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

CRG UZ Brussel

Status and phase: Withdrawn; Phase 4

Conditions: Poor Response to Ovulation Induction

Treatments: Drug: Lutropin alfa; Diagnostic Test: Endometrial biopsy; Drug: Follitropin alfa

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05405686

LHinPOR

Details and patient eligibility

About

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.

Full 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.

Sex: Female

Ages: 35 to 40 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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0 participants in 2 patient groups

Control arm

Active Comparator group

Description:

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

Treatment:

Diagnostic Test: Endometrial biopsy

Drug: Follitropin alfa

Study arm

Experimental group

Description:

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

Treatment:

Drug: Lutropin alfa

Diagnostic Test: Endometrial biopsy

Drug: Follitropin alfa