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Luteal Phase Ovarian Stimulation With Follitropin Delta and Dydrogesterone (LadyDe)

Primary Purpose

Oocyte Donors, Oocyte Donation

Status
Recruiting
Phase
Not Applicable
Locations
Belgium
Study Type
Interventional
Intervention
Follitropin delta (Rekovelle)
Duphaston
GnRH agonist (Gonapeptyl)
Sponsored by
CRG UZ Brussel
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Oocyte Donors focused on measuring cumulus-oocyte complexes, progestin primed ovarian stimulation, controlled ovarian stimulation, luteal phase ovarian stimulation, follicular phase ovarian stimulation, follitropin delta, dydrogesterone

Eligibility Criteria

18 Years - 36 Years (Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

  • Body mass Index (BMI) ≥18 to < 28
  • Signed informed consent
  • Regular menstrual cycle length i.e. 24-35 days

Exclusion Criteria:

  • Contraindications to the use of gonadotropins
  • Endometriosis grade 3-4
  • Patients with Anti-mullerian hormone (AMH) <1.1 ng/ml and/or antral follicular count (AFC)<7
  • Patients with Follicle Number Per Ovary (FNPO) ≥ 19 and/or AMH >5ng/ml
  • Patients under contraception with hormonal intrauterine device (IUD)
  • Any untreated endocrine abnormality

Sites / Locations

  • Brussels IvfRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

Follitropin delta and dydrogesterone (treatment A followed by treatment B)

Follitropin delta and dydrogesterone (treatment B followed by treatment A)

Arm Description

Treatment A: Ovarian stimulation is started with daily subcutaneous injections of Follitropin delta (Rekovelle) 12 mcg/daily from day 2 of the follicular phase onwards. Dydrogesterone (Duphaston) 20mg/day will be initiated on stimulation day 7 until the criteria for oocyte trigger are achieved. Treatment B: From day 20 of the menstrual cycle onwards, daily subcutaneous injections of Follitropin delta (Rekovelle) 12 mcg/daily will be administered. Dydrogesterone (Duphaston) 20mg/day will be initiated on stimulation day 7 or when serum LH > 10 IU/L until day of trigger. For both treatment (A and B) oocyte maturation trigger will be planned when transvaginal ultrasound shows at least 3 follicles >20mm in diameter with a single subcutaneous injection of GnRH agonist (Gonapeptyl 0.2 mg). Oocyte retrieval will be performed 36 hours after trigger. The retrieved cumulus oocyte complexes will be counted, denuded and the number of mature oocytes evaluated.

Treatment B: From day 20 of the menstrual cycle onwards, daily subcutaneous injections of Follitropin delta (Rekovelle) 12 mcg/daily will be administered. Dydrogesterone (Duphaston) 20mg/day will be initiated on stimulation day 7 or when serum LH > 10 IU/L until day of trigger. Treatment A: Ovarian stimulation is started with daily subcutaneous injections of Follitropin delta12 mcg/daily (Rekovelle) from day 2 of the follicular phase onwards. Dydrogesterone (Duphaston) 20mg/day will be initiated on stimulation day 7 until the criteria for oocyte trigger are achieved. For both treatment (B and A) oocyte maturation trigger will be planned when transvaginal ultrasound shows at least 3 follicles >20mm in diameter with a single subcutaneous injection of GnRH agonist (Gonapeptyl 0.2 mg). Oocyte retrieval will be performed 36 hours after trigger. The retrieved cumulus oocyte complexes will be counted, denuded and the number of mature oocytes evaluated.

Outcomes

Primary Outcome Measures

number of retrieved COCs in both treatment groups
number of retrieved cumulus-oocyte complexes

Secondary Outcome Measures

Endocrine profile in both treatment groups
evaluation of serum E2, FSH, LH, Progesterone
Consumption of gonadotrophins in both treatment groups
(mcg) of gonadotrophins used during ovarian stimulation
Duration of ovarian stimulation in both treatment groups
days of ovarian stimulation
Days of progestin use in both treatment groups
days of progestin use during ovarian stimulation
Total number of MII oocytes in both treatment groups
the number of MII oocytes retrieved that will be assessed after denudation

Full Information

First Posted
August 25, 2022
Last Updated
August 28, 2023
Sponsor
CRG UZ Brussel
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1. Study Identification

Unique Protocol Identification Number
NCT05521828
Brief Title
Luteal Phase Ovarian Stimulation With Follitropin Delta and Dydrogesterone
Acronym
LadyDe
Official Title
Luteal Phase Ovarian Stimulation With Follitropin Delta and Dydrogesterone: a Randomized Cross Over Pilot Trial
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 1, 2023 (Actual)
Primary Completion Date
September 30, 2023 (Anticipated)
Study Completion Date
May 15, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
CRG UZ Brussel

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The last decade has shown a progressive scientific interest for new strategies to improve the outcomes of controlled ovarian stimulation (COS). Given the fact that interovulatory period has been described to have multiple waves of follicular recruitment, luteal phase ovarian stimulation (LPOS) has been proposed as new protocol for COS, with satisfactory ovarian response and pregnancy outcomes. On the other hand progestin-primed ovarian stimulation (PPOS) is today considered an innovative protocol aiming to achieve multi-follicle recruitment and block the luteinizing hormone (LH) surge through progesterone administration in place of the traditional down regulating or gonadotropin-releasing hormone (GnRH) antagonist. This protocol has been shown to be equally effective as LH suppression with GnRH antagonist reporting equivalent oocyte retrieval rates, endocrine profiles, viable embryo numbers, and pregnancy outcomes. Due to the feasibility and patients-friendly characteristics of PPOS in oocytes donors, the current study aims to investigate the impact on the number of cumulus-oocyte complexes (COCs) when a PPOS protocol is associated to both conventional follicular phase stimulation and LPOS for vitrification of oocytes in oocyte donors. Moreover, it aims to determine whether LPOS using PPOS protocol has comparable outcomes to conventional follicular phase stimulation with PPOS protocol, in oocyte donor patients.
Detailed Description
The current study is a single centre randomized, crossover, open label, pilot trial. The study will be conducted on 50 patients who wish to donate their oocytes. All participants will be informed about the nature of the study and informed consent will be taken from all of them. Patients will randomly undergo two treatment sequences, treatment sequence 1 and treatment sequence 2. Treatment sequence 1 consists of treatment A followed by treatment B; treat-ment sequence 2 consists of treatment B followed by treatment A. The time-interval between the two treatments (washout period) will be minimum two months after trigger and maximum twelve months. All patients will undergo PPOS: one cycle with follicular phase ovarian stimulation and one cycle with LPOS. Work up: Complete history, hormonal investigations (FSH, LH, E2, Progesterone, Prolactine, AMH, TSH), Basal transvaginal ultrasound Treatment A: Ovarian stimulation is started on day 2 of the follicular phase with daily subcutaneous injections of Follitropin delta (Rekovelle) 12 mcg/daily from day 2 of the follicular phase onwards. Dydrogesterone (Duphaston) 20mg/day will be initiated on stimulation day 6 until the day of trigger. Patients response will be monitored by: Serum E2, P, FSH, LH and human chorionic gonadotropin (HCG) levels on day 2 of the follicular phase. Patients will be reevaluated on stimulation day 8 every 2 days with ultrasound scan to assess follicular growth and endocrine monitoring with E2, P, FSH and LH levels until the criteria for oocyte trigger are achieved. Treatment B: From day 20 of the menstrual cycle onwards, daily subcutaneous injections of Follitropin delta (Rekovelle) 12 mcg/daily will be administered. Dydrogesterone (Duphaston) 20mg/day will be initiated on stimulation day 6 or when serum LH > 10 IU/L until day of trigger. Patients response will be monitored by: Serum estradiol E2, P, FSH, LH and HCG levels on day 20 of the follicular phase In case of absence of luteal phase values (progesterone > 1.5 ng/ml) at the blood sample of day 20, stimulation will not be started. In this case, hormonal serum assessment with evaluation of E2, P, FSH and LH levels will be repeated every 2 days until luteal phase values will be achieved, and the stimulation will be started. Patient will be reevaluated on stimulation day 8 every 2 days with ultrasound scan to assess follicular growth and endocrine monitoring with E2, P, FSH and LH levels until the criteria for oocyte trigger are achieved. Both treatments: Oocyte maturation trigger will be planned when transvaginal ultrasound shows at least 3 follicles >20mm in diameter with a single subcutaneous injection of GnRH agonist (0.2 mg Gonapeptyl). Oocyte retrieval will be performed 36 hours after trigger. The retrieved cumulus oocyte complexes will be counted, denuded and the number of mature oocytes evaluated Statistical Considerations and Sample size Justification Fifty - patients (25 for each sequence) need to be included. Considering a dropout rate of about 15%, 66 patients will probably be required to reach an adequate sample size.This is a pilot study, and 50 subjects is considered both practically feasible and sufficient to get reliable results in order to guide further trials in this research area. The primary endpoint, the total number of cumulus-oocyte complexes, will be compared between the two treatments using an analysis of variance model with subject, period, and treatment as factors. The mean difference between the two treatments and its 95% confidence interval will be estimated from the model.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Oocyte Donors, Oocyte Donation
Keywords
cumulus-oocyte complexes, progestin primed ovarian stimulation, controlled ovarian stimulation, luteal phase ovarian stimulation, follicular phase ovarian stimulation, follitropin delta, dydrogesterone

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Follitropin delta and dydrogesterone (treatment A followed by treatment B)
Arm Type
Other
Arm Description
Treatment A: Ovarian stimulation is started with daily subcutaneous injections of Follitropin delta (Rekovelle) 12 mcg/daily from day 2 of the follicular phase onwards. Dydrogesterone (Duphaston) 20mg/day will be initiated on stimulation day 7 until the criteria for oocyte trigger are achieved. Treatment B: From day 20 of the menstrual cycle onwards, daily subcutaneous injections of Follitropin delta (Rekovelle) 12 mcg/daily will be administered. Dydrogesterone (Duphaston) 20mg/day will be initiated on stimulation day 7 or when serum LH > 10 IU/L until day of trigger. For both treatment (A and B) oocyte maturation trigger will be planned when transvaginal ultrasound shows at least 3 follicles >20mm in diameter with a single subcutaneous injection of GnRH agonist (Gonapeptyl 0.2 mg). Oocyte retrieval will be performed 36 hours after trigger. The retrieved cumulus oocyte complexes will be counted, denuded and the number of mature oocytes evaluated.
Arm Title
Follitropin delta and dydrogesterone (treatment B followed by treatment A)
Arm Type
Other
Arm Description
Treatment B: From day 20 of the menstrual cycle onwards, daily subcutaneous injections of Follitropin delta (Rekovelle) 12 mcg/daily will be administered. Dydrogesterone (Duphaston) 20mg/day will be initiated on stimulation day 7 or when serum LH > 10 IU/L until day of trigger. Treatment A: Ovarian stimulation is started with daily subcutaneous injections of Follitropin delta12 mcg/daily (Rekovelle) from day 2 of the follicular phase onwards. Dydrogesterone (Duphaston) 20mg/day will be initiated on stimulation day 7 until the criteria for oocyte trigger are achieved. For both treatment (B and A) oocyte maturation trigger will be planned when transvaginal ultrasound shows at least 3 follicles >20mm in diameter with a single subcutaneous injection of GnRH agonist (Gonapeptyl 0.2 mg). Oocyte retrieval will be performed 36 hours after trigger. The retrieved cumulus oocyte complexes will be counted, denuded and the number of mature oocytes evaluated.
Intervention Type
Drug
Intervention Name(s)
Follitropin delta (Rekovelle)
Intervention Description
12 mcg/day will be used for ovarian stimulation in both arms
Intervention Type
Drug
Intervention Name(s)
Duphaston
Intervention Description
20 mg/day will be used for pituitary suppression in both arms
Intervention Type
Drug
Intervention Name(s)
GnRH agonist (Gonapeptyl)
Intervention Description
(2 ampules:0.2 mg) will be used for ovulation triggering in both arms
Primary Outcome Measure Information:
Title
number of retrieved COCs in both treatment groups
Description
number of retrieved cumulus-oocyte complexes
Time Frame
10-20 minutes after oocyte retrieval
Secondary Outcome Measure Information:
Title
Endocrine profile in both treatment groups
Description
evaluation of serum E2, FSH, LH, Progesterone
Time Frame
through study completion, an average of 1 year
Title
Consumption of gonadotrophins in both treatment groups
Description
(mcg) of gonadotrophins used during ovarian stimulation
Time Frame
through study completion, an average of 1 year
Title
Duration of ovarian stimulation in both treatment groups
Description
days of ovarian stimulation
Time Frame
through study completion, an average of 1 year
Title
Days of progestin use in both treatment groups
Description
days of progestin use during ovarian stimulation
Time Frame
through study completion, an average of 1 year
Title
Total number of MII oocytes in both treatment groups
Description
the number of MII oocytes retrieved that will be assessed after denudation
Time Frame
1-2 hours after oocyte retrieval

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
36 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Body mass Index (BMI) ≥18 to < 28 Signed informed consent Regular menstrual cycle length i.e. 24-35 days Exclusion Criteria: Contraindications to the use of gonadotropins Endometriosis grade 3-4 Patients with Anti-mullerian hormone (AMH) <1.1 ng/ml and/or antral follicular count (AFC)<7 Patients with Follicle Number Per Ovary (FNPO) ≥ 19 and/or AMH >5ng/ml Patients under contraception with hormonal intrauterine device (IUD) Any untreated endocrine abnormality
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Christophe Blockeel, Prof, MD
Phone
+ 32 2 4776699
Email
Christophe.Blockeel@uzbrussel.be
First Name & Middle Initial & Last Name or Official Title & Degree
Elsie Nulens
Email
Elsie.Nulens@uzbrussel.be
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christophe Blockeel, Prof, MD
Organizational Affiliation
Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Belgium
Official's Role
Study Director
Facility Information:
Facility Name
Brussels Ivf
City
Brüssel
ZIP/Postal Code
1090
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christophe Blockeel, Professor

12. IPD Sharing Statement

Plan to Share IPD
No
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Luteal Phase Ovarian Stimulation With Follitropin Delta and Dydrogesterone

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