LE + CC vs. LE for Ovulation Induction

NCT06934785 | Recruiting DMC

• 1 other identifier: 02/25/DD/BVMD
• Study Type: interventional
• Target: 600
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized controlled trial (RCT) aims to evaluate whether, in infertile women with WHO II/IV ovulatory disorders, a combination of letrozole (LE) and clomiphene citrate (CC) compared to LE alone, result in higher live birth rates. The study is designed as an open-label, multicenter RCT across six fertility clinics in Vietnam. Participants will be randomized into two groups: (1) LE + CC , (2) LE alone. The primary outcome measure is the live birth rate after one treatment cycle. Based on prior data, the live birth rate for IUI in letrozole cycles is estimated at 12%. To detect a 10% increase in live birth rates with CC, 436 couples are needed (α = 0.05, power = 80%). Additionally, the live birth rate after IUI with LE-induced ovulation is approximately 18.7% (Diamond et al., 2015). To detect a 10% increase with CC, 560 couples are required (α = 0.05, power = 80%). Considering a 5% loss to follow-up and protocol deviations, the study plans to recruit 600 participants (150 per arm).

Conditions

Letrozole; Clomiphene Citrate; Ovulation Disorder; Ovulation Induction

Outcome Measures

Primary Outcomes (1)

• Live birth after one treatment cycle

  Live birth will be defined as the complete expulsion or extraction from a woman of a product of fertilization, after 22 completed weeks of gestational age; which, after such separation, breathes or shows any other evidence of life, such as heart beat, umbilical cord pulsation or definite movement of voluntary muscles, irrespective of whether the umbilical cord has been cut or the placenta is attached.

  At 22 weeks of gestation

Secondary Outcomes (31)

• Duration of stimulation

  During the intervention

• Number of follicles ≥14mm on day of hCG

  During the intervention

• Endometrial thickness on day of hCG

  During the intervention

• Cycle cancellation

  At 21 day of the ovulation induction cycle

• Ovulation

  At day 7 after the hCG injection

Study Arms (2)

Combination of LE and CC group

ACTIVE COMPARATOR

5 milligrams LE per day (Femara® 2.5 milligrams, Novartis, Switzerland) and 50 milligrams CC (Duinum 50 milligrams, Medochemie, Cyprus) per day, starting on the second to the fourth day of the cycle, for five consecutive days.

Procedure: IUI or intercourse

LE alone group

ACTIVE COMPARATOR

5 milligrams LE per day (Femara® 2.5 milligrams, Novartis, Switzerland), starting on the second to the fourth day of cycle, for five consecutive days.

Procedure: IUI or intercourse

Interventions

IUI or intercourse PROCEDURE

5 milligrams LE per day (Femara® 2.5 milligrams, Novartis, Switzerland) and 50 milligrams CC (Duinum 50 milligrams, Medochemie, Cyprus) or 5 milligrams LE per day (Femara® 2.5 milligrams, Novartis, Switzerland) will be started on the second to the fourth day of the cycle, for five consecutive days. An ultrasound will be carried out three days after the last dose of medicine (day 8 of OI) to evaluate ovarian follicles' growth and the endometrium's thickness. If the follicular diameter reach ≥14 millimetres, check-up will be planned every two days until it reaches 18 millimetres. If there is the appearance of at least one follicle reaching 18 millimetres or more, a human chorionic gonadotropin (hCG) injection (IVF-C 5000 IU, LG Life Science, Korea) will be administered on the same day of the ultrasound in order to induce ovulation. IUI will be scheduled 36 - 38 hours after hCG injection or intercourse will be scheduled in the next day.

Combination of LE and CC group; LE alone group

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mỹ Đức Hospital: lead

Study Sites (1)

My Duc Hospital

Ho Chi Minh City, Ho Chi Minh City, 70000, Vietnam

RECRUITING

Related Publications (4)

• Teede HJ, Tay CT, Laven JJE, Dokras A, Moran LJ, Piltonen TT, Costello MF, Boivin J, Redman LM, Boyle JA, Norman RJ, Mousa A, Joham AE. Recommendations From the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2023 Sep 18;108(10):2447-2469. doi: 10.1210/clinem/dgad463.

  PMID: 37580314 BACKGROUND

• Weiss NS, Nahuis MJ, Bordewijk E, Oosterhuis JE, Smeenk JM, Hoek A, Broekmans FJ, Fleischer K, de Bruin JP, Kaaijk EM, Laven JS, Hendriks DJ, Gerards MH, van Rooij IA, Bourdrez P, Gianotten J, Koks C, Lambalk CB, Hompes PG, van der Veen F, Mol BWJ, van Wely M. Gonadotrophins versus clomifene citrate with or without intrauterine insemination in women with normogonadotropic anovulation and clomifene failure (M-OVIN): a randomised, two-by-two factorial trial. Lancet. 2018 Feb 24;391(10122):758-765. doi: 10.1016/S0140-6736(17)33308-1. Epub 2017 Dec 19.

  PMID: 29273245 BACKGROUND

• Mejia RB, Summers KM, Kresowik JD, Van Voorhis BJ. A randomized controlled trial of combination letrozole and clomiphene citrate or letrozole alone for ovulation induction in women with polycystic ovary syndrome. Fertil Steril. 2019 Mar;111(3):571-578.e1. doi: 10.1016/j.fertnstert.2018.11.030. Epub 2019 Jan 22.

  PMID: 30683591 BACKGROUND

• Diamond MP, Legro RS, Coutifaris C, Alvero R, Robinson RD, Casson P, Christman GM, Ager J, Huang H, Hansen KR, Baker V, Usadi R, Seungdamrong A, Bates GW, Rosen RM, Haisenleder D, Krawetz SA, Barnhart K, Trussell JC, Ohl D, Jin Y, Santoro N, Eisenberg E, Zhang H; NICHD Reproductive Medicine Network. Letrozole, Gonadotropin, or Clomiphene for Unexplained Infertility. N Engl J Med. 2015 Sep 24;373(13):1230-40. doi: 10.1056/NEJMoa1414827.

  PMID: 26398071 BACKGROUND

MeSH Terms

Interventions

Sex

Intervention Hierarchy (Ancestors)

Reproductive Physiological Phenomena; Reproductive and Urinary Physiological Phenomena

Study Officials

• Lan N Vuong, PhD,MD

  University of Medicine and Pharmacy at Ho Chi Minh City

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Van TT Tran, MD

CONTACT

+84353345020; bsvan.ttt@myduchospital.vn

Vinh Q Dang, MSc,MD

CONTACT

vinh.dang@monash.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2025
• First Posted: April 18, 2025
• Study Start: April 28, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: September 11, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

VN (1)