Luteal Phase-start Ovarian Stimulation With Corifollitropin Alfa

Sponsor

Institut Universitari Dexeus (Other)

Overall Status

Completed

CT.gov ID

NCT03555942

Collaborator

(none)

Enrollment

Locations

Arms

42.8

Actual Duration (Months)

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Infertility	Drug: Follicular phase corifollitropin alfa Drug: Luteal phase corifollitropin alfa	N/A

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

44 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Intervention 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 phaseOverall, 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)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

May 8, 2018

Actual Primary Completion Date :

Nov 30, 2021

Actual Study Completion Date :

Dec 1, 2021

Arms and Interventions

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)

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)

Outcome Measures

Primary Outcome Measures

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

Number of oocytes [9 -20 days from initiation of ovarian stimulation]
The outcome will be evaluated on the day of oocyte retrieval
Number of MIIs [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
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 35 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Consultorio Dexeus	Barcelona		Spain	08028
2	Departamento de Ginecología Obstetricia y Reproducción. Hospital Universitari Dexeus	Barcelona		Spain	08037

Sponsors and Collaborators

Institut Universitari Dexeus

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Nikolaos Polyzos, Clinical and Scientific Director, Institut Universitari Dexeus

ClinicalTrials.gov Identifier:

NCT03555942

Other Study ID Numbers:

FSD-COR-2017-01

First Posted:

Jun 14, 2018

Last Update Posted:

Mar 31, 2022

Last Verified:

Mar 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Infertility

Study Results

No Results Posted as of Mar 31, 2022