Interest of Estrogen Scheduling Before Ovarian Stimulation With Corifollitropin Alfa

NCT ID: NCT02884245

Last Updated: 2023-02-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 334 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-04
• Study Completion Date: 2023-01-04

Brief Summary

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).

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.

Conditions

Infertility

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Estrogens

Intervention Type: DRUG

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

Arm S: without estrogens pretreatment

No estrogen pretreatment will be delivered

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Estrogens

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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 38 Years
• Maximum Eligible Age: 47 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Centre Hospitalier Intercommunal Creteil

OTHER

Sponsor Role: lead

Responsible Party

Anne GUIVARC'H-LEVEQUE

Reproductive Endocrinologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Anne GUIVARC'H - LEVEQUE, MD

Role: PRINCIPAL_INVESTIGATOR

Clinique de la Sagesse

Isabelle CEDRIN - DURNERIN, MD

Role: PRINCIPAL_INVESTIGATOR

CHU Jean Verdier - APHP

Nathalie MASSIN, MD

Role: PRINCIPAL_INVESTIGATOR

CHI Créteil

Locations

Hôpital Jean Verdier

Bondy, , France

CHI Creteil

Créteil, , France

Clinique de la Sagesse

Rennes, , France

Countries

France

References

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Other Identifiers

PRESCORI

Identifier Type: -

Identifier Source: org_study_id