Oral Dydrogesterone (OD) Versus Micronized Vaginal Progesterone (MVP) for Luteal Phase Support (LPS) in IVF/ICSI

CRG UZ Brussel30 enrolled

Overview

Female inability to conceive a child. The purpose of this prospective randomized, double-blinded, double dummy, two-arm cross-over study is to investigate the difference on histological, transcriptional and immunological level in endometrium between 3x10mg Dydrogesterone oral tablets and 3x200 mg Micronized progesterone intravaginal capsules for the luteal support in egg cell donors. Beside that, the pharmacokinetics, the impact on the peripheral immunology (by blood sampling) and the microbiota (by genital swabs) will be investigated.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Infertility, Female Infertility Genital Diseases, Male Genital Diseases, Female Progesterone

Interventions

Dydrogesterone Oral TabletDRUG

Tablet, oral, 10 mg, 3 times daily, starting on the day of oocyte retrieval in the morning and during 8 days

Micronized progesteroneDRUG

Capsule, vaginal, 200 mg, 3 times daily, starting on the day of oocyte retrieval in the morning and during 8 days

Placebo Dydrogesterone oral tabletDRUG

Tablet, indistinguishable from dydrogesterone oral tablet

Placebo Micronized progesteroneDRUG

Capsule, indistinguishable from micronized vaginal progesterone capsules

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 35 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Oocyte donor candidates * Regularly cycling * BMI ≥18 and ≤ 29 kg/m2 * Signed informed consent * Non-smokers. * AMH \<7,53 and \>1,18 ng/mL (90th and 10th percentile for healthy women aged 25-29 according to the used Elecsys® AMH kit by Roche) * PRL, T and TSH within the normal limits for the clinical laboratory, or considered not clinically significant by the investigator within 6 months prior or at screening Exclusion Criteria: * Intra-uterine device * Previous enrollment * Evidence of cardiovascular, respiratory, urogenital, gastrointestinal/hepatic, hematologic/immunologic, HEENT (head, ears, eyes, nose, throat), dermatologic/connective tissue, musculoskeletal, metabolic/nutritional, endocrine, neurologic/psychiatric, allergy, recent major surgery (\< 3 months), or other relevant diseases as revealed by history, physical examination and/or laboratory assessments which could limit participation in or completion of the study * Acute urogenital disease during the course of the study * Known allergic reactions to progesterone / dydrogesterone products (active substance or to any of the excipients) * Intake of any experimental drug or any participation in any other clinical trial within 30 days prior to study start. * Mental disability or any other lack of fitness, in the investigator's opinion, to preclude subjects in or to complete the study. * Current or recent substance abuse, including alcohol and tobacco (patients who stopped tobacco usage at least 3 months prior to screening visit would be allowed) * Refusal or inability to comply with the requirements of the study protocol for any reason, including scheduled clinic visits and laboratory tests. * Known or suspected progestogen dependent neoplasms (e.g. meningioma) * Serum progesterone level \>1.5 ng/mL at ovulation triggering

Outcomes

Primary Outcomes

Molecular endometrial level using illumina RNA-seq

To study the difference of OD versus MVP as LPS after controlled ovarian stimulation (COS) on the molecular endometrial level using Illumina RNA-seq on endometrial derived single cell suspensions

Time frame: On the eight day (at 8am) of LPS intake

Molecular endometrial level using immunohistochemistry

To study the difference of OD versus MVP as LPS after controlled ovarian stimulation (COS) on the molecular endometrial level using immunohistochemistry on endometrial derived single cell suspensions

Time frame: On the eight day (at 8am) of LPS intake

Molecular endometrial level using flow cytometry

To study the difference of OD versus MVP as LPS after controlled ovarian stimulation (COS) on the molecular endometrial level using flow cytometry on endometrial derived single cell suspensions

Time frame: On the eight day (at 8am) of LPS intake