Broughton Darcy E, Moley Kelle H
Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri.
Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri.
Fertil Steril. 2017 Apr;107(4):840-847. doi: 10.1016/j.fertnstert.2017.01.017. Epub 2017 Mar 11.
The worldwide upward trend in obesity has been dramatic, now affecting more than 20% of American women of reproductive age. Obesity is associated with many adverse maternal and fetal effects prenatally, but it also exerts a negative influence on female fertility. Obese women are more likely to have ovulatory dysfunction due to dysregulation of the hypothalamic-pituitary-ovarian axis. Women with polycystic ovarian syndrome who are also obese demonstrate a more severe metabolic and reproductive phenotype. Obese women have reduced fecundity even when eumenorrheic and demonstrate poorer outcomes with the use of in vitro fertilization. Obesity appears to affect the oocyte and the preimplantation embryo, with disrupted meiotic spindle formation and mitochondrial dynamics. Excess free fatty acids may have a toxic effect in reproductive tissues, leading to cellular damage and a chronic low-grade inflammatory state. Altered levels of adipokines, such as leptin, in the obese state can affect steroidogenesis and directly affect the developing embryo. The endometrium is also susceptible, with evidence of impaired stromal decidualization in obese women. This may explain subfecundity due to impaired receptivity, and may lead to placental abnormalities as manifested by higher rates of miscarriage, stillbirth, and preeclampsia in the obese population. Many interventions have been explored to mitigate the effect of obesity on infertility, including weight loss, physical activity, dietary factors, and bariatric surgery. These data are largely mixed, with few high quality studies to guide us. As we improve our understanding of the pathophysiology of obesity in human reproduction we hope to identify novel treatment strategies.
全球肥胖率呈显著上升趋势，目前影响着超过20%的美国育龄女性。肥胖在产前与许多不良的母婴影响相关，但它也对女性生育能力产生负面影响。肥胖女性由于下丘脑 - 垂体 - 卵巢轴调节异常，更易出现排卵功能障碍。患有多囊卵巢综合征且肥胖的女性表现出更严重的代谢和生殖表型。即使月经正常，肥胖女性的生育力也会降低，并且在使用体外受精时效果更差。肥胖似乎会影响卵母细胞和植入前胚胎，导致减数分裂纺锤体形成和线粒体动力学紊乱。过量的游离脂肪酸可能对生殖组织产生毒性作用，导致细胞损伤和慢性低度炎症状态。肥胖状态下，诸如瘦素等脂肪因子水平的改变会影响类固醇生成，并直接影响发育中的胚胎。子宫内膜也很敏感，有证据表明肥胖女性的基质蜕膜化受损。这可能解释了由于接受性受损导致的生育力低下，并可能导致肥胖人群中流产、死产和先兆子痫发生率较高所表现出的胎盘异常。人们已经探索了许多干预措施来减轻肥胖对不孕症的影响，包括减肥、体育锻炼、饮食因素和减肥手术。这些数据大多参差不齐，高质量研究很少，难以指导我们。随着我们对肥胖在人类生殖中的病理生理学理解的提高，我们希望能确定新的治疗策略。
