Journal of Reproductive Medicine Gynaecology & Obstetrics Category: Medical Type: Review Article
The Impact of Obesity on Fertility
- Alpizar-Salazar Melchor1, Jose Manuel Lozano Sánchez2, Paola Berenice Merchand Álvarez2, José Alfonso Gutiérrez Frusch3, Ricardo Mera Mejía4, Julio César Avilés Durán4, Zoraida Axtle Serrano5*
- 1 Centro Especializado En Diabetes, Obesidad Y Prevención De Enfermedades Cardiovasculares, SC (CEDOPEC), México City, Mexico
- 2 Centro Especializado En Diabetes, Obesidad Y Prevención De Enfermedades Cardiovasculares, SC (CEDOPEC), México City, Mexico
- 3 Reproduccion Y Genetica Agn Y Asociados, México City, Mexico
- 4 Department Of Nutrition And Metabolism, Centro De Salud Integral Del Hombre Y La Mujer (CSIHM), México City, Mexico
- 5 Department Of Nutrition And Metabolism, Centro De Salud Integral Del Hombre Y La Mujer (CSIHM), Tehuantepec 251 Cons 506, México City, Mexico
*Corresponding Author:Zoraida Axtle Serrano
Department Of Nutrition And Metabolism, Centro De Salud Integral Del Hombre Y La Mujer (CSIHM), Tehuantepec 251 Cons 506, México City, Mexico
Received Date: Apr 18, 2018 Accepted Date: Jun 01, 2018 Published Date: Jun 15, 2018
Objectives: To describe the impact of obesity in childhood and the possible negative prognosis on future fertility.
Methods: Literature search was performed in PubMed from January 2000 to March 2017 using the search terms child obesity, infertility, spermiogenesis, spermatogenesis, ovulation, oocyte and pregnancy rates.
Conclusion: Obesity affects fertility from intrauterine development all the way though adult life. Obesity has multiple effects with respect to fertility and creates a constant pro-inflammatory microenvironment in germ cells, which in turn has a negative impact on reproduction in adulthood of both sexes.
The classification by age group is:
• Adults: WHO defines obesity as a BMI greater than or equal to 30
• Children under 5 years of age: Obesity is weight-for-height greater than 3 standard deviations above the WHO child growth standards median
• Children aged between 5-19 years: Obesity is greater than 2 standard deviations above the WHO growth reference median
New studies report that the microenvironment in the uterus defines the obesity of the future newborn affecting males in a higher proportion [2,3]. Animal models have demonstrated the expression and suppression of genes associated with the mother’s diet that affects the placental microenvironment and promotes obesity [4-6]. These states correlate with the chronic low-grade inflammation and immune system activation accompanied by insulin resistance [7-9]. In the long term, there is a long (intrauterine-pre-puberty-puberty-post puberty) proinflammatory environment on germ cells .
CHILDHOOD AND PUBERTY
Insulin and Luteinizing Hormone (LH) contribute to increased levels of testosterone in obese peripubertal adolescents, although other factors associated with obesity may also mediate this association. Obesity is associated with low overnight LH pulse frequency in prepubertal and early pubertal girls, whereas by Tanner stages 3-5, LH frequency is abnormally elevated in obese girls, possibly reflecting the effects of hyperandrogenism and resembling findings of adult polycystic ovary syndrome. Interestingly, weight loss has been associated with a significant decrease in testosterone concentrations in obese boys and girls . These suggest that childhood obesity contribute to the appearance of endocrine disturbances during adolescence and increase the risk of developing infertility later in life.
Adult male fertility effects associated with obesity
Testosterone is involved in insulin regulation, metabolism of lipids and body composition. Hyperinsulinemia has been shown to have a negative effect on spermatogenesis with a significantly higher level of nuclear and mitochondrial DNA damage. At the same time, increased concentration of estrogen diminishes SHBG levels . Leptin is a hormone secreted by adipocytes to regulate satiety but is also involved in sexual maturation and reproduction . Leptin stimulates Gonadotropin Releasing Hormone (GnRH) secretion; in obesity, excess leptin causes a resistance later in life . The production of inhibin B by Sertoli cells is the most effective marker for normal spermatogenesis. Inhibin B is a growth-like factor which acts in the testes to inhibit Follicle Stimulating Hormone (FSH) production and to stimulate testosterone production by Leydig cells . The reduced levels of inhibin B found in obese males are indicative of seminiferous tubule dysfunction and it is hypothesized to be due to a lower number of Sertoli cells . However, a compensatory increase in FSH levels in response to low inhibin B has not been observed, indicating potential partial dysregulation of the HPG axis .
Obesity causes a chronic inflammatory state resulting in formation of Reactive Oxygen Species (ROS) which can induce damage to sperm DNA and membrane, as well as increase stress on the testicular environment . Obesity during childhood increases the insult time creating more profound damage on DNA fragmentation that affects fertilization and embryo development .
Adult female fertility effects associated with obesity
Ovulation disorders: Most of the ovulation disorders in obese patients are oligo or anovulation. The endocrine activity of the hypothalamus-hypophysis-ovary axis in the prepubertal female will remain dormant until she reaches a critical weight and composition, liberating pulses of kisspeptin and secondly FSH-LH activation that marks the onset of puberty continuing into their reproductive lives . Obesity is associated with Polycystic Ovarian Syndrome (PCOS) which is marked by hyperandrogenemia. Hyperandrogenemia induces apoptosis in granulosa cells, dysregulating pituitary function due to increased aromatase activity in peripheral tissues and an increased negative feedback on gonadotrophin secretion. At the same time, insulin resistance is associated with ovarian steroidogenesis and a decrease of sex hormone-binding globulin and leptin levels .
Hormonal alterations associated with obesity affects the endometrium with a higher incidence of endometrial cancer in obese patients . Animal models have shown that leptin and Leptin Receptor (LEPR) play a relevant role in the regulation of implantation. Obesity disrupts leptin/LEPR which may disturb endometrial receptivity and implantation leading to impaired fecundity. The effects of leptin on reproduction are not homogenous and both stimulatory and inhibitory functions have been described . Although it is known that leptin has a complex role in endometrium functionality, basic science and clinical studies are necessary to comprehend the effect of obesity on implantation and early pregnancy.
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Citation: Melchor A-S, Sánchez JML, Álvarez PBM, Frusch JAG, Mejía RM, et al. (2018) The Impact of Obesity on Fertility. J Reprod Med Gynecol Obstet 3: 009.
Copyright: © 2018 Alpizar-Salazar Melchor, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.