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).
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
334
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
Hôpital Jean Verdier
Bondy, France
CHI Creteil
Créteil, France
Clinique de la Sagesse
Rennes, France
Number of selected oocytes
Time frame: At time of ovarian puncture
Number of days of pretreatment
Time frame: 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
Number of days of antagonist
Time frame: 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
Estradiol rate
Time frame: 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
Progesterone rate
Time frame: 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
Follicles number > 14 mm
Time frame: 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
Total number of embryos with good quality
Time frame: At time of fertilization procedure
early pregnancy
Beta Human chorionic gonadotropin\>100 U/l
Time frame: 14 days after embryo transfer
ongoing pregnancy rate
on ultrasound procedure
Time frame: 12 weeks after embryo transfer
miscarriage before 12 weeks of amenorrhea
Time frame: From embryo transfer to 12 weeks after embryo transfer
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