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Impact of Body Mass Index on Female Fertility and ART Outcomes

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Impact of Body Mass Index on Female Fertility and ART Outcomes •C 2018 EDIZIONIMil\1lRVAMED!CA PanmincrvaMcdica 2019 March:61{1):58-67 Online version at http:/!\,.\,.\,·.111111ervi1med1ca.1t DOI 10.21716/SOOl l-OROR.18.01490-0 REVIEW HOT TOPICS IN FEMALE INFERTILITY Impact of Body Mass Index on female fertility and ART outcomes Majdi IMTERAT 1, Ashok AGARWAL 2, Sandro C. ESTEVES\ Jenna MEYER 4, Avi HARLEY 1, 2 * JDepanmenL of Obstetrics and Gynecology. Soroka University Medical Center, Ben-Gurion University of the Negev. Beer-Sheva, Israel; 2American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, CSA; 3Andrology and Human Reproduction Clinic, Al\-nROFERT. Referral CenLer for :Viale Reproduction, Campinas. Brazil; 4f'aculty of Health Sciences, Ben-Gurion University of Lhe Negev, Beer-Sheva, Israel �conesponding author: Avi Harlev, Depa1tment of Obstetricsand Gynecolq,,y, Soroka University rv!edical Center, l 5 l l7ak H.ager Ave. Heer-Sheva 84101, Israel. E-mail: harlev(fi;b1,'l1ac. il ABSTRACT As the global mean Body l\fass Index (B!l:fI) is on the rise, the importance of understanding exactly how female fertility is impacted by once outlier BMl values, becomes ever more important. Studies have 1mphcatcd abnormal BMl on the female reproductive system by contributing to anovulatio11, irregular menses, adverse oocyte quality, endometrial alterations,and hormonal imbalances. These well ultimately result in female infertility, which could complicate natural conception efforts and request considcrmg assisted reproductrve technology ( ART) in such couples. vVitl1 an increase in the demand for ART, it is crucial to understand what factors can be alteredby the female BMI in order to maximize tl1e op­ porn1nityfor successfulpregmmcy. The current manuscnpt aimed to review the information about the effectof Bl\:11 on the female fertilityand ART out.rnmes. The cmnplex nature orthe remale repruduct.ive sysle111 leaves space for multiple ractors lo adversely affectits processes. Tmbal­ ances in tl1e hypothalamus-pituitary-ovarian a,"is can impede efforts for couples to conceive. Leptin and estrogen are two hormones tliat have been implicated in regulatingBMl as well as reproductive physiology. Lifestyle modificationspnor to. and dmmg ART have shown promise in enhancing fecundity. The intricacies in female reproductive system leaves much to tl1e unknown, and often witl1 conflicting results. Furtl1er research is rcqmrcd to fully elucidate what aspectsof femalefertility arc mfluencedby B!Vll, and how the healthcare provider can facilitatesuc­ cessful outcomes. The current review will enable a better consultation and treatment. (Ote this arflcle a�: lmterat rvl, Agarwal A. Esteves SC, t>.foyerJ. Harlev A. Impact of Body Mass Index on female fettility and Alff outcomes. Pan­ minc1va Med 2019;61:58-67. DOl: 10.23736/S0031-0808.18.03490-0) KEY WORDS: Fertility - Infertility - Body Mass Index - Estrogens - Insulin - Life style. ody Mass Index (BMI) has long been known to af­ result from impaired follicular recmitment, impedance of Bfect various aspects of human health. An abnormal oocyte development, and reduced fertilization rates. This BMI alters the ability for the body to function normally; lack of accord on pathophysiology and impactof an abnor­ whether above or below a healthy range, lhcsc extremes mal B:rvII,compl icates the caregiver 's ability to adequately hinder regular physiology. The cffccls of BMT on female address and counteract the effects abnomial BMT on lhc fertility have been detailed lo a degree. There has not been reproductive syslcm function in general and fertility in a consensus on how exactly BMI impacts the reproduc­ particular. tive system, and even less agreement on the effects BMI The goal of this review is to provide a comprehensive has had on assisted reproductive technology (ART) out­ accumulation of the literature regarding the various effects comes. Thus, conflicting reports on how exactly BMI af­ of BMI and associated molecular pathways on ART, as fects femalefert ility are abundant in the literature. It has ,vell as to assess any modifications necessary when treat­ been suggested that reproductive system malfunctionmay ing individuals outside the normal BMI range. 58 PANMJNl-:RVA_v llilJlCJ\ l\.hlrdt2lll9 It.IPA.CTOF BM! ON FEIVIALE FERTILITYAND ART OUTCOMES IMTERAT Overview of BMI BMT required forregular menscs.1 0, 11 Below this level, the body's available energy to use towards cellular processes, E11idemiology growth, and reproduction is diminished. A study conduct­ ed by Loucks et al.,10 defined energy availability as the BMT is a simple calculation using a person's height and energy intake minus the energy expendihire. In women weight in order to qmmtify an individual's amount of tis­ sufferingfrom anorexia who reduce the energy intake, less sue mass. BMl>25.0kg/m2 is considered ovenveight, and is available for health maintenance, including reproduc­ < l 8.5kg/m2 is undenveight. An individual with a BMI Livc processcs.1 o greater than 30.0kg/m2 is obese, and those over 40.0kg/m2, or are 35.0kg/m2 and su.ITer from obesity related hyperten­ Pathways associating BMI and the rcprnductivc system sion or diabetes, are defined as morbidly obese.1 Though this measurement does not consider distribution of weight Numerous pathv,;ays were suggested Lo associate an ab­ in Lcm1s of muscle or fat, iL has long been used as a stan­ normal BMl and the reproductive system. Two major ones dardized measurement of hcallh.1 will be described. Increased BMI ,md obesity has plagued the modem world and has become an international public health con­ Leptin cem.2 Over the past three decades, the average BMI rose ln lnunans, leptin has been shown to have a direct asso­ dramatically in 200 countries worldwidc.3 Data collected ciationwith adipose density.12 Since leptin is produced by from 1980 and 2000, showed the BMI lo have increased adipose tissue, circulating serum levels of leptin correlates at an annual rate of 0.4 kg/m2 per decade formen and 0.5 1 2 Yvith the amount of adipose tissue present in the body. 3 kg/m forwomen. In 2008, the prevalence of overweight ln order to regulate energy expenditure and appetite ho­ adults reached alanning 1.47 billion people across the meostasis, leptin acts on the arcuate nucleus in the hypo­ globe.' Another assessment of 1698 population-based data thalamus via a single lransmcmbranc Lypc T cytokinc rc­ sets that involved more than 19 million adults, sho\ved ccptor.12 Additionally, lcptin helps lo control the levels of global age-standardized mean BMI to have increased from insulin, insulin-likegrowth factor, and growth hormone.14 21. 7 kg/m2 in 1975 to 24.2 kg/m2 in 2014 in men, and from In this w , leptin plays an integral role in monitoring 2 2 4 ay 22.1 kg/m in 1975 Lo 24.4 kg/111 in 2014 in womcn. For the pathogenesis of obesity and other eating disorders. In women of reproductive age in particular, the prevalence of obese women, there is an increased resistance to leptin, obesity has markedly increased within the past decade. A disrupting their ability to control energy intake, 13 while in 2 review by Jungheim et al., reported that 35.8 percent of undern'eight women low energy availability dysregulates menstruating,,,omen had a higher than normal BMI, with the diurnal leptin sccrclion.15 a mean BMT of28.7 kg/m2. Beyond its substantial central effectson the hypothalam­ On the other end of the spectrum, low BMI (such as an­ ic-pih1itacy axis, leptin has significant regulatoryresponsi­ orexia nervosa) is an important factor affecting fertility in bilities in peripheral physiology as well. Leptin deficiency women of reproductiveage. This disorder is characterized may lead to obesity, bone mincrali:r.alionissues, and repro­ by a tremendously low BML due to intense fear of gain­ ductive cycle changes.13 Ovulatory cycles in females are ing weight, and body image issues. Although its reported connected to energy stores, thatas aforementioned,are rep­ prevalence is between 0.9% and 4.3% in women, this val­ resented by leptin levels.12 A study conducted in hypogo­ ue does not reflectthe trueseverity of this disorder. 5 In sur­ nadolropic hypogonadism leplin-dcficicnl transgenic mice, veys completed by university aged women, 26% of them showed that administration of leptin corrected the amenor­ were reported to have abnonnal altitudes about ealing.h rhea and restored reproductivestatus. 16 This study conclud­ Though recently there has been an increase in anorexia di­ ed that lcplin helps Lo regulate honnonc axis contributing lo agnoses in young women, it is unclear as to whether this is reproductive capabilities when in BMT extremes. a trueupward trendin the disorder, or whether the medical ln healthy individuals, leptin was shown to have an ef­ practice is clumging to recognize this devastating mental fecton luteinizing hormone (LH) and estradiol levels, sug­ illness more readily. 7, s Contrastingly, some large reviews gesting that lepLin may have a distinct regulatory effect conducted at mulliplc institutions failed lo show any sig­ on hormones involved in reproductive processes. 16 Thus, nificantincrease in the prevalence of this disorder. h, 9 leptin has an integral role in maintaining normal homeo­ Yet what is known is that there is indeed a minimum stasis and body physiology beyond that of hunger. Vul.61-Nu. l P:\Mv!INbRVA MEO JC:\ 59 IMTERAT Th1PACT OF BM! ON FE:VIALEFERTILITY AND ART OUTCOJ\,1ES Estrogen talivc hypotheses implicate the negative impact BMT has on embryo quality and endometrial function. Estrogen is the primary hormone of nonnal female repro­ A studv conducted bv Gaskins et al. found that in fe­ ductive physiology. Estrogen is responsible for inducing males of 18 years of age: both a BMT>25, and a BMT<l 8.5 the developmentof secondary sex characteristics in females were associated with reduced fecundity.19 A systematic and controls the monthly menstrual cycle.
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