Dr Gautam Allahbadia states impact of obesity on female infertility and its management
Obesity is on the rise worldwide, reaching epidemic proportions. As a result, more obese women are being seen in infertility clinics around the world. Dr. Gautam Allahbadia, Mumbai-based IVF expert, reviewed the aetiopathogenesis and how it affects management in his early reviews. He emphasises and updates its effects on infertility treatment and management.
Obesity reduces reproductive potential by causing functional changes in the Hypothalamo-Pituitary-Ovarian (HPO) axis. Obesity is frequently associated with hyperinsulinemia, which is a known inducer of increased androgen production. Androgens are converted to oestrogen (Og) in the periphery, specifically in adipose tissue (AT), resulting in negative feedback on the HPO axis and thus influencing gonadotropin production. This is characterised by menstrual irregularities as well as ovulatory dysfunction. Hyperinsulinemia is frequently identified as an aetiopathological factor in PCOS. “Obesity contributes to insulin resistance (IR) and worsens PCOS symptoms, with obese women having a more severe phenotype,” informs Dr Gautam Allahbadia, Mumbai based IVF expert. Increased androgen levels in PCOS = increased visceral fat accumulation, accelerating IR and hyperinsulinemia, and thus stimulating more ovarian and adrenal androgen production in a perceptual cycle. He has to his name, over one hundred fifty peer-reviewed publications, 134 book chapters, and twenty-five textbooks, the newest being a comprehensive text published by Springer Nature, entitled “The Art & Science of ART”, and is on the Editorial Board of many International Journals. Dr. Allahbadia was appointed as the vice-president of the World Association of Reproductive Medicine (WARM), headquartered in Rome, and “Mumbai’s prime Doc” for 2012 by a peer nomination process.
Although the causative role of obesity in PCOS development has not been established, the prevalence of PCOS in some obese populations approaches 30%. Obese women take longer to conceive, according to various studies. Fecundity ratios decreased with increasing BMI in a Danish cohort of women planning pregnancies. Despite not having ovulatory dysfunction, obese women do not conceive. Law et al discovered reduced fecundity in eumenorrheic obese women after examining a large American cohort of >7000 women.
Obesity has an effect on the HPO axis, according to animal models and human studies. Tortorellello et al. demonstrated that there was a 60% reduction in natural pregnancy rates in a DIO mouse model, but that the defect could be overcome with the use of exogenous gonadotropins, implying a central mechanism. The same group created a mouse model with genetic mutations that resulted in an obese and infertile phenotype independent of diet. They discovered mice with >levels of leptin receptors in the hypothalamus who were resistant to developing the phenotype.
“Obese women have higher levels of leptin, a cell signalling protein, than normal matched controls, possibly due to downregulation of its receptor in the brain. Women with higher leptin concentrations and higher leptin-BMI ratios have lower rates of IVF pregnancy. Eumenorrheic obese women and discovered that the amplitude of LH pulsatility was significantly reduced, indicating that obesity has a significant central defect,” explains Dr Gautam Allahbadia, Mumbai-based IVF expert.
Obese women undergoing IVF have an altered follicular environment with elevated insulin and triglyceride levels, as well as inflammation markers like lactate and CRP in follicular fluid (FF). There is also a need for higher gonadotropin doses and longer treatment courses for follicular development. Oocyte yield is also lower in obese women who have a high number of cycle cancellations. In DIO mouse models, the ovaries have more apoptotic follicles and smaller, more likely to mature oocytes. Meiotic aneuploidy is more common, as are fragmented, disorganised meiotic spindles and chromosomes that are not aligned on the metaphase plate. Raised leptin, in addition to acting centrally, has a direct negative impact on the developing embryo. “Leptin stimulates the growth of human trophoblastic stem cells, while inhibiting it reduces proliferation and dramatically increases apoptosis. Increased leptin levels in obesity may reduce trophoblast sensitivity to its effect,” Dr Gautam Allahbadia says.
Obesity has been linked to an increase in the risk of infertility. It does so not only by reducing fecundity, but also by causing suboptimal responses to ART. Various mechanisms have been discovered in the laboratory that affect the oocyte, endometrium, and pre-implantation embryo by inducing weight loss, physical activity, dietary changes, and bariatric surgery. There is some hope for obese patients who want to have children. More research is needed to understand the relationship between obesity and reproduction in order to build healthy families.