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

Study Overview

• Status: Completed
• Conditions: Infertility
• Intervention / Treatment: Drug: Follicular phase corifollitropin alfa; Drug: Luteal phase corifollitropin alfa

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 Type: Interventional
• Enrollment (Actual): 44
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08028
    • Consultorio Dexeus
  • Barcelona, Spain, 08037
    • Departamento de Ginecología Obstetricia y Reproducción. Hospital Universitari Dexeus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Early follicular phase protocol; 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; GnRH antagonist protocol with corifollitropin alfa initiated in the follicular phase (day 2 or 3 of the menstrual cycle)
Experimental: Luteal phase protocol; 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; GnRH antagonist protocol with corifollitropin alfa initiated in the luteal phase (5 days after an LH peak)

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

Collaborators and Investigators

• Sponsor: Institut Universitari Dexeus

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 8, 2018
• Primary Completion (Actual): November 30, 2021
• Study Completion (Actual): December 1, 2021

Study Registration Dates

• First Submitted: May 8, 2018
• First Submitted That Met QC Criteria: June 1, 2018
• First Posted (Actual): June 14, 2018

Study Record Updates

• Last Update Posted (Actual): March 31, 2022
• Last Update Submitted That Met QC Criteria: March 29, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infertility
• Other Study ID Numbers: FSD-COR-2017-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No