Luteal Phase-start Ovarian Stimulation With Corifollitropin Alfa

Not Applicable

Completed

• Conditions: Infertility
• Interventions: Drug: Follicular phase corifollitropin alfa; Drug: Luteal phase corifollitropin alfa

• Registration Number: NCT03555942
• Lead Sponsor: Institut Universitari Dexeus

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:

1. Potentially immediate synchronization of oocyte donors with recipients aiming to fresh oocyte donation.

2. Fertility preservation patients for medical, oncological and non-medical indication

3. Any situation in which endometrial receptivity is not pursued.

Study Timeline

• Study Start: 2018-05-08
• Study First Submitted: 2018-05-08
• Study First Submitted QC: 2018-06-01
• Study First Posted: 2018-06-14
• Primary Completion: 2021-11-30
• Study Completion: 2021-12-01
• Status Verified: 2022-03
• Last Update Submitted: 2022-03-29
• Last Update Posted: 2022-03-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 44

Inclusion Criteria

1. Healthy eligible oocyte donors
2. Age 18-34 years
3. AFC >12 and AMH>1.5 ng/ml
4. BMI 19-28kg/m2
5. Body weight >60kg
6. Both ovaries present
7. Willing to participate in the study
8. 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

1. Endometriosis
2. AFC>20
3. PCOS
4. Low ovarian reserve
5. Endocrine abnormalities
6. Hormonal contraception
7. Contraindication of hormonal treatment
8. History of Ovarian Hyperstimulation Syndrome or hyper-response (> 30 follicles .

11mm)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Early follicular phase protocol	Follicular phase corifollitropin alfa	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.
Luteal phase protocol	Luteal phase corifollitropin alfa	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.

Primary Outcome Measures

Name	Time	Method
Mean number of euploid embryos	15-45 days following oocyte retrieval procedure	Number of euploid embryos between oocytes received from follicular phase or luteal phase initiation of ovarian stimulation.

Secondary Outcome Measures

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

Trial Locations

Locations (2)

Consultorio Dexeus; 🇪🇸 Barcelona, Spain

Departamento de Ginecología Obstetricia y Reproducción. Hospital Universitari Dexeus; 🇪🇸 Barcelona, Spain