ReviewThe effect of excess body fat on female and male reproduction
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.
References (187)
- et al.
Limitations of body mass index as an obesity measure of perioperative risk
Br J Anaesth
(2016) - et al.
The epidemiology of obesity
Metabolism
(2019) - et al.
Obesity: seize the day, fight the fat
Metabolism
(2019) - et al.
Connecting metabolism and gonadal function: novel central neuropeptide pathways involved in the metabolic control of puberty and fertility
Front Neuroendocrinol
(2018) - et al.
The hypothalamus-pituitary-gonad axis: tales of mice and men
Metabolism
(2018) - et al.
Immunoelectron microscopic observation of the subcellular localization of kisspeptin, neurokinin B and dynorphin A in KNDy neurons in the arcuate nucleus of the female rat
Neurosci Lett
(2016) - et al.
Obesity: pathophysiology and management
J Am Coll Cardiol
(2018) - et al.
Genetics and epigenetics in obesity
Metabolism
(2019) The genetics of human obesity
Transl Res
(2014)- et al.
Prader Willi syndrome: genetics, metabolomics, hormonal function, and new approaches to therapy
Adv Pediatr
(2016)
The complex interaction between obesity, metabolic syndrome and reproductive axis: a narrative review
Metabolism
Adipose tissue and reproductive health
Metabolism
Obesity, male infertility, and the sperm epigenome
Fertil Steril
Placental maternal and fetal vascular circulation in healthy non-obese and metabolically healthy obese pregnant women
Atherosclerosis
Impact of male obesity on infertility: a critical review of the current literature
Fertil Steril
Evidence of a treatable endocrinopathy in infertile men
J Urol
The effect of aromatase inhibitor letrozole on body mass index, serum hormones, and sperm parameters in infertile men
Fertil Steril
Aromatase inhibitors for male infertility
Fertil Steril
The complex association between metabolic syndrome and male hypogonadism
Metabolism
Withania somnifera improves semen quality by combating oxidative stress and cell death and improving essential metal concentrations
Reprod Biomed Online
Connecting metabolism and reproduction: roles of central energy sensors and key molecular mediators
Mol Cell Endocrinol
Current knowledge of obesity’s effects in the pre-and periconceptional periods and avenues for future research
Am J Obstet Gynecol
Obesity and female infertility: potential mediators of obesity’s impact
Fertil Steril
Association of body mass index with embryonic aneuploidy
Fertil Steril
The international glossary on infertility and fertility care, 2017
Hum Reprod
Definitions of infertility and recurrent pregnancy loss: a committee opinion
Fertil Steril
National, regional, and global trends in infertility prevalence since 1990: a systematic analysis of 277 health surveys
PLoS Med
Obesity: global epidemiology and pathogenesis
Nat Rev Endocrinol
Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults
Lancet
Overcoming obesity: an initial economic analysis
Body fatness and cancer — viewpoint of the IARC working group
N Engl J Med
World fertility patterns data booklet
A unique view on male infertility around the globe
Reprod Biol Endocrinol
Prevalence of infertility and help seeking among 15 000 women and men
Hum Reprod
The diagnosis of male infertility: an analysis of the evidence to support the development of global WHO guidance-challenges and future research opportunities
Hum Reprod Update
Body weight and food intake as initiating factors for puberty in the rat
J Physiol
The right weight: body fat, menarche and fertility
Proc Nutr Soc
Control of puberty onset and fertility by gonadotropin-releasing hormone neurons
Nat Rev Endocrinol
GnRH neurons elaborate a long-range projection with shared axonal and dendritic functions
J Neurosci
The gonadotropin-releasing hormone pulse generator
Endocrinology
Pulsatile secretion of gonadotropin-releasing hormone by rat hypothalamic explants of GnRH neurons without cell bodies
Neuroendocrinology
Central electrophysiologic correlates of pulsatile luteinizing hormone secretion in the rhesus monkey
Neuroendocrinology
Definition of the hypothalamic GnRH pulse generator in mice
Proc Natl Acad Sci U S A
GnRH pulse generator activity across the estrous cycle of female mice
Endocrinology
Hypogonadotropic hypogonadism in mice lacking a functional Kiss1 gene
Proc Natl Acad Sci U S A
Inactivating KISS1 mutation and hypogonadotropic hypogonadism
N Engl J Med
Neuroanatomical framework of the metabolic control of reproduction
Physiol Rev
Cited by (53)
The effect of diet density on allometry in pullet growth and early egg production
2024, Poultry ScienceObesity and male infertility
2023, Best Practice and Research: Clinical Obstetrics and GynaecologyMetabolism, Clinical and Experimental: seventy years young and growing
2022, Metabolism: Clinical and ExperimentalBody fatness associations with cancer from recent epidemiologic studies
2022, Metabolism: Clinical and ExperimentalCitation Excerpt :In peri- and postmenopausal women, high BMI associates with higher levels of bioavailable estradiol [168] and testosterone [168–170], whereas in men, high BMI associates with lower testosterone levels [170–172]. Obese men commonly present with hypogonadotropic hypogonadism [172]. MR studies have provided evidence of causal relationships of higher circulating SHBG levels with decreased risk of endometrial cancer [111] and of higher endogenous levels of total estradiol (proxied by a single genetic variant in the CYP19A gene, which encodes aromatase) with increased risk of cancers of the corpus uteri (particularly the endometroid subtype) [111,173] and breast (particularly estrogen receptor positive tumors) and possibly ovarian cancer of the endometrioid subtype as well as stomach cancer in women [173].
Liraglutide improved the reproductive function of obese mice by upregulating the testicular AC3/cAMP/PKA pathway
2024, Reproductive Biology and Endocrinology