Interest of Estrogen Scheduling Before Ovarian Stimulation With Corifollitropin Alfa
- Conditions
- Infertility
- Interventions
- Drug: Estrogens
- Registration Number
- NCT02884245
- Lead Sponsor
- 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).
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 334
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm E2: With estrogens pretreatment 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
- Primary Outcome Measures
Name Time Method Number of selected oocytes At time of ovarian puncture
- Secondary Outcome Measures
Name Time Method The day of the trigger At time of the trigger ongoing pregnancy rate 12 weeks after embryo transfer on ultrasound procedure
Number of days of pretreatment From inclusion visit date to the beginning of stimulation, up to 15 days Number of days of antagonist From date of stimulation until the date of the trigger, up to 30 days Follicles number > 14 mm From 1 day before the day of trigger or the day of trigger Total number of embryos with good quality At time of fertilization procedure Cancellation rate From date of inclusion visit until the date of embryo transfer, up to 90 days Luteinizing hormone rate 8 days from the beginning of stimulation and the day of the trigger Follicles number > 10 mm 8 days from the beginning of stimulation early pregnancy 14 days after embryo transfer Beta Human chorionic gonadotropin\>100 U/l
Estradiol rate 8 days from the beginning of stimulation and the day of the trigger Number of oocytes in metaphase 2 At time of ovarian puncture Progesterone rate 8 days from the beginning of stimulation and the day of the trigger miscarriage before 12 weeks of amenorrhea From embryo transfer to 12 weeks after embryo transfer
Trial Locations
- Locations (3)
Clinique de la Sagesse
🇫🇷Rennes, France
CHI Creteil
🇫🇷Créteil, France
Hôpital Jean Verdier
🇫🇷Bondy, France