Luteal Phase-start Ovarian Stimulation With Corifollitropin Alfa

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

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

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.

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

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.

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.

GnRH antagonist protocol with corifollitropin alfa initiated in the follicular phase (day 2 or 3 of the menstrual cycle)

GnRH antagonist protocol with corifollitropin alfa initiated in the luteal phase (5 days after an LH peak)

Number of euploid embryos between oocytes received from follicular phase or luteal phase initiation of ovarian stimulation.

Addition total units of FSH following corifollitropin alfa.The outcome will be evaluated on the day of final oocyte maturation

Total days of ovarian stimulation .The outcome will be evaluated on the day of final oocyte maturation

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

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)

Martinez F, Clua E, Roca M, Garcia S, Polyzos NP. Comparison of blastocyst euploidy rates following luteal versus follicular phase stimulation in a GnRH antagonist protocol: a prospective study with repeated ovarian stimulation cycles. Hum Reprod. 2022 Nov 24;37(12):2777-2786. doi: 10.1093/humrep/deac222.