Breaking the cycle of infertility with clomiphene citrate and letrozole for successful ovulation induction for obese women with PCOS
Downloads
HIGHLIGHTS
- Polycystic ovarian syndrome (PCOS) is a hyperandrogenous state with oligo-anovulation.
- Letrozole is more efficient than CC in promoting ovulation and facilitating pregnancy in women with PCOS who are overweight or obese.
ABSTRACT
Objective: Indonesia has a higher prevalence of PCOS, a common endocrine disorder that affects 4% to 8% of women who are of reproductive age. Obesity, insulin resistance, and anovulatory infertility are all linked to PCOS. The ability of letrozole and clomiphene citrate (CC) to induce ovulation in overweight or obese PCOS patients was examined in this meta-analysis.
Materials and Methods: PRISMA criteria were followed when conducting a systematic literature search utilizing PubMed, Google Scholar, Cochrane Library, and ScienceDirect. Keywords included PCOS, obesity, clomiphene, and letrozole. Studies published between 2000 and 2024 in English, with full-text accessibility, were included. The search yielded 260 studies, of which nine were selected for quantitative synthesis.
Results: Letrozole showed a 12% increase in ovulation and a 33% increase in pregnancy rates compared to clomiphene citrate (CC). There was no discernible difference in the two groups' endometrial thickness. This meta-analysis finds that letrozole is more successful than CC in triggering ovulation and achieving conception in overweight or obese PCOS patients.
Conclusion: In women with PCOS who are overweight or obese, letrozole works better than clomiphene citrate (CC) to induce ovulation. Because it is accessible and reasonably priced, CC is still the first-line treatment, even if its efficacy is lesser. As a second-line therapy, letrozole is advised for women who are resistant to or do not react to CC.
R. Rehman dan A. Sheikh, Polycystic Ovary Syndrome Basic Science to Clinical Advances Across the Lifespan, Philadelphia: Elsevier, 2024.
R. Deans, “Polycystic Ovary Syndrome in Adolescence,” Medical Sciences, vol. 7, no. 10, p. 101, 2019.
H. M. Sadeghi, I. Adeli, D. Calina, A. O. Docea, T. Mousavi, M. Daniali dan S. Nikfar, “Polycystic Ovary Syndrome: A Comprehensive Review of Pathogenesis, Management, and Drug Repurposing,” International Journal of Molecular Sciences, vol. 23, no. 2, p. 583, 2022.
R. Azziz, K. S. Woods, R. Reyna, T. J. Key, E. S. Knochenhauer dan B. O. Yildiz, “The prevalence and features of the polycystic ovary syndrome in an unselected population,” Journal of Clinic Endocrinology and Metabolic, vol. 89, no. 6, pp. 2745-2749, 2004.
S. M. Sirmans dan K. A. Pate, “Epidemiology, diagnosis, and management of polycystic ovary syndrome,” Clinical epidemiology, vol. 6, pp. 1-13, 2014.
D. A. Sari, E. Y. Kurniawati dan M. A. Ashari, “Skrining dan Determinan Kejadian Sindrom Ovarium Polikistik (SOPK) Pada Remaja,” Jurnal ilmu kebidanan poltekkes ummi khasanah, vol. 9, no. 2, pp. 102-106, 2023.
M. A. Ganie, V. Vassudevan, I. Wani, M. S. Baba, T. Arif dan A. Rashid, “Epidemiology, pathogenesis, genetics & management of polycystic ovary syndrome in India,” Indian Journal of Medical Research, vol. 150, no. 4, pp. 333-344, 2019.
C. J. Glueck, N. Goldenberg, P. Wang, M. Loftspring dan A. Sherman, “Metformin during pregnancy reduces insulin, insulin resistance, insulin secretion, weight, testosterone and development of gestational diabetes: prospective longitudinal assessment of women with polycystic ovary syndrome from preconception throughout preg,” Human Reproductions, vol. 19, no. 3, pp. 510-521, 2004.
K. Passarello, S. Kurian dan V. Villanueva , “Endometrial Cancer: An Overview of Pathophysiology, Management, and Care,” Seminars in Oncologic Nursing, vol. 35, no. 2, pp. 157-165, 2019.
H. J. Teede, A. E. Joham, E. Paul, L. J. Moran, D. Loxton, D. Jolley dan C. Lombard, “Longitudinal weight gain in women identified with polycystic ovary syndrome: results of an observational study in young women,” Obesity (Silver Spring), vol. 21, no. 8, pp. 1526-1532, 2013.
D. Fariley dan A. Taylor, “Anovulation,” BMJ, vol. 327, no. 7414, pp. 546-549, 2003.
D. A. Rees, S. J. Jones dan C. L. Morgan, “Contemporary Reproductive Outcomes for Patients With Polycystic Ovary Syndrome: A Retrospective Observational Study,” Journal of Clinical Endocrinology and Metabolism, vol. 101, no. 4, pp. 1664-1672, 2016.
A. Cunha dan A. M. Povoa, “Infertility management in women with polycystic ovary syndrome: a review,” Porto Biomedical Journal, vol. 6, no. 1, p. 116, 2021.
J. Collee, M. Mawet, L. Tebache, M. Nisolle dan G. Brichant, “Polycystic ovarian syndrome and infertility: overview and insights of the putative treatments,” Gynecology and Endocrinology, vol. 37, no. 10, pp. 869-874, 2021.
F. Seyedoshohadaei, L. Tangestani, F. Zandvakii dan N. Rashadmanesh, “Comparison of the Effect of Clomiphene- Estradiol Valerate vs Letrozole on Endometrial Thickness, Abortion and Pregnancy Rate in Infertile Women with Polycystic Ovarian Syndrome,” Journal of Clinical Diagnostic Research, vol. 10, no. 8, pp. 10-13, 2016.
S. Franik, S. M. Eltrop, J. A. Kremer, L. Kiesel dan C. Farquhar, “Aromatase inhibitors (letrozole) for subfertile women with polycystic ovary syndrome,” Cochrane Database of Systematic Review, vol. 5, no. 5, p. 10287, 2018.
A. S. Melo, R. A. Ferriani dan P. A. Navarro, “Treatment of infertility in women with polycystic ovary syndrome: approach to clinical practice,” Clinics (Sao Paulo), vol. 70, no. 11, pp. 765-769, 2015.
M. F. Costello, M. L. Misso, A. Balen, A. Boyle, L. Devoto, R. M. Garad, R. Hart, L. Johnson, C. Jordan dan R. S. Legro, “Evidence summaries and recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome: assessment and treatment of infertility,” Human Reproduction Open, vol. 2019, no. 1, p. 021, 2019.
P. B. Ray, A. Ray dan P. S. Chakraborti, “Comparison of efficacy of letrozole and clomiphene citrate in ovulation induction in Indian women with polycystic ovarian syndrome,” Archive of Gynecology and Obstetric, vol. 285, no. 3, pp. 873-877, 2012.
S. S. Basakarod, M. Bharadwaj, P. Raj V dan C. N, “The effect of letrozole vs clomiphene citrate for ovulation induction in patients of infertility with polycystic ovarian syndrome,” International Journal of Reproduction, Contraception, Obstetrics and Gynecology, vol. 12, no. 10, 2023.
K. K. Roy, J. Baruah, S. Singla, J. B. Sharma, N. Singh, S. K. Jain dan M. Goyal, “A prospective randomized trial comparing the efficacy of Letrozole and Clomiphene citrate in induction of ovulation in polycystic ovarian syndrome,” Journal of Human Reproduction, vol. 5, no. 1, pp. 20-25, 2012.
S. Kar, “Clomiphene citrate or letrozole as first-line ovulation induction drug in infertile PCOS women: A prospective randomized trial,” Journal of Human Reproductive Sciences, vol. 5, no. 3, pp. 262-265, 2012.
S. S. Nambiar, “Clomiphene Citrate versus Letrozole for Ovulation Induction in PCOS: A Comparative Study,” JSAFOG, vol. 10, no. 2, pp. 384-399, 2018.
R. S. Legro, R. G. Brzyski, M. P. Diamond, C. Coutifaris, W. D. Schlaff dan P. Casson, “Letrozole versus clomiphene for infertility in the polycystic ovary syndrome,” New England Journal of Medicine, vol. 371, no. 2, pp. 119-129, 2014.
A. F. Bigawy, U. M. F. Fouda dan H. A. E. Wahab, “A randomized trial of letrozole versus clomiphene citrate in induction of ovulation in patients with polycystic ovary syndrome (PCOS),” Middle East Fertility Society Journal, vol. 13, no. 1, 2008.
S. Arya, K. R. Hansen, J. D. Peck dan R. a. Wild , “Metabolic syndrome in obesity: treatment success and adverse pregnancy outcomes with ovulation induction in polycystic ovary syndrome,” American Journal of Obstetric and gynecology, vol. 225, no. 3, p. 280, 2021.
T. Wasim, T. Nasrin, J. Zunair dan S. Irshad , “Efficacy of Letrozole vs Clomiphene Citrate for induction of ovulation in women with polycystic ovarian syndrome,” Pakistan Journal of Medical Sciences, vol. 40, no. 1, pp. 78-83, 2024.
L. C. Morley, T. Tang, E. Yasmin, R. J. Norman dan A. H. Balen, “Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility,” Cochrane database of systematic review, vol. 11, no. 1, 2017.
J. Zhao, Q. Zhang dan Y. Li, “The effect of endometrial thickness and pattern measured by ultrasonography on pregnancy outcomes during IVF-ET cycles,” Reproduction Biology and Endocrinology, vol. 100, no. 10, 2012.
I. E. Messinis, “Ovulation induction: a mini review,” Human Reproduction, vol. 20, no. 10, pp. 2688-2697, 2005.
S. Kafy dan T. Tulandi, “New advances in ovulation induction,” Current Opinion in Obstetrics and Gynecology, vol. 19, no. 3, pp. 248-252, 2007.
H. J. Teede, M. L. Misso, M. F. Costello, A. Dokras, J. Laven, L. Moran, T. Piltonen dan R. J. Norman, “Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome†,” Human Reproduction, vol. 33, no. 9, pp. 1602-1618, 2018.
M. F. Mitally dan R. F. Casper, “Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate,” Fertility and Sterility, vol. 75, no. 2, pp. 305-309, 2001.
V. Atay, C. Cam, M. Muhcu dan M. Cam, “Comparison of letrozole and clomiphene citrate in women with polycystic ovaries undergoing ovarian stimulation,” Journal of International Medical Research, vol. 34, no. 1, pp. 73-76, 2006.

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
1. Copyright of the article is transferred to the journal, by the knowledge of the author, whilst the moral right of the publication belongs to the author.
2. The legal formal aspect of journal publication accessibility refers to Creative Commons Attribution-Non Commercial-Share alike (CC BY-NC-SA), (https://creativecommons.org/licenses/by-nc-sa/4.0/)
3. The articles published in the journal are open access and can be used for non-commercial purposes. Other than the aims mentioned above, the editorial board is not responsible for copyright violation
The manuscript authentic and copyright statement submission can be downloaded ON THIS FORM.