Comparative Evaluation of Early Pregnancy Outcomes Following Ovulation Induction with Letrozole Versus Clomiphene Citrate: Evidence from a Prospective Iraqi Cohort Study

Authors

  • Weqar Akram Hussein Department of Obstetrics and Gynecology, Al-Kindy College of Medicine, University of Baghdad, Baghdad, Iraq.
  • Bushra Mohammed Majeed Department of Obstetrics and Gynecology, Al-Kindy College of Medicine, University of Baghdad, Baghdad, Iraq.
  • Zahraa Muhmmed Jameel Al-Sattam Department of Obstetrics and Gynecology, Al-Kindy College of Medicine, University of Baghdad, Baghdad, Iraq.

DOI:

https://doi.org/10.22317/jcms.v11i5.1834

Abstract

Objectives: To compare early pregnancy outcomes, including miscarriage, ectopic pregnancy, multiple pregnancy, and congenital anomalies, among women who conceived following ovulation induction with letrozole or clomiphene citrate.

Methods: A prospective comparative observational study was conducted at Al-Elwiya Maternity Teaching Hospital and a private clinic in Baghdad, Iraq, from March 2023 to December 2024. One hundred infertile women aged 21–35 years who conceived after ovulation induction with either letrozole (5 mg/day) or clomiphene citrate (100 mg/day) for five days (cycle days 3–7) were enrolled. Participants were followed through early pregnancy with serial sonography at 6, 8–11, and 18–20 weeks of gestation. Data were analyzed using SPSS version 23, and a p-value <0.05 was considered statistically significant.

Results: Adverse pregnancy outcomes occurred in 19.0% of women in the clomiphene group and 8.6% in the letrozole group, a difference that was not statistically significant (χ²(1)=2.342, p=0.126). Normal singleton pregnancies were more frequent with letrozole (91.4%) than with clomiphene (81.0%). The odds ratio for adverse outcomes in the clomiphene group was 2.49 (95% CI: 0.75–8.26). Twin pregnancies were observed only in the clomiphene group (7.1%). Congenital anomalies were rare and comparable between groups.

Conclusion: Although not statistically significant, letrozole was associated with fewer early pregnancy complications and a trend toward safer outcomes compared with clomiphene citrate. Both agents remain effective for ovulation induction, but letrozole may offer a more favorable safety profile for women at risk of early pregnancy loss.

References

Zegers-Hochschild F, Adamson GD, Dyer S, et al. The International Glossary on Infertility and Fertility Care, 2017. Hum Reprod. 2017;32(9):1786–801.

Greil AL, Slauson-Blevins K, McQuillan J. The experience of infertility: a review of recent literature. Sociol Health Illn. 2010;32(1):140–62.

Cousineau TM, Domar AD. Psychological impact of infertility. Best Pract Res Clin Obstet Gynaecol. 2007;21(2):293–308.

World Health Organization (WHO). Infertility fact sheet. Available from: https://www.who.int/news-room/fact-sheets/detail/infertility [Accessed 2025 May 14].

Valeria Cetorelli. The effect on fertility of the 2003-2011 war in Iraq.Population and development review .2014;40(4):581-604.

Alhassan A, Ziblim A, Muntaka S. A survey on knowledge and perception of infertility among women in Northern Ghana. Int J Womens Health. 2014;6:587–93.

Eskew AM, Bedrick BS, Hardi A. Letrozole compared with clomiphene citrate for unexplained infertility: A systemic review and meta-analysis .Obstet Gynecol 2019;133(3):437-444.

Fauser BC, Tarlatzis BC, Rebar RW, et al. Consensus on women's health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group. Fertil Steril. 2012;97(1):28–38.

Mascarenhas MN, Flaxman SR, Boerma T, Vanderpoel S, Stevens GA. National, regional, and global trends in infertility prevalence since 1990: a systematic analysis of 277 health surveys. PLoS Med. 2012;9(12):e1001356.

Ludwig M, Finas DF, Al-Hasani S, et al. Clinical use of hysteroscopy in the diagnosis and treatment of infertility. Gynaecol Endosc. 2011;10(1):5–10.

Pandian Z, Gibreel A, Bhattacharya S. In vitro fertilisation for unexplained subfertility. Cochrane Database Syst Rev. 2015;(11): CD003357.

Leila Pourali, Sedigheh Ayati, Shirin Tavakolizadeh. Clomiphene citrate versus letrozole with gonadotropins in intrauterine insemination cycle: A randomized trial.Int J Reprod Bio Med.2017;12(1):49-54.

World Health Organization (WHO). Application for the inclusion of aromatase inhibitors as ovulation induction agents in the WHO Model list of Essential Medicines(2023) for adult . Available from: https://www.who.int/news-room/fact-sheets/detail [Accessed 2022 December 14th].

Yang X, Lin G, Lu G, Gong F. Letrozole supplementation during controlled ovarian stimulation in expected high responders: a pilot randomized controlled study. Reprod Biol Endocrinol. 2019;17(1):43.

T. Tatsumi, S.C.Jwa,A.Kuwahara,M.Irahara. No increased risk of major congenital anomalies oradverse pregnancy or neonatal outcomes following letrozoleuse in assisted reproductive technology.Human Reproduction.2017;32(1):125-132.

Bayar U, Tanriverdi HA, Barut A, Ayoglu F, Ozcan O, Kaya E. Letrozole vs. clomiphene citrate in patients with ovulatory infertility. Fertil Steril. 2006;85(4):1045–8.

Legro RS, Brzyski RG, Diamond MP, et al. Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. N Engl J Med. 2014;371(2):119–29.

Badawy A, Shokeir T, Allam AF, Abdelhafez MS. Pregnancy outcome after ovulation induction with letrozole or clomiphene citrate. Fertil Steril. 2009;92(3):849–52.

Li X, Zhao L, Chen Y, Wang Z, Liu X. Letrozole vs. clomiphene citrate in ovulation induction: a systematic review and meta-analysis. Reprod Biomed Online. 2021;42(2):303–12.

Wang R, Lin J, Shao D, Li T. Comparative effectiveness of letrozole and clomiphene in PCOS-related infertility. Hum Reprod Update. 2023;29(1):112–29.

Mitwally MFM, Casper RF. Aromatase inhibitors versus SERMs in ovulation induction. Fertil Steril. 2020;113(1):39–46.

Norman RJ, Codner E, Wang Y, Teede H. Ovulation induction pharmacology: comparing agents. J Clin Endocrinol Metab. 2021;106(5):e2068–75.

Al-Rashid F, Ali Z, Hassan M, Kareem D. Incidence of multiple pregnancies following ovulation induction: letrozole vs. clomiphene. Middle East Fertil Soc J. 2024;29(1):102–8.

Ganesh A, Menon V, Subramaniam P, Rao P. Risk of congenital anomalies with letrozole: a meta-analysis. Fertil Steril. 2022;117(3):522–30.

Eapen A, Patel R, Shinde S, Thomas A. Patient experience and tolerability of ovulation induction drugs: a cohort study. Int J Gynaecol Obstet. 2020;149(2):172–9.

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Published

2025-10-26

How to Cite

Weqar Akram Hussein, Bushra Mohammed Majeed, & Al-Sattam, Z. M. J. (2025). Comparative Evaluation of Early Pregnancy Outcomes Following Ovulation Induction with Letrozole Versus Clomiphene Citrate: Evidence from a Prospective Iraqi Cohort Study. Journal of Contemporary Medical Sciences, 11(5), 367–371. https://doi.org/10.22317/jcms.v11i5.1834

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