Semin Reprod Med 2023; 41(03/04): 87-96
DOI: 10.1055/s-0043-1776420
Review Article

Obesity and In Vitro Fertilization

Emily L. Ferrell
1   Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan
,
Abira A. Choudhry
2   University of Michigan Medical School, Ann Arbor, Michigan
,
Samantha B. Schon
1   Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan
› Author Affiliations

Abstract

Obesity is a highly prevalent chronic disease with a significant effect on reproductive-age women. The clinical implications of obesity on fertility and pregnancy are well studied citing ovulatory dysfunction, hormonal imbalances, higher miscarriage rates, and increased maternal and neonatal risks. For this reason, many patients with obesity seek reproductive specialists to help build their families. Despite this literature base, the effect of weight loss interventions prior to assisted reproductive technology (ART) is lacking. This review aims to outline the impact of obesity on ART, specifically in vitro fertilization (IVF). Response differences to treatment protocols compared with normal weight counterparts, limitations of access to care, and the mixed results of weight-reduction strategies prior to fertility treatment will be addressed. The known data surrounding benefits of lifestyle modification, pharmacologic therapies, and surgical interventions for obesity prior to IVF are outlined and found to emphasize a need for further research to determine the optimal approach for infertility patients with obesity.



Publication History

Article published online:
01 November 2023

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  • References

  • 1 Hales CM, Carroll MD, Fryar CD, Ogden CL. Prevalence of obesity and severe obesity among adults: United States, 2017-2018. NCHS Data Brief 2020; (360) 1-8
  • 2 Driscoll AK, Gregory ECW. Increases in prepregnancy obesity: United States, 2016-2019. NCHS Data Brief 2020; (392) 1-8
  • 3 Practice Committee of the American Society for Reproductive Medicine. Electronic address: asrm@asrm.org, Practice Committee of the American Society for Reproductive Medicine. Obesity and reproduction: a committee opinion. Fertil Steril 2021; 116 (05) 1266-1285
  • 4 Obesity in pregnancy: ACOG Practice Bulletin, Number 230. Obstet Gynecol 2021; 137 (06) e128-e144
  • 5 World Health Organization. Infertility. Published April 3, 2023. Accessed October 13, 2023 at: https://www.who.int/news-room/fact-sheets/detail/infertility
  • 6 Wise LA, Rothman KJ, Mikkelsen EM, Sørensen HT, Riis A, Hatch EE. An internet-based prospective study of body size and time-to-pregnancy. Hum Reprod 2010; 25 (01) 253-264
  • 7 Itriyeva K. The effects of obesity on the menstrual cycle. Curr Probl Pediatr Adolesc Health Care 2022; 52 (08) 101241
  • 8 Wang P, Mariman E, Renes J, Keijer J. The secretory function of adipocytes in the physiology of white adipose tissue. J Cell Physiol 2008; 216 (01) 3-13
  • 9 Silvestris E, de Pergola G, Rosania R, Loverro G. Obesity as disruptor of the female fertility. Reprod Biol Endocrinol 2018; 16 (01) 22
  • 10 Tersigni C, Di Nicuolo F, D'Ippolito S, Veglia M, Castellucci M, Di Simone N. Adipokines: new emerging roles in fertility and reproduction. Obstet Gynecol Surv 2011; 66 (01) 47-63
  • 11 Dos Santos E, Serazin V, Morvan C. et al. Adiponectin and leptin systems in human endometrium during window of implantation. Fertil Steril 2012; 97 (03) 771-8.e1
  • 12 Kawano J, Arora R. The role of adiponectin in obesity, diabetes, and cardiovascular disease. J Cardiometab Syndr 2009; 4 (01). DOI: 10.1111/j.1559-4572.2008.00030.x.
  • 13 Shi M, Sirard MA. Metabolism of fatty acids in follicular cells, oocytes, and blastocysts. Reprod Fertil 2022; 3 (02) R96-R108
  • 14 Wołodko K, Castillo-Fernandez J, Kelsey G, Galvão A. Revisiting the impact of local leptin signaling in folliculogenesis and oocyte maturation in obese mothers. Int J Mol Sci 2021; 22 (08) 4270
  • 15 Gautam D, Purandare N, Maxwell CV. et al; FIGO Committee on Impact of Pregnancy on Long-term Health and the FIGO Committee on Reproductive Medicine, Endocrinology and Infertility. The challenges of obesity for fertility: a FIGO literature review. Int J Gynaecol Obstet 2023; 160 (Suppl 1, Suppl 1): 50-55
  • 16 Sermondade N, Huberlant S, Bourhis-Lefebvre V. et al. Female obesity is negatively associated with live birth rate following IVF: a systematic review and meta-analysis. Hum Reprod Update 2019; 25 (04) 439-451
  • 17 Souter I, Baltagi LM, Kuleta D, Meeker JD, Petrozza JC. Women, weight, and fertility: the effect of body mass index on the outcome of superovulation/intrauterine insemination cycles. Fertil Steril 2011; 95 (03) 1042-1047
  • 18 Wittemer C, Ohl J, Bailly M, Bettahar-Lebugle K, Nisand I. Does body mass index of infertile women have an impact on IVF procedure and outcome?. J Assist Reprod Genet 2000; 17 (10) 547-552
  • 19 Tamer Erel C, Senturk LM. The impact of body mass index on assisted reproduction. Curr Opin Obstet Gynecol 2009; 21 (03) 228-235
  • 20 Fedorcsák P, Dale PO, Storeng R. et al. Impact of overweight and underweight on assisted reproduction treatment. Hum Reprod 2004; 19 (11) 2523-2528
  • 21 Kim J, Patounakis G, Juneau C. et al. The Appraisal of Body Content (ABC) trial: Increased male or female adiposity does not significantly impact in vitro fertilization laboratory or clinical outcomes. Fertil Steril 2021; 116 (02) 444-452
  • 22 Bernardi LA, Carnethon MR, de Chavez PJ. et al. Relationship between obesity and anti-Müllerian hormone in reproductive-aged African American women. Obesity (Silver Spring) 2017; 25 (01) 229-235
  • 23 Shah DK, Missmer SA, Berry KF, Racowsky C, Ginsburg ES. Effect of obesity on oocyte and embryo quality in women undergoing in vitro fertilization. Obstet Gynecol 2011; 118 (01) 63-70
  • 24 Schon SB, Yang K, Schindler R. et al. Obesity-related alterations in protein expression in human follicular fluid from women undergoing in vitro fertilization. F S Sci 2022; 3 (04) 331-339
  • 25 Gonzalez MB, Lane M, Knight EJ, Robker RL. Inflammatory markers in human follicular fluid correlate with lipid levels and Body Mass Index. J Reprod Immunol 2018; 130: 25-29
  • 26 Robker RL, Akison LK, Bennett BD. et al. Obese women exhibit differences in ovarian metabolites, hormones, and gene expression compared with moderate-weight women. J Clin Endocrinol Metab 2009; 94 (05) 1533-1540
  • 27 Jungheim ES, Lanzendorf SE, Odem RR, Moley KH, Chang AS, Ratts VS. Morbid obesity is associated with lower clinical pregnancy rates after in vitro fertilization in women with polycystic ovary syndrome. Fertil Steril 2009; 92 (01) 256-261
  • 28 Coyne K, Whigham LD, O'Leary K, Yaklic JK, Maxwell RA, Lindheim SR. Gestational carrier BMI and reproductive, fetal and neonatal outcomes: are the risks the same with increasing obesity?. Int J Obes 2016; 40 (01) 171-175
  • 29 Jungheim ES, Moley KH. Current knowledge of obesity's effects in the pre- and periconceptional periods and avenues for future research. Am J Obstet Gynecol 2010; 203 (06) 525-530
  • 30 Rittenberg V, Sobaleva S, Ahmad A. et al. Influence of BMI on risk of miscarriage after single blastocyst transfer. Hum Reprod 2011; 26 (10) 2642-2650
  • 31 Metwally M, Cutting R, Tipton A, Skull J, Ledger WL, Li TC. Effect of increased body mass index on oocyte and embryo quality in IVF patients. Reprod Biomed Online 2007; 15 (05) 532-538
  • 32 Goldman KN, Hodes-Wertz B, McCulloh DH, Flom JD, Grifo JA. Association of body mass index with embryonic aneuploidy. Fertil Steril 2015; 103 (03) 744-748
  • 33 Boots CE, Bernardi LA, Stephenson MD. Frequency of euploid miscarriage is increased in obese women with recurrent early pregnancy loss. Fertil Steril 2014; 102 (02) 455-459
  • 34 Lee JC, Bernardi LA, Boots CE. The association of euploid miscarriage with obesity. F S Rep 2020; 1 (02) 142-148
  • 35 Wise MR, Jordan V, Lagas A. et al. Obesity and endometrial hyperplasia and cancer in premenopausal women: a systematic review. Am J Obstet Gynecol 2016; 214 (06) 689.e1-689.e17
  • 36 Bellver J, Martínez-Conejero JA, Labarta E. et al. Endometrial gene expression in the window of implantation is altered in obese women especially in association with polycystic ovary syndrome. Fertil Steril 2011; 95 (07) 2335-2341 , 2341.e1–2341.e8
  • 37 Bellver J, Pellicer A, García-Velasco JA, Ballesteros A, Remohí J, Meseguer M. Obesity reduces uterine receptivity: clinical experience from 9,587 first cycles of ovum donation with normal weight donors. Fertil Steril 2013; 100 (04) 1050-1058
  • 38 Pinborg A, Gaarslev C, Hougaard CO. et al. Influence of female bodyweight on IVF outcome: a longitudinal multicentre cohort study of 487 infertile couples. Reprod Biomed Online 2011; 23 (04) 490-499
  • 39 Luke B, Brown MB, Stern JE, Missmer SA, Fujimoto VY, Leach R. SART Writing Group. Female obesity adversely affects assisted reproductive technology (ART) pregnancy and live birth rates. Hum Reprod 2011; 26 (01) 245-252
  • 40 Petersen GL, Schmidt L, Pinborg A, Kamper-Jørgensen M. The influence of female and male body mass index on live births after assisted reproductive technology treatment: a nationwide register-based cohort study. Fertil Steril 2013; 99 (06) 1654-1662
  • 41 Moragianni VA, Jones SML, Ryley DA. The effect of body mass index on the outcomes of first assisted reproductive technology cycles. Fertil Steril 2012; 98 (01) 102-108
  • 42 Provost MP, Acharya KS, Acharya CR. et al. Pregnancy outcomes decline with increasing body mass index: analysis of 239,127 fresh autologous in vitro fertilization cycles from the 2008-2010 Society for Assisted Reproductive Technology registry. Fertil Steril 2016; 105 (03) 663-669
  • 43 Akpınar F, Demir B, Dilbaz S, Kaplanoğlu I, Dilbaz B. Obesity is not associated with the poor pregnancy outcome following intracytoplasmic sperm injection in women with polycystic ovary syndrome. J Turk Ger Gynecol Assoc 2014; 15 (03) 144-148
  • 44 Kaye L, Sueldo C, Engmann L, Nulsen J, Benadiva C. Survey assessing obesity policies for assisted reproductive technology in the United States. Fertil Steril 2016; 105 (03) 703-706.e2
  • 45 Gillett WR, Peek JC, Herbison GP. Development of clinical priority access criteria for assisted reproduction and its evaluation on 1386 infertile couples in New Zealand. Hum Reprod 2012; 27 (01) 131-141
  • 46 Balen AH, Anderson RA. Policy & Practice Committee of the BFS. Impact of obesity on female reproductive health: British Fertility Society, Policy and Practice Guidelines. Hum Fertil (Camb) 2007; 10 (04) 195-206
  • 47 Turner-McGrievy GM, Grant BL. Prevalence of body mass index and body weight cut-off points for in vitro fertilization treatment at U.S. clinics and current clinic weight loss strategy recommendations. Hum Fertil (Camb) 2015; 18 (03) 215-219
  • 48 Kelley AS, Badon SE, Lanham MSM, Fisseha S, Moravek MB. Body mass index restrictions in fertility treatment: a national survey of OB/GYN subspecialists. J Assist Reprod Genet 2019; 36 (06) 1117-1125
  • 49 Romanski PA, Farland LV, Tsen LC, Ginsburg ES, Lewis EI. Effect of class III and class IV obesity on oocyte retrieval complications and outcomes. Fertil Steril 2019; 111 (02) 294-301.e1
  • 50 Petersen R, Pan L, Blanck HM. Racial and ethnic disparities in adult obesity in the United States: CDC's tracking to inform state and local action. Prev Chronic Dis 2019; 16: E46
  • 51 Slocum B, Schon SB. Body size, fertility, and reproductive justice: examining the complex interplay between BMI, reproductive health, and access to care. Women 2022; 2 (02) 93-101
  • 52 Chavarro JE, Ehrlich S, Colaci DS. et al. Body mass index and short-term weight change in relation to treatment outcomes in women undergoing assisted reproduction. Fertil Steril 2012; 98 (01) 109-116
  • 53 Sim KA, Dezarnaulds GM, Denyer GS, Skilton MR, Caterson ID. Weight loss improves reproductive outcomes in obese women undergoing fertility treatment: a randomized controlled trial. Clin Obes 2014; 4 (02) 61-68
  • 54 Espinós JJ, Polo A, Sánchez-Hernández J. et al. Weight decrease improves live birth rates in obese women undergoing IVF: a pilot study. Reprod Biomed Online 2017; 35 (04) 417-424
  • 55 Wu L, Fang Q, Wang M. et al. Effect of weight loss on pregnancy outcomes, neuronal-reproductive-metabolic hormones and gene expression profiles in granulosa cells in obese infertile PCOS patients undergoing IVF-ET. Front Endocrinol (Lausanne) 2022; 13: 954428
  • 56 Moran L, Tsagareli V, Norman R, Noakes M. Diet and IVF pilot study: short-term weight loss improves pregnancy rates in overweight/obese women undertaking IVF. Aust N Z J Obstet Gynaecol 2011; 51 (05) 455-459
  • 57 Einarsson S, Bergh C, Friberg B. et al. Weight reduction intervention for obese infertile women prior to IVF: a randomized controlled trial. Hum Reprod 2017; 32 (08) 1621-1630
  • 58 Yanovski SZ, Yanovski JA. Long-term drug treatment for obesity: a systematic and clinical review. JAMA 2014; 311 (01) 74-86
  • 59 Novograd J, Mullally J, Frishman WH. Semaglutide for weight loss: Was it worth the weight?. Cardiol Rev 2022; 30 (06) 324-329
  • 60 Wang Z, Zhao J, Ma X. et al. Effect of orlistat on live birth rate in overweight or obese women undergoing IVF-ET: a randomized clinical trial. J Clin Endocrinol Metab 2021; 106 (09) e3533-e3545
  • 61 Tong J, Xiang L, Niu Y, Zhang T. Effect of orlistat intervention on in vitro fertilization/intracytoplasmic sperm injection outcome in overweight/obese infertile women. Gynecol Endocrinol 2022; 38 (03) 253-257
  • 62 Aronne LJ, Wadden TA, Peterson C, Winslow D, Odeh S, Gadde KM. Evaluation of phentermine and topiramate versus phentermine/topiramate extended-release in obese adults. Obesity (Silver Spring) 2013; 21 (11) 2163-2171
  • 63 Khera R, Murad MH, Chandar AK. et al. Association of pharmacological treatments for obesity with weight loss and adverse events: a systematic review and meta-analysis. JAMA 2016; 315 (22) 2424-2434
  • 64 Vitek WS, Hoeger KM. Worth the wait? Preconception weight reduction in women and men with obesity and infertility: a narrative review. Fertil Steril 2022; 118 (03) 447-455
  • 65 Chao AM, Tronieri JS, Amaro A, Wadden TA. Semaglutide for the treatment of obesity. Trends Cardiovasc Med 2023; 33 (03) 159-166
  • 66 O'Neil PM, Birkenfeld AL, McGowan B. et al. Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial. Lancet 2018; 392 (10148): 637-649
  • 67 Wilding JPH, Batterham RL, Calanna S. et al; STEP 1 Study Group. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med 2021; 384 (11) 989-1002
  • 68 Salamun V, Jensterle M, Janez A, Vrtacnik Bokal E. Liraglutide increases IVF pregnancy rates in obese PCOS women with poor response to first-line reproductive treatments: a pilot randomized study. Eur J Endocrinol 2018; 179 (01) 1-11
  • 69 Gosman GG, King WC, Schrope B. et al. Reproductive health of women electing bariatric surgery. Fertil Steril 2010; 94 (04) 1426-1431
  • 70 Estimate of Bariatric Surgery Numbers. 2011–2021. American Society for Metabolic and Bariatric Surgery; . Published June 27, 2022. Accessed August 13, 2023 at: https://asmbs.org/resources/estimate-of-bariatric-surgery-numbers
  • 71 Milone M, De Placido G, Musella M. et al. Incidence of successful pregnancy after weight loss interventions in infertile women: a systematic review and meta-analysis of the literature. Obes Surg 2016; 26 (02) 443-451
  • 72 Tsur A, Orvieto R, Haas J, Kedem A, Machtinger R. Does bariatric surgery improve ovarian stimulation characteristics, oocyte yield, or embryo quality?. J Ovarian Res 2014; 7: 116
  • 73 Milone M, Sosa Fernandez LM, Sosa Fernandez LV. et al. Does bariatric surgery improve assisted reproductive technology outcomes in obese infertile women?. Obes Surg 2017; 27 (08) 2106-2112
  • 74 Grzegorczyk-Martin V, Fréour T, De Bantel Finet A. et al. IVF outcomes in patients with a history of bariatric surgery: a multicenter retrospective cohort study. Hum Reprod 2020; 35 (12) 2755-2762
  • 75 Nilsson-Condori E, Mattsson K, Thurin-Kjellberg A, Hedenbro JL, Friberg B. Outcomes of in-vitro fertilization after bariatric surgery: a national register-based case-control study. Hum Reprod 2022; 37 (10) 2474-2481