Effectiveness of Estradiol Valerate Pretreatment in Antagonist Protocol for Poor Ovarian Response Patient

January 9, 2022 updated by: Reproductive & Genetic Hospital of CITIC-Xiangya

A Randomized Study to Analysis the Effectiveness of Estradiol Valerate Pretreatment in Antagonist Protocol for Poor Ovarian Response Patient

The purpose of study is to assess the efficacy of add-on estrogen pretreatment in GnRH antagonist protocol on oocyte retrieval as compared with GnRH antagonist protocol for patients with poor ovarian response Add-on estrogen pretreatment protocol is superior to none pretreatment GnRH antagonist protocol for the number of oocytes retrieval

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Women of advanced maternal age seeking ART treatment are characterized as poor ovarian responders in the process of ovarian simulation. Poor response to ovarian stimulation causes high cycle cancellation rate and extremely low pregnancy rate.

More attention has been paid to the potential interest of steroid pretreatments in GnRH antagonist cycles; not only for scheduling the GnRH antagonist cycles, but also for synchronizing the follicular growth which may result in more oocytes retrieved. But available clinical results are controversial.

Previous studies have shown that utilizing the natural negative feedback of the hypothalamus-pituitary-ovary axis induced by estradiol valerate pretreatment effectively prevented inter-cycle increases in follicle-stimulating hormone, improved follicle synchronization, and resulted in a more coordinated follicular development, leading to the recovery of more mature oocytes. However none of the randomized controlled studies compared estradiol valerate pretreatment or not on treatment outcomes, ongoing pregnancy rate, directly on poor response patients using estradiol valerate pretreatment in GnRH antagonist protocol.

Study Type

Interventional

Enrollment (Actual)

552

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

  • China
    • Hunan
      • Changsha, Hunan, China
        • Reproductive & Genetic Hospital of Citic-Xiangya

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

40 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:Bologna criteria

  • At least two of the following three features must be present:

    1. Advanced maternal age (≥40 years) or any other risk factor for POR
    2. A previous POR (≤3 oocytes with a conventional stimulation protocol)
    3. An abnormal ovarian reserve test (i.e. antral follicle count < 5-7 follicles or AMH< 0.5 - 1.1 ng/mL)

Exclusion Criteria:

  1. Age ≥45 years,
  2. Patients who conducted PGD/PGS, and donor egg cycles were excluded.
  3. Presence of unilateral ovary absence
  4. Abnormal uterine deformity or structure.
  5. Spontaneous abortion patients with three or more (including biochemical pregnancy abortion)
  6. With other endocrine disease, ovulation disorders such as adrenal cortex function or thyroid dysfunction
  7. Have assisted reproductive technology contraindications or pregnancy contraindication of patients

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
Other: pretreatment group
the pretreatment group underwent a modified treatment protocol with pretreatment with estogen administering during the cycle preceding the IVF/ICSI cycle. daily dose of 4 mg (2 mg twice a day) estradiol valerate was given orally in the middle luteal phase which is confirmed seven days after ovulation monitoring by the ultrasound up to 2 days of the next menstrual cycle.Recombinant FSH (Puregon) was initiated on menstrual cycle day 2- 3 at an initial dose of 300 IU/day.A daily administration of ganirelix (0.25 mg Orgalutran; Organon) was introduced when the leading follicle is near 13mm, and was repeated up to the time of hCG administration.Ovulation was triggered when the leading follicles reach 18-20mm and at least two follicles 17-18mm , HCG 10000 IU is used to trigger.
Drug: Follitropin Beta;MSD
Patients will start stimulation with a daily s.c. injection of follitropin beta( 300IU Puregonon;MSD) menstrual cycle day 2 or 3.
Other Names:
  • Puregon
Drug: Ganirelix
A daily administration of ganirelix (0.25 mg Orgalutran; MSD) was introduced when the leading follicle is near 13mm, and was repeated up to the time of hCG administration.
Other Names:
  • Orgalutran
Drug: hCG
Ovulation was triggered when the leading follicles reach 18-20mm and at least two follicles 17-18mm , HCG 10000 IU is used to trigger
Other Names:
  • Ovidrel
Drug: estradiol valerate
Estradiol valerate (progynova,Schering) daily dose of 4 mg (2 mg twice a day) was given orally, started 7 days before the presumed onset of menses and administered up to 2 days of the next menstrual cycle
Other Names:
  • progynova
Other: control groups
In the control groups standard GnRH-antagonist protocol was applied.Recombinant FSH (Puregon) was initiated on menstrual cycle day 2- 3 at an initial dose of 300 IU/day.A daily administration of ganirelix (0.25 mg Orgalutran; Organon) was introduced when the leading follicle is near 13mm, and was repeated up to the time of hCG administration.Ovulation was triggered when the leading follicles reach 18-20mm and at least two follicles 17-18mm , HCG 10000 IU is used to trigger.
Drug: Follitropin Beta;MSD
Patients will start stimulation with a daily s.c. injection of follitropin beta( 300IU Puregonon;MSD) menstrual cycle day 2 or 3.
Other Names:
  • Puregon
Drug: Ganirelix
A daily administration of ganirelix (0.25 mg Orgalutran; MSD) was introduced when the leading follicle is near 13mm, and was repeated up to the time of hCG administration.
Other Names:
  • Orgalutran
Drug: hCG
Ovulation was triggered when the leading follicles reach 18-20mm and at least two follicles 17-18mm , HCG 10000 IU is used to trigger
Other Names:
  • Ovidrel

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The number of oocytes retrieved by the IVG 36 hours after hCG administration
Time Frame: 36 hours after hCG administration
The total MII oocytes retrievedd
36 hours after hCG administration

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical pregnancy rate
Time Frame: 6weeks
clinical pregnancy, defined as intrauterine pregnancy with a positive heartbeat at 6 weeks of gestation.Clinical pregnancy rate:Number of clinical pregnancies expressed per 100 initiated cycles, aspiration cycles, or embryo transfer cycles. When clinical pregnancy rates are given, the denominator must be specified.
6weeks
ongoing pregnancy rate
Time Frame: 12weeks
ongoing pregnancy defined as an intact pregnancy at 12 weeks of gestation
12weeks
Optimal number of embryo
Time Frame: 1 week
According to the embryonic developmental rate and morphology, the high quality embryos were defined as the next day (D2) transplanted embryos reached 3 or 4 cells and the third day (D3) transplanted embryos reached 6 to 8 cells with morphological grade 1 or 2
1 week

Collaborators and Investigators

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

Sponsor

Reproductive & Genetic Hospital of CITIC-Xiangya

Collaborators

Merck Sharp & Dohme LLC

Investigators

  • Study Director: Fei Gong, Doctor, Reproductive & Genetic Hospital of Citic-Xiangya

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)

November 15, 2017

Primary Completion (Actual)

June 18, 2021

Study Completion (Actual)

August 18, 2021

Study Registration Dates

First Submitted

September 28, 2017

First Submitted That Met QC Criteria

September 28, 2017

First Posted (Actual)

October 3, 2017

Study Record Updates

Last Update Posted (Actual)

January 11, 2022

Last Update Submitted That Met QC Criteria

January 9, 2022

Last Verified

January 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MSD-MISP-ZX-01

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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