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Reproductive Endocrinology and Infertility

Introduction to Impact of Obesity on Reproductive Health

This paper discusses how obesity impacts the reproductive health of men and women. Obesity has been a leading cause of various diseases and it negatively impacts various physiological functions in the body. There are several studies which studies how reproductive health is affected by obesity. This paper reviews some of those studies. Obesity and its definition are listed and endocrine changes brought about by obesity are discussed. The paper lists studies where obesity effects on female menstruation, infertility and pregnancy are discussed. It also discusses the obesity effects on artificial reproductive techniques. Male reproductive health consequences of obesity are also discussed.

Obesity

Obesity has become a disease of epidemic proportion worldwide. There has been an increasing number of studies which show that obesity has adverse effects on health. It is that condition in which excess body fat accumulation is such that it is causing adverse health effect. When body mass index (BMI) of a person is more than 30 kg/m2, then he or she is considered obese. BMI is measured by dividing the person’s weight by square of his or her height. According to the BMI scale, overweight is characterized between 25–30 kg / m2 scale, extremely obese at BMI > 35 and morbidly obese at BMI > 40 kg / m2. BMI usually corresponds with the scale of a person’s waist measurement. In case of normal weight, the circumference of the waist will be under 35 inches for women and it will be under 40 inches for men. Obesity is a complex disease impacted by multiple factors including components of genetics, physiology, environment and psychogenic. The entry for ICD-10 is in Endocrinology E66. Multiple factors combine to cause obesity like excessive caloric food intake, lack of physical activity or exercise, genetic predisposition. Gene deficiencies, medications, mental illness, endocrine disorders also causes obesity.

Sexual Dysfunction

Many studies have identified the correlation between obesity and sexual dysfunction. Neurophysiological, hormone levels, vascular and psychological disorders are the main causes in both males and females. In a study in Brazil, postmenopausal women’s interview data about sexual dysfunction was analyzed. Sexual desire and sexual arousal scores were less in women with obesity than those with normal BMI. The sexual satisfaction scores were also significantly higher for normal BMI than for obese women. Thus obesity hurts sexual desire, sexual arousal and sexual satisfaction in postmenopausal women (1). In another descriptive and comparative study, how body image due to obesity impacts sexual quality in obese women was evaluated in Turkey. In obese women sexual quality and body image satisfaction levels were low. (2).

Intra-abdominal deposition of fat is linked to poor eating habits and aninactive lifestyle. A review by Deb et al (2019) studies the relationship between central obesity and ED (erectile dysfunction) suggests that ED is aobesityrelated problem even though the processes on how ED is affected by obesity at molecular levels are not well established (3).

Menstruation

Kafaei et al (2019) cites that several mechanisms which shows how adipose tissue affects ovulation and menstrual cycle. Androgens are converted into estrogens by adipose tissue. Estrogen metabolism is influenced by obesity, compare to non-obese womenestrogen metabolism will be affected by obese women. Obesity impacts the ability to join estrogen with STG ( sexually transmitted) globulin, which results in estrogen becoming inactivated and increases the level of free estradiolof serum. Adipocytes produce adipokines that stopsthe function of ovaries by changing the communication of HPO (Hypothalamus-pituitary-ovarian)axis, causing menstrual disorder. (4).

Mathew et al (2018) review the function of adipose tissue in obesity quantity of adipose tissue rises. It is the largest endocrine organ in the body and many processes are dependent on it. Some of them are, balancing of insulin and glucagon hormones; production of steroids like testosterone, androstenedione, DHEA, androstenediol, estrone, and estradiol; immunoregulation, hematopoiesis and reproduction. It can also to convert androgens to estrogens, estradiol to estrone and dehydroepiandrosterone to androstenediol which are involved in sexual functions. When adipocyte mass increases in obesity, it can change the balance between the sex hormones. It could lead to changes in the HPG(hypothalamic-pituitary-gonadal axis)functioning. Obesity causes inflammatory responses in adipose tissue to produce adipokines which is another mechanism by which risks of irregular menses and anovulation increases. Adipokines inhibit ovulation by effecting HPG signalling and communication. Leptin, adiponectin and resistin are the main adipokines that impacts reproductive health in obese women. In obesitySHBG (sex hormone-binding globulin) and IGFBP (insulin-like growth factor binding proteins) goes down,,GH (growth hormone) decreases, leptin levels are increased in obesity(5).

Several studies were conducted to find an association between obesity and menstruation. In one such study among Korean girls, there is a strong association found between consuming high sugar beverages, obesity, metabolic syndrome and age at menarche. High-calorie intake is associated with early menarche and obesity(6). There is a strong association between menstrual blood loss and BMI(7). In a study conducted among female school girls in Iran, analysis of results indicated that BMI and other body weight and size-related parameters is associated significantly with menstrual disorders (8).

Infertility In Female

There is three times as much risk of infertility in women who are obese than non-obese women. Also, obese women get pregnant after a long time. In one study performed on Danish women who were planning for pregnancies, there was an inverse relation of BMI increase with fecundity ( the capacity to produce offspring). In another study, even when there is no underlying ovulatory dysfunction obese women remain subfertile. (9). Obesity in childhood before age twelve tends to raise the likelihood of later-life female infertility. In one study association was found that in comparison with non-obese girls, the girls who are obese and aged between seven to eleven years, will in later years would likely report infertility, and would have difficulty in conceiving. (10)

A study in Karachi among infertile women under the age of 42 found a significant correlation between Obesity and PCOs with infertility (11). Polycystic ovarian syndrome ( PCOS) is a condition in which hormone levels are affected by a woman. Higher than normal levels of male hormones are produced in PCOS. This imbalance in hormones causes them to miss menses, and pregnancy becomes more difficult in those women. PCOS is a genetic condition, which is made worse by obesity(Barber, Hanson, Weickert, & Franks, 2019). In a study among PCOS patients in India, obese PCOS havegreater likelihood than non-obese PCOS for risk of negative consequences like preeclampsia, endometrial hyperplasia, metabolic syndrome, and insulin resistance(12).

In a prospective comparative study among infertile women, obesity was suggested to negatively impact the dynamics of ovulatory hormones, oocyte quality and endometrium thickness and thus may increase infertility(13).

In a clinical review by Catalano and Shankar, obesity has both short term and long term harmful aftereffects on both mother and her child, during pregnancy. Obesity causes miscarriage and congenital abnormalities. Obese women tend to have increase insulin resistance which can become glucose intolerance and overgrowth of fetus. There is a greater risk of caesarean delivery and wound complications at delivery. After birth, obesewomentend to have greater risk of depression, breastfeeding difficulty and venous thromboembolism. Newborns of obese women have greater body fat at birth, leading to the risk of childhood obesity (14).

In another review by Stubert et al (2018), risks to mother and child have a linear relation with BMI. For each addition of 1kg/m2 of BMI conception probability declines by 4 per cent. There is approximately 10 per cent increase in the risk of preeclampsia and gestational diabetes with a 10 per cent increase in BMI (15). In a study by Davies-Tuch et al (2016),it was found that there exists asignificant association between obesity and gestational hypertension, gestational diabetes mellitus, and preeclampsia (16)

In a review by Supramaniam et al (2018) which examined the correlation between the raised BMI and the outcomes of assisted reproductive treatment, it was found that overweight and obese women have less chance of live birth after Assisted Reproductive Technology (ART) treatment (17).

There is increasing evidence to support that modification in lifestyle and weightloss can have positive impact on fertility . Obese women who seek help with fertility treatment can have better chance of conception by engagine in lifestyle modification , which would reduce the costs of fertility treatment, and decrease prenatal and perinatal complications. Also there would be less risk of transgenerational transmission of metabolic and cardio diseases(18).

Male Reproductive Health

Male hypogonadism is a condition which results from testosterone deficiency. In a review by Carrageta et al (2019), obesity-related hypogonadism by impairing sexual function and fertility reduction puts a limit on the potential of male reproductive health(19). Obese patients had lesser serum testosterone count than normal-weight patients in a recent study done on infertile Taiwanese males. In a review by Martins et al (2019), it was found in many studies that there exists a clear association between obesity and changes in hormone levels, fragmentation in DNA and changed sperm parameters(20). Several mechanisms may lead to these effects of obesity on sperm activity and male fertility, for example, because of adipocytes activity there is an imbalance between the ratio of testosterone and estradiol and as a result changes in levels of other sexual hormones; because of the inflammatory response and oxidative stress in obese men due to excessive adipokines; and increase in scrotal temperature due to excessive fat tissue resulting in gonadal temperature, and changes in several hormone levels due to obesity which alters the hypothalamus-pituitary-gonad axis.In males, obesity is associated with erectile dysfunction, subclinical prostatitis and poor quality of semen (21).

Similar observations were made byMermer and Akdeveliglu (2018) in a review studying obesity effect on male infertility. In obese men, the levels of oestrogen were found to be high and the levels of gonadotropin and testosterone were found below. High BMI is negatively correlated with various sperm parameters. Leptin and Ghrelin are metabolic hormones that regulates eating behaviours and body weight. Increased serum leptin levels were positively correlated with abnormal sperm structure, serum follicle-stimulating hormone, luteinizing hormone, serum prolactin and negatively correlated with sperm parameters. Obesity leads to decreased physical activity, prolong seating causes temperature increase in scrotal region and sperm production is negatively affected(22).

Conclusion on Impact of Obesity on Reproductive Health

The effect of obesity on both male and female reproductive health is well documented and just as obesity hasnegative on various health parameters, reproductive health is also negatively impacted. The effect of obesity is especially well studied in females and many aspects of female reproductive health are reported. From menarche to menopause female reproductive health is negatively affected by obesity. Infertility is one of the direct results of obesity in females. Obesity consequences are especially pronounced in case of pregnancy where it is a significant reason for complications and mortality of both mother and child. Obesity causes additional complication when trying artificial conception where it is the leading cause of negative outcomes. Male reproductive health is negatively impacted by obesity. From sexual dysfunction to infertility, obesity is a significant cause of negative consequences. There is a requirement for more studies on the effect of obesity on male reproductive health.

References for Impact of Obesity on Reproductive Health

Silva GMD da, Lima SMRR, Reis BF dos, Macruz CF, Postigo S, Silva GMD da, et al. Evaluation of Obesity Influence in the Sexual Function of Postmenopausal Women: A Cross- Sectional Study. RevistaBrasileira de Ginecologia e Obstetrícia. 2019 Nov;41(11):660–7.

Yılmaz F, Kumsar A, Demirel G. The effect of body image on sexual quality of life in obese married women. Health Care for Women International. 2018 Nov 26;40:1–14.

Deb AA, Okechukwu CE, Emara S, Gillott L, Abbas SA. Central obesity and erectile dysfunction in men. International Journal of Family & Community Medicine [Internet]. 2019 Dec 1 [cited 2020 May 31];3(3). Available from: https://medcrave.org/index.php/IJFCM/article/view/11073

Kafaei-Atrian M, Mohebbi-Dehnavi Z, Sayadi L, Asghari-Jafarabadi M, Karimian-Taheri Z, Afshar M. The relationship between the duration of menstrual bleeding and obesity-related anthropometric indices in students. J Educ Health Promot [Internet]. 2019 Apr 24 [cited 2020 May 31];8. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512224/

Mathew H, Castracane VD, Mantzoros C. Adipose tissue and reproductive health. Metab Clin Exp. 2018;86:18–32.

Kim JH, Lim JS. Early menarche and its consequence in Korean female: reducing fructose intake could be one solution. J Korean Pediatr Soc [Internet]. 2020 May 14;0. Available from: https://doi.org/10.3345/cep.2019.00353

Tang Y, Chen Y, Feng H, Zhu C, Tong M, Chen Q. Is body mass index associated with irregular menstruation: A questionnaire study? [Internet]. In Review; 2020 Apr [cited 2020 May 30]. Available from: https://www.researchsquare.com/article/rs-19639/v1

Rad M, TorkmannejadSabzevary M, MohebbiDehnavi Z. Association Between Menstrual Disorders and Obesity-Related Anthropometric Indices in Female High School Students: A Cross-Sectional Study. International Journal of School Health. 2018 Apr 1;5(2):1–8.

Mahutte N, Kamga-Ngande C, Sharma A, Sylvestre C. Obesity and Reproduction. Journal of Obstetrics and Gynaecology Canada. 2018 Jul 1;40(7):950–66.

He Y, Tian J, Oddy WH, Dwyer T, Venn AJ. Association of childhood obesity with female infertility in adulthood: a 25-year follow-up study. Fertility and Sterility. 2018 Sep 1;110(4):596-604.e1.

Akhter A, Mushtaq R, Karim A, Khwaja S, Akram A. RELATIONSHIP OF INFERTILITY WITH WEIGHT AND POLYCYSTIC OVARIAN SYNDROME (PCOS) IN SPECIFIC FEMALE POPULATION OF KARACHI, PAKISTAN. FUUAST Journal of Biology. 2018 Dec 18;8(2):293–7.

Sachdeva G, Gainder S, Suri V, Sachdeva N, Chopra S. Obese and non-obese polycystic ovarian syndrome: Comparison of clinical, metabolic, hormonal parameters, and their differential response to clomiphene. Indian Journal of Endocrinology and Metabolism. 2019 Mar 1;23(2):257.

Helmy HK, Mohamed AAE, Mohamed MZ, Arafa AEED. The Effect of Obesity on Ovulation; A Prospective Study on Females Seeking Fertility in Beni-Suef, Egypt. International Journal of Nursing. 2016;6(3):67–72.

Catalano PM, Shankar K. Obesity in pregnancy. Obstetrics: Normal and Problem Pregnancies 7th ed Philadelphia, PA: Elsevier. 2017;

Stubert J, Reister F, Hartmann S, Janni W. The Risks Associated With Obesity in Pregnancy. DtschArztebl Int. 2018 Apr;115(16):276–83.

Davies-Tuck M, Mockler JC, Stewart L, Knight M, Wallace EM. Obesity and pregnancy outcomes: Do the relationships differ by maternal region of birth? A retrospective cohort study. BMC Pregnancy and Childbirth. 2016 Sep 29;16(1):288.

Supramaniam PR, Mittal M, McVeigh E, Lim LN. The correlation between raised body mass index and assisted reproductive treatment outcomes: a systematic review and meta-analysis of the evidence. Reproductive Health. 2018 Feb 27;15(1):34.

Belan M, Harnois-Leblanc S, Laferrère B, Baillargeon J-P. Optimizing reproductive health in women with obesity and infertility. CMAJ. 2018 Jun 18;190(24):E742–5.

Carrageta DF, Oliveira PF, Alves MG, Monteiro MP. Obesity and male hypogonadism: Tales of a vicious cycle. Obesity Reviews. 2019;20(8):1148–58.

Martins AD, Majzoub A, Agawal A. Metabolic Syndrome and Male Fertility. The World Journal of Men’s Health. 2019 May 1;37(2):113–27.

Leisegang K, Henkel R, Agarwal A. Obesity and metabolic syndrome associated with systemic inflammation and the impact on the male reproductive system. American Journal of Reproductive Immunology. 2019;82(5):e13178.

Mermer M, Akdevelioğlu Y. The role of obesity in male fertility. International Journal of Reproduction, Contraception, Obstetrics and Gynecology. 2018 Aug 27;7(9):3435–40.

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