Luteal Phase-start Ovarian Stimulation With Corifollitropin Alfa

Study Overview
=================
Brief Summary
-----------------
To evaluate the effect of random-start of ovarian stimulation initiated in the early follicular or luteal phase on the pharmacokinetics and follicular dynamics and embryo euploidy rates in oocyte donors treated with identical ovarian stimulation protocols with corifollitropin alfa and GnRH antagonist pituitary downregulation

Detailed Description
-----------------
The scope of the current prospective trial is to investigate whether Luteal Stimulation (LS) results in equivalent euploid embryos with Follicular Stimulation (FS) in young reproductive age women. The use of the oocyte donor model allows extrapolation of the results and application of LS routinely not only in healthy women undergoing fertility preservation but also in all patients irrespective of the menstrual date. This may indeed allow widespread introduction of LS in IVF programs which may result in proper scheduling of ovarian stimulation which is a major issue in everyday clinical practice. Given that the pharmacokinetics and follicular dynamics of 150μg corifollitropin alfa for luteal stimulation has never been evaluated, the current study of luteal stimulation with corifollitropin alfa could be very interesting for several reasons: Potentially immediate synchronization of oocyte donors with recipients aiming to fresh oocyte donation. Fertility preservation patients for medical, oncological and non-medical indication Any situation in which endometrial receptivity is not pursued.

Official Title
-----------------
Follicular or Luteal Start Ovarian Stimulation With Corifollitropin Alfa. A Prospective Equivalence Study With Repeated Ovarian Stimulation in Oocyte Donors

Conditions
-----------------
Infertility

Intervention / Treatment
-----------------
* Drug: Follicular phase corifollitropin alfa
* Drug: Luteal phase corifollitropin alfa


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy eligible oocyte donors Age 18-34 years AFC >12 and AMH>1.5 ng/ml BMI 19-28kg/m2 Body weight >60kg Both ovaries present Willing to participate in the study Willing to use non-hormonal contraception or not needing contraception Recipients will be eligible only if their partners' sperm which will be used for ICSI will be normal. Couples will be excluded in case of moderate to severe oligoasthenospermia. Exclusion Criteria: Endometriosis AFC>20 PCOS Low ovarian reserve Endocrine abnormalities Hormonal contraception Contraindication of hormonal treatment History of Ovarian Hyperstimulation Syndrome or hyper-response (> 30 follicles . 11mm)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Overall, 44 oocyte donors women will be asked to participate in a trial in which they will undergo 2 consecutive ovarian stimulation protocols within a period of 6 months with 150μg corifollitropin alfa followed by 200 IU rFSH in a fixed GnRH antagonist protocol starting in the early follicular, and luteal menstrual cycle phase
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Early follicular phase protocol<br>On day 2 or 3 of the menstrual cycle, following baseline blood sampling, a single SC injection of 150 ìg corifollitropin alfa will be administered (Stimulation Day 1). Starting on Stimulation Day 6, the subject will receive a daily SC injection of 0.25 mg ganirelix up to and including the day of GnRH agonist triggering administration to prevent premature LH surges. From Stimulation Day 8 onwards treatment is continued with a daily SC dose of rFSH (200IU/day) up to the day of GnRHa administration. | Drug: Follicular phase corifollitropin alfa<br>* GnRH antagonist protocol with corifollitropin alfa initiated in the follicular phase (day 2 or 3 of the menstrual cycle)<br>|
| Experimental: Luteal phase protocol<br>Following baseline blood sampling on cycle day 2 of 3 of the menstrual cycle, patients will be followed up with blood and ultrasound from cycle day 10 onwards till the detection of serum LH peak. LH peak will be defined as an increase in serum LH above 20IU/LH. Five (5) days after the LH peak a single SC injection of 150 ìg corifollitropin alfa will be administered (Stimulation Day 1). Starting on Stimulation Day 6, the subject will receive a daily SC injection of 0.25 mg ganirelix up to and including the day of GnRH agonist triggering administration to prevent premature LH surges. From Stimulation Day 8 onwards treatment is continued with a daily SC dose of rFSH (200IU/day) up to the day of GnRHa administration. | Drug: Luteal phase corifollitropin alfa<br>* GnRH antagonist protocol with corifollitropin alfa initiated in the luteal phase (5 days after an LH peak)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean number of euploid embryos | Number of euploid embryos between oocytes received from follicular phase or luteal phase initiation of ovarian stimulation. | 15-45 days following oocyte retrieval procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of oocytes | The outcome will be evaluated on the day of oocyte retrieval | 9 -20 days from initiation of ovarian stimulation | 
| Number of MIIs | The outcome will be evaluated on the day of oocyte retrieval | 9 -20 days from initiation of ovarian stimulation | 
| Total additional dose of rFSH (IU) | Addition total units of FSH following corifollitropin alfa.The outcome will be evaluated on the day of final oocyte maturation | 9 -20 days from initiation of ovarian stimulation | 
| Duration of ovarian stimulation | Total days of ovarian stimulation .The outcome will be evaluated on the day of final oocyte maturation | 9 -20 days from initiation of ovarian stimulation | 
| Endocrine profile at specific intervals | Estradiol, LH, FSH, Progesterone | Stimulation day 1, day 6, day 8, and Day of final oocyte maturation (actual day may vary between 9-15) | 
| Clinical pregnancy rates following transfer of embryos generated from oocytes from follicular phase vs. luteal phase stimulation | Clinical pregnancy rates , presence of intrauterine gestational sac with an embryonic pole demonstrating cardiac activity | 5-8 weeks after embryo transfer procedure |