Letrozole plus clomiphene versus letrozole alone to help ovulate

The Combination of Letrozole (LE) and Clomiphene Citrate (CC) or LE Alone for Ovulation Induction in Women With WHO Group II/IV Ovulatory Disorders: A Randomized Controlled Trial

This trial will test whether adding clomiphene citrate to letrozole helps women with WHO II/IV ovulatory disorders have more live births after ovulation induction.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 600 (estimated)
• Ages: 18 Years to 40 Years
• Sex: Female
• Sponsor: Mỹ Đức Hospital (Academic / other)
• Locations: 1 site (Ho Chi Minh City, Ho Chi Minh City)
• Trial ID: NCT06934785 on ClinicalTrials.gov

What this trial studies

This is an open-label, multicenter randomized controlled trial conducted across six fertility clinics in Vietnam that randomizes participants to letrozole plus clomiphene citrate versus letrozole alone. Eligible women with WHO II/IV ovulatory disorders will receive one cycle of ovulation induction with either the combination or letrozole alone, with intercourse or IUI as the method of conception. The primary outcome is live birth rate after one treatment cycle, and the study plans to enroll approximately 600 participants to detect a clinically meaningful difference. Secondary and safety outcomes, and prior smaller trials on ovulation rates, will be considered in the analysis.

Who should consider this trial

Good fit: Women aged 18–40 with WHO II/IV ovulatory disorders, adequate partner semen parameters (progressive motility ≥32% and sperm concentration ≥5 million/ml), no untreated thyroid or prolactin disorders, no tubal blockage, and who can give informed consent are ideal candidates.

Not a fit: Patients with untreated endocrine disorders, confirmed unilateral or bilateral tubal blockage, severe male factor infertility outside the entry criteria, or allergy/contraindication to letrozole or clomiphene are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, the combination could raise live birth rates for women undergoing ovulation induction for WHO II/IV ovulatory disorders.

How similar studies have performed: Previous small randomized trials have reported higher ovulation rates with the combination but results for live birth have been mixed and not consistently significant.

Eligibility criteria

Inclusion Criteria:

* Women 18-40 years of age
* Having WHO II/IV ovulatory disorders (length of cycle \< 21 or \> 35 days or having \< 8 cycles per year)
* Progressive motility (PR) ≥ 32%, sperm concentration ≥ 5 million/ml, total progressive motility sperm count \> 5 million (World Health Organization, 2021)
* Written informed consent.
* Not participating in other studies.

Exclusion Criteria:

* Untreated thyroid disease; Thyroid disease is suspected if patients have one of these (Bednarczuk et al., 2021); TSH ≥4 mIU/L or TSH ≥2.5mIU/L and TPOAb (+) or TSH \<0.1mIU/L
* Untreated hyper-prolactinemia; Hyperprolactinemia is suspected if patients have prolactinemia concentration \>50 ng/mL (The sample is collected after an overnight fast, at least 2 hours after waking up, ensuring that venipuncture does not cause excessive stress.)
* Allergy or having contraindications to LE or CC;
* Unilateral or Bilateral fallopian tube blockage (HSG, HyFoSy or surgery confirmation)
* Untreated endometrial abnormalities include endometrial hyperplasia, intrauterine adhesions, endometrial polyp, or chronic endometritis.
* Uterine abnormalities include leiomyomas L0, L1, or L2; severe adenomyosis; congenital uterine abnormalities, include didelphus, arcuate, unicornuate, bicornuate, septate.

Where this trial is running

Ho Chi Minh City, Ho Chi Minh City

• My Duc Hospital — Ho Chi Minh City, Ho Chi Minh City, Vietnam (Recruiting)

Study contacts

• Principal investigator: Lan N Vuong, PhD,MD — University of Medicine and Pharmacy at Ho Chi Minh City
• Study coordinator: Van TT Tran, MD

Conditions Letrozole; Clomiphene Citrate; Ovulation Disorder; Ovulation Induction