LETROZOLE EXTENDED VS TRADITIONAL THERAPY FOR OVULATION INDUCTION IN WOMEN WITH PCOS: A RANDOMIZED CONTROLLED TRIAL

Not Applicable

Recruiting

• Conditions: PCOS (Polycystic Ovary Syndrome); Infertility; Anovulation
• Interventions: Drug: Letrozole (aromatase inhibitor)

• Registration Number: NCT07159880
• Lead Sponsor: GABRIEL MONTEIRO PINHEIRO

Brief Summary

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).

Detailed Description

Polycystic ovary syndrome (PCOS) is one of the leading causes of anovulatory infertility, affecting women of reproductive age worldwide. Letrozole, an aromatase inhibitor, is currently recommended as a first-line pharmacological treatment for ovulation induction in PCOS. However, there is still debate regarding the most effective duration of letrozole administration to optimize ovulatory and pregnancy outcomes.

This randomized clinical trial will compare two therapeutic regimens of letrozole: the extended regimen (5 mg/day from cycle day 2 to day 12) and the standard regimen (5 mg/day from cycle day 2 to day 6). The trial will be conducted at the outpatient gynecology and obstetrics clinic of Hospital Wladimir Arruda, São Paulo, Brazil, and will include 84 women between 18 and 40 years of age, diagnosed with PCOS according to the Rotterdam criteria.

Participants will be randomized into two groups: 1. Extended therapy group: 5 mg/day of letrozole for 10 days (cycle days 2-12); and 2. Standard therapy group: 5 mg/day of letrozole for 5 days (cycle days 2-6). Ovulation will be monitored by transvaginal ultrasound and confirmed through detection of the urinary LH surge and/or visualization of corpus luteum.

The primary outcome is ovulation rate. Secondary outcomes include number of mature follicles (≥18 mm), follicular size, clinical pregnancy rate (confirmed by ultrasound visualization of a gestational sac), miscarriage rate, multiple pregnancy rate, number of cycles until conception, and the incidence of ovarian hyperstimulation syndrome (OHSS).

Data will be analyzed using R software. Continuous variables will be evaluated using linear regression models, while categorical variables will be compared using logistic regression models, with a significance threshold of p \< 0.05.

All participants will sign informed consent prior to enrollment. Risks include OHSS, conception failure, and miscarriage, which are inherent to pharmacological ovulation induction. The potential benefits include achieving ovulation and clinical pregnancy in women with PCOS and anovulatory infertility.

This trial is designed to provide robust evidence on whether extending letrozole therapy offers superior reproductive outcomes compared with the standard regimen, potentially influencing future clinical protocols for ovulation induction in women with PCOS.

Study Timeline

• Status Verified: 2025-08
• Study Start: 2025-08-26
• Study First Submitted: 2025-08-29
• Study First Submitted QC: 2025-08-29
• Last Update Submitted: 2025-08-29
• Study First Posted: 2025-09-08
• Last Update Posted: 2025-09-08
• Primary Completion: 2026-07-30
• Study Completion: 2026-07-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 20

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 gynecological or breast cancer;
• Known hypersensitivity or contraindication to letrozole;
• Severe uncontrolled systemic disease (e.g., cardiovascular, renal, or hepatic disorders);
• Pregnancy or breastfeeding at the time of screening.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Traditional Letrozole Therapy	Letrozole (aromatase inhibitor)	Participants in this group will receive standard letrozole therapy for ovulation induction. Letrozole will be administered orally at a dose of 5 mg/day from cycle day 2 through cycle day 6 (5 consecutive days). Ovulation monitoring will be performed by transvaginal ultrasound and confirmed with urinary LH testing and/or corpus luteum visualization. This arm serves as the active comparator against the extended regimen for evaluating efficacy and safety outcomes.
Extended Letrozole Therapy	Letrozole (aromatase inhibitor)	Participants in this group will receive extended letrozole therapy for ovulation induction. Letrozole will be administered orally at a dose of 5 mg/day from cycle day 2 through cycle day 12 (10 consecutive days). Ovulation monitoring will be performed by transvaginal ultrasound and confirmed with urinary LH testing and/or corpus luteum visualization. This arm will be compared with the standard regimen to assess differences in ovulation rate, follicular development, pregnancy outcomes, and safety.

Primary Outcome Measures

Name	Time	Method
Ovulation rate	Assessed within one treatment cycle (up to 6 weeks from the start of medication).	Proportion of participants achieving ovulation, defined as the presence of a dominant follicle ≥18 mm on transvaginal ultrasound with confirmation by urinary LH surge and/or visualization of corpus luteum.

Secondary Outcome Measures

Name	Time	Method
Clinical Pregnancy Rate	Assessed within 8 weeks after the start of treatment.	Proportion of participants achieving clinical pregnancy, defined as visualization of a gestational sac by transvaginal ultrasound.
Number of Mature Follicles	Assessed during one treatment cycle (up to 6 weeks).	Number of follicles ≥18 mm observed by transvaginal ultrasound in the stimulated cycle.
Follicular Size	Assessed during one treatment cycle (up to 6 weeks).	Maximum diameter (in millimeters) of the leading follicle(s) observed by transvaginal ultrasound.
Miscarriage Rate	Assessed up to 12 weeks of gestation.	Proportion of participants with spontaneous pregnancy loss within the first trimester (\<12 weeks of gestation).
Multiple Pregnancy Rate	Assessed within 8 weeks after the start of treatment.	Proportion of participants with multiple gestations, confirmed by transvaginal ultrasound.
Incidence of Ovarian Hyperstimulation Syndrome (OHSS)	Assessed within one treatment cycle (up to 6 weeks).	Proportion of participants presenting clinical or ultrasound signs of OHSS during treatment.

Trial Locations

Locations (1)

Health Complex Dr Wladimir Arruda; 🇧🇷 São Paulo, São Paulo, Brazil