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

Endometrial Gene Expression Profiles During Ovarian Stimulation With Recombinant FSH With or Without the Addition of Recombinant LH in Genuine Poor Responders

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.

Study Overview

• Status: Withdrawn
• Conditions: Poor Response to Ovulation Induction
• Intervention / Treatment: Drug: Follitropin alfa; Diagnostic test: Endometrial biopsy; Drug: Lutropin alfa

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.

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 40 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control arm; In the control group, 225 IU of recombinant FSH will be administered in a fixed antagonist protocol.	Drug: Follitropin alfa; recombinant follicle stimulating hormone (FSH); Diagnostic test: Endometrial biopsy; pipelle de cornier biopsy
Experimental: Study arm; In the study group, 225 IU of recombinant FSH plus 112,5 IU of recombinant LH will be administered.	Drug: Follitropin alfa; recombinant follicle stimulating hormone (FSH); Diagnostic test: Endometrial biopsy; pipelle de cornier biopsy; Drug: Lutropin alfa; addition of recombinant luteinizing hormone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
endometrial gene expression	gene expression profile of the endometrium	7 days after finale oocyte maturation trigger

Secondary Outcome Measures

Outcome Measure	Time Frame
cumulus cell gene expression	3-6 months
endometrial histologic analysis based on Noyes' classification system	3-6 months
progesterone level at oocyte triggering	3-6 months
follicular fluid (FF) hormonal analysis	3-6 months
number of preovulatory follicles	3-6 months
number of MII oocytes	3-6 months
number of oocytes fertilized	3-6 months
number of good quality embryos	3-6 months
total dose of gonadotropins administered	3-6 months
duration of stimulation	3-6 months
endometrial thickness at the day of endometrial biopsy	3-6 months
implantation rate	6-12 months
clinical pregnancy rate	6-12 months
live birth rate	20 months

Collaborators and Investigators

• Sponsor: CRG UZ Brussel
• Collaborators: Merck KGaA, Darmstadt, Germany
• Investigators: Principal Investigator: Christophe Blockeel, UZ Brussels

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2023
• Primary Completion (Estimated): August 1, 2023
• Study Completion (Estimated): August 1, 2024

Study Registration Dates

• First Submitted: June 1, 2022
• First Submitted That Met QC Criteria: June 3, 2022
• First Posted (Actual): June 6, 2022

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: IVF; LH supplementation; endometrial gene expression
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Follicle Stimulating Hormone
• Other Study ID Numbers: LHinPOR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No