Progesterone Primed Ovarian Stimulation Versus GnRH Antagonist Protocols in Women with Polycystic Ovarian Syndrome

February 21, 2025 updated by: Aly Hussein, El Shatby University Hospital for Obstetrics and Gynecology

Progesterone Primed Ovarian Stimulation Versus Gonadotrophin-Releasing Hormone Antagonist in Women with Polycystic Ovarian Syndrome

The purpose of this study is to compare the use of the progesterone-primed ovarian stimulation protocol versus GnRH antagonist protocol in women with polycystic ovarian syndrome (PCOS) regarding the number of oocytes retrieved, percentage of MII oocytes, and the rate of good quality blastocysts available for cryopreservation.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The syndrome of polycystic ovary (PCOS) is a common endocrine disease. It accounts for about 80% of women with anovulatory infertility. In vitro fertilization (IVF) is a commonly used infertility treatment for PCOS patients who fail to conceive with ovulation induction or if there are concomitant infertility factors such as tubal damage or male subfertility.

Patients with polycystic ovary syndrome (PCOS) are at high risk of ovarian hyperstimulation syndrome (OHSS) during in vitro fertilization (IVF) / intracytoplasmic sperm injection (ICSI) treatment which may lead to cycle cancellation to prevent their high morbidity or death rates. Increasing evidence has confirmed that frozen embryo transfer (FET) is related to a lower risk of OHSS. The 'freeze-all' strategy is recommended for PCOS patients to reduce the potential of moderate/severe OHSS.

Controlled ovarian stimulation (COS) is a key step in assisted reproductive technology (ART). In addition to the use of gonadotropins to recruit multiple follicles, it is mandatory to use a drug to prevent luteinizing hormone (LH) surge and premature ovulation.

Early LH surge is a main cause of cycle cancellation during controlled ovarian stimulation (COH) for women receiving IVF/ICSI therapy. The release of LH causes ovulation in response to rapidly increasing levels of E2 in the normal cycle, and a premature LH increase may impair IVF/ICSI egg production.

Gonadotropin-releasing hormone (GnRH) antagonist protocol has emerged as a routine ovulation stimulation protocol in recent decades due to its comparable convenience, safety, and efficacy compared to GnRH agonists. GnRH antagonist protocol is now the most commonly used COS protocol in PCOS patients due to the significantly reduced risk of OHSS especially when gonadotropin-releasing hormone agonist (GnRHa) was used for ovulation trigger. The GnRH antagonists were used primarily to reduce the incidence of the early LH surge. However, GnRH antagonists are expensive and sometimes difficult to manage with high rates of cycle cancellation and premature LH surges.

In past decades, when IVF relied on fresh embryo transfer, progesterone could not be considered during COS as early exposure to progesterone could lead to embryo-endometrium asynchrony. Advances in vitrification have made cryopreservation and thawing of embryos in a reliable manner, which has eliminated concerns about the deleterious effects of progesterone exposure on endometrial receptivity. Although controversies remain regarding the selection of when to choose FET, the ''freeze-all'' strategy could make the use of P formulations for the suppression of premature LH surge during COH feasible regardless of the effects of P on endometrial receptivity. Therefore, the PPOS protocol may be a suitable option when fresh embryo transfer is not required.

Progesterone-primed ovarian stimulation is a recent stimulation protocol, which was first suggested in 2015 by Dr. Yanping Kuang of China, it is a novel ovarian stimulation system utilizing progestin coupled with exogenous gonadotrophin, and ovulation triggered by a GnRH agonist, via 'freeze-all' methods. Oral progestin are used as an alternative to GnRH antagonist to prevent premature LH surges during ovarian stimulation. This novel ovarian stimulation regimen has shown successful prevention of a premature LH surge in cycles followed by embryo cryopreservation. In addition, oral progestin has the advantage of being convenient, given orally, cheap, and available readily.

The mechanism of LH suppression using GnRH-ant or progestin is distinct. GnRH-ant administration could lead to rapid suppression of pituitary LH secretion by competitively blocking the GnRH receptor, with an obvious dose-dependent suppression effect. In contrast, the inhibition of LH levels with progestin is indirect by regulating the hypothalamus GnRH secretion and requires sufficient duration before estrogen priming.

Study Type

Observational

Enrollment (Actual)

100

Contacts and Locations

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

Study Locations

  • Egypt
      • Alexandria, Egypt, 21648
        • ELShatby University Hospital

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

  • Child
  • Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

History taking and examination:

  • Basal ultrasound scanning includes 3D assessment of the uterine cavity and a basal hormonal profile.
  • Semen analysis.

Ovarian stimulation:

  • Will be on day 2 or 3 of the menstrual cycle
  • Using rFSH SC injections with a dose of 150 to 225 IU per day and highly purified hMG with a dose of 75 IU per day.

These patients will be divided into two equal groups:

Group 1 (Fixed GnRH antagonist protocol) (n= 50):

• GnRH antagonist (Cetrotide 0.25 mg) SC injection will be added daily from the 6th day of COH and will be continued till the day of the GnRH agonist trigger.

Group 2 (Progesterone-primed ovarian stimulation) (n= 50):

• A daily dose of 20 mg dydrogesterone (2 Duphastone 10 mg tablets) will be added from day 1 or 2 of the menstrual cycle till day of trigger

Description

Inclusion Criteria:

  1. Female age <37 years.
  2. Body mass index (BMI) between (≥18 kg/m2 and ≤35 kg/m2).
  3. Polycystic ovarian syndrome patients (according to Rotterdam criteria).
  4. Patients suffering from primary or secondary infertility who are candidates for ICSI.

Exclusion Criteria:

  1. Uncorrected Uterine factor of infertility: intrauterine adhesions, submucosal fibroids, and septate uterus.
  2. Severe male factor infertility

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

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Progesterone-primed ovarian stimulation Group
• A daily dose of 20 mg dydrogesterone (2 Duphastone 10 mg tablets) will be added from day 1 or 2 of the menstrual cycle and will be continued till the day of the GnRH agonist trigger.
Drug: Progesterone
compare the use of the progesterone-primed ovarian stimulation protocol versus GnRH antagonist protocol in women with polycystic ovarian syndrome (PCOS) regarding the number of oocytes retrieved, percentage of MII oocytes, and the rate of good quality blastocysts available for cryopreservation.
Other Names:
  • Duphaston 10mg Tablets
Antagonist protocol
• GnRH antagonist (Cetrotide 0.25 mg) subcutaneous injection will be added daily from the 6th day of ovarian stimulation and will be continued till the day of the GnRH agonist trigger.
Drug: GnRH antagonist (Cetrorelix)
Subcutaneous injection
Other Names:
  • Cetrotide 0.25mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of oocytes retrieved (ovarian response).
Time Frame: Baseline
Total number of oocytes retrieved (in both groups)
Baseline
Percentage of MII oocytes.
Time Frame: Baseline
Number of MII oocytes to the total number of oocytes retrieved (in both groups)
Baseline
Rate of good-quality blastocysts available for cryopreservation
Time Frame: Baseline
percentage of the number of good-quality blastocysts to the number of 2PN fertilized oocytes cultured
Baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Fertilization rate
Time Frame: Baseline
Percentage of the number of MII oocytes microinjected which transform into 2PN
Baseline
Rate of blastocyst formation
Time Frame: Baseline
percentage of the number of blastocysts formed to the number of 2PN fertilized oocytes cultured
Baseline
Clinical pregnancy rate after 1st FET
Time Frame: Baseline
defined as elevated serum β-HCG (+) the presence of gestational sac(s) or fetal heartbeats (fetal pole) by ultrasonography
Baseline

Collaborators and Investigators

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

Sponsor

El Shatby University Hospital for Obstetrics and Gynecology

Investigators

  • Principal Investigator: Ismail E Khalifa, Ass.lecturer, ELShatby University Hospital
  • Principal Investigator: Sherif S Gafaar, Professor, ELShatby University Hospital

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

Helpful Links

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)

December 1, 2023

Primary Completion (Actual)

February 1, 2025

Study Completion (Actual)

February 1, 2025

Study Registration Dates

First Submitted

February 2, 2025

First Submitted That Met QC Criteria

February 2, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 21, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PPOS vs Antagonist Protocols

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

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.

Clinical Trials on Polycystic Ovarian Syndrome

Clinical Trials on Progesterone

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Myanmar

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe