Dataset Information

Association of Metformin With Pregnancy Outcomes in Women With Polycystic Ovarian Syndrome Undergoing In Vitro Fertilization: A Systematic Review and Meta-analysis.

ABSTRACT: Importance:Metformin is widely used among women with polycystic ovary syndrome (PCOS). However, its associations with outcomes of in vitro fertilization or intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) in women with PCOS remain controversial. Objective:To assess whether metformin is associated with improved outcomes of IVF/ICSI-ET in women with PCOS. Data Sources:PubMed, Embase, and Cochrane were searched from database inception to January 31, 2020. Study Selection:Only randomized clinical trials (RCTs) were included. Eligible studies enrolled women with PCOS undergoing infertility treatment with IVF/ICSI-ET and reported at least 1 outcome of IVF/ICSI-ET. Data Extraction and Synthesis:This study followed the Preferred Reporting Items for Systematic Reviews and Meta analyses guidelines. Two authors independently extracted the data. Study quality was evaluated using the GRADE system. Treatment effect was quantified using odds ratios (ORs) with 95% CIs using random-effect models with the Mantel-Haenszel method. Main Outcomes and Measures:Ovarian hyperstimulation syndrome (OHSS), clinical pregnancy rate, and live birth rate. Results:A total of 12 RCTs, which collectively included 1123 women with PCOS undergoing infertility treatment with IVF/ICSI-ET, were identified. The risk of OHSS in women randomized to metformin was lower than in women not randomized to metformin (OR, 0.43; 95% CI, 0.24-0.78), although this difference was not significant for women with PCOS with a body mass index of less than 26 (OR, 0.67; 95% CI, 0.30-1.51). There was no significant difference in clinical pregnancy rate (OR, 1.24; 95% CI, 0.82-1.86) or live birth rate (OR, 1.23; 95% CI, 0.74-2.04) in the total population studied. However, in a post hoc analysis among women with a body mass index of 26 or greater, metformin treatment was associated with increased clinical pregnancy rates (OR, 1.71; 95% CI, 1.12-2.60). Conclusions and Relevance:In this study, metformin treatment was associated with a decreased risk of OHSS but had no association with the overall clinical pregnancy rate or live birth rate among women with PCOS undergoing IVF/ICSI-ET. Metformin treatment should be carefully considered for women with PCOS undergoing IVF/ICSI-ET and may be more preferred for women with a body mass index greater than 26.

SUBMITTER: Wu Y

PROVIDER: S-EPMC7399751 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Association of Metformin With Pregnancy Outcomes in Women With Polycystic Ovarian Syndrome Undergoing In Vitro Fertilization: A Systematic Review and Meta-analysis.

Wu Yiqing Y Tu Mixue M Huang Yun Y Liu Yifeng Y Zhang Dan D

JAMA network open 20200803 8

<h4>Importance</h4>Metformin is widely used among women with polycystic ovary syndrome (PCOS). However, its associations with outcomes of in vitro fertilization or intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) in women with PCOS remain controversial.<h4>Objective</h4>To assess whether metformin is associated with improved outcomes of IVF/ICSI-ET in women with PCOS.<h4>Data sources</h4>PubMed, Embase, and Cochrane were searched from database inception to January 31, 2020.<h4> ...[more]

PMID: 32744629

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Project description:ObjectiveThe current study was undertaken to investigate the relationship between antimüllerian hormone (AMH) and polycystic ovarian syndrome (PCOS) phenotypes and to determine whether AMH is associated with pregnancy outcomes in infertile women undergoing their first in vitro fertilization (IVF) treatment.MethodsWe performed a retrospective cohort study of 2973 infertile women, including 418 women with PCOS undergoing their first IVF treatment at a private fertility center from January 2014 to March 2018. Women were stratified into three groups using cutoffs defined by the 25th and 75th percentiles of the serum AMH level: 746 women had AMH ≤ 2.25 ng/mL; 1486 women had AMH between 2.25 to 5.71 ng/mL; and 741 women had AMH > 5.71 ng/mL. Endocrine characteristics, PCOS phenotypes, stimulation outcomes, pregnancy outcomes were compared among these groups. When there were any statistical differences (P < 0.05) among the three groups, Bonferroni test was performed as post-hoc tests to determine where the statistical differences existed. To assess the relationships between AMH and pregnancy outcomes in total patients and PCOS patients, logistic regression analysis, adjusted for potential confounding covariates, were performed.ResultsWomen with high AMH had greater prevalence of hyperandrogenism (HA), polycystic ovarian morphology (PCOM) and amenorrhea than women with low or average AMH. The clinical pregnancy rate were significantly higher in the high-AMH group compared with low- and average-AMH groups (69.9% vs. 58.8% and 64.7% respectively; P < 0.001). The live birth rate was significantly lower in women with AMH ≤ 2.25 ng/mL compared with average- and high-AMH groups (47.6% vs. 55.2 and 59.5% respectively; P < 0.001). However, after controlling for maternal age, oocyte yield, as well as other confounders, AMH was no longer associated with a higher live birth rate (aOR 1.037, 95% CI 0.853-1.261, P = 0.717; aOR 1.099, 95% CI 0.858-1.408, P = 0.455, respectively) and clinical pregnancy rate (aOR 1.064, 95% CI 0.834-1.359, P = 0.617; aOR 1.181, 95% CI 0.875-1.595, P = 0.276, respectively). Moreover, pregnancy outcomes did not differ in PCOS women according to AMH quartiles.ConclusionIncreased AMH levels associated with PCOS severity and greater ovarian stimulation. However, AMH was not associated with clinical pregnancy rate and live birth rate after controlling for other confounders in women undergoing IVF. Thus, AMH should not be used to alter clinical decisions and exclude patients based on a low or even undetectable AMH value.

Project description:BackgroundThe risk of adverse pregnancy outcomes is increased by having a polycystic ovary syndrome (PCOS) diagnosis. However, the confounders in previous studies preclude firm conclusions, and further studies are warranted.ObjectivesTo investigate whether PCOS affects pregnancy outcomes and complications in infertile women undergoing their first in vitro fertilization (IVF) treatment, taking into account important confounders.MethodsWe performed a retrospective cohort study of 7,678 infertile women, including 666 women with PCOS and 7,012 controls undergoing their first IVF treatment at a private fertility center from January 2010 to December 2017. Our main outcome was the impact of PCOS on adverse pregnancy outcomes (miscarriage, preterm delivery, pregnancy-induced hypertension) and pregnancy outcomes (live birth rate, clinical pregnancy rate, implantation rate). PCOS effects were summarized by adjusted odds ratios (aORs) with 95% confidence intervals (CIs) after controlling for maternal characteristics.ResultsAfter adjusting for differences in maternal age, BMI, infertility duration, total dose of gonadotropin, serum E2 and endometrial thickness on the day of hCG trigger, number of fertilized occytes, number of embryos transferred, embryo type (cleavage-stage embryo or blastocyst) and quality, women with PCOS had an increased risk of developing unfavorable pregnancy complications, including miscarriage (aOR 1.629, 95% CI 1.240-2.141), very preterm delivery (< 32 weeks) (aOR 2.072, 95% CI 1.133-3.791). For pregnancy outcomes, PCOS was associated with higher clinical pregnancy rate (aOR 1.248, 95% CI 1.038-1.501) and implantation rate (aOR 1.238, 95% CI 1.030-1.489) after adjusting for the above-mentioned confounders.ConclusionsWomen with PCOS are at increased risk of adverse pregnancy outcomes after adjusting for differences in maternal characteristics. These women may need more frequent medical consultants and management during pregnancy and parturition.

Project description:BackgroundEvidence from animal studies suggests that exposure to organophosphate flame retardants (PFRs) can disrupt endocrine function and impair embryo development. However, no epidemiologic studies have been conducted to evaluate effects on fertility and pregnancy outcomes.ObjectivesWe evaluated associations between urinary concentrations of PFR metabolites and outcomes of in vitro fertilization (IVF) treatment among couples recruited from an academic fertility clinic.MethodsThis analysis included 211 women enrolled in the Environment And Reproductive Health (EARTH) prospective cohort study (2005-2015) who provided one or two urine samples per IVF cycle. We measured five urinary PFR metabolites [bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPHP), isopropylphenyl phenyl phosphate (ip-PPP), tert-butylphenyl phenyl phosphate (tb-PPP), and bis(1-chloro-2-propyl) phosphate (BCIPP)] using negative electrospray ionization liquid chromatography tandem mass spectrometry (LC-MS/MS). Molar concentrations of the urinary PFR metabolites were summed. We used multivariable generalized linear mixed models to evaluate the association of the PFR metabolites with IVF outcomes, accounting for multiple IVF cycles per woman.ResultsDetection frequencies were high for BDCIPP (87%), DPHP (94%), and ip-PPP (80%), but low for tb-PPP (14%) and BCIPP (0%). We observed decreased success for several IVF outcomes across increasing quartiles of both summed and individual PFR metabolites (DPHP and ip-PPP) in our adjusted multivariable models. Significant declines in adjusted means from the lowest to highest quartile of ?PFR were observed for the proportion of cycles resulting in successful fertilization (10% decrease), implantation (31%), clinical pregnancy (41%), and live birth (38%).ConclusionsUsing IVF to investigate human reproduction and pregnancy outcomes, we found that concentrations of some urinary PFR metabolites were negatively associated with proportions of successful fertilization, implantation, clinical pregnancy, and live birth. https://doi.org/10.1289/EHP1021.

Project description:BackgroundPolycystic Ovary Syndrome (PCOS) is an endocrine disorder that affects women in reproductive age and represents an unfavourable risk factor for several pregnancy and perinatal outcomes. Despite, no guidelines or pharmaceutical strategies for treating PCOS during pregnancy are available. The aim of this study is to determine the association between polycystic ovary syndrome with or without metformin and the pregnancy, perinatal outcomes as well as the risk of obesity in children born to these mothers.MethodsIn this nationwide population-based cohort study based in Swedish population, all singleton births (n = 1,016,805) from 686,847 women since 2006 up to 2016 were included. Multivariable logistic and Cox regression modelling with odds ratios (OR) and hazard ratios (HR) and 95% confidence intervals were used to study the association between the exposure of maternal PCOS, metformin during pregnancy (or the combination of both) and: 1) Pregnancy outcomes: preeclampsia, gestational diabetes, caesarean section, and acute caesarean section, 2) Perinatal outcomes: preterm birth, stillbirth, low birth weight, macrosomia, Apgar < 7 at 5 min, small for gestational age and large for gestational age, and 3) Childhood Obesity.ResultsPCOS in women without metformin use during pregnancy was associated with higher risks of preeclampsia (OR = 1.09, 1.02-1.17), gestational diabetes (OR = 1.71, 1.53-1.91) and caesarean section (OR = 1.08, 1.04-1.12), preterm birth (OR = 1.30, 1.23-1.38), low birth weight (OR = 1.29, 1.20-1.38), low Apgar scores (OR = 1.17, 1.05-1.31) and large for gestational age (OR = 1.11, 1.03-1.20). Metformin use during pregnancy (in women without PCOS) was associated with a 29% lower risks of preeclampsia (OR = 0.71, 0.51-0.97), macrosomia and large for gestational age. Obesity was more common among children born to mothers with PCOS without metformin (HR = 1.61, 1.44-1.81); and those with metformin without PCOS (HR = 1.67, 1.05-2.65). PCOS with metformin was not associated with any adverse outcome.ConclusionPCOS was associated with increased risks of adverse pregnancy and perinatal outcomes and childhood obesity. Metformin appears to reduce these risks in mothers with polycystic ovary syndrome and their children; but may increase the risk of childhood-obesity in children form women without PCOS.

Dataset Information

Association of Metformin With Pregnancy Outcomes in Women With Polycystic Ovarian Syndrome Undergoing In Vitro Fertilization: A Systematic Review and Meta-analysis.

Publications

Association of Metformin With Pregnancy Outcomes in Women With Polycystic Ovarian Syndrome Undergoing In Vitro Fertilization: A Systematic Review and Meta-analysis.

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