Overview
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).
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.
Eligibility
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.