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

January 8, 2026 updated by: Goksu Goc, American Hospital 2 Kosovo

OPTIMAL-DOSE: A Randomized, Open-Label, Non-Inferiority Trial Comparing Fixed Daily Doses of 150 IU Versus 225 IU of Follicle-Stimulating Hormone in Predicted Normal Responders Undergoing In Vitro Fertilization/Intracytoplasmic Sperm Injection

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

440

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: Follicle-stimulating hormone (FSH)
Daily subcutaneous injection of 150 IU FSH
Drug: Follicle-stimulating hormone (FSH)
Daily subcutaneous injection of 225 IU FSH
Active Comparator: 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.
Drug: Follicle-stimulating hormone (FSH)
Daily subcutaneous injection of 150 IU FSH
Drug: Follicle-stimulating hormone (FSH)
Daily subcutaneous injection of 225 IU FSH

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cumulative Live Birth Rate per Initiated Cycle
Time Frame: Up to 12 months after randomization
The delivery of at least one live-born infant at ≥24 weeks of gestation resulting from the first fresh embryo transfer or any subsequent frozen embryo transfer from a single stimulation cycle.
Up to 12 months after randomization

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Oocytes Retrieved
Time Frame: Up to 2 weeks
Total number of oocytes retrieved at oocyte pick-up.
Up to 2 weeks
Incidence of Moderate/Severe OHSS
Time Frame: Up to 4 weeks after oocyte retrieval
Proportion of participants developing moderate or severe OHSS according to Golan classification.
Up to 4 weeks after oocyte retrieval
Total FSH Consumption
Time Frame: Up to 2 weeks
Total amount of FSH (in IU) used during the stimulation cycle.
Up to 2 weeks
Clinical Pregnancy Rate
Time Frame: 7 weeks of gestation
Presence of a gestational sac with fetal heartbeat on ultrasound at 7 weeks of gestation.
7 weeks of gestation
Live Birth Rate per Transfer
Time Frame: Up to 12 months after randomization
Delivery of a live-born infant per embryo transfer procedure.
Up to 12 months after randomization
Cycle Cancellation Rate
Time Frame: Up to 2 weeks
Proportion of cycles cancelled before oocyte retrieval.
Up to 2 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

American Hospital 2 Kosovo

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 1, 2026

Primary Completion (Estimated)

January 1, 2028

Study Completion (Estimated)

January 15, 2029

Study Registration Dates

First Submitted

December 28, 2025

First Submitted That Met QC Criteria

January 8, 2026

First Posted (Estimated)

January 16, 2026

Study Record Updates

Last Update Posted (Estimated)

January 16, 2026

Last Update Submitted That Met QC Criteria

January 8, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OPTIMAL-DOSE-2026-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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