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

Sponsor

CRG UZ Brussel (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05405686

Collaborator

Merck KGaA, Darmstadt, Germany (Industry)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Poor Response to Ovulation Induction	Drug: Lutropin alfa Drug: Follitropin alfa Diagnostic Test: Endometrial biopsy	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Non-Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

prospective randomized open-label cross-over studyprospective randomized open-label cross-over study

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

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

Anticipated Study Start Date :

Sep 1, 2022

Anticipated Primary Completion Date :

Aug 1, 2023

Anticipated Study Completion Date :

Aug 1, 2024

Arms and Interventions

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: Lutropin alfa addition of recombinant luteinizing hormone Drug: Follitropin alfa recombinant follicle stimulating hormone (FSH) Diagnostic Test: Endometrial biopsy pipelle de cornier biopsy

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: Lutropin alfa

addition of recombinant luteinizing hormone

Drug: Follitropin alfa

recombinant follicle stimulating hormone (FSH)

Diagnostic Test: Endometrial biopsy

pipelle de cornier biopsy

Outcome Measures

Primary Outcome Measures

endometrial gene expression [7 days after finale oocyte maturation trigger]
gene expression profile of the endometrium

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

35 Years to 40 Years

Sexes Eligible for Study:

Female

Accepts 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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

CRG UZ Brussel
Merck KGaA, Darmstadt, Germany

Investigators

Principal Investigator: Christophe Blockeel, UZ Brussels

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Liese Boudry, Principal investigator, CRG UZ Brussel

ClinicalTrials.gov Identifier:

NCT05405686

Other Study ID Numbers:

LHinPOR

First Posted:

Jun 6, 2022

Last Update Posted:

Jun 9, 2022

Last Verified:

Jun 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Keywords provided by Liese Boudry, Principal investigator, CRG UZ Brussel

IVF

LH supplementation

endometrial gene expression

Additional relevant MeSH terms:

Follicle Stimulating Hormone

Study Results

No Results Posted as of Jun 9, 2022