Obesity and Miscarriage

Abstract

Obesity affects nearly 40% of reproductive-aged women and has serious implications for women's overall and reproductive health. Women with an elevated body mass index (BMI) have higher rates of anovulation and irregular menses, lower success with fertility treatment, and significantly higher rates of pregnancy complications, such as hypertension/preeclampsia, gestational diabetes, and preterm delivery. Many studies have also shown an association between obesity and early pregnancy loss. However, the causal association between BMI and miscarriage has not been elucidated, likely due to the multifactorial effects that BMI may have on early pregnancy development. In addition, BMI as an isolated variable fails to capture other relevant confounding health risk factors, such as nutrition, physical activity, and insulin resistance. In this review, we will summarize the current literature demonstrating the association between BMI and miscarriage, highlight the research that attempts to explain the association, and finally provide data on therapeutic interventions to improve reproductive outcomes in women suffering from obesity and early pregnancy loss.

Keywords

obesity - body mass index - miscarriage - pregnancy loss

Publikationsverlauf

Artikel online veröffentlicht:
15. Dezember 2023

• 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 Sagi-Dain L. Obesity in pregnancy: ACOG Practice Bulletin, Number 230. Obstet Gynecol 2021; 138 (03) 489
• 3 Singh GK, DiBari JN. Marked Disparities in pre-pregnancy obesity and overweight prevalence among US women by race/ethnicity, nativity/immigrant status, and sociodemographic characteristics, 2012-2014. J Obes 2019; 2019: 2419263
• 4 Practice Committee of the American Society for Reproductive Medicine. Electronic address: [e-mail], Practice Committee of the American Society for Reproductive Medicine. Obesity and reproduction: a committee opinion. Fertil Steril 2021; 116 (05) 1266-1285
• 5 Bhattacharya S, Campbell DM, Liston WA, Bhattacharya S. Effect of body mass index on pregnancy outcomes in nulliparous women delivering singleton babies. BMC Public Health 2007; 7: 168
• 6 Marshall NE, Spong CY. Obesity, pregnancy complications, and birth outcomes. Semin Reprod Med 2012; 30 (06) 465-471
• 7 Zhou Y, Li H, Zhang Y, Zhang L, Liu J, Liu J. Association of maternal obesity in early pregnancy with adverse pregnancy outcomes: a Chinese prospective cohort analysis. Obesity (Silver Spring) 2019; 27 (06) 1030-1036
• 8 Boots C, Stephenson MD. Does obesity increase the risk of miscarriage in spontaneous conception: a systematic review. Semin Reprod Med 2011; 29 (06) 507-513
• 9 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
• 10 Metwally M, Ong KJ, Ledger WL, Li TC. Does high body mass index increase the risk of miscarriage after spontaneous and assisted conception? A meta-analysis of the evidence. Fertil Steril 2008; 90 (03) 714-726
• 11 Zhang J, Liu H, Mao X. et al. Effect of body mass index on pregnancy outcomes in a freeze-all policy: an analysis of 22,043 first autologous frozen-thawed embryo transfer cycles in China. BMC Med 2019; 17 (01) 114
• 12 Eapen A, Hayes ET, McQueen DB, Beestrum M, Eyck PT, Boots C. Mean differences in maternal body mass index and recurrent pregnancy loss: a systematic review and meta-analysis of observational studies. Fertil Steril 2021; 116 (05) 1341-1348
• 13 Cavalcante MB, Sarno M, Peixoto AB, Araujo Júnior E, Barini R. Obesity and recurrent miscarriage: a systematic review and meta-analysis. J Obstet Gynaecol Res 2019; 45 (01) 30-38
• 14 Wang Q, Ratchford AM, Chi MM. et al. Maternal diabetes causes mitochondrial dysfunction and meiotic defects in murine oocytes. Mol Endocrinol 2009; 23 (10) 1603-1612
• 15 Grindler NM, Moley KH. Maternal obesity, infertility and mitochondrial dysfunction: potential mechanisms emerging from mouse model systems. Mol Hum Reprod 2013; 19 (08) 486-494
• 16 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
• 17 Setton R, Chung A, Zimmerman L, Melnick A, Rosenwaks Z, Spandorfer SD. Body mass index is not associated with donor oocyte recipient success: an ideal study using a paired analysis of sibling-oocytes. F S Rep 2020; 1 (01) 25-29
• 18 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
• 19 Hughes LM, McQueen DB, Jungheim ES, Merrion K, Boots CE. Maternal body mass index is not associated with increased rates of maternal embryonic aneuploidy. Fertil Steril 2022; 117 (04) 783-789
• 20 Bonus ML, McQueen DB, Ruderman R. et al. Relationship between paternal factors and embryonic aneuploidy of paternal origin. Fertil Steril 2022; 118 (02) 281-288
• 21 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
• 22 Lee JC, Bernardi LA, Boots CE. The association of euploid miscarriage with obesity. F S Rep 2020; 1 (02) 142-148
• 23 Jain A, Polotsky AJ, Rochester D. et al. Pulsatile luteinizing hormone amplitude and progesterone metabolite excretion are reduced in obese women. J Clin Endocrinol Metab 2007; 92 (07) 2468-2473
• 24 Simón C, Garcia Velasco JJ, Valbuena D. et al. Increasing uterine receptivity by decreasing estradiol levels during the preimplantation period in high responders with the use of a follicle-stimulating hormone step-down regimen. Fertil Steril 1998; 70 (02) 234-239
• 25 Bellver J, Marín C, Lathi RB. et al. Obesity affects endometrial receptivity by displacing the window of implantation. Reprod Sci 2021; 28 (11) 3171-3180
• 26 Bartha I, Joumady I, Cuerva M, Bartha JL. The effect of maternal obesity and lipid profile on first-trimester serum progesterone levels. Am J Obstet Gynecol MFM 2023; 5 (07) 100959
• 27 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
• 28 Santoro N, Lasley B, McConnell D. et al. Body size and ethnicity are associated with menstrual cycle alterations in women in the early menopausal transition: the Study of Women's Health across the Nation (SWAN) Daily Hormone Study. J Clin Endocrinol Metab 2004; 89 (06) 2622-2631
• 29 Gosman GG, Katcher HI, Legro RS. Obesity and the role of gut and adipose hormones in female reproduction. Hum Reprod Update 2006; 12 (05) 585-601
• 30 Levens ED, Skarulis MC. Assessing the role of endometrial alteration among obese patients undergoing assisted reproduction. Fertil Steril 2008; 89 (06) 1606-1608
• 31 Moschos S, Chan JL, Mantzoros CS. Leptin and reproduction: a review. Fertil Steril 2002; 77 (03) 433-444
• 32 Laird SM, Quinton ND, Anstie B, Li TC, Blakemore AI. Leptin and leptin-binding activity in women with recurrent miscarriage: correlation with pregnancy outcome. Hum Reprod 2001; 16 (09) 2008-2013
• 33 Jungheim ES, Schon SB, Schulte MB, DeUgarte DA, Fowler SA, Tuuli MG. IVF outcomes in obese donor oocyte recipients: a systematic review and meta-analysis. Hum Reprod 2013; 28 (10) 2720-2727
• 34 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
• 35 Xu J, Hipp HS, Capelouto SM. et al. The effects of oocyte donor and recipient body mass index on live birth rates and pregnancy outcomes following assisted reproduction. F S Rep 2020; 2 (01) 58-66
• 36 Chavarro JE, Rich-Edwards JW, Rosner BA, Willett WC. Diet and lifestyle in the prevention of ovulatory disorder infertility. Obstet Gynecol 2007; 110 (05) 1050-1058
• 37 Chung Y, Melo P, Pickering O, Dhillon-Smith R, Coomarasamy A, Devall A. The association between dietary patterns and risk of miscarriage: a systematic review and meta-analysis. Fertil Steril 2023; 120 (02) 333-357
• 38 Gaskins AJ, Chavarro JE. Diet and fertility: a review. Am J Obstet Gynecol 2018; 218 (04) 379-389
• 39 Physical Activity Guidelines for Americans. Office of Disease Prevention and Health Promotion; 2018
• 40 Syed H, Slayman T, DuChene Thoma K. ACOG Committee Opinion No. 804: physical activity and exercise during pregnancy and the postpartum period. Obstet Gynecol 2021; 137 (02) 375-376
• 41 Alexander EK, Pearce EN, Brent GA. et al. 2017 Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Thyroid 2017; 27 (03) 315-389
• 42 Levine LD, Holland TL, Kim K, Sjaarda LA, Mumford SL, Schisterman EF. The role of aspirin and inflammation on reproduction: the EAGeR trial. Can J Physiol Pharmacol 2019; 97 (03) 187-192
• 43 Eng GS, Sheridan RA, Wyman A. et al. AMP kinase activation increases glucose uptake, decreases apoptosis, and improves pregnancy outcome in embryos exposed to high IGF-I concentrations. Diabetes 2007; 56 (09) 2228-2234
• 44 Palomba S, Falbo A, Orio Jr F, Zullo F. Effect of preconceptional metformin on abortion risk in polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Fertil Steril 2009; 92 (05) 1646-1658
• 45 Morin-Papunen L, Rantala AS, Unkila-Kallio L. et al. Metformin improves pregnancy and live-birth rates in women with polycystic ovary syndrome (PCOS): a multicenter, double-blind, placebo-controlled randomized trial. J Clin Endocrinol Metab 2012; 97 (05) 1492-1500
• 46 Tang T, Lord JM, Norman RJ, Yasmin E, Balen AH. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database Syst Rev 2010; (01) CD003053
• 47 Practice Committee of the American Society for Reproductive Medicine.. Obesity and reproduction: a committee opinion. . Fertil Steril 2021; (116) 1266-1285
• 48 Clark AM, Ledger W, Galletly C. et al. Weight loss results in significant improvement in pregnancy and ovulation rates in anovulatory obese women. Hum Reprod 1995; 10 (10) 2705-2712
• 49 Reynolds KA, Boudoures AL, Chi MM, Wang Q, Moley KH. Adverse effects of obesity and/or high-fat diet on oocyte quality and metabolism are not reversible with resumption of regular diet in mice. Reprod Fertil Dev 2015; 27 (04) 716-724
• 50 Legro RS, Dodson WC, Kris-Etherton PM. et al. Randomized controlled trial of preconception interventions in infertile women with polycystic ovary syndrome. J Clin Endocrinol Metab 2015; 100 (11) 4048-4058
• 51 Mutsaerts MA, van Oers AM, Groen H. et al. Randomized trial of a lifestyle program in obese infertile women. N Engl J Med 2016; 374 (20) 1942-1953
• 52 Legro RS, Hansen KR, Diamond MP. et al; Reproductive Medicine Network. Effects of preconception lifestyle intervention in infertile women with obesity: the FIT-PLESE randomized controlled trial. PLoS Med 2022; 19 (01) e1003883
• 53 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