Interest of Estrogen Scheduling Before Ovarian Stimulation With Corifollitropin Alfa (PRESCORI)

February 7, 2023 updated by: Anne GUIVARC'H-LEVEQUE, Centre Hospitalier Intercommunal Creteil

Interest of Estrogen Scheduling Before Ovarian Stimulation With Corifollitropin Alfa in Women Older Than 38 Years Old Undergoing in Vitro Fertilization

E2 given in late luteal phase can be extended beyond the onset of menses for a period of at least eight days before the start of the stimulation, allowing scheduling of stimulation in order to limit oocytes retrievals during weekends .

Administration of corifollitropin alfa, a Follicule stimulating Hormone (FSH) with extended release kinetics, seems particularly interesting for a synchronous recruitment of follicles after homogenization of the cohort.

The objective of this study is to evaluate the impact on the response to ovarian stimulation with corifollitropin alfa of E2 scheduling versus no scheduling for women over 38 years, age at which declining of ovarian reserve usually begins. The management of these patients in terms of organization of the center is also evaluated.

The scheduling of IVF cycles represents a double benefit. On one hand, to enable a "synchronization" of the follicular cohort for a best response and a higher number of mature oocytes. On the other hand, a more efficient organization for both the center (avoiding retrievals on weekends and public holidays, organize and distribute equally the activity, reduce cost operations) and couples (personal and professional organization).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

With advanced age, ovarian reserve decreases, follicular cohort becomes heterogeneous under the influence of higher FSH rise in late luteal phase. It has been shown that estrogens (E2) taken in the late luteal phase homogenized follicular cohort by inhibiting inter cycle FSH peak ,and that this inhibition is immediately reversible after discontinuation of treatment .

E2 given in late luteal phase can also be extended beyond the onset of menses for a period of at least eight days before the start of the stimulation, allowing scheduling of stimulation in order to limit oocytes retrievals during weekends . A prospective randomized study comparing E2 scheduling and no scheduling has shown that there was no difference in birth rate in a population of normo-responders women . While in these patients, the number of oocytes was not different in the two arms, a recent pilot study founded a significant increase in the number of oocytes retrieved after E2 luteal phase priming compared to the absence of priming in a population of poor responders .

In 2013, a report of the French governmental BioMedicine Agency warned about the thrombo-embolic risk associated with the use of the contraceptive pill for IVF scheduling, especially in women over 35.

Administration of corifollitropin alfa, an FSH with extended release kinetics, seems particularly interesting for a synchronous recruitment of follicles after homogenization of the cohort. In the Pursue study, an equivalent efficacy has been shown with the daily administration of 300 IU FSH and corifollitropin alfa in patients over 35 years .

The objective of this study is to evaluate the impact of the response to ovarian stimulation with corifollitropin alfa of E2 scheduling versus no scheduling for women over 38 years, age at which declining of ovarian reserve usually begins. The management of these patients in terms of organization of the center is also evaluated.

The scheduling of IVF cycles represents a double benefit. On one hand, to enable a "synchronization" of the follicular cohort for a best response and a higher number of mature oocytes. On the other hand, a more efficient organization for both the center (avoiding retrievals on weekends and public holidays, organize and distribute equally the activity, reduce cost operations) and couples (personal and professional organization). This can be done with pills but there are controversial data on its impact on the chances of birth. It has been shown that estrogen scheduling provides opportunities for success equivalent to the absence of scheduling for patients with good prognosis . If this study confirms the initial hypothesis, it will show that a less favorable public can profit from the benefits of scheduling by estrogen on both the organization of the attempt and the chances of pregnancy through better ovarian response.

Study Type

Interventional

Enrollment (Actual)

334

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 Locations

      • Bondy, France, 93140
        • Hôpital Jean Verdier
      • Créteil, France, 94000
        • CHI Créteil
      • Rennes, France, 35043
        • Clinique de la Sagesse

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

38 years to 47 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Patient of 38 years or more
  • Planned in invitro fertilization or intracytoplasmic sperm injection rank 1 or 2 (rank = retrieval with transfer)
  • With regular cycles from 26 to 35 days
  • Weight > 50 kg and body mass index< or equal to 32
  • Affiliation to the general system of French social security and reimbursement for fertility problems

Exclusion Criteria:

  • Irregular cycles and/or polycystic ovarian syndrome
  • Previous History of ovarian hyperstimulation syndrome
  • Rank puncture > 2
  • Uterine malformation
  • Presence of hydrosalpinges
  • Endometriosis stage III or IV

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
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Arm E2: With estrogens pretreatment
The estrogens pretreatment will began between the day 20 and the day 24 of an ovarian cycle and should be continued until Wednesday beyond the onset of menses
The estrogens pretreatment will began between the day 20 and the day 24 of an ovarian cycle and should be continued until Wednesday beyond the onset of menses
NO_INTERVENTION: Arm S: without estrogens pretreatment
No estrogen pretreatment will be delivered

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of selected oocytes
Time Frame: At time of ovarian puncture
At time of ovarian puncture

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of days of pretreatment
Time Frame: From inclusion visit date to the beginning of stimulation, up to 15 days
From inclusion visit date to the beginning of stimulation, up to 15 days
Cancellation rate
Time Frame: From date of inclusion visit until the date of embryo transfer, up to 90 days
From date of inclusion visit until the date of embryo transfer, up to 90 days
Number of days of antagonist
Time Frame: From date of stimulation until the date of the trigger, up to 30 days
From date of stimulation until the date of the trigger, up to 30 days
The day of the trigger
Time Frame: At time of the trigger
At time of the trigger
Estradiol rate
Time Frame: 8 days from the beginning of stimulation and the day of the trigger
8 days from the beginning of stimulation and the day of the trigger
Luteinizing hormone rate
Time Frame: 8 days from the beginning of stimulation and the day of the trigger
8 days from the beginning of stimulation and the day of the trigger
Progesterone rate
Time Frame: 8 days from the beginning of stimulation and the day of the trigger
8 days from the beginning of stimulation and the day of the trigger
Follicles number > 10 mm
Time Frame: 8 days from the beginning of stimulation
8 days from the beginning of stimulation
Follicles number > 14 mm
Time Frame: From 1 day before the day of trigger or the day of trigger
From 1 day before the day of trigger or the day of trigger
Number of oocytes in metaphase 2
Time Frame: At time of ovarian puncture
At time of ovarian puncture
Total number of embryos with good quality
Time Frame: At time of fertilization procedure
At time of fertilization procedure
early pregnancy
Time Frame: 14 days after embryo transfer
Beta Human chorionic gonadotropin>100 U/l
14 days after embryo transfer
ongoing pregnancy rate
Time Frame: 12 weeks after embryo transfer
on ultrasound procedure
12 weeks after embryo transfer
miscarriage before 12 weeks of amenorrhea
Time Frame: From embryo transfer to 12 weeks after embryo transfer
From embryo transfer to 12 weeks after embryo transfer

Collaborators and Investigators

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

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 4, 2016

Primary Completion (ACTUAL)

July 1, 2022

Study Completion (ACTUAL)

January 4, 2023

Study Registration Dates

First Submitted

August 22, 2016

First Submitted That Met QC Criteria

August 25, 2016

First Posted (ESTIMATE)

August 30, 2016

Study Record Updates

Last Update Posted (ACTUAL)

February 8, 2023

Last Update Submitted That Met QC Criteria

February 7, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

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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