Progesterone-modified Natural Cycle for FET (COMPROSET)

April 23, 2026 updated by: Jing-Yan Song, Shandong University of Traditional Chinese Medicine

Comparison of Progesterone-modified Natural Cycle and Hormone Replacement Therapy Cycle for Endometrial Preparation in Single Frozen Blastocyst Transfer

Hormone replacement therapy (HRT) cycles, despite the ease of synchronizing embryo thawing and embryo transfer timing, increase the risk of pregnancies and obstetric complications compared to natural cycles (NC). By ensuring the presence of the corpus luteum while reducing the number of monitoring sessions, the progesterone modified natural cycle (P4mNC) offers more convenience for the patient than the normal NC. This study is designed to compare the effects of P4mNC and HRT cycles on FET outcomes.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

336

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

  • China
    • Shandong
      • Jinan, Shandong, China, 250014
        • Recruiting
        • Affiliated Hospital of Shandong University of Traditional Chinese Medicine
        • Contact:

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:

  • Patients aged 21 to 44 years undergoing FBT
  • Body mass index (BMI) 18-35 kg/m2
  • Having regular ovulatory cycles

Exclusion Criteria:

  • Untreated uterine adhesions
  • Medical contraindications to estrogen and progesterone therapy
  • Illnesses contraindicating assisted reproductive technology or pregnancy
  • History of recurrent implantation failures (> 2 embryo transfer failures)

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: P4mNC group
On days 8-12 of the menstrual cycle (MC), depending on the length of the patient's MC, transvaginal ultrasound is used to monitor follicular development and endometrial growth. Vaginal micronized progesterone (Utrogestan, Besins, Belgium) is started at 200 mg in the afternoon and 200 mg in the evening when the dominant follicle reached ≥16 mm and the endometrial thickness is at least 7 mm. A blastocyst is transferred on day 5 after the addition of progesterone. On day 14 after blastocyst transfer, serum β-hCG levels are measured. Upon positive serum pregnancy testing, progesterone support will continue until 8-10 weeks of gestation. However, afternoon progesterone use is eliminated for 30 days after embryo transfer.
Drug: Progesterone-modified natural cycle preparation for frozen embryo transfer
A novel endometrial preparation protocol that optimizes the natural cycle, whereby as long as the thickness of the endometrium is suitable for embryo transfer, vaginal progesterone can be used to transform the endometrium before ovulation and subsequently FET.
Active Comparator: HRT group
Endometrial preparation will begin on the second day of the menstrual cycle with oral estradiol (E2) valerate at a dose of 2 mg twice daily. When the patient's endometrial thickness is ≥7 mm, vaginal progesterone administration will be initiated at a dose of 200 mg 3 times daily. On day 5 of the progesterone administration, blastocysts are thawed and transferred. For patients with endometrial thickness <7 mm, patients continued oral E2 until the endometrium is ≥7 mm. On day 14 after blastocyst transfer, serum β-hCG levels are measured. Upon positive serum pregnancy testing, E2 and progesterone supplementation is continued for 8-10 weeks of gestation.
Drug: Hormone replacement therapy cycle preparation for frozen embryo transfer
A traditional endometrial preparation protocol is used for FET, which involves using fixed or flexible exogenous estradiol for artificial cycles. This protocol typically involves starting exogenous estradiol on day 3 or 4 of the cycle, continuing for 7-10 days, and then discontinuing. Upon determining that the endometrial thickness meets the standard, progesterone conversion of the endometrium can be performed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Live birth
Time Frame: Within 1 year after randomization
A live birth is defined as the delivery of any surviving newborn at 28 weeks or more of gestation.
Within 1 year after randomization

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Biochemical pregnancy
Time Frame: Two weeks after embryo transfer
Serum level of ß-hCG > 50 mIU/mL
Two weeks after embryo transfer
Clinical pregnancy
Time Frame: Five weeks after embryo transfer
Fetal heartbeat observed by vaginal ultrasound
Five weeks after embryo transfer
Ongoing pregnancy
Time Frame: Ten weeks after embryo transfer
The presence of a gestational sac and fetal heartbeat after 12 weeks of gestation
Ten weeks after embryo transfer
Miscarriage
Time Frame: Within 28 weeks of pregnancy
A condition in which the embryo or fetus does not survive and is not spontaneously absorbed or expelled from the uterus
Within 28 weeks of pregnancy

Collaborators and Investigators

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

Sponsor

Shandong University of Traditional Chinese Medicine

Investigators

  • Principal Investigator: Zhen-Gao Sun, MD, Affiliated Hospital of Shandong University of Traditional Chinese Medicine

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 (Actual)

March 5, 2025

Primary Completion (Estimated)

September 10, 2027

Study Completion (Estimated)

December 1, 2028

Study Registration Dates

First Submitted

October 12, 2024

First Submitted That Met QC Criteria

October 14, 2024

First Posted (Actual)

October 16, 2024

Study Record Updates

Last Update Posted (Actual)

April 29, 2026

Last Update Submitted That Met QC Criteria

April 23, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P4mNC@SDUTCM

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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