150 IU vs. 225 IU FSH in Normal Responders: The OPTIMAL-DOSE Trial

NCT ID: NCT07346235

Last Updated: 2026-01-16

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 440 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-03-01
• Study Completion Date: 2029-01-15

Brief Summary

This is a single-center, randomized, open-label, non-inferiority trial comparing two fixed daily doses of follicle-stimulating hormone (FSH): 150 IU versus 225 IU in women with predicted normal ovarian response undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) with a gonadotropin releasing hormone (GnRH) antagonist protocol. The primary objective is to determine whether the 150 IU dose is noninferior to the 225 IU dose regarding the cumulative live birth rate per initiated cycle. Secondary objectives include comparing oocyte yield, incidence of OHSS, treatment costs, and patient-reported outcomes.

Detailed Description

Background: Controlled ovarian stimulation (COS) with exogenous FSH is a cornerstone of IVF treatment. The optimal starting dose of FSH for women with normal ovarian reserve remains controversial, with doses ranging from 150 IU to 300 IU used in clinical practice.

Both 150 IU and 225 IU are widely used, but no randomized controlled trial has directly compared these two specific doses in predicted normal responders.

Objective: To determine if a fixed daily dose of 150 IU FSH is non-inferior to 225 IU FSH with respect to cumulative live birth rate per initiated cycle.

Methods: A total of 440 women (220 per group) will be randomized 1:1 to receive either 150 IU or 225 IU of FSH daily, starting on day 2-3 of the menstrual cycle. All participants will follow a standard GnRH antagonist protocol. The primary outcome is cumulative live birth rate, defined as the delivery of at least one live-born infant at ≥24 weeks of gestation from the first fresh or any subsequent frozen embryo transfer from a single stimulation cycle. The non-inferiority margin is set at -10% (absolute difference).

Significance: If 150 IU is proven non-inferior, this would support the use of a lower dose, potentially reducing treatment costs and the risk of ovarian hyperstimulation syndrome (OHSS) without compromising efficacy.

Conditions

Infertility, Female

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

150 IU FSH Group

Participants receive a fixed daily dose of 150 IU of recombinant or urinary FSH starting on day 2-3 of the menstrual cycle, continuing until trigger day.

Group Type: EXPERIMENTAL

Follicle-stimulating hormone (FSH)

Intervention Type: DRUG

Daily subcutaneous injection of 150 IU FSH

225 IU FSH Group

Participants receive a fixed daily dose of 225 IU of recombinant or urinary FSH starting on day 2-3 of the menstrual cycle, continuing until trigger day.

Group Type: ACTIVE_COMPARATOR

Follicle-stimulating hormone (FSH)

Intervention Type: DRUG

Daily subcutaneous injection of 225 IU FSH

Interventions

Follicle-stimulating hormone (FSH)

Daily subcutaneous injection of 150 IU FSH

Intervention Type: DRUG

Follicle-stimulating hormone (FSH)

Daily subcutaneous injection of 225 IU FSH

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Body Mass Index (BMI) 18-30 kg/m².

2. Predicted normal ovarian reserve:

3. Anti-Müllerian Hormone (AMH) 1.2-3.5 ng/mL (measured within 12 months), AND Antral Follicle Count (AFC) 8-20 (both ovaries combined, measured on day 2-5 of the cycle).

4. First or second IVF/ICSI cycle.

5. Planned GnRH antagonist protocol.

6. Both ovaries present and accessible.

7. Written informed consent provided voluntarily.

Exclusion Criteria

1. Predicted poor or high ovarian response (AMH <1.2 or >3.5 ng/mL; AFC <8 or >20).

2. Polycystic Ovary Syndrome (PCOS) according to Rotterdam criteria.

3. Severe endometriosis (Stage III-IV per ASRM).

4. Severe uterine abnormalities affecting implantation.

5. Previous complete fertilization failure (fertilization rate <30%).

6. Severe male factor (sperm count <5 million/mL, or requirement for donor sperm/TESE).

7. Uncontrolled endocrine disorders (uncontrolled hypothyroidism, hyperprolactinemia, diabetes).

8. Contraindications to pregnancy or gonadotropins.

9. Participation in another clinical trial within 30 days.

10. Inability to provide informed consent.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 39 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

American Hospital 2 Kosovo

OTHER

Sponsor Role: lead

Responsible Party

Goksu Goc

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

American Hospital Kosova

Pristina, , Kosovo

Countries

Kosovo

Central Contacts

Goksu Goc, MD

Role: CONTACT

goksu.goc@gmail.com

+38349878550

Facility Contacts

Role: primary

info@spitaliamerikan.com

References

van Tilborg TC, Torrance HL, Oudshoorn SC, Eijkemans MJC, Koks CAM, Verhoeve HR, Nap AW, Scheffer GJ, Manger AP, Schoot BC, Sluijmer AV, Verhoeff A, Groen H, Laven JSE, Mol BWJ, Broekmans FJM; OPTIMIST study group. Individualized versus standard FSH dosing in women starting IVF/ICSI: an RCT. Part 1: The predicted poor responder. Hum Reprod. 2017 Dec 1;32(12):2496-2505. doi: 10.1093/humrep/dex318.

Reference Type: BACKGROUND

PMID: 29121326 (View on PubMed)

Other Identifiers

OPTIMAL-DOSE-2026-001

Identifier Type: -

Identifier Source: org_study_id