Reduced Fertility in Obese Women May Be Related to Dysfunctional Insulin Pathway

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The researchers hypothesized that in overweight and obese women, insulin pathway dysfunction may interfere with FSH receptor expression and estradiol production.
The researchers hypothesized that in overweight and obese women, insulin pathway dysfunction may interfere with FSH receptor expression and estradiol production.

A high body mass index (BMI) is associated with reduced follicle-stimulating hormone (FSH) receptor expression in human chorionic gonadotropins (hGCs), reduced expression of estradiol synthesis-related genes, and reduced production of estradiol, according to study results published in The Journal of Clinical Endocrinology & Metabolism.

Obesity is one of the underlying causes of reduced fertility in women, and assisted reproductive technology including in vitro fertilization is often less successful in women with infertility with elevated BMI. In this study, researchers investigated the underlying mechanisms of BMI-related associations with poor reproductive outcomes in obese women.

In this case control study, 82 obese and 457 overweight women undergoing in vitro fertilization were matched with 1790 normal-weight controls. Findings showed that FSH receptor gene expression in hGCs was lower in women with a high BMI in both mRNA (P =.02) and protein (P =.001) levels. Insulin (P <.001) and glucose (P =.0017) levels were both correlated positively with BMI in fasting blood and follicular fluids on the day of hCG administration for ovulation, but this was not observed in follicular fluid leptin levels. In addition, an elevated BMI was associated with compromised production of estradiol; mRNA expression of steroidogenesis-related genes including LHR, CYP17A1, and CYP19A1 was significantly lower in hGCs from obese women (P <.05). In particular, the CYP19A1 gene mRNA expression was significantly reduced in hGCs in obese women vs other groups (P <.01).

Based on these results, increased insulin levels in obese women could decrease FSH receptor expression and aromatase protein levels. “Further research into the underlying mechanisms responsible for poor reproductive outcomes in obese women will help to improve the metabolic disorders, which [put] obese woman at risk for poor reproductive performance,” wrote the researchers.

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Reference

Xu P, Huang BY, Zhan JH, et al. Insulin reduces reaction of follicular granulosa cell to FSH stimulation in obesity-related infertility women during IVF [published online November 21, 2018]. J Clin Endocrinol Metab. doi:10.1210/jc.2018-00686

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