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

February 7, 2024 updated by: Federica Di Guardo, CRG UZ Brussel

Luteal Phase Ovarian Stimulation With Follitropin Delta and Dydrogesterone: a Randomized Cross Over Pilot Trial

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

50

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Belgium
      • Brüssel, Belgium, 1090
        • Recruiting
        • Brussels IVF
        • Contact:
          • Christophe Blockeel, Professor

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 36 years (Adult)

Accepts Healthy Volunteers

Yes

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Follitropin delta and dydrogesterone (treatment A followed by treatment B)

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.
Drug: Follitropin delta (Rekovelle)
12 mcg/day will be used for ovarian stimulation in both arms
Drug: Duphaston
20 mg/day will be used for pituitary suppression in both arms
Drug: GnRH agonist (Gonapeptyl)
(2 ampules:0.2 mg) will be used for ovulation triggering in both arms
Other: Follitropin delta and dydrogesterone (treatment B followed by treatment A)

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.
Drug: Follitropin delta (Rekovelle)
12 mcg/day will be used for ovarian stimulation in both arms
Drug: Duphaston
20 mg/day will be used for pituitary suppression in both arms
Drug: GnRH agonist (Gonapeptyl)
(2 ampules:0.2 mg) will be used for ovulation triggering in both arms

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
number of retrieved COCs in both treatment groups
Time Frame: 10-20 minutes after oocyte retrieval
number of retrieved cumulus-oocyte complexes
10-20 minutes after oocyte retrieval

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Endocrine profile in both treatment groups
Time Frame: through study completion, an average of 1 year
evaluation of serum E2, FSH, LH, Progesterone
through study completion, an average of 1 year
Consumption of gonadotrophins in both treatment groups
Time Frame: through study completion, an average of 1 year
(mcg) of gonadotrophins used during ovarian stimulation
through study completion, an average of 1 year
Duration of ovarian stimulation in both treatment groups
Time Frame: through study completion, an average of 1 year
days of ovarian stimulation
through study completion, an average of 1 year
Days of progestin use in both treatment groups
Time Frame: through study completion, an average of 1 year
days of progestin use during ovarian stimulation
through study completion, an average of 1 year
Total number of MII oocytes in both treatment groups
Time Frame: 1-2 hours after oocyte retrieval
the number of MII oocytes retrieved that will be assessed after denudation
1-2 hours after oocyte retrieval

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

CRG UZ Brussel

Investigators

  • Study Director: Christophe Blockeel, Prof, MD, Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Belgium

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2023

Primary Completion (Estimated)

September 30, 2024

Study Completion (Estimated)

December 31, 2024

Study Registration Dates

First Submitted

August 25, 2022

First Submitted That Met QC Criteria

August 26, 2022

First Posted (Actual)

August 30, 2022

Study Record Updates

Last Update Posted (Actual)

February 8, 2024

Last Update Submitted That Met QC Criteria

February 7, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CS-10459

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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