Semin Reprod Med 2023; 41(03/04): 108-118
DOI: 10.1055/s-0043-1776795
Review Article

Navigating the Role of Anti-Obesity Agents Prior to Pregnancy: A Narrative Review

Alyse S. Goldberg
1   Department of Medicine, University of Toronto, Toronto, Ontario, Canada
Samin Dolatabadi
2   Department of Medicine, University of Calgary, Calgary, Canada
Heidi Dutton
3   Department of Medicine, University of Ottawa, Ottawa, Canada
Jamie L. Benham
4   Department of Medicine and Community Health Sciences, University of Calgary, Calgary, Canada
› Author Affiliations


Utilization of anti-obesity agents is rising in reproductive-age females with some planning for future pregnancy. Lifestyle-induced weight loss has been shown to increase spontaneous conception rate, improve rates of fertility intervention complications, and decrease pregnancy comorbidities. However, the definitive role of assisting weight loss with medication prior to pregnancy remains to be established. The implications of anti-obesity agent used prior to pregnancy are explored in this narrative review, considering benefits of weight loss as well as available evidence for use and risks of anti-obesity agents prior to pregnancy.

Publication History

Article published online:
16 November 2023

© 2023. Thieme. All rights reserved.

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  • References

  • 1 van Vliet-Ostaptchouk JV, Snieder H, Lagou V. Gene-lifestyle interactions in obesity. Curr Nutr Rep 2012; 1 (03) 184-196
  • 2 Gesink Law DC, Maclehose RF, Longnecker MP. Obesity and time to pregnancy. Hum Reprod 2007; 22 (02) 414-420
  • 3 Imani B, Eijkemans MJC, te Velde ER, Habbema JDF, Fauser BCJM. A nomogram to predict the probability of live birth after clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility. Fertil Steril 2002; 77 (01) 91-97
  • 4 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
  • 5 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
  • 6 Kawwass JF, Kulkarni AD, Hipp HS, Crawford S, Kissin DM, Jamieson DJ. Extremities of body mass index and their association with pregnancy outcomes in women undergoing in vitro fertilization in the United States. Fertil Steril 2016; 106 (07) 1742-1750
  • 7 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
  • 8 Bellver J. BMI and miscarriage after IVF. Curr Opin Obstet Gynecol 2022; 34 (03) 114-121
  • 9 Creanga AA, Catalano PM, Bateman BT. Obesity in pregnancy. N Engl J Med 2022; 387 (03) 248-259
  • 10 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
  • 11 Hoek A, Wang Z, van Oers AM, Groen H, Cantineau AEP. Effects of preconception weight loss after lifestyle intervention on fertility outcomes and pregnancy complications. Fertil Steril 2022; 118 (03) 456-462
  • 12 Mutsaerts MAQ, 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
  • 13 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
  • 14 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
  • 15 Espinós JJ, Solà I, Valli C, Polo A, Ziolkowska L, Martínez-Zapata MJ. The effect of lifestyle intervention on pregnancy and birth outcomes on obese infertile women: a systematic review and meta-analysis. Int J Fertil Steril 2020; 14 (01) 1-9
  • 16 Penzias A, Azziz R, Bendikson K. et al; Practice Committee of the American Society for Reproductive Medicine. Electronic address:, Practice Committee of the American Society for Reproductive Medicine. Obesity and reproduction: a committee opinion. Fertil Steril 2021; 116 (05) 1266-1285
  • 17 Shen C, Fu W, Fang C, Zhou H, Wang L. The impact of weight loss for obese infertile women prior to in vitro fertilization: a retrospective cohort study. Medicine (Baltimore) 2023; 102 (10) e33009
  • 18 Van Oers AM, Mutsaerts MAQ, Burggraaff JM. et al. Association between periconceptional weight loss and maternal and neonatal outcomes in obese infertile women. PLOS One 2018; 13 (03) e0192670
  • 19 Nagpal TS, Souza SCS, Moffat M. et al. Does prepregnancy weight change have an effect on subsequent pregnancy health outcomes? A systematic review and meta-analysis. Obes Rev 2022; 23 (01) e13324
  • 20 Tabet M, Banna S, Luong L, Kirby R, Chang JJ. Pregnancy outcomes after preeclampsia: the effects of interpregnancy weight change. Am J Perinatol 2021; 38 (13) 1393-1402
  • 21 Oteng-Ntim E, Mononen S, Sawicki O, Seed PT, Bick D, Poston L. Interpregnancy weight change and adverse pregnancy outcomes: a systematic review and meta-analysis. BMJ Open 2018; 8 (06) e018778
  • 22 Schummers L, Hutcheon JA, Bodnar LM, Lieberman E, Himes KP. Risk of adverse pregnancy outcomes by prepregnancy body mass index: a population-based study to inform prepregnancy weight loss counseling. Obstet Gynecol 2015; 125 (01) 133-143
  • 23 Adams TD, Pendleton RC, Strong MB. et al. Health outcomes of gastric bypass patients compared to nonsurgical, nonintervened severely obese. Obesity (Silver Spring) 2010; 18 (01) 121-130
  • 24 Johansson K, Cnattingius S, Näslund I. et al. Outcomes of pregnancy after bariatric surgery. N Engl J Med 2015; 372 (09) 814-824
  • 25 Mechanick JI, Apovian C, Brethauer S. et al. Clinical practice guidelines for the perioperative nutrition, metabolic, and nonsurgical support of patients undergoing bariatric procedures - 2019 update: cosponsored by American Association of Clinical Endocrinologists/American College of Endocrinology, The Obesity Society, American Society for Metabolic & Bariatric Surgery, Obesity Medicine Association, and American Society of Anesthesiologists. Surg Obes Relat Dis 2020; 16 (02) 175-247
  • 26 Legro RS. Preconception weight loss in the obese patient: overhyped or underutilized?. Fertil Steril 2022; 118 (03) 431-433
  • 27 LaMoia TE, Shulman GI. Cellular and molecular mechanisms of metformin action. Endocr Rev 2021; 42 (01) 77-96
  • 28 Teede HJ, Tay CT, Laven JJE. et al. Recommendations From the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome. J Clin Endocrinol Metab 2023; 108 (10) 2447-2469 DOI: 10.1210/clinem/dgad463.
  • 29 Levri KM, Slaymaker E, Last A. et al. Metformin as treatment for overweight and obese adults: a systematic review. Ann Fam Med 2005; 3 (05) 457-461
  • 30 Diabetes Prevention Program Research Group. Long-term safety, tolerability, and weight loss associated with metformin in the Diabetes Prevention Program Outcomes Study. Diabetes Care 2012; 35 (04) 731-737
  • 31 Nestler JE, Stovall D, Akhter N, Iuorno MJ, Jakubowicz DJ. Strategies for the use of insulin-sensitizing drugs to treat infertility in women with polycystic ovary syndrome. Fertil Steril 2002; 77 (02) 209-215
  • 32 Given JE, Loane M, Garne E. et al. Metformin exposure in first trimester of pregnancy and risk of all or specific congenital anomalies: exploratory case-control study. BMJ 2018; 361: k2477
  • 33 Syngelaki A, Nicolaides KH, Balani J. et al. Metformin versus placebo in obese pregnant women without diabetes mellitus. N Engl J Med 2016; 374 (05) 434-443
  • 34 Rowan JA, Rush EC, Plank LD. et al. Metformin in gestational diabetes: the offspring follow-up (MiG TOFU): body composition and metabolic outcomes at 7-9 years of age. BMJ Open Diabetes Res Care 2018; 6 (01) e000456
  • 35 Hanem LGE, Salvesen Ø, Juliusson PB. et al. Intrauterine metformin exposure and offspring cardiometabolic risk factors (PedMet study): a 5-10 year follow-up of the PregMet randomised controlled trial. Lancet Child Adolesc Health 2019; 3 (03) 166-174
  • 36 Heck AM, Yanovski JA, Calis KA. Orlistat, a new lipase inhibitor for the management of obesity. Pharmacotherapy 2000; 20 (03) 270-279
  • 37 Zhi J, Melia AT, Guerciolini R. et al. Retrospective population-based analysis of the dose-response (fecal fat excretion) relationship of orlistat in normal and obese volunteers. Clin Pharmacol Ther 1994; 56 (01) 82-85
  • 38 Hvizdos KM, Markham A. Orlistat: a review of its use in the management of obesity. Drugs 1999; 58 (04) 743-760
  • 39 Padwal R, Kezouh A, Levine M, Etminan M. Long-term persistence with orlistat and sibutramine in a population-based cohort. Int J Obes 2007; 31 (10) 1567-1570
  • 40 Padwal RS, Majumdar SR. Drug treatments for obesity: orlistat, sibutramine, and rimonabant. Lancet 2007; 369 (9555) 71-77
  • 41 Ballinger A, Peikin SR. Orlistat: its current status as an anti-obesity drug. Eur J Pharmacol 2002; 440 (2-3): 109-117
  • 42 Källén BAJ. Antiobesity drugs in early pregnancy and congenital malformations in the offspring. Obes Res Clin Pract 2014; 8 (06) e571-e576
  • 43 Greenway FL, Whitehouse MJ, Guttadauria M. et al. Rational design of a combination medication for the treatment of obesity. Obesity (Silver Spring) 2009; 17 (01) 30-39
  • 44 Greenway FL, Fujioka K, Plodkowski RA. et al; COR-I Study Group. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2010; 376 (9741) 595-605
  • 45 Alwan S, Reefhuis J, Botto LD, Rasmussen SA, Correa A, Friedman JM. National Birth Defects Prevention Study. Maternal use of bupropion and risk for congenital heart defects. Am J Obstet Gynecol 2010; 203 (01) 52.e1-52.e6
  • 46 Turner E, Jones M, Vaz LR, Coleman T. Systematic review and meta-analysis to assess the safety of bupropion and varenicline in pregnancy. Nicotine Tob Res 2019; 21 (08) 1001-1010
  • 47 Chun-Fai-Chan B, Koren G, Fayez I. et al. Pregnancy outcome of women exposed to bupropion during pregnancy: a prospective comparative study. Am J Obstet Gynecol 2005; 192 (03) 932-936
  • 48 Towers CV, Katz E, Weitz B, Visconti K. Use of naltrexone in treating opioid use disorder in pregnancy. Am J Obstet Gynecol 2020; 222 (01) 83.e1-83.e8
  • 49 Hulse GK, O'Neil G, Arnold-Reed DE. Methadone maintenance vs. implantable naltrexone treatment in the pregnant heroin user. Int J Gynaecol Obstet 2004; 85 (02) 170-171
  • 50 Jones HE, Chisolm MS, Jansson LM, Terplan M. Naltrexone in the treatment of opioid-dependent pregnant women: the case for a considered and measured approach to research. Addiction 2013; 108 (02) 233-247
  • 51 Smith SM, Meyer M, Trinkley KE. Phentermine/topiramate for the treatment of obesity. Ann Pharmacother 2013; 47 (03) 340-349
  • 52 Gadde KM, Allison DB, Ryan DH. et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet 2011; 377 (9774) 1341-1352
  • 53 Garvey WT, Ryan DH, Look M. et al. Two-year sustained weight loss and metabolic benefits with controlled-release phentermine/topiramate in obese and overweight adults (SEQUEL): a randomized, placebo-controlled, phase 3 extension study. Am J Clin Nutr 2012; 95 (02) 297-308
  • 54 Allison DB, Gadde KM, Garvey WT. et al. Controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP). Obesity (Silver Spring) 2012; 20 (02) 330-342
  • 55 Grunvald E, Shah R, Hernaez R. et al; AGA Clinical Guidelines Committee. AGA Clinical Practice Guideline on pharmacological interventions for adults with obesity. Gastroenterology 2022; 163 (05) 1198-1225
  • 56 D'Adesky N, Ghosh S. Phentermine use during first and second trimesters associated with fetal stroke. Cureus 2019; 11 (11) e6170
  • 57 Mines D, Tennis P, Curkendall SM. et al. Topiramate use in pregnancy and the birth prevalence of oral clefts. Pharmacoepidemiol Drug Saf 2014; 23 (10) 1017-1025
  • 58 Margulis AV, Mitchell AA, Gilboa SM. et al; National Birth Defects Prevention Study. Use of topiramate in pregnancy and risk of oral clefts. Am J Obstet Gynecol 2012; 207 (05) 405.e1-405.e7
  • 59 Halpern B, Mancini MC. Safety assessment of combination therapies in the treatment of obesity: focus on naltrexone/bupropion extended release and phentermine-topiramate extended release. Expert Opin Drug Saf 2017; 16 (01) 27-39
  • 60 Alfaris N, Minnick AM, Hopkins CM, Berkowitz RI, Wadden TA. Combination phentermine and topiramate extended release in the management of obesity. Expert Opin Pharmacother 2015; 16 (08) 1263-1274
  • 61 Vilsbøll T, Christensen M, Junker AE, Knop FK, Gluud LL. Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials. BMJ 2012; 344: d7771
  • 62 OZEMPIC. (Semaglutide) injection, for subcutaneous use. Highlights of prescribing information. Accessed May 3, 2023 at:
  • 63 Pi-Sunyer X, Astrup A, Fujioka K. et al; SCALE Obesity and Prediabetes NN8022-1839 Study Group. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. N Engl J Med 2015; 373 (01) 11-22
  • 64 Greco D. Normal pregnancy outcome after first-trimester exposure to liraglutide in a woman with Type 2 diabetes. Diabet Med 2015; 32 (10) e29-e30
  • 65 LIRAGLUTIDE. FDA Center for Drug Evaluation and Research. Approval package for: application number: NDA 206321/S-004 (trade name: SAXENDA; generic or proper name: liraglutide injection). Accessed July 7, 2023 at:
  • 66 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
  • 67 Davies M, Færch L, Jeppesen OK. et al; STEP 2 Study Group. Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. Lancet 2021; 397 (10278): 971-984
  • 68 Rubino D, Abrahamsson N, Davies M. et al; STEP 4 Investigators. Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: the STEP 4 randomized clinical trial. JAMA 2021; 325 (14) 1414-1425
  • 69 Jastreboff AM, Aronne LJ, Ahmad NN. et al; SURMOUNT-1 Investigators. Tirzepatide once weekly for the treatment of obesity. N Engl J Med 2022; 387 (03) 205-216
  • 70 Frías JP, Davies MJ, Rosenstock J. et al; SURPASS-2 Investigators. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med 2021; 385 (06) 503-515
  • 71 MOUNJARO. (Tirzepatide) injection for subcutaneous use. Highlight of prescribing information. Accessed May 3, 2023 at:
  • 72 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
  • 73 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
  • 74 Legro RS, Hansen KR, Diamond MP. et al. Effects of preconception lifestyle intervention in infertile women with obesity: the FIT-PLESE randomized controlled trial. PLOS Med 2022; 19 (01) e1003883
  • 75 Kumar P, Arora S. Orlistat in polycystic ovarian syndrome reduces weight with improvement in lipid profile and pregnancy rates. J Hum Reprod Sci 2014; 7 (04) 255-261
  • 76 Chen Z, Cai Z. Effects of oral contraceptives plus orlistat in patients with polycystic ovary syndrome and overweight/obesity: a meta-analysis. J Obstet Gynaecol Res 2022; 48 (06) 1399-1408
  • 77 Metwally M, Amer S, Li TC, Ledger WL. An RCT of metformin versus orlistat for the management of obese anovulatory women. Hum Reprod 2009; 24 (04) 966-975
  • 78 Chang JJ, Lathi RB, Kim SH. A retrospective study examining phentermine on preconception weight loss and pregnancy outcomes. Endocr Pract 2020; 26 (09) 990-996
  • 79 Rodrigo N, Chen H, Pollock CA, Glastras SJ. Preconception weight loss improves fertility and maternal outcomes in obese mice. J Endocrinol 2022; 253 (01) 27-38
  • 80 Yang Q, Wang F. Successful pregnancy after improving insulin resistance with the glucagon-like peptide-1 analogue in a woman with polycystic ovary syndrome: a case report and review of the literature. Gynecol Obstet Invest 2016; 81 (05) 477-480
  • 81 Halpern B, Pepe RB. Preconception diabetes remission, a viable approach to reduce pregnancy risks in women with recent diagnosis of Type 2 diabetes: case report and clinical discussion. Clin Obes 2022; 12 (01) e12495
  • 82 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
  • 83 Liu X, Zhang Y, Zheng SY. et al. Efficacy of exenatide on weight loss, metabolic parameters and pregnancy in overweight/obese polycystic ovary syndrome. Clin Endocrinol (Oxf) 2017; 87 (06) 767-774
  • 84 Li R, Mai T, Zheng S, Zhang Y. Effect of metformin and exenatide on pregnancy rate and pregnancy outcomes in overweight or obese infertility PCOS women: long-term follow-up of an RCT. Arch Gynecol Obstet 2022; 306 (05) 1711-1721
  • 85 Kapitza C, Nosek L, Jensen L, Hartvig H, Jensen CB, Flint A. Semaglutide, a once-weekly human GLP-1 analog, does not reduce the bioavailability of the combined oral contraceptive, ethinylestradiol/levonorgestrel. J Clin Pharmacol 2015; 55 (05) 497-504
  • 86 Sisson EM. Liraglutide: clinical pharmacology and considerations for therapy. Pharmacotherapy 2011; 31 (09) 896-911
  • 87 Joshi G, Ahbelmalak B, Weigel W. et al. American Society of Anesthesiologists Consensus-Based Guidance on Preoperative Management of Patients (Adults and Children) on Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists. Published June 29, 2023 . Accessed July 2, 2023 at:
  • 88 Carey KJ, Vitek W. Weight cycling in women: adaptation or risk?. Semin Reprod Med 2022; 40 (5-06): 277-282
  • 89 Kluge L, Bergh C, Einarsson S, Pinborg A, Mikkelsen Englund AL, Thurin-Kjellberg A. Cumulative live birth rates after weight reduction in obese women scheduled for IVF: follow-up of a randomized controlled trial. Hum Reprod Open 2019; 2019 (04) hoz030
  • 90 Piccinini-Vallis H, Woolcott C, Miller L, Snelgrove-Clarke E, Cahill S. The relationship between pre-pregnancy attempts to lose weight and gestational weight gain: an exploratory primary care prospective cohort study. J Obstet Gynaecol Can 2021; 43 (03) 337-343.e1
  • 91 XENICAL® (Orlistat) product monograph. Accessed July 19, 2023 at:
  • 92 Srivastava G, Apovian CM. Current pharmacotherapy for obesity. Nat Rev Endocrinol 2018; 14 (01) 12-24
  • 93 CONTRAVE. Highlights of prescribing information. Accessed July 19, 2023 at:
  • 94 QSYMIA. Highlights of prescribing information. Accessed July 19, 2023 at: