Infertility in women with obesity

Abstract

The negative impact of obesity on reproductive function is not only linked to infertility but also to adverse perinatal outcomes and increased maternal and fetal morbidity and mortality¹.

The obese patient is three times more likely to suffer infertility than the patient with normal BMI both in natural cycles and in assisted reproductive therapy. Obese patients with PCOS have a more complex metabolic and reproductive phenotype. The most characteristic alteration of obesity, increased insulin secretion, impacts on the functioning of the hypothalamic-pituitary-ovarian axis.

Adipose tissue is an endocrine organ that generates proinflammatory adipokines and obesity is considered a chronic inflammatory state. The main hormone it secretes is leptin, which is increased in obese patients and may have a negative effect on fertility by inhibiting folliculogenesis through direct and indirect control of LH and FSH secretion, but also by affecting perifollicular blood flow and endometrial receptivity². Adipose tissue produces steroid hormones by conversion of inactive forms resulting in decreased SHBG, increased peripheral aromatisation of androgens to oestrogens and relative hyperandrogenemia. The ovary has receptors for insulin and IGF-1 receptors in the granulosa, theca and stroma. Modulation of sex steroid bioavailability by insulin inhibiting hepatic synthesis of SHBG results in obese patients having a lower response to ovarian stimulation with gonadotrophins, lower oocyte quality and lower pregnancy rate than those with normal BMI³.

At the endometrial level, the hyperestrogenism present in obesity can negatively affect endometrial receptivity. Reduced glycodelin, secreted by endometrial glands and decidua, a paracrine regulator of pregnancy in the endometrium, and reduced IGF-1 involved in embryo adhesion, are associated with high levels of circulating insulin and increased recurrent pregnancy loss. Obese women have elevated levels of acute phase proteins and pro-inflammatory cytokines (including IL6, PAI1 and TNF) and these inflammatory markers are thought to have a negative effect on implantation and early embryo development⁴.