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An escalating letrozole dosing strategy is emerging as a potential way to accelerate follicular maturation and optimize fertility outcomes in women with PCOS-related anovulatory infertility.
Polycystic ovary syndrome (PCOS) remains the predominant cause of ovulation-related infertility, making effective ovulation induction a cornerstone of fertility treatment. Although letrozole is widely established as first-line therapy, questions remain regarding the ideal dosing approach to maximize ovarian response. Pushpita Sharmin and other investigators therefore evaluated whether a progressively increasing letrozole regimen could outperform the conventional fixed-dose schedule in PCOS.
They conducted an open-label randomized controlled trial involving women with PCOS-associated infertility who were candidates for ovulation induction therapy. Participants were assigned equally to receive either a dose-escalation letrozole regimen initiated at a low dose with gradual daily increases or a conventional fixed-dose protocol administered over five days. Follicular development was monitored across treatment cycles, with analyses focusing on the timing of follicular maturation, the number of mature follicles generated, and cumulative pregnancy outcomes.
Seventy women underwent randomization, with 35 participants allocated to each treatment strategy. The escalating-dose regimen demonstrated earlier ovarian responsiveness and generated a more robust follicular response across treatment cycles than the standard protocol (Table 1).
Women receiving the escalating regimen achieved mature follicular development earlier during treatment and experienced more frequent multifollicular growth. Although pregnancy rates numerically favored the step-up approach, the observed advantage did not reach statistical significance. To sum up, treatment optimization may be as important as treatment selection in ovulation induction strategies for PCOS. While larger studies remain necessary to establish definitive reproductive benefits, gradual letrozole dose escalation appeared to boost ovarian responsiveness and may offer clinicians additional flexibility when tailoring fertility treatment protocols.
Middle East Fertility Society Journal
Letrozole step-up protocol for ovulation induction in infertile women with polycystic ovary syndrome – a randomized controlled trial
Pushpita Sharmin et al.
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