Metabolic Syndrome in Obesity: Treatment Success and Adverse
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Obesity is common in women with polycystic ovary syndrome (PCOS). PCOS and obesity are associated with reduced fertility. Metabolic syndrome’s (MetS) effect on infertility treatment success and pregnancy outcomes in women with PCOS undergoing ovulation induction (OI) has not been investigated. The objectives of this study were to determine the associations of MetS with OI live birth rate and pregnancy complications in obese women with PCOS, and to see if these outcomes differ by specific agent used for OI.

This prospective cohort analysis was from data collected from participants in the Pregnancy in Polycystic Ovary Syndrome II (PPCOSII) clinical trial conducted by the Reproductive Medicine Network. In PPCOSII, 750 women with PCOS and infertility were randomized to either clomiphene citrate or letrozole for OI for 1-5 cycles or until pregnancy occurred. Cox regression and modified Poisson regression, Chi-square and Student’s t or Wilcoxon tests were applied. Outcomes of interest were live birth and clinical pregnancy rates, and pregnancy complications. Having MetS was defined by the presence of at least 3 out of 5 cardiometabolic risk factors (waist circumference > 88cm, low high-density lipoprotein cholesterol < 50mg/dL, triglycerides 150mg/dL, systolic BP 130 or diastolic BP 85 mmHg, and fasting glucose > 100mg/dl). We also used a continuous MetS Z-score. BMI categories were defined as normal (BMI < 25 kg/m2), high (25 to 35 kg/m2), and very high (> 35 kg/m2).

Fewer women achieved a clinical pregnancy (20.5% vs. 29.7%, p=.007) or had a live birth (16.5% vs. 27%, p=.001) in the presence of MetS. Early pregnancy losses were not different by MetS status. At least one pregnancy complication occurred more often with MetS, 61.9% (26/42) compared to 44.4% (59/133) (p=.05) without it. Gestational diabetes (35.7% vs. 18.2 %, p=.02) and macrosomia (21.4% vs. 8.3%, p=.02) were more common in the presence of MetS. After adjustment for other potential confounders, the live birth rate ratio for a one-unit change in the MetS z-score was 0.89 (95% CI 0.79, 1.00, p=.04) for those whose BMI was 25-35 kg/m2 . For the very high BMI subgroup (>35 kg/m2) the independent effects of MetS from obesity were harder to discern. The live birth rate was higher with letrozole, although MetS had a different detrimental effect by medication given. The overall incidence of pregnancy complications was high ( 49%) in PPCOSII, and similar with either agent. Letrozole was associated with more obstetrical complications in the presence of MetS and clomiphene was associated with a lower live birth rate when MetS was present.

MetS is a risk factor that lowers the live birth rate with OI for women with PCOS independent of obesity, and it is particularly associated with a lower live birth rate for clomiphene compared to letrozole users. It is also a risk factor for pregnancy complications for obese letrozole users. Having the MetS is a risk factor for gestational diabetes and macrosomia.

Read more : https://www.ajog.org/article/S0002-9378(21)00447-6/fulltext?rss=yes
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