Extended Letrozole Regimen for Enhancing Follicular Response in PCOS-related Infertility
Dr Bhavneet Kaur, Dr Archana Kumari, Professor Reeta Mahey, Professor Maroof Ahmad Khan, Dr Aarthi K Jayraj, Professor Neena Malhotra
All India Institute of Medical Sciences, New Delhi, India
Introduction
•PCOS is a major cause of anovulatory infertility.
•Letrozole is now the first-line agent for ovulation induction due to its superior efficacy and safety profile.1
•While the standard regimen (2.5 mg for 5 days) is effective, extended regimens may enhance ovulatory response especially in resistant cases.
Objective
•PRIMARY OBJECTIVE:
To compare the efficacy of a 10-day versus 5-day letrozole regimen in improving follicular response and pregnancy outcomes in women with PCOS-related infertility.
•SECONDARY OBJECTIVES: Need for dose escalation
•Need for injection gonadotropin
•Multi-follicular development
•Ovarian hyperstimulation syndrome (OHSS) rate
•Clinical pregnancy rate and pregnancy rate per cycle
•Multiple pregnancy rate and abortion rate
Methods
•Prospective randomized controlled trial, conducted at a tertiary care center in North India.
•Between October 2023 to November 2024
Consort diagram: "IMAGE"
Results
Primary Outcome: Follicular Response: "TABLE" & "GRAPH"
Need for 5 mg dose: "IMAGE"
Pregnancy Outcomes: "TABLE"
•None required Injection Gonadotropin in extended regimen (0% vs. 15.8%, p = 0.025)
•Multi-follicular development (15.0% (6/40) vs. 17.5% (7/40), p = 0.762) were comparable
•No OHSS in either group
Discussion
•Extended letrozole regimen (2.5 mg for 10 days) led to significantly higher follicular response (85% vs 52.5%, p = 0.002).
•Zhu et al. (2022) and Mandelbaum et al. (2024) all reported improved ovulation outcomes with extended letrozole regimens, supporting our findings.2,3
•The extended regimen demonstrated a higher pregnancy rate per cycle (22.58% vs. 15.29%), indicating a potential for improved conception efficiency, although the difference was not statistically significant.
Conclusion
The extended 10-day letrozole regimen significantly improved follicular response without increasing adverse outcomes like OHSS. It reduced the need for dose escalation or gonadotropin use and showed a trend toward higher per-cycle conception. These findings support the extended regimen as a safe and effective option for ovulation induction in women with PCOS.
References
1.Misso ML, Wong JLA, Teede HJ, Hart R, Rombauts L, Melder AM, et al. Aromatase inhibitors for PCOS: a systematic review and meta-analysis. Hum Reprod Update. 2012;18(3):301–12.
2.Zhu X, Fu Y. Extending letrozole treatment duration is effective in inducing ovulation in women with polycystic ovary syndrome and letrozole resistance. Fertil Steril. 2023;119(1):107–13.
3.Mandelbaum RS, Agarwal R, Melville S, Violette CJ, Winer S, Shoupe D, et al. A comparison of letrozole regimens for ovulation induction in women with polycystic ovary syndrome. F&S Rep. 2024;5(2):170–5.
