Letrozole Extended vs Traditional Therapy for Ovulation Induction in Women With PCOS (PROLEx-PCOS)

Extended Therapy Versus Traditional Therapy With Letrozole for Ovulation Induction in Women With Polycystic Ovary Syndrome: A Randomized Controlled Trial

This randomized clinical trial aims to compare the efficacy and safety of extended letrozole therapy (5 mg/day for 10 days) versus standard letrozole therapy (5 mg/day for 5 days) for ovulation induction in women with polycystic ovary syndrome (PCOS). A total of 84 women aged 18-40 years will be randomized into two groups. Ovulation will be monitored by transvaginal ultrasound and confirmed with urinary LH testing and/or corpus luteum presence. The primary outcome is ovulation rate, while secondary outcomes include number and size of mature follicles, clinical pregnancy rate, multiple pregnancy rate, miscarriage rate, number of cycles until pregnancy, and incidence of ovarian hyperstimulation syndrome (OHSS).

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder and one of the leading causes of anovulatory infertility worldwide. Letrozole, an aromatase inhibitor, has emerged as the preferred first-line pharmacological agent for ovulation induction in women with PCOS. Despite its widespread use, there is ongoing debate regarding the optimal duration of therapy to maximize ovulatory and pregnancy outcomes.

This randomized clinical trial is designed to evaluate whether an extended regimen of letrozole provides superior reproductive outcomes compared with the standard regimen. The extended protocol consists of daily administration of 5 mg letrozole from cycle day 2 through day 12, whereas the standard regimen involves 5 mg daily from cycle day 2 through day 6. Ovulatory response will be monitored through serial transvaginal ultrasound and biochemical markers of ovulation.

The trial aims to generate high-quality evidence on the efficacy and safety of extended letrozole therapy. The findings may inform future clinical guidelines on ovulation induction strategies in women with PCOS and contribute to optimizing treatment protocols for anovulatory infertility.

Inclusion Criteria:

• Women aged 18 to 40 years;
• BMI between 18,5 and 31 kg/m2
• Diagnosis of Polycystic Ovary Syndrome (PCOS) according to the Rotterdam criteria (2003) (presence of at least two of the following: oligo/anovulation, clinical and/or biochemical hyperandrogenism, polycystic ovarian morphology on ultrasound);
• Active desire for pregnancy at the time of enrollment;
• Ability and willingness to provide written informed consent (ICF).

Exclusion Criteria:

• Age <18 or >40 years;
• Presence of confirmed bilateral tubal factor, severe male factor infertility, premature ovarian insufficiency, uncontrolled hyperprolactinemia or thyroid dysfunction);
• Congenital or acquired uterine malformations;
• History of gynecologic or breast cancer;
• Known hypersensitivity to, or contraindication for, letrozole;
• Severe uncontrolled systemic disease (e.g., cardiovascular, renal, or hepatic disorders);
• Pregnancy or breastfeeding at the time of screening.