINLAND – Women with threatened miscarriage early in pregnancy are at increased risk of developing complications that can contribute to term stillbirths, according to the findings of a systematic review and meta-analysis.
The meta-analysis of data from 14 prospective studies – including 36,601 women with threatened miscarriage prior to 24 weeks of gestation – showed that the women were at significantly increased risk of preterm birth (odds ratio, 2.65), preterm premature rupture of membranes (OR, 2.98), placental abruption (OR, 2.95), placenta previa (OR, 4.37), low birth weight (OR, 1.57), and neonatal asphyxia (OR, 1.8), compared with women without threatened miscarriage, Rekha N. Pillai, MBBS, reported at the annual meeting of the European Society of Human Reproduction and Embryology.
The risk of stillbirth/intrauterine death in the study was more than double in patients with threatened miscarriage early in pregnancy, (OR, 2.02), said Dr. Pillai of University Hospitals of Leicester NHS Trust, England.
Early threatened miscarriage also was associated with preeclampsia, intrauterine growth restriction, neonatal death, and cesarean section, she noted.
Bleeding in early pregnancy occurs in 16%-25% of pregnant women, and women with this type of bleeding and a viable pregnancy noted on an ultrasound scan are diagnosed with threatened miscarriage, which can indicate a problem with placental development and dysfunction. This, in turn, explains the increased incidence of maternal and perinatal complications in women with early bleeding, Dr. Pillai explained.
A 2009 review and meta-analysis highlighted a need for more prospective studies, and several have been published since then. The current study represents an “updated systematic review,” she said.
Studies included in the current review were published between 1946 and 2015. Though limited by questionable quality of some of the studies included in the review, and potential confounding variables such as maternal age, ethnicity, body mass index, and obstetric history – which were not accounted for in some studies – the findings suggest a need for increased surveillance during the prenatal period in women with threatened miscarriage in early pregnancy to improve outcomes, she said.
Dr. Pillai reported having no financial disclosures.
HELSINKI, FINLAND – Women with threatened miscarriage early in pregnancy are at increased risk of developing complications that can contribute to term stillbirths, according to the findings of a systematic review and meta-analysis.
The meta-analysis of data from 14 prospective studies – including 36,601 women with threatened miscarriage prior to 24 weeks of gestation – showed that the women were at significantly increased risk of preterm birth (odds ratio, 2.65), preterm premature rupture of membranes (OR, 2.98), placental abruption (OR, 2.95), placenta previa (OR, 4.37), low birth weight (OR, 1.57), and neonatal asphyxia (OR, 1.8), compared with women without threatened miscarriage, Rekha N. Pillai, MBBS, reported at the annual meeting of the European Society of Human Reproduction and Embryology.
The risk of stillbirth/intrauterine death in the study was more than double in patients with threatened miscarriage early in pregnancy, (OR, 2.02), said Dr. Pillai of University Hospitals of Leicester NHS Trust, England.
Early threatened miscarriage also was associated with preeclampsia, intrauterine growth restriction, neonatal death, and cesarean section, she noted.
Bleeding in early pregnancy occurs in 16%-25% of pregnant women, and women with this type of bleeding and a viable pregnancy noted on an ultrasound scan are diagnosed with threatened miscarriage, which can indicate a problem with placental development and dysfunction. This, in turn, explains the increased incidence of maternal and perinatal complications in women with early bleeding, Dr. Pillai explained.
A 2009 review and meta-analysis highlighted a need for more prospective studies, and several have been published since then. The current study represents an “updated systematic review,” she said.
Studies included in the current review were published between 1946 and 2015. Though limited by questionable quality of some of the studies included in the review, and potential confounding variables such as maternal age, ethnicity, body mass index, and obstetric history – which were not accounted for in some studies – the findings suggest a need for increased surveillance during the prenatal period in women with threatened miscarriage in early pregnancy to improve outcomes, she said.
Dr. Pillai reported having no financial disclosures.
HELSINKI, FINLAND – Women with threatened miscarriage early in pregnancy are at increased risk of developing complications that can contribute to term stillbirths, according to the findings of a systematic review and meta-analysis.
The meta-analysis of data from 14 prospective studies – including 36,601 women with threatened miscarriage prior to 24 weeks of gestation – showed that the women were at significantly increased risk of preterm birth (odds ratio, 2.65), preterm premature rupture of membranes (OR, 2.98), placental abruption (OR, 2.95), placenta previa (OR, 4.37), low birth weight (OR, 1.57), and neonatal asphyxia (OR, 1.8), compared with women without threatened miscarriage, Rekha N. Pillai, MBBS, reported at the annual meeting of the European Society of Human Reproduction and Embryology.
The risk of stillbirth/intrauterine death in the study was more than double in patients with threatened miscarriage early in pregnancy, (OR, 2.02), said Dr. Pillai of University Hospitals of Leicester NHS Trust, England.
Early threatened miscarriage also was associated with preeclampsia, intrauterine growth restriction, neonatal death, and cesarean section, she noted.
Bleeding in early pregnancy occurs in 16%-25% of pregnant women, and women with this type of bleeding and a viable pregnancy noted on an ultrasound scan are diagnosed with threatened miscarriage, which can indicate a problem with placental development and dysfunction. This, in turn, explains the increased incidence of maternal and perinatal complications in women with early bleeding, Dr. Pillai explained.
A 2009 review and meta-analysis highlighted a need for more prospective studies, and several have been published since then. The current study represents an “updated systematic review,” she said.
Studies included in the current review were published between 1946 and 2015. Though limited by questionable quality of some of the studies included in the review, and potential confounding variables such as maternal age, ethnicity, body mass index, and obstetric history – which were not accounted for in some studies – the findings suggest a need for increased surveillance during the prenatal period in women with threatened miscarriage in early pregnancy to improve outcomes, she said.
Dr. Pillai reported having no financial disclosures.
AT ESHRE 2016
Key clinical point: Threatened miscarriage in early pregnancy increases the risk of developing complications that can contribute to term stillbirths.
Major finding: The risk of stillbirth/intrauterine death was more than double in patients with threatened miscarriage early in pregnancy (odds ratio, 2.02).
Data source: A systematic review and meta-analysis of 14 prospective studies involving 36,601 women.
Disclosures: Dr. Pillai reported having no financial disclosures.
Jury still out on value of r-HGH with IVF
HELSINKI, FINLAND – Recombinant human growth hormone, or r-HGH, offered no advantage over placebo with respect to improving the live birth rate among poor-responding women undergoing in vitro fertilization in a randomized controlled study.
The current findings and those from previous studies leave questions about the value of r-HGH supplementation unanswered, Robert Norman, MD, said at the annual meeting of the European Society of Human Reproduction and Embryology.
An “extremely large” randomized trial would be needed to definitively show whether poor IVF responders benefit from r-HGH supplementation, he said.
The clinical pregnancy rate in 66 women randomized to receive r-HGH in the current study was 9.1%, compared with 9.2% in 65 patients in the placebo group. In the groups, respectively, the mean number of oocytes collected was 5.38 and 4.96, median embryo quality was 2.00 and 2.14, median days of a study drug were 8 and 9, and in both groups the median number of days of follicle stimulating hormone was 8, and the mean number of embryos transferred was 1.
The overall live birth rate per patient randomized was 12.3%; the groups did not differ significantly on any of these measures, said Dr. Norman of the University of Adelaide, and Fertility SA, Australia.
Human growth hormone is known to be important for ovarian steroidogenesis and follicular development, and prior research, including a recent Cochrane Review, has suggested it is associated with a trend toward improved live birth rates when used as an adjunct to IVF in poor responders (though not in routine IVF). The prior studies, however, have been underpowered, involved significant clinical heterogeneity between study groups, were not placebo controlled, and used pregnancy rather than live birth as the endpoint. Further, safety outcomes among patients treated with r-HGH were uncertain, Dr. Norman said.
For the current study, women were recruited from nine fertility centers in Australia and from one center in New Zealand. All met the criteria for poor response, having had a previous IVF cycle with no more than five eggs collected following maximum stimulation. Of the 131 women randomized, all underwent ovarian stimulation with the same previous drug dose, and 116 had oocyte retrieval, 97 had embryo transfer, 25 reported a positive pregnancy test, and 16 had a live birth, which was the primary endpoint of the study. Three sets of twins were born – all to women in the r-HGH group. Four serious adverse events – all congenital abnormalities – were noted, including three in the r-HGH group and one in the placebo group. No serious adverse events occurred.
Of note, the study, which was expected to be completed in 2 years, was terminated after 4 years because of slow recruitment. Since the 390 patients required to demonstrate a difference between the groups were not enrolled, the study remained underpowered, Dr. Norman said.
Nonetheless, the findings, which highlight the challenges in answering the questions that could shed light on the best clinical treatment for a poor IVF responder, fail to provide any evidence either for benefit or for lack of benefit with the use of r-HGH in this group.
“If it were cheap, it might find a place in poor responders, but normal doses cost more than $1,000,” he said in a press statement regarding the findings.
Poor responders are a notoriously difficult group to treat, and although many strategies have been tried, there is no solid evidence that any of them improve the outcome of most concern to women undergoing IVF: the live birth rate, he added, noting that 30% of patients who are poor IVF responders and who have low pregnancy rates are over 40 years old.
Dr. Norman reported having no financial disclosures.
HELSINKI, FINLAND – Recombinant human growth hormone, or r-HGH, offered no advantage over placebo with respect to improving the live birth rate among poor-responding women undergoing in vitro fertilization in a randomized controlled study.
The current findings and those from previous studies leave questions about the value of r-HGH supplementation unanswered, Robert Norman, MD, said at the annual meeting of the European Society of Human Reproduction and Embryology.
An “extremely large” randomized trial would be needed to definitively show whether poor IVF responders benefit from r-HGH supplementation, he said.
The clinical pregnancy rate in 66 women randomized to receive r-HGH in the current study was 9.1%, compared with 9.2% in 65 patients in the placebo group. In the groups, respectively, the mean number of oocytes collected was 5.38 and 4.96, median embryo quality was 2.00 and 2.14, median days of a study drug were 8 and 9, and in both groups the median number of days of follicle stimulating hormone was 8, and the mean number of embryos transferred was 1.
The overall live birth rate per patient randomized was 12.3%; the groups did not differ significantly on any of these measures, said Dr. Norman of the University of Adelaide, and Fertility SA, Australia.
Human growth hormone is known to be important for ovarian steroidogenesis and follicular development, and prior research, including a recent Cochrane Review, has suggested it is associated with a trend toward improved live birth rates when used as an adjunct to IVF in poor responders (though not in routine IVF). The prior studies, however, have been underpowered, involved significant clinical heterogeneity between study groups, were not placebo controlled, and used pregnancy rather than live birth as the endpoint. Further, safety outcomes among patients treated with r-HGH were uncertain, Dr. Norman said.
For the current study, women were recruited from nine fertility centers in Australia and from one center in New Zealand. All met the criteria for poor response, having had a previous IVF cycle with no more than five eggs collected following maximum stimulation. Of the 131 women randomized, all underwent ovarian stimulation with the same previous drug dose, and 116 had oocyte retrieval, 97 had embryo transfer, 25 reported a positive pregnancy test, and 16 had a live birth, which was the primary endpoint of the study. Three sets of twins were born – all to women in the r-HGH group. Four serious adverse events – all congenital abnormalities – were noted, including three in the r-HGH group and one in the placebo group. No serious adverse events occurred.
Of note, the study, which was expected to be completed in 2 years, was terminated after 4 years because of slow recruitment. Since the 390 patients required to demonstrate a difference between the groups were not enrolled, the study remained underpowered, Dr. Norman said.
Nonetheless, the findings, which highlight the challenges in answering the questions that could shed light on the best clinical treatment for a poor IVF responder, fail to provide any evidence either for benefit or for lack of benefit with the use of r-HGH in this group.
“If it were cheap, it might find a place in poor responders, but normal doses cost more than $1,000,” he said in a press statement regarding the findings.
Poor responders are a notoriously difficult group to treat, and although many strategies have been tried, there is no solid evidence that any of them improve the outcome of most concern to women undergoing IVF: the live birth rate, he added, noting that 30% of patients who are poor IVF responders and who have low pregnancy rates are over 40 years old.
Dr. Norman reported having no financial disclosures.
HELSINKI, FINLAND – Recombinant human growth hormone, or r-HGH, offered no advantage over placebo with respect to improving the live birth rate among poor-responding women undergoing in vitro fertilization in a randomized controlled study.
The current findings and those from previous studies leave questions about the value of r-HGH supplementation unanswered, Robert Norman, MD, said at the annual meeting of the European Society of Human Reproduction and Embryology.
An “extremely large” randomized trial would be needed to definitively show whether poor IVF responders benefit from r-HGH supplementation, he said.
The clinical pregnancy rate in 66 women randomized to receive r-HGH in the current study was 9.1%, compared with 9.2% in 65 patients in the placebo group. In the groups, respectively, the mean number of oocytes collected was 5.38 and 4.96, median embryo quality was 2.00 and 2.14, median days of a study drug were 8 and 9, and in both groups the median number of days of follicle stimulating hormone was 8, and the mean number of embryos transferred was 1.
The overall live birth rate per patient randomized was 12.3%; the groups did not differ significantly on any of these measures, said Dr. Norman of the University of Adelaide, and Fertility SA, Australia.
Human growth hormone is known to be important for ovarian steroidogenesis and follicular development, and prior research, including a recent Cochrane Review, has suggested it is associated with a trend toward improved live birth rates when used as an adjunct to IVF in poor responders (though not in routine IVF). The prior studies, however, have been underpowered, involved significant clinical heterogeneity between study groups, were not placebo controlled, and used pregnancy rather than live birth as the endpoint. Further, safety outcomes among patients treated with r-HGH were uncertain, Dr. Norman said.
For the current study, women were recruited from nine fertility centers in Australia and from one center in New Zealand. All met the criteria for poor response, having had a previous IVF cycle with no more than five eggs collected following maximum stimulation. Of the 131 women randomized, all underwent ovarian stimulation with the same previous drug dose, and 116 had oocyte retrieval, 97 had embryo transfer, 25 reported a positive pregnancy test, and 16 had a live birth, which was the primary endpoint of the study. Three sets of twins were born – all to women in the r-HGH group. Four serious adverse events – all congenital abnormalities – were noted, including three in the r-HGH group and one in the placebo group. No serious adverse events occurred.
Of note, the study, which was expected to be completed in 2 years, was terminated after 4 years because of slow recruitment. Since the 390 patients required to demonstrate a difference between the groups were not enrolled, the study remained underpowered, Dr. Norman said.
Nonetheless, the findings, which highlight the challenges in answering the questions that could shed light on the best clinical treatment for a poor IVF responder, fail to provide any evidence either for benefit or for lack of benefit with the use of r-HGH in this group.
“If it were cheap, it might find a place in poor responders, but normal doses cost more than $1,000,” he said in a press statement regarding the findings.
Poor responders are a notoriously difficult group to treat, and although many strategies have been tried, there is no solid evidence that any of them improve the outcome of most concern to women undergoing IVF: the live birth rate, he added, noting that 30% of patients who are poor IVF responders and who have low pregnancy rates are over 40 years old.
Dr. Norman reported having no financial disclosures.
AT ESHRE 2016
Key clinical point: Recombinant human growth hormone appears not to improve the live birth rate among poor-responding women undergoing in vitro fertilization.
Major finding: The overall live birth rate per patient randomized was 12.3% and did not differ between those who did and did not receive r-HGH.
Data source: A randomized controlled study involving 131 women.
Disclosures: Dr. Norman reported having no financial disclosures.
Study shows no benefit with brief immobilization after IUI
HELSINKI, FINLAND – A brief period of immobilization after intrauterine insemination did not improve pregnancy rates and was actually associated with a slight reduction in the pregnancy rate in a large single-center, randomized controlled trial.
The findings conflict with those of some prior smaller studies and contradict a widely held belief in the benefit of immobilization, which is usually carried out while the patient is in a supine position with the knees raised, Joukje van Rijswijk, MD, reported at the annual meeting of the European Society of Human Reproduction and Embryology.
In 479 patients with idiopathic or mild male subfertility and an indication for IUI who were randomized to 15 minutes of immobilization following IUI (950 cycles) or immediate mobilization (984 cycles), the cumulative ongoing pregnancy rate per couple was 32.2% and 40.3% in the groups, respectively (odds ratio, 0.70). The difference between the groups was not statistically significant, said Dr. van Rijswijk of VU University Medical Center, Amsterdam, The Netherlands.
Randomization in the study was stratified for the diagnosis of idiopathic or mild male subfertility. After adjustment for duration of subfertility, the difference between the group still did not reach statistical significance (odds ratio, 0.72), Dr. van Rijswijk said.
IUI is an established treatment for idiopathic and mild male subfertility, and while several factors are associated with pregnancy outcomes, the role of direct mobilization has remained controversial. Two recent studies showed a beneficial effect but were of questionable quality. For example, one of the studies found that 10 and 15 minutes of immobilization, vs. 5 minutes, had a beneficial effect on pregnancy rates, but the results were based on just one treatment cycle and “not on the more real-world context of multiple cycles,” according to an ESHRE press release.
The responsible mechanism for the benefit of immobilization remains unclear, Dr. van Rijswijk said, explaining that it is known from other studies that sperm cells can reach the fallopian tube 5 minutes after intravaginal insemination and can survive for several days in the womb.
“Why should bed rest affect that? There’s no biological explanation for a positive effect of immobilization,” she said.
“In our opinion, immobilization after IUI has no positive effect on pregnancy rates, and there is no reason why patients should stay immobilized after treatment,” she concluded, adding that the findings are “sufficiently strong to render the recommendation for bed rest obsolete.”
As for whether immobilization is also unwarranted for natural conception, Dr. van Rijswijk said the two insemination techniques are too different, thus the findings are not generalizable.
She reported having no relevant financial disclosures. The trial was funded by the VU University Medical Center.
HELSINKI, FINLAND – A brief period of immobilization after intrauterine insemination did not improve pregnancy rates and was actually associated with a slight reduction in the pregnancy rate in a large single-center, randomized controlled trial.
The findings conflict with those of some prior smaller studies and contradict a widely held belief in the benefit of immobilization, which is usually carried out while the patient is in a supine position with the knees raised, Joukje van Rijswijk, MD, reported at the annual meeting of the European Society of Human Reproduction and Embryology.
In 479 patients with idiopathic or mild male subfertility and an indication for IUI who were randomized to 15 minutes of immobilization following IUI (950 cycles) or immediate mobilization (984 cycles), the cumulative ongoing pregnancy rate per couple was 32.2% and 40.3% in the groups, respectively (odds ratio, 0.70). The difference between the groups was not statistically significant, said Dr. van Rijswijk of VU University Medical Center, Amsterdam, The Netherlands.
Randomization in the study was stratified for the diagnosis of idiopathic or mild male subfertility. After adjustment for duration of subfertility, the difference between the group still did not reach statistical significance (odds ratio, 0.72), Dr. van Rijswijk said.
IUI is an established treatment for idiopathic and mild male subfertility, and while several factors are associated with pregnancy outcomes, the role of direct mobilization has remained controversial. Two recent studies showed a beneficial effect but were of questionable quality. For example, one of the studies found that 10 and 15 minutes of immobilization, vs. 5 minutes, had a beneficial effect on pregnancy rates, but the results were based on just one treatment cycle and “not on the more real-world context of multiple cycles,” according to an ESHRE press release.
The responsible mechanism for the benefit of immobilization remains unclear, Dr. van Rijswijk said, explaining that it is known from other studies that sperm cells can reach the fallopian tube 5 minutes after intravaginal insemination and can survive for several days in the womb.
“Why should bed rest affect that? There’s no biological explanation for a positive effect of immobilization,” she said.
“In our opinion, immobilization after IUI has no positive effect on pregnancy rates, and there is no reason why patients should stay immobilized after treatment,” she concluded, adding that the findings are “sufficiently strong to render the recommendation for bed rest obsolete.”
As for whether immobilization is also unwarranted for natural conception, Dr. van Rijswijk said the two insemination techniques are too different, thus the findings are not generalizable.
She reported having no relevant financial disclosures. The trial was funded by the VU University Medical Center.
HELSINKI, FINLAND – A brief period of immobilization after intrauterine insemination did not improve pregnancy rates and was actually associated with a slight reduction in the pregnancy rate in a large single-center, randomized controlled trial.
The findings conflict with those of some prior smaller studies and contradict a widely held belief in the benefit of immobilization, which is usually carried out while the patient is in a supine position with the knees raised, Joukje van Rijswijk, MD, reported at the annual meeting of the European Society of Human Reproduction and Embryology.
In 479 patients with idiopathic or mild male subfertility and an indication for IUI who were randomized to 15 minutes of immobilization following IUI (950 cycles) or immediate mobilization (984 cycles), the cumulative ongoing pregnancy rate per couple was 32.2% and 40.3% in the groups, respectively (odds ratio, 0.70). The difference between the groups was not statistically significant, said Dr. van Rijswijk of VU University Medical Center, Amsterdam, The Netherlands.
Randomization in the study was stratified for the diagnosis of idiopathic or mild male subfertility. After adjustment for duration of subfertility, the difference between the group still did not reach statistical significance (odds ratio, 0.72), Dr. van Rijswijk said.
IUI is an established treatment for idiopathic and mild male subfertility, and while several factors are associated with pregnancy outcomes, the role of direct mobilization has remained controversial. Two recent studies showed a beneficial effect but were of questionable quality. For example, one of the studies found that 10 and 15 minutes of immobilization, vs. 5 minutes, had a beneficial effect on pregnancy rates, but the results were based on just one treatment cycle and “not on the more real-world context of multiple cycles,” according to an ESHRE press release.
The responsible mechanism for the benefit of immobilization remains unclear, Dr. van Rijswijk said, explaining that it is known from other studies that sperm cells can reach the fallopian tube 5 minutes after intravaginal insemination and can survive for several days in the womb.
“Why should bed rest affect that? There’s no biological explanation for a positive effect of immobilization,” she said.
“In our opinion, immobilization after IUI has no positive effect on pregnancy rates, and there is no reason why patients should stay immobilized after treatment,” she concluded, adding that the findings are “sufficiently strong to render the recommendation for bed rest obsolete.”
As for whether immobilization is also unwarranted for natural conception, Dr. van Rijswijk said the two insemination techniques are too different, thus the findings are not generalizable.
She reported having no relevant financial disclosures. The trial was funded by the VU University Medical Center.
AT ESHRE 2016
Key clinical point: Brief immobilization after intrauterine insemination did not improve pregnancy rates.
Major finding: The cumulative ongoing pregnancy rate per couple was 32.2% in the immobilization group, compared with 40.3% in the mobilization group (odds ratio, 0.70).
Data source: A single center, randomized controlled trial of 479 patients and 1,934 IUI cycles.
Disclosures: Dr. van Rijswijk reported having no financial disclosures. The trial was funded by the VU University Medical Center.
Low serum AMH level does not predict clinical pregnancy after ICSI
HELSINKI, FINLAND – Serum anti-Müllerian hormone levels do not predict clinical pregnancy, according to findings from a retrospective cohort study of patients undergoing intra-cytoplasmic sperm injection.
Indeed, although serum anti-Müllerian hormone (AMH) levels are closely related to female age and are a robust marker of ovarian reserve and ovarian response to gonadotropins, even patients with very low serum AMH levels in the study had a reasonable reproductive outcome, Alberto Pacheco Castro, PhD, of IVI Madrid, reported at the annual meeting of the European Society of Human Reproduction and Embryology.
The positive correlation between serum AMH and ovarian responses is well known, but there has been no consensus about whether ovarian stimulation should or should not be recommended for infertile women with low AMH values, he said. The new findings suggest that serum AMH levels should not be used to guide decision-making about ovarian stimulation in infertile women.
In the study, 5,570 intracytoplasmic sperm injection (ICSI) cycles between 2008 and 2014 were evaluated. No differences were seen in implantation rates or spontaneous abortion rates across six patient groups classified according to AMH levels. The groups had AMH levels less than or equal to 0.21 mg/mL, 0.22-0.8 ng/mL, 0.81-1.7 ng/mL, 1.71-3.2 ng/mL, 3.21-5.39 mg/mL, and greater than or equal to 5.40 mg/mL, respectively; the corresponding implantation rates were 28.9%, 25%, 29%, 28.8%, 30.5%, 35.3%, and the corresponding spontaneous abortion rates were 27.9%, 26.8%, 31%, 28.8%, 25.7%, and 22.1%, Dr. Pacheco said.
The clinical pregnancy rates in the groups were 45.3%, 48.1%, 47.4%, 45.2%, 48.0%, and 54.1%, respectively. Although the clinical pregnancy rates differed significantly between the highest and lowest AMH level groups, even the groups with the lowest levels had relatively good clinical pregnancy rates, and the receiver operating characteristic (ROC) curve showed no predictive value of AMH levels for clinical pregnancy, he noted.
The study comprised women from a university-affiliated infertility clinic, and their AMH levels were measured with a commercial test kit. Cycles were performed after controlled ovarian stimulation, pertinent data were collected for each cycle, and clinical results after embryo transfer were recorded.
The groups as classified by AMH levels differed significantly (lowest vs. highest level groups) with respect to age (mean age of 39 years vs. 36 years), antral follicle count (1.93 vs. 6.35), follicle-stimulating hormone dose (1606 IU vs. 1392 IU), oocytes retrieved (2.9 vs. 14), and mature oocytes (2.9 vs. 14.0), but not with respect to years of sterility, body mass index, or days of stimulation.
However, the study is limited by its retrospective design – it is possible that patients with very low AMH levels decided against ovulation stimulation – thus, prospective validation of the findings is required, Dr. Pacheco said.
He reported having no disclosures.
HELSINKI, FINLAND – Serum anti-Müllerian hormone levels do not predict clinical pregnancy, according to findings from a retrospective cohort study of patients undergoing intra-cytoplasmic sperm injection.
Indeed, although serum anti-Müllerian hormone (AMH) levels are closely related to female age and are a robust marker of ovarian reserve and ovarian response to gonadotropins, even patients with very low serum AMH levels in the study had a reasonable reproductive outcome, Alberto Pacheco Castro, PhD, of IVI Madrid, reported at the annual meeting of the European Society of Human Reproduction and Embryology.
The positive correlation between serum AMH and ovarian responses is well known, but there has been no consensus about whether ovarian stimulation should or should not be recommended for infertile women with low AMH values, he said. The new findings suggest that serum AMH levels should not be used to guide decision-making about ovarian stimulation in infertile women.
In the study, 5,570 intracytoplasmic sperm injection (ICSI) cycles between 2008 and 2014 were evaluated. No differences were seen in implantation rates or spontaneous abortion rates across six patient groups classified according to AMH levels. The groups had AMH levels less than or equal to 0.21 mg/mL, 0.22-0.8 ng/mL, 0.81-1.7 ng/mL, 1.71-3.2 ng/mL, 3.21-5.39 mg/mL, and greater than or equal to 5.40 mg/mL, respectively; the corresponding implantation rates were 28.9%, 25%, 29%, 28.8%, 30.5%, 35.3%, and the corresponding spontaneous abortion rates were 27.9%, 26.8%, 31%, 28.8%, 25.7%, and 22.1%, Dr. Pacheco said.
The clinical pregnancy rates in the groups were 45.3%, 48.1%, 47.4%, 45.2%, 48.0%, and 54.1%, respectively. Although the clinical pregnancy rates differed significantly between the highest and lowest AMH level groups, even the groups with the lowest levels had relatively good clinical pregnancy rates, and the receiver operating characteristic (ROC) curve showed no predictive value of AMH levels for clinical pregnancy, he noted.
The study comprised women from a university-affiliated infertility clinic, and their AMH levels were measured with a commercial test kit. Cycles were performed after controlled ovarian stimulation, pertinent data were collected for each cycle, and clinical results after embryo transfer were recorded.
The groups as classified by AMH levels differed significantly (lowest vs. highest level groups) with respect to age (mean age of 39 years vs. 36 years), antral follicle count (1.93 vs. 6.35), follicle-stimulating hormone dose (1606 IU vs. 1392 IU), oocytes retrieved (2.9 vs. 14), and mature oocytes (2.9 vs. 14.0), but not with respect to years of sterility, body mass index, or days of stimulation.
However, the study is limited by its retrospective design – it is possible that patients with very low AMH levels decided against ovulation stimulation – thus, prospective validation of the findings is required, Dr. Pacheco said.
He reported having no disclosures.
HELSINKI, FINLAND – Serum anti-Müllerian hormone levels do not predict clinical pregnancy, according to findings from a retrospective cohort study of patients undergoing intra-cytoplasmic sperm injection.
Indeed, although serum anti-Müllerian hormone (AMH) levels are closely related to female age and are a robust marker of ovarian reserve and ovarian response to gonadotropins, even patients with very low serum AMH levels in the study had a reasonable reproductive outcome, Alberto Pacheco Castro, PhD, of IVI Madrid, reported at the annual meeting of the European Society of Human Reproduction and Embryology.
The positive correlation between serum AMH and ovarian responses is well known, but there has been no consensus about whether ovarian stimulation should or should not be recommended for infertile women with low AMH values, he said. The new findings suggest that serum AMH levels should not be used to guide decision-making about ovarian stimulation in infertile women.
In the study, 5,570 intracytoplasmic sperm injection (ICSI) cycles between 2008 and 2014 were evaluated. No differences were seen in implantation rates or spontaneous abortion rates across six patient groups classified according to AMH levels. The groups had AMH levels less than or equal to 0.21 mg/mL, 0.22-0.8 ng/mL, 0.81-1.7 ng/mL, 1.71-3.2 ng/mL, 3.21-5.39 mg/mL, and greater than or equal to 5.40 mg/mL, respectively; the corresponding implantation rates were 28.9%, 25%, 29%, 28.8%, 30.5%, 35.3%, and the corresponding spontaneous abortion rates were 27.9%, 26.8%, 31%, 28.8%, 25.7%, and 22.1%, Dr. Pacheco said.
The clinical pregnancy rates in the groups were 45.3%, 48.1%, 47.4%, 45.2%, 48.0%, and 54.1%, respectively. Although the clinical pregnancy rates differed significantly between the highest and lowest AMH level groups, even the groups with the lowest levels had relatively good clinical pregnancy rates, and the receiver operating characteristic (ROC) curve showed no predictive value of AMH levels for clinical pregnancy, he noted.
The study comprised women from a university-affiliated infertility clinic, and their AMH levels were measured with a commercial test kit. Cycles were performed after controlled ovarian stimulation, pertinent data were collected for each cycle, and clinical results after embryo transfer were recorded.
The groups as classified by AMH levels differed significantly (lowest vs. highest level groups) with respect to age (mean age of 39 years vs. 36 years), antral follicle count (1.93 vs. 6.35), follicle-stimulating hormone dose (1606 IU vs. 1392 IU), oocytes retrieved (2.9 vs. 14), and mature oocytes (2.9 vs. 14.0), but not with respect to years of sterility, body mass index, or days of stimulation.
However, the study is limited by its retrospective design – it is possible that patients with very low AMH levels decided against ovulation stimulation – thus, prospective validation of the findings is required, Dr. Pacheco said.
He reported having no disclosures.
At ESHRE 2016
Most women conceive within 5 years of starting fertility treatment
HELSINKI, FINLAND – The overall birth rate within 5 years of initiating fertility treatment with homologous gametes was 71% among nearly 20,000 women in a Danish assisted reproductive technology registry.
Conception occurred after treatment in 57% of the women, and conception was spontaneous in 14%, Sara Malchau, MD, reported at the annual meeting of the European Society of Human Reproduction and Embryology.
The findings allow physicians to give couples a comprehensible, age-stratified, long-term prognosis at the start of treatment, said Dr. Malchau of Copenhagen University Hospital, Hvidovre, Denmark.
To assess long-term outcomes, Dr. Malchau and her colleagues identified all women in the mandatory Danish ART Registry who initiated fertility treatments with homologous gametes in pubic and private clinics in Denmark between 1997 and 2010. The 19,884 subjects’ treatment cycles were cross-linked with the country’s Medical Birth Registry to identify live births after treatment and spontaneous conception. Follow-up was available for up to 2 years for all of the women, up to 3 years for 14,445 women, and up to 5 years for 5,165 women.
The total live birth rates at 2, 3, and 5 years after the first treatment using ART or intrauterine insemination (IUI) were 57%, 65% and 71%, respectively. Dr. Malchau reported.
In women who had ART as the first treatment, the corresponding ART-conception live birth rates were 46.1%, 51.1%, and 52.9%, and the birth rates with spontaneous conception and IUI after 5 years were 11.2% and 0.6%, respectively.
In those with IUI first, 34.2% delivered after IUI conceptions within 2 years, with no significant increase in birth rates after 3 and 5 years. Shifting to ART in these women resulted in birth rates for ART conceptions of 15.1%, 21.1%, and 23.7% after 2, 3, and 5 years, respectively. After 5 years, the birth rate from spontaneous conception in all women starting treatment with IUI was 16.6%, she noted.
Stratification by age showed that the birth rates at 5 years were 80% for women under age 35 years, 60.5% for those aged 35-40 years, and 26.2% for those aged 40 and older.
While the national ART registry in Denmark is compulsory, underreporting can occur. However, it is cycle based, and since most women have repeated treatments, is it unlikely that the number of women with no birth was underestimated in this study, Dr. Malchau noted.
The findings – which reflect the Danish treatment strategy of three to six cycles of IUI followed by ART, explaining why birth rates after IUI did not increase after 2 years – help answer important patient questions, she said.
“Infertility patients have two key questions: What are our chances of having a baby and when will it happen?” said Dr. Malchau. “Overall chances of a live birth are good, but successful treatment takes time. Couples will often need several treatment cycles. And even though the greatest chance of conception is following treatment, there is still a reasonable chance of spontaneous conception.”
Spontaneous conception is most common in women under age 35 starting IUI (18% vs. 8% in those over 35 starting IVF treatment).
The findings are “robust and realistic,” and since those undergoing treatment have no idea how many treatment cycles they will need or have, a “prognosis based on fixed points in time better reflects their prospect of conception and delivery than birth rates after different numbers of attempts,” Dr. Malchau said.
Copenhagen University Hospital Hvidovre and Ferring Pharmaceuticals funded the study.
HELSINKI, FINLAND – The overall birth rate within 5 years of initiating fertility treatment with homologous gametes was 71% among nearly 20,000 women in a Danish assisted reproductive technology registry.
Conception occurred after treatment in 57% of the women, and conception was spontaneous in 14%, Sara Malchau, MD, reported at the annual meeting of the European Society of Human Reproduction and Embryology.
The findings allow physicians to give couples a comprehensible, age-stratified, long-term prognosis at the start of treatment, said Dr. Malchau of Copenhagen University Hospital, Hvidovre, Denmark.
To assess long-term outcomes, Dr. Malchau and her colleagues identified all women in the mandatory Danish ART Registry who initiated fertility treatments with homologous gametes in pubic and private clinics in Denmark between 1997 and 2010. The 19,884 subjects’ treatment cycles were cross-linked with the country’s Medical Birth Registry to identify live births after treatment and spontaneous conception. Follow-up was available for up to 2 years for all of the women, up to 3 years for 14,445 women, and up to 5 years for 5,165 women.
The total live birth rates at 2, 3, and 5 years after the first treatment using ART or intrauterine insemination (IUI) were 57%, 65% and 71%, respectively. Dr. Malchau reported.
In women who had ART as the first treatment, the corresponding ART-conception live birth rates were 46.1%, 51.1%, and 52.9%, and the birth rates with spontaneous conception and IUI after 5 years were 11.2% and 0.6%, respectively.
In those with IUI first, 34.2% delivered after IUI conceptions within 2 years, with no significant increase in birth rates after 3 and 5 years. Shifting to ART in these women resulted in birth rates for ART conceptions of 15.1%, 21.1%, and 23.7% after 2, 3, and 5 years, respectively. After 5 years, the birth rate from spontaneous conception in all women starting treatment with IUI was 16.6%, she noted.
Stratification by age showed that the birth rates at 5 years were 80% for women under age 35 years, 60.5% for those aged 35-40 years, and 26.2% for those aged 40 and older.
While the national ART registry in Denmark is compulsory, underreporting can occur. However, it is cycle based, and since most women have repeated treatments, is it unlikely that the number of women with no birth was underestimated in this study, Dr. Malchau noted.
The findings – which reflect the Danish treatment strategy of three to six cycles of IUI followed by ART, explaining why birth rates after IUI did not increase after 2 years – help answer important patient questions, she said.
“Infertility patients have two key questions: What are our chances of having a baby and when will it happen?” said Dr. Malchau. “Overall chances of a live birth are good, but successful treatment takes time. Couples will often need several treatment cycles. And even though the greatest chance of conception is following treatment, there is still a reasonable chance of spontaneous conception.”
Spontaneous conception is most common in women under age 35 starting IUI (18% vs. 8% in those over 35 starting IVF treatment).
The findings are “robust and realistic,” and since those undergoing treatment have no idea how many treatment cycles they will need or have, a “prognosis based on fixed points in time better reflects their prospect of conception and delivery than birth rates after different numbers of attempts,” Dr. Malchau said.
Copenhagen University Hospital Hvidovre and Ferring Pharmaceuticals funded the study.
HELSINKI, FINLAND – The overall birth rate within 5 years of initiating fertility treatment with homologous gametes was 71% among nearly 20,000 women in a Danish assisted reproductive technology registry.
Conception occurred after treatment in 57% of the women, and conception was spontaneous in 14%, Sara Malchau, MD, reported at the annual meeting of the European Society of Human Reproduction and Embryology.
The findings allow physicians to give couples a comprehensible, age-stratified, long-term prognosis at the start of treatment, said Dr. Malchau of Copenhagen University Hospital, Hvidovre, Denmark.
To assess long-term outcomes, Dr. Malchau and her colleagues identified all women in the mandatory Danish ART Registry who initiated fertility treatments with homologous gametes in pubic and private clinics in Denmark between 1997 and 2010. The 19,884 subjects’ treatment cycles were cross-linked with the country’s Medical Birth Registry to identify live births after treatment and spontaneous conception. Follow-up was available for up to 2 years for all of the women, up to 3 years for 14,445 women, and up to 5 years for 5,165 women.
The total live birth rates at 2, 3, and 5 years after the first treatment using ART or intrauterine insemination (IUI) were 57%, 65% and 71%, respectively. Dr. Malchau reported.
In women who had ART as the first treatment, the corresponding ART-conception live birth rates were 46.1%, 51.1%, and 52.9%, and the birth rates with spontaneous conception and IUI after 5 years were 11.2% and 0.6%, respectively.
In those with IUI first, 34.2% delivered after IUI conceptions within 2 years, with no significant increase in birth rates after 3 and 5 years. Shifting to ART in these women resulted in birth rates for ART conceptions of 15.1%, 21.1%, and 23.7% after 2, 3, and 5 years, respectively. After 5 years, the birth rate from spontaneous conception in all women starting treatment with IUI was 16.6%, she noted.
Stratification by age showed that the birth rates at 5 years were 80% for women under age 35 years, 60.5% for those aged 35-40 years, and 26.2% for those aged 40 and older.
While the national ART registry in Denmark is compulsory, underreporting can occur. However, it is cycle based, and since most women have repeated treatments, is it unlikely that the number of women with no birth was underestimated in this study, Dr. Malchau noted.
The findings – which reflect the Danish treatment strategy of three to six cycles of IUI followed by ART, explaining why birth rates after IUI did not increase after 2 years – help answer important patient questions, she said.
“Infertility patients have two key questions: What are our chances of having a baby and when will it happen?” said Dr. Malchau. “Overall chances of a live birth are good, but successful treatment takes time. Couples will often need several treatment cycles. And even though the greatest chance of conception is following treatment, there is still a reasonable chance of spontaneous conception.”
Spontaneous conception is most common in women under age 35 starting IUI (18% vs. 8% in those over 35 starting IVF treatment).
The findings are “robust and realistic,” and since those undergoing treatment have no idea how many treatment cycles they will need or have, a “prognosis based on fixed points in time better reflects their prospect of conception and delivery than birth rates after different numbers of attempts,” Dr. Malchau said.
Copenhagen University Hospital Hvidovre and Ferring Pharmaceuticals funded the study.
AT ESHRE 2016
Key clinical point: The overall birth rate within 5 years of starting fertility treatment with homologous gametes was more than 70%.
Major finding: Within 5 years, conception occurred after treatment in 57% of the women, and conception was spontaneous in 14%.
Data source: A population-based cohort study involving 19,884 Danish women.
Disclosures: Copenhagen University Hospital Hvidovre and Ferring Pharmaceuticals funded the study.
Cochrane review: Endometrial scratching may promote implantation
HELSINKI, FINLAND – Scratching the endometrium to create a “favorable inflammation” may improve the likelihood of embryo implantation in subfertile women trying to conceive either naturally or by intrauterine insemination, according to a Cochrane review.
The “injury” caused by the process, which is known as endometrial scratching, has been reported to increase the probability of pregnancy in women undergoing in vitro fertilization, especially those with recurrent implantation failure. The inflammatory response to the injury, which is performed by pipelle biopsy or a similar device, is thought to make the endometrium more receptive to implantation.
In the current meta-analysis and systematic review of eight trials comprising 1,180 women, endometrial scratching appeared to approximately double the chance of clinical pregnancy and live birth/ongoing pregnancy (relative risk, 1.92 and 2.26, respectively), compared with either no procedure or a placebo procedure, lead author Sarah Lensen reported in a poster at the annual meeting of the European Society of Human Reproduction and Embryology.
The difference between the groups was statistically significant.
The evidence suggests that endometrial scratching would increase the normal chance of a live birth or ongoing pregnancy over a set period of time from 9% to between 14% and 28%, explained Ms. Lensen, a PhD candidate at the University of Auckland, New Zealand.
No evidence was seen that endometrial scratching has any effect on miscarriage, ectopic pregnancy, or multiple pregnancy.
Pain during the procedure was reported in one of the eight studies, in which the average pain score was 6 out of 10.
Endometrial scratching is a simple and inexpensive procedure that can be conducted without analgesia during a short clinic visit, although the internal examination that is required can be associated with pain and discomfort, Ms. Lensen said.
For the review, she and her colleagues looked at randomized controlled trials evaluating endometrial scratching in women planning to have intrauterine insemination or attempting to conceive spontaneously (with or without ovulation induction), compared with either no intervention, mock intervention, or endometrial scratching performed at a different time or to a greater or lesser degree.
The researchers acknowledged that the quality of the evidence is quite low, with a risk of bias associated with most of the included trials. For this reason, the results should be viewed with caution, they said.
“High quality randomized controlled trials which recruit sufficient numbers of women are needed to confirm to refute these findings,” they wrote.
Ms. Lensen reported having no financial disclosures.
HELSINKI, FINLAND – Scratching the endometrium to create a “favorable inflammation” may improve the likelihood of embryo implantation in subfertile women trying to conceive either naturally or by intrauterine insemination, according to a Cochrane review.
The “injury” caused by the process, which is known as endometrial scratching, has been reported to increase the probability of pregnancy in women undergoing in vitro fertilization, especially those with recurrent implantation failure. The inflammatory response to the injury, which is performed by pipelle biopsy or a similar device, is thought to make the endometrium more receptive to implantation.
In the current meta-analysis and systematic review of eight trials comprising 1,180 women, endometrial scratching appeared to approximately double the chance of clinical pregnancy and live birth/ongoing pregnancy (relative risk, 1.92 and 2.26, respectively), compared with either no procedure or a placebo procedure, lead author Sarah Lensen reported in a poster at the annual meeting of the European Society of Human Reproduction and Embryology.
The difference between the groups was statistically significant.
The evidence suggests that endometrial scratching would increase the normal chance of a live birth or ongoing pregnancy over a set period of time from 9% to between 14% and 28%, explained Ms. Lensen, a PhD candidate at the University of Auckland, New Zealand.
No evidence was seen that endometrial scratching has any effect on miscarriage, ectopic pregnancy, or multiple pregnancy.
Pain during the procedure was reported in one of the eight studies, in which the average pain score was 6 out of 10.
Endometrial scratching is a simple and inexpensive procedure that can be conducted without analgesia during a short clinic visit, although the internal examination that is required can be associated with pain and discomfort, Ms. Lensen said.
For the review, she and her colleagues looked at randomized controlled trials evaluating endometrial scratching in women planning to have intrauterine insemination or attempting to conceive spontaneously (with or without ovulation induction), compared with either no intervention, mock intervention, or endometrial scratching performed at a different time or to a greater or lesser degree.
The researchers acknowledged that the quality of the evidence is quite low, with a risk of bias associated with most of the included trials. For this reason, the results should be viewed with caution, they said.
“High quality randomized controlled trials which recruit sufficient numbers of women are needed to confirm to refute these findings,” they wrote.
Ms. Lensen reported having no financial disclosures.
HELSINKI, FINLAND – Scratching the endometrium to create a “favorable inflammation” may improve the likelihood of embryo implantation in subfertile women trying to conceive either naturally or by intrauterine insemination, according to a Cochrane review.
The “injury” caused by the process, which is known as endometrial scratching, has been reported to increase the probability of pregnancy in women undergoing in vitro fertilization, especially those with recurrent implantation failure. The inflammatory response to the injury, which is performed by pipelle biopsy or a similar device, is thought to make the endometrium more receptive to implantation.
In the current meta-analysis and systematic review of eight trials comprising 1,180 women, endometrial scratching appeared to approximately double the chance of clinical pregnancy and live birth/ongoing pregnancy (relative risk, 1.92 and 2.26, respectively), compared with either no procedure or a placebo procedure, lead author Sarah Lensen reported in a poster at the annual meeting of the European Society of Human Reproduction and Embryology.
The difference between the groups was statistically significant.
The evidence suggests that endometrial scratching would increase the normal chance of a live birth or ongoing pregnancy over a set period of time from 9% to between 14% and 28%, explained Ms. Lensen, a PhD candidate at the University of Auckland, New Zealand.
No evidence was seen that endometrial scratching has any effect on miscarriage, ectopic pregnancy, or multiple pregnancy.
Pain during the procedure was reported in one of the eight studies, in which the average pain score was 6 out of 10.
Endometrial scratching is a simple and inexpensive procedure that can be conducted without analgesia during a short clinic visit, although the internal examination that is required can be associated with pain and discomfort, Ms. Lensen said.
For the review, she and her colleagues looked at randomized controlled trials evaluating endometrial scratching in women planning to have intrauterine insemination or attempting to conceive spontaneously (with or without ovulation induction), compared with either no intervention, mock intervention, or endometrial scratching performed at a different time or to a greater or lesser degree.
The researchers acknowledged that the quality of the evidence is quite low, with a risk of bias associated with most of the included trials. For this reason, the results should be viewed with caution, they said.
“High quality randomized controlled trials which recruit sufficient numbers of women are needed to confirm to refute these findings,” they wrote.
Ms. Lensen reported having no financial disclosures.
AT ESHRE 2016
Key clinical point: Endometrial scratching may improve the likelihood of embryo implantation in subfertile women.
Major finding: Endometrial scratching would increase the normal chance of a live birth or ongoing pregnancy over a set period of time from 9% to between 14% and 28%.
Data source: A meta-analysis and systematic review of eight randomized controlled studies.
Disclosures: Dr. Lensen reported having no financial disclosures.
mtDNA level predicts IVF embryo viability
HELSINKI – Mitochondrial DNA level appears to be a useful biomarker for in vitro fertilization embryo viability, according to findings from a blinded prospective non-selection study.
An analysis of 280 chromosomally normal blastocysts showed that 15 (5.4%) contained unusually high levels of mitochondrial DNA (mtDNA) and the remaining blastocysts had normal or low mtDNA levels. Of 111 of the blastocyst transfers for which outcome data were available, 78 (70%) led to ongoing pregnancies, and all of those involved blastocysts with normal or low mtDNA levels, while 8 of the 33 blastocysts that failed to implant (24%) had unusually high mtDNA levels, Elpida Fragouli, PhD, reported at the annual meeting of the European Society of Human Reproduction and Embryology.
Thus, the ongoing pregnancy rate for morphologically good, euploid blastocysts was 76% for those with normal/low mtDNA levels, compared with 0% for those with elevated mtDNA levels – a highly statistically significant difference. The overall pregnancy rate was 70%, said Dr. Fragouli of Reprogenetics UK and the University of Oxford.
The blastocysts in the study were generated by 143 couples who underwent IVF in a single clinic. All blastocysts were biopsied and shown to be chromosomally normal using preimplantation genetic screening.
“The study demonstrates that mitochondrial DNA levels are highly predictive of an embryo’s implantation potential,” Dr. Fragouli said, noting that the “very robust” findings could potentially enhance embryo selection and improve IVF outcomes.
The methodology used in the study has been extensively validated, she said. However, a randomized clinical trial will be necessary to determine the true extent of any clinical benefit, she added, noting that research is also needed to improve understanding of the biology of mtDNA expansion.
The findings are of particular interest, because while it is well known that chromosomal abnormality in embryos is common and increases with age, and is the main cause of implantation failure, it has been less clear why about a third of euploid embryos fail to produce a pregnancy.
“The combination of chromosome analysis and mitochondrial assessment may now represent the most accurate and predictive measure of embryo viability with great potential for improving IVF outcome,” according to an ESHRE press release on the findings.
Levels of mtDNA can be quickly measured using polymerase chain reaction. Next generation sequencing can also be used, Dr. Fragouli noted. However, since aneuploidy remains the most common cause of embryo implantation failure, mtDNA and chromosome testing would be necessary.
“Mitochondrial analysis does not replace [aneuploidy screening]. It is the combination of the two methods ... that is so powerful,” she said, noting that efforts are underway to develop an approach to assessing chromosome content and mtDNA simultaneously to reduce the extra cost.
The group has started offering mtDNA quantification clinically in the United States and has applied to the Human Fertilisation and Embryology Authority for a license to use the testing in the United Kingdom.
Reprogenetics provided funding for this study.
HELSINKI – Mitochondrial DNA level appears to be a useful biomarker for in vitro fertilization embryo viability, according to findings from a blinded prospective non-selection study.
An analysis of 280 chromosomally normal blastocysts showed that 15 (5.4%) contained unusually high levels of mitochondrial DNA (mtDNA) and the remaining blastocysts had normal or low mtDNA levels. Of 111 of the blastocyst transfers for which outcome data were available, 78 (70%) led to ongoing pregnancies, and all of those involved blastocysts with normal or low mtDNA levels, while 8 of the 33 blastocysts that failed to implant (24%) had unusually high mtDNA levels, Elpida Fragouli, PhD, reported at the annual meeting of the European Society of Human Reproduction and Embryology.
Thus, the ongoing pregnancy rate for morphologically good, euploid blastocysts was 76% for those with normal/low mtDNA levels, compared with 0% for those with elevated mtDNA levels – a highly statistically significant difference. The overall pregnancy rate was 70%, said Dr. Fragouli of Reprogenetics UK and the University of Oxford.
The blastocysts in the study were generated by 143 couples who underwent IVF in a single clinic. All blastocysts were biopsied and shown to be chromosomally normal using preimplantation genetic screening.
“The study demonstrates that mitochondrial DNA levels are highly predictive of an embryo’s implantation potential,” Dr. Fragouli said, noting that the “very robust” findings could potentially enhance embryo selection and improve IVF outcomes.
The methodology used in the study has been extensively validated, she said. However, a randomized clinical trial will be necessary to determine the true extent of any clinical benefit, she added, noting that research is also needed to improve understanding of the biology of mtDNA expansion.
The findings are of particular interest, because while it is well known that chromosomal abnormality in embryos is common and increases with age, and is the main cause of implantation failure, it has been less clear why about a third of euploid embryos fail to produce a pregnancy.
“The combination of chromosome analysis and mitochondrial assessment may now represent the most accurate and predictive measure of embryo viability with great potential for improving IVF outcome,” according to an ESHRE press release on the findings.
Levels of mtDNA can be quickly measured using polymerase chain reaction. Next generation sequencing can also be used, Dr. Fragouli noted. However, since aneuploidy remains the most common cause of embryo implantation failure, mtDNA and chromosome testing would be necessary.
“Mitochondrial analysis does not replace [aneuploidy screening]. It is the combination of the two methods ... that is so powerful,” she said, noting that efforts are underway to develop an approach to assessing chromosome content and mtDNA simultaneously to reduce the extra cost.
The group has started offering mtDNA quantification clinically in the United States and has applied to the Human Fertilisation and Embryology Authority for a license to use the testing in the United Kingdom.
Reprogenetics provided funding for this study.
HELSINKI – Mitochondrial DNA level appears to be a useful biomarker for in vitro fertilization embryo viability, according to findings from a blinded prospective non-selection study.
An analysis of 280 chromosomally normal blastocysts showed that 15 (5.4%) contained unusually high levels of mitochondrial DNA (mtDNA) and the remaining blastocysts had normal or low mtDNA levels. Of 111 of the blastocyst transfers for which outcome data were available, 78 (70%) led to ongoing pregnancies, and all of those involved blastocysts with normal or low mtDNA levels, while 8 of the 33 blastocysts that failed to implant (24%) had unusually high mtDNA levels, Elpida Fragouli, PhD, reported at the annual meeting of the European Society of Human Reproduction and Embryology.
Thus, the ongoing pregnancy rate for morphologically good, euploid blastocysts was 76% for those with normal/low mtDNA levels, compared with 0% for those with elevated mtDNA levels – a highly statistically significant difference. The overall pregnancy rate was 70%, said Dr. Fragouli of Reprogenetics UK and the University of Oxford.
The blastocysts in the study were generated by 143 couples who underwent IVF in a single clinic. All blastocysts were biopsied and shown to be chromosomally normal using preimplantation genetic screening.
“The study demonstrates that mitochondrial DNA levels are highly predictive of an embryo’s implantation potential,” Dr. Fragouli said, noting that the “very robust” findings could potentially enhance embryo selection and improve IVF outcomes.
The methodology used in the study has been extensively validated, she said. However, a randomized clinical trial will be necessary to determine the true extent of any clinical benefit, she added, noting that research is also needed to improve understanding of the biology of mtDNA expansion.
The findings are of particular interest, because while it is well known that chromosomal abnormality in embryos is common and increases with age, and is the main cause of implantation failure, it has been less clear why about a third of euploid embryos fail to produce a pregnancy.
“The combination of chromosome analysis and mitochondrial assessment may now represent the most accurate and predictive measure of embryo viability with great potential for improving IVF outcome,” according to an ESHRE press release on the findings.
Levels of mtDNA can be quickly measured using polymerase chain reaction. Next generation sequencing can also be used, Dr. Fragouli noted. However, since aneuploidy remains the most common cause of embryo implantation failure, mtDNA and chromosome testing would be necessary.
“Mitochondrial analysis does not replace [aneuploidy screening]. It is the combination of the two methods ... that is so powerful,” she said, noting that efforts are underway to develop an approach to assessing chromosome content and mtDNA simultaneously to reduce the extra cost.
The group has started offering mtDNA quantification clinically in the United States and has applied to the Human Fertilisation and Embryology Authority for a license to use the testing in the United Kingdom.
Reprogenetics provided funding for this study.
AT ESHRE 2016
Key clinical point: Mitochondrial DNA level may offer a way to assess embryo viability when doing in vitro fertilization.
Major finding: The ongoing pregnancy rate for euploid blastocysts was 76% for those with normal/low mtDNA levels, compared with 0% for those with elevated mtDNA levels.
Data source: A blinded prospective non-selection study of 280 blastocysts.
Disclosures: Reprogenetics provided funding for this study.
