Anovulation, Infertility, PCOS (Polycystic Ovary Syndrome)
Conditions
Keywords
polycystic ovary syndrome, PCOS, Ovulation induction, Letrozole, Aromatase Inhibitor, Extended letrozole therapy, traditional letrozole therapy, standart letrozole therapy, infertility, anovulation, ovulation rate, pregnancy rate
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 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.
Interventions
DRUGTraditional Letrozole Therapy
Traditional therapy group: 5 mg/day of letrozole for 5 days (cycle days 2-6).
DRUGExtended Letrozole Therapy
Extended therapy group: 5 mg/day of letrozole for 10 days (cycle days 2-12)
Sponsors
GABRIEL MONTEIRO PINHEIRO
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a randomized, controlled, parallel assignment clinical trial designed to compare extended letrozole therapy with standard letrozole therapy for ovulation induction in women with polycystic ovary syndrome (PCOS). Participants will be randomized in a 1:1 ratio into two groups: extended therapy (letrozole 5 mg/day from cycle days 2-12) and standard therapy (letrozole 5 mg/day from cycle days 2-6). Ovulation will be monitored by transvaginal ultrasound and confirmed with urinary LH testing. The primary outcome is ovulation rate. Secondary outcomes include number and size of mature follicles, clinical pregnancy rate, miscarriage rate, multiple pregnancy rate, time to conception, and incidence of ovarian hyperstimulation syndrome (OHSS).
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| Miscarriage Rate | Assessed up to 12 weeks of gestation. | Proportion of participants with spontaneous pregnancy loss within the first trimester (\<12 weeks of gestation). |
Countries
Brazil
Contacts
Primary ContactKatherine Ann R Miller, Medical student
Backup ContactGabriel M Pinheiro, MD
Outcome results
None listed