Micronized Progesterone vs Gonadotropin-releasing Hormone (GnRH) Antagonist in Freeze-all IVF Cycles. (Prog_STIM)

May 12, 2023 updated by: Nikolaos Polyzos, Institut Universitari Dexeus

Suppression of Endogenous Luteinizing Hormone (LH) Surge With Progesterone vs GnRH Antagonist in Freeze-all IVF Cycles. A Prospective Equivalence Study With Repeated Ovarian Stimulation Cycles.

To examine whether the number of euploid embryos following ovarian stimulation with micronized progesterone is equivalent as compared with the number of embryos after ovarian stimulation with the use of a GnRH antagonist in patients undergoing ovarian stimulation for IVF or intracytoplasmatic sperm injection (ICSI).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The pre-ovulatory surges of GnRH and LH are activated by increased concentrations of circulating estradiol, but ovulation is blocked when progesterone concentrations are elevated, due to a central inhibition of the GnRH surge. Although traditionally GnRH has been traditionally considered the drug of choice to control endogenous LH in controlled ovarian stimulation (COS) cycles, recently, micronized progesterone has been shown to be an effective oral alternative for preventing premature LH surges during COS in women undergoing IVF/ICSI treatments, with excellent results, whereas their safety during pregnancy is well-established. This novel protocol, has several advantages (good tolerance, user convenience, and cost reduction), that are very attractive when it comes to establishing a convenient user regimen in combination with a ''freeze all'' strategy. However, the comparative efficacy of this novel protocol with the more universal use of GnRH-antagonist protocol for the treatment of IVF patients in terms of embryo ploidy has never been evaluated up to date. The current study aims, for the first time, to examine whether the number of euploid embryos following ovarian stimulation with micronized progesterone is equivalent as compared with the number of embryos after ovarian stimulation with the use of a GnRH antagonist in patients undergoing ovarian stimulation for IVF/ICSI.

If efficacy would prove to be similar, with no impact on the chromosomal constitution of embryos, there will be obvious advantages for the preferential use of micronized progesterone over the antagonist protocol: oral administration is preferred over subcutaneous injection, and total cost of medication would be lower. This would be particularly interesting for the future in all "freeze all" protocols such as women undergoing ovarian stimulation for fertility preservation, preimplantation genetic screening and oocyte donation programs.

Study Type

Interventional

Enrollment (Actual)

44

Phase

  • Not Applicable

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

  • Spain
    • Catalunya
      • Barcelona, Catalunya, Spain, 08028
        • Institut Universitari Dexeus

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

36 years to 40 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Infertile patients
  • Age 36-40 years old
  • BMI 18-30 kg/m2
  • Undergoing preimplantation genetic screening cycles
  • Planned to undergo at least two treatment cycles, to accumulate embryos to increase the chance of obtaining euploid embryos for transfer
  • Willing to participate in the study

Exclusion Criteria:

  • Age> 41
  • Severe male factor requiring TESE (testicular sperm extraction)
  • Low ovarian reserve (AMH < 1.2 ng/ml)
  • Administration of any other drug potentially interfering with the treatment.

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: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: GnRH antagonist
In the antagonist cycle, LH suppression will be accomplished by subcutaneous (SC) injections of 0.25 mg of Cetrorelix or Ganirelix starting in the presence of follicles >14mm or E2 levels >400 pg/ml and continuing until ovulation triggering.
Drug: GnRh antagonist
In the antagonist cycle, LH suppression will be accomplished by subcutaneous (SC) injections of 0.25 mg of Cetrorelix or Ganirelix starting in the presence of follicles >14mm or E2 levels >400 pg/ml and continuing until ovulation triggering to avoid LH surge in COS
Other Names:
  • Cetrorelix or Ganirelix
Experimental: Micronized progesterone
In the progesterone cycle, endogenous LH suppression will be accomplished by oral administration of micronized progesterone (200 mg) once a day at bed time, from stimulation day 1 and continuing until ovulation triggering.
Drug: Micronized progesterone
Micronized progesterone protocol to avoid LH surge in COS, from stimulation day 1 and continuing until ovulation triggering.
Other Names:
  • Utrogestan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of euploid embryos as compared between the 2 ovarian stimulation cycles
Time Frame: 15-45 days following oocyte retrieval procedure
Number of euploid embryos between oocytes received from the antagonist GnRh protocol or the micronized progesterone protocol.
15-45 days following oocyte retrieval procedure

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Endocrine profile at specific intervals
Time Frame: Stimulation day 0, day 6, day 8, day of final oocyte maturation and day +1 after oocyte maturation (actual day may vary between 9-15)
To evaluate the difference in the mean serum estradiol (E2) levels (measured in pg/mL) at the predefined intervals treatment days.
Stimulation day 0, day 6, day 8, day of final oocyte maturation and day +1 after oocyte maturation (actual day may vary between 9-15)
Endocrine profile at specific intervals
Time Frame: Stimulation day 0, day 6, day 8, day of final oocyte maturation and day +1 after oocyte maturation (actual day may vary between 9-15)
To evaluate the difference in the mean serum follicle stimulating hormone levels (FSH, measured in IU/mL) at the predefined intervals treatment days.
Stimulation day 0, day 6, day 8, day of final oocyte maturation and day +1 after oocyte maturation (actual day may vary between 9-15)
Endocrine profile at specific intervals
Time Frame: Stimulation day 0, day 6, day 8, day of final oocyte maturation and day +1 after oocyte maturation (actual day may vary between 9-15)
To evaluate the difference in the mean serum progesterone levels (measured in ng/mL) at the predefined intervals treatment days.
Stimulation day 0, day 6, day 8, day of final oocyte maturation and day +1 after oocyte maturation (actual day may vary between 9-15)
Duration of stimulation
Time Frame: 9-20 days from initiation of ovarian stimulation
Total days of ovarian stimulation. The outcome will be evaluated on the of final oocyte maturation.
9-20 days from initiation of ovarian stimulation
Incidence of premature LH rise
Time Frame: 9-20 days from initiation of ovarian stimulation
9-20 days from initiation of ovarian stimulation
Total dose of gonadotropins
Time Frame: 9-20 days from initiation of ovarian stimulation
Total units of recombinant FSH. The outcome will be evaluated on the day of final oocyte maturation.
9-20 days from initiation of ovarian stimulation
Number of mature oocytes
Time Frame: 9-20 days from initiation of ovarian stimulation
The outcome will be evaluated on the day of oocyte retrieval
9-20 days from initiation of ovarian stimulation
Ultrasound ovarian follicles diameter measurement
Time Frame: 9-20 days from initiation of ovarian stimulation
During the regular follicular scan, two diameters of each ovarian follicle will be recorded: the maximum diameters in the transverse and longitudinal scan planes.
9-20 days from initiation of ovarian stimulation
Fertilization rate
Time Frame: 1 day after oocyte retrieval
The outcome will be evaluated the day after the of oocyte retrieval
1 day after oocyte retrieval

Collaborators and Investigators

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

Sponsor

Institut Universitari Dexeus

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)

September 25, 2019

Primary Completion (Actual)

January 15, 2022

Study Completion (Actual)

May 15, 2022

Study Registration Dates

First Submitted

September 20, 2019

First Submitted That Met QC Criteria

September 26, 2019

First Posted (Actual)

September 27, 2019

Study Record Updates

Last Update Posted (Actual)

May 15, 2023

Last Update Submitted That Met QC Criteria

May 12, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FSD-PRG-2019-02

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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