Elsevier

Metabolism

Volume 107, June 2020, 154193
Metabolism

Review
The effect of excess body fat on female and male reproduction

https://doi.org/10.1016/j.metabol.2020.154193Get rights and content

Highlights

  • Inflammation, genetic and epigenetic factors, and adipokines form the pathophysiologic basis of excess body fat.

  • Obesity per se, even in the case of being obese but metabolically healthy, is associated with adverse reproductive outcomes.

  • Obesity has a negative impact on oocyte quality and assisted reproduction outcomes.

  • Weight loss can improve reproductive outcomes and restore fertility.

Abstract

The dramatic increase in the prevalence of obesity coincides with a decline in reproductive health indices in both sexes. Energy excess mediates changes to the regulatory mechanisms of the reproductive system. Obese individuals exhibit increased estrogen concentrations, due to the overexpression of aromatase in the adipose tissue; via a negative feedback loop, men present with symptoms of hypogonadotropic hypogonadism. These hormonal changes, along with increased oxidative stress, lipotoxicity and disturbances in the concentrations of adipokines, directly affect the gonads, peripheral reproductive organs and the embryo. Clinical evidence is somewhat contradicting, with only some studies advocating worse semen parameters, increased incidence of erectile dysfunction, increased doses of ovulation induction medications, and worse live birth rates in assisted reproductive technology (ART) cycles in obese individuals compared with those of normal weight. Similar conclusions are drawn about patients with insulin resistance syndromes, namely polycystic ovary syndrome (PCOS). As far as treatment options are concerned, lifestyle changes, medical therapy and bariatric surgery may improve the reproductive outcome, although the evidence remains inconclusive. In this review, we summarize the evidence on the association of obesity and reproductive health on both the molecular and the clinical level, and the effect of weight-loss interventions on reproductive potential.

Introduction

Obesity represents a familiar concept both in the medical community and the general public. It is typically defined by using the weight and height measurements to calculate the body mass index (BMI), with patients having measurements of ≥30 kg/m2 being classified as “obese.” However, this is not without limitations. Given the possibility for BMI to misrepresent changes in age, muscle mass and race, alternate measures have been proposed. These include waist circumference (WC), skinfold thickness, body impedance, and body composition. With benefits and drawbacks for each of these [1], both the scientific literature and clinical practice continue to rely on BMI for obesity classification.

Reproductive health can be assessed via many potential outcomes. The most profound are those related to fertility and infertility. The 2017 International Glossary on Infertility and Fertility Care defines fertility as the “ability to achieve a clinical pregnancy” [2], while infertility as the “disease characterized by the failure to establish a clinical pregnancy after 12 months of regular, unprotected, sexual intercourse” [2] or “therapeutic donor insemination” [3]. Infertility is considered a disease of the reproductive system and disability by the World Health Organization (WHO) [4]. It can be further defined as primary (inability to have a first live birth) or secondary (failure to have a subsequent live birth after prior births) [5]. These are distinct from measures of fecundability and fecundity, which are the probability of achieving conception and capacity to have a live birth, respectively. In population reports, the total fertility rate (TFR) is often utilized, representing the average number of births per woman [2]. What remains uncaptured by these indices are other facets of reproduction, which may encompass disorders, such as polycystic ovary syndrome (PCOS), abnormal uterine bleeding, endometriosis, erectile dysfunction or reproductive malignancies.

Both metabolic and reproductive health represent complex and diverse topics. The present review aimed to provide the current body of evidence regarding their association.

Section snippets

Global prevalence of excess body fat

It is commonly accepted that overweight and obesity have reached a pandemic level. Notably, even though all countries around the world have been affected, heterogeneity with regards to socio-economic factors, body size preferences, local environment factors and regional disparities suggest that the etiology of this pandemic is substantially complex [6].

A recent analysis of data by the Global Burden of Disease suggests a 50% and an 80% increase over the last 40 years for overweight and obesity,

Reproduction

The realm of reproductive health in mammals expands grosso modo from puberty and its onset, gamete, and sex steroid production to mating, pregnancy and lactation. It is commonly accepted that these events require a significant and also specific amount of energy other than that spent for essential biologic processes (e.g. cardiovascular function, digestion). More specifically, the idea of a minimal fat threshold permissive for pubertal onset has long been known both in mice and in humans [18,19

Male infertility

Data from observational studies in the USA, Norway, and Denmark in 2006–2007 suggested that male BMI is inversely associated with fertility and fecundity [[96], [97], [98]]. One of them, examining the effect of both male and female BMI, suggested a dose-response association and a cumulative result of male and female obesity [98], whereas another suggested a J-shaped association of male infertility in relation to BMI [98].

Many studies assessed the association between obesity and semen

Lifestyle

Obesity has been associated with adverse reproductive outcomes, in pregnancies achieved either spontaneously or after IVF [49]. Obese women have lower birth and higher miscarriage rates after IVF compared with counterparts of normal weight [156]. Additionally, obese women may need higher doses of clomiphene citrate or FSH for ovulation induction or controlled ovarian hyperstimulation (COH) [156]. Finally, obesity is associated with pregnancy complications, such as gestational diabetes mellitus

Conclusions

Although, historically, energy deficit and low body weight have been associated with infertility, the opposite side of the spectrum, obesity and overweight, has comparable adverse effects on reproduction. The main pathophysiologic mechanisms include increased oxidative stress, lipotoxicity and disturbances in the concentrations of adipokines that directly affect the gonads. Both natural conception and ART outcomes are affected by obesity. Clinical evidence is contradicting, with some, but not

Funding

There was no funding support for this work.

Declaration of competing interest

The authors have no conflict of interest to declare.

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