The adverse effects of obesity on conception and implantation

Abstract

Whilst many multiparous women are obese (body mass index O30 kg/m 2 ), obesity has been associated with impaired fecundity; however, the mechanism which links obesity to reduced fertility remains to be fully elucidated. Obese women, particularly those with central obesity, are less likely to conceive per cycle. Obese women suffer perturbations to the hypothalamic-pituitary-ovarian axis, menstrual cycle disturbance and are up to three times more likely to suffer oligo-/anovulation. A fine hormonal balance regulates follicular development and oocyte maturation, and it has been observed that obesity can alter the hormonal milieu. Leptin, a hormone produced by adipocytes, is elevated in obese women, and raised leptin has been associated with impaired fecundity. Obesity impairs ovulation but has also been observed to detrimentally affect endometrial development and implantation. The expression of polycystic ovary syndrome (PCOS) is regulated, in part, by weight, and so obese women with PCOS often have a more severe phenotype and experience more subfertility. Obesity also impairs the response of women to assisted conception treatments. Weight loss through lifestyle modification or bariatric surgery has been demonstrated to restore menstrual cyclicity and ovulation and improve the likelihood of conception. In this article, we will discuss the effect of obesity upon key reproductive mechanisms and its relation to fertility treatments.

The impact of obesity on egg quality

“…One of the major effects of obesity is increased serum insulin concentrations and resistance to insulin action in cells. Excess insulin can decrease steroid hormone binding globulin (SHBG), which elevates testosterone, dihydrotestosterone, and androstenediol [21]. In response to decreased peripheral insulin sensitivity, insulin production increases leading to further decreases in SHBG and increases in androgens [21].…”

“…Excess insulin can decrease steroid hormone binding globulin (SHBG), which elevates testosterone, dihydrotestosterone, and androstenediol [21]. In response to decreased peripheral insulin sensitivity, insulin production increases leading to further decreases in SHBG and increases in androgens [21]. In women, increasing BMI was associated with decreased SHBG and increased insulin, glucose, lactate, triglycerides, and C-reactive protein, an inflammatory marker in follicular fluid [33].…”

“…In the theca and granulosa cells of the ovary, insulin also stimulates steroidogenesis and upregulates LH receptor expression [34]. Due to LH hypersecretion and altered LH:FSH ratio, ovulation and the resumption of oocyte maturation is frequently impacted by obesity in women [21,35].…”

“…Adiponectin has been found in the ovary and oocyte [61]. While its role in the ooctye is unknown, it can alter folliculogenesis in animal models [21]. Other adipokines such as interluekin-6 (IL6), plasminogen activator inhibitor (PAI) type-1, or tumor necrosis factor (TNF) family members may affect oocyte competence or maturation through alterations in steroidogenesis and interaction with other metabolic hormones [21].…”

“…In regards to the effect of obesity on (1) oocyte retrieval: eight studies reported lower numbers, nine found no difference; (2) oocyte quality or maturity: six studies found an adverse effect, one found no effect; (3) fertilization: three studies found decreased rates, eight found no difference; (4) embryo quality: two found decreased quality, two found no difference [20]. Other recent reviews have also shown conflicting reports on oocyte number, oocyte maturity, and fertilization rate [21,22]. Recently, a very large study of 45,163 ART cycles in the US reported that increasing obesity (based on BMI) is associated with decreased clinical pregnancy rates from autologous oocytes, but not donor oocytes indicating that the oocyte quality alone can affect pregnancy [23].…”