Effect of LH Supplementation on the Endometrial Gene Expression Profile in Poor Ovarian Responders

NCT ID: NCT05405686

Last Updated: 2024-02-28

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE4
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-05-01
• Study Completion Date: 2024-08-01

Brief Summary

This is a prospective randomized open-label cross-over study. Poor responder patients will undergo two ovarian stimulation cycles. One with recombinant follicle stimulation hormone (FSH), and an other stimulation with recombinant FSH and recombinant luteinizing hormone (LH). In both groups, a freeze-all strategy will be applied and an endometrial biopsy will be taken 7 days after final oocyte maturation trigger. Endometrial gene expression analysis will be performed on both biopsies. After completion of both treatment cycles, a frozen embryo transfer of a single embryo will be performed.

Detailed Description

This is a prospective randomized open-label cross-over study, in which patients will be randomized to either start in the control group or in the study group. Participants will undergo both treatments with an interval of minimum 1 and maximum 6 months. In both treatment arms, ovarian stimulation will be started at day 2/3 of the menstrual cycle. In the control group, 225 IU of recombinant FSH will be administered in a fixed antagonist protocol. In the study group, 225 IU of recombinant FSH plus 112,5 IU of recombinant LH will be administered. Cycle monitoring will be performed through serum estradiol (E2), progesterone (P), and luteinizing hormone (LH) assessments, combined with serial ultrasound examinations. Both groups will undergo dual triggering with gonadotropin releasing hormone agonist (GnRHa) 0,2ml and human chorionic gonadotrophin (hCG) 6500IU if one or more follicles of ≥ 17 mm are observed. The oocyte retrieval (OR) will be performed between 34 and 36 hours after final oocyte maturation trigger. At each OR, follicles will be individually meas-ured, aspirated and searched for the presence of cumulus oocyte complexes (COC). Metaphase II (MII) oocytes will then be injected to standard intra-cytoplasmatic sperm injection (ICSI) procedures. In both groups, a freeze-all strategy will be applied. An endometrial biopsy (Pipelle de Cornier ®) will be taken 7 days after final oocyte maturation trigger. After completion of both treatment cycles, a frozen embryo transfer of a single embryo will be performed.

Conditions

Poor Response to Ovulation Induction

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Control arm

In the control group, 225 IU of recombinant FSH will be administered in a fixed antagonist protocol.

Group Type: ACTIVE_COMPARATOR

Follitropin alfa

Intervention Type: DRUG

recombinant follicle stimulating hormone (FSH)

Endometrial biopsy

Intervention Type: DIAGNOSTIC_TEST

pipelle de cornier biopsy

Study arm

In the study group, 225 IU of recombinant FSH plus 112,5 IU of recombinant LH will be administered.

Group Type: EXPERIMENTAL

Lutropin alfa

Intervention Type: DRUG

addition of recombinant luteinizing hormone

Follitropin alfa

Intervention Type: DRUG

recombinant follicle stimulating hormone (FSH)

Endometrial biopsy

Intervention Type: DIAGNOSTIC_TEST

pipelle de cornier biopsy

Interventions

Lutropin alfa

addition of recombinant luteinizing hormone

Intervention Type: DRUG

Follitropin alfa

recombinant follicle stimulating hormone (FSH)

Intervention Type: DRUG

Endometrial biopsy

pipelle de cornier biopsy

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• Age 35-40 years
• Undergoing IVF/ICSI
• BMI ≥ 19 and ≤ 30
• AMH <1.2 ng/mL
• Previous conventional ovarian stimulation (OS) with < 4 metaphase II (MII) oocytes
• Regular menstrual cycle (26-35 days)
• Non-smokers
• Acceptance to do 2 consecutive ovarian stimulation cycles (between 1-6 months)
• Signed informed consent

Exclusion Criteria

• Endometriosis > rAFS grade II
• Testicular sperm extraction
• Recurrent miscarriage (>2 previous miscarriages)
• Ovarian stimulation for pre-implantation genetic testing (PGT-A/M)
• Medical/social oocyte vitrification
• In vitro maturation (IVM)
• Untreated auto-immune, endocrine or metabolic disorders
• Asherman's syndrome

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: collaborator

CRG UZ Brussel

OTHER

Sponsor Role: lead

Responsible Party

Liese Boudry

Principal investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Christophe Blockeel

Role: PRINCIPAL_INVESTIGATOR

UZ Brussels

Other Identifiers

LHinPOR

Identifier Type: -

Identifier Source: org_study_id