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

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ClinicalTrials.gov Identifier: NCT02884245
Recruitment Status : Recruiting
First Posted : August 30, 2016
Last Update Posted : August 2, 2017
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Anne GUIVARC'H-LEVEQUE, Centre Hospitalier Intercommunal Creteil

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).


Condition or disease Intervention/treatment Phase
Infertility Drug: Estrogens Phase 3

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  (Clinical Trial)
Estimated Enrollment : 360 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Interest of Estrogen Scheduling Before Ovarian Stimulation With Corifollitropin Alfa in Women Older Than 38 Years Old Undergoing in Vitro Fertilization
Study Start Date : October 2016
Estimated Primary Completion Date : November 2018
Estimated Study Completion Date : November 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Estrogens

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
Drug: 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

No Intervention: Arm S: without estrogens pretreatment
No estrogen pretreatment will be delivered



Primary Outcome Measures :
  1. Number of selected oocytes [ Time Frame: At time of ovarian puncture ]

Secondary Outcome Measures :
  1. Number of days of pretreatment [ Time Frame: From inclusion visit date to the beginning of stimulation, up to 15 days ]
  2. Cancellation rate [ Time Frame: From date of inclusion visit until the date of embryo transfer, up to 90 days ]
  3. Number of days of antagonist [ Time Frame: From date of stimulation until the date of the trigger, up to 30 days ]
  4. The day of the trigger [ Time Frame: At time of the trigger ]
  5. Estradiol rate [ Time Frame: 8 days from the beginning of stimulation and the day of the trigger ]
  6. Luteinizing hormone rate [ Time Frame: 8 days from the beginning of stimulation and the day of the trigger ]
  7. Progesterone rate [ Time Frame: 8 days from the beginning of stimulation and the day of the trigger ]
  8. Follicles number > 10 mm [ Time Frame: 8 days from the beginning of stimulation ]
  9. Follicles number > 14 mm [ Time Frame: From 1 day before the day of trigger or the day of trigger ]
  10. Number of oocytes in metaphase 2 [ Time Frame: At time of ovarian puncture ]
  11. Total number of embryos with good quality [ Time Frame: At time of fertilization procedure ]
  12. early pregnancy [ Time Frame: 14 days after embryo transfer ]
    Beta Human chorionic gonadotropin>100 U/l

  13. ongoing pregnancy rate [ Time Frame: 12 weeks after embryo transfer ]
    on ultrasound procedure

  14. miscarriage before 12 weeks of amenorrhea [ Time Frame: From embryo transfer to 12 weeks after embryo transfer ]


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Ages Eligible for Study:   38 Years to 47 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02884245


Contacts
Contact: Anne GUIVARC'H - LEVEQUE, MD anne.guivarch@orange.fr

Locations
France
Hôpital Jean Verdier Recruiting
Bondy, France, 93140
Contact: Isabelle MD DURNERIN, MD       isabelle.cedrin-durnerin@aphp.fr   
Principal Investigator: Isabelle DURNERIN, MD         
Sub-Investigator: Michael GRYNBERG, MD         
Sub-Investigator: Alice SEROKA, MD         
Sub-Investigator: Julie BERNARD, MD         
Sub-Investigator: Claire VINOLAS, MD         
CHI Creteil Recruiting
Créteil, France, 94000
Contact: Amelle ISSA       amelle.issa@chicreteil.fr   
Contact: Nathalie MASSIN       nathalie.massin@chicreteil.fr   
Principal Investigator: Nathalie MASSIN, MD         
Sub-Investigator: Hélène BRY GAUILLARD, MD         
Sub-Investigator: Maud PASQUIER, MD         
Sub-Investigator: Claire PIETIN VIALLE, MD         
Sub-Investigator: Annina LOBERSZTAJN, MD         
Clinique de la Sagesse Recruiting
Rennes, France, 35043
Contact: Anne MD GUIVARCH LEVEQUE       anne.guivarch@orange.fr   
Principal Investigator: Anne GUIVARCH LEVEQUE, MD         
Sub-Investigator: Sylvie FROMENTIN, MD         
Sub-Investigator: Maud BIDET, MD         
Sub-Investigator: Pierre BROUX, MD         
Sub-Investigator: Ludovic MOY, MD         
Sub-Investigator: Nicolas LUCAS, MD         
Sub-Investigator: Frédérique JAFFRE, MD         
Sponsors and Collaborators
Centre Hospitalier Intercommunal Creteil
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Anne GUIVARC'H - LEVEQUE, MD Clinique de la Sagesse
Principal Investigator: Isabelle CEDRIN - DURNERIN, MD CHU Jean Verdier - APHP
Principal Investigator: Nathalie MASSIN, MD CHI Créteil

Publications:

Responsible Party: Anne GUIVARC'H-LEVEQUE, Reproductive Endocrinologist, Centre Hospitalier Intercommunal Creteil
ClinicalTrials.gov Identifier: NCT02884245     History of Changes
Other Study ID Numbers: PRESCORI
First Posted: August 30, 2016    Key Record Dates
Last Update Posted: August 2, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Anne GUIVARC'H-LEVEQUE, Centre Hospitalier Intercommunal Creteil:
Fertility
Reproductive processes
In vitro fertilization
Intracytoplasmic sperm injection
Estrogens
Follicule Stimulating Hormon

Additional relevant MeSH terms:
Infertility
Genital Diseases, Male
Genital Diseases, Female
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs