Departments of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
Departments of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
Am J Obstet Gynecol. 2021 Sep;225(3):280.e1-280.e11. doi: 10.1016/j.ajog.2021.03.048. Epub 2021 Apr 20.
Obesity is common in women with polycystic ovary syndrome. polycystic ovary syndrome and obesity are associated with reduced fertility. The effect of metabolic syndrome on the success of infertility treatment and pregnancy outcomes in women with polycystic ovary syndrome undergoing ovulation induction has not been investigated.
The objectives of this study were to determine the associations of metabolic syndrome on the rate of live birth after ovulation induction and pregnancy complications in obese women with polycystic ovary syndrome and determine whether there is a difference in outcomes concerning specific medications used for ovulation induction.
This prospective cohort analysis used data collected from participants in the Pregnancy in Polycystic Ovary Syndrome II clinical trial conducted by the Reproductive Medicine Network. In the Pregnancy in Polycystic Ovary Syndrome II trial, 750 women with polycystic ovary syndrome and infertility were randomized to either clomiphene citrate or letrozole for ovulation induction for 1 to 5 cycles or until pregnancy occurred. Cox regression and modified Poisson regression, chi-square test, and Student t test or Wilcoxon test were used in this study. Outcomes of interest were rates of live birth and clinical pregnancy and pregnancy complications. Having metabolic syndrome was defined by the presence of at least 3 of 5 cardiometabolic risk factors (waist circumference of >88 cm, low high-density lipoprotein cholesterol of <50 mg/dL, triglycerides of ≥150 mg/dL, systolic blood pressure of ≥130 or diastolic blood pressure of ≥85 mm Hg, and fasting glucose of >100 mg/dL). In addition, we used a continuous metabolic syndrome z score. Body mass index categories were defined as normal (body mass index of <25 kg/m), high (25 to 35 kg/m), and very high (>35 kg/m).
As illustrated in the Table, early pregnancy losses showed no difference by metabolic syndrome. 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 metabolic syndrome. Early pregnancy losses showed no difference by metabolic syndrome status. However, at least 1 pregnancy complication occurred more often with metabolic syndrome: 61.9% (26 of 42 cases) with metabolic syndrome vs 44.4% (59 of 133 cases) (P=.05) without metabolic syndrome. Gestational diabetes mellitus (35.7% vs 18.2%; P=.02) and macrosomia (21.4% vs 8.3%; P=.02) were more common in the presence of metabolic syndrome. After adjustment for other potential confounders, the rate ratio for live births for a 1-unit change in the metabolic syndrome z score was 0.89 (95% confidence interval, 0.79-1.00; P=.04) for those whose body mass index was 25 to 35 kg/m. For the very high body mass index subgroup (>35 kg/m), the independent effects of metabolic syndrome from obesity were harder to discern. The rate of live birth was higher with the use of letrozole, although metabolic syndrome had a different detrimental effect concerning the medication given. The overall incidence of pregnancy complications was high (approximately 49%) in the Pregnancy in Polycystic Ovary Syndrome II trial and the 2 medications. Letrozole was associated with more obstetrical complications in the presence of metabolic syndrome, and clomiphene was associated with a lower rate of live birth rate when metabolic syndrome was present.
Metabolic syndrome is a risk factor that lowers the rate of live birth after ovulation for women with polycystic ovary syndrome, independent of obesity, and it is particularly associated with a lower rate of live birth for women using clomiphene compared with women using letrozole. In addition, metabolic syndrome is a risk factor for pregnancy complications for women with obesity using letrozole. Furthermore, having metabolic syndrome is a risk factor for gestational diabetes mellitus and macrosomia.
多囊卵巢综合征患者中肥胖较为常见。多囊卵巢综合征和肥胖与生育能力降低有关。代谢综合征对接受排卵诱导的多囊卵巢综合征患者的不孕治疗成功率和妊娠结局的影响尚未得到研究。
本研究旨在确定代谢综合征对接受排卵诱导的肥胖多囊卵巢综合征患者活产率和妊娠并发症的影响，并确定用于排卵诱导的特定药物的治疗效果是否存在差异。
本前瞻性队列分析使用了生殖医学网络妊娠多囊卵巢综合征 II 临床试验参与者的数据。在妊娠多囊卵巢综合征 II 试验中，750 名多囊卵巢综合征和不孕的妇女被随机分为氯米芬或来曲唑进行 1-5 个周期的排卵诱导，或直到怀孕发生。本研究使用了 Cox 回归和修正泊松回归、卡方检验、学生 t 检验或 Wilcoxon 检验。感兴趣的结局是活产率和临床妊娠率以及妊娠并发症。代谢综合征的定义是至少存在 5 种心血管代谢危险因素中的 3 种（腰围>88cm、低高密度脂蛋白胆固醇<50mg/dL、甘油三酯≥150mg/dL、收缩压≥130 或舒张压≥85mmHg、空腹血糖>100mg/dL）。此外，我们还使用了代谢综合征 z 评分的连续变量。体重指数类别定义为正常（体重指数<25kg/m）、高（25-35kg/m）和极高（>35kg/m）。
如表所示，代谢综合征组的早期妊娠丢失无差异。代谢综合征组的临床妊娠率（20.5%比 29.7%；P=.007）和活产率（16.5%比 27%；P=.001）较低。代谢综合征组的早期妊娠丢失无差异。然而，至少有一种妊娠并发症在代谢综合征组中更常见：61.9%（42 例中有 26 例）有代谢综合征，44.4%（133 例中有 59 例）无代谢综合征（P=.05）。妊娠糖尿病（35.7%比 18.2%；P=.02）和巨大儿（21.4%比 8.3%；P=.02）在代谢综合征组中更为常见。在调整了其他潜在的混杂因素后，对于 BMI 在 25-35kg/m 的患者，代谢综合征 z 评分每增加 1 个单位，活产率的比值比为 0.89（95%置信区间，0.79-1.00；P=.04）。对于极高体重指数亚组（>35kg/m），代谢综合征与肥胖之间的独立影响更难区分。尽管代谢综合征对所用药物有不同的不利影响，但使用来曲唑的活产率更高。妊娠多囊卵巢综合征 II 试验和两种药物的妊娠并发症总发生率均较高（约 49%）。在存在代谢综合征的情况下，来曲唑与更多的产科并发症相关，而氯米芬与活产率降低相关。
代谢综合征是多囊卵巢综合征患者排卵后活产率降低的一个危险因素，独立于肥胖，并且对于使用氯米芬的患者，特别是与使用来曲唑的患者相比，代谢综合征与较低的活产率相关。此外，代谢综合征是肥胖患者使用来曲唑时发生妊娠并发症的一个危险因素。此外，代谢综合征是妊娠糖尿病和巨大儿的一个危险因素。
