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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

Status
Withdrawn
Phases
Phase 4
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT05405686
Enrollment
0
Registered
2022-06-06
Start date
2023-05-01
Completion date
2024-08-01
Last updated
2024-02-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Poor Response to Ovulation Induction

Keywords

IVF, LH supplementation, endometrial gene expression

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.

Interventions

addition of recombinant luteinizing hormone

recombinant follicle stimulating hormone (FSH)

DIAGNOSTIC_TESTEndometrial biopsy

pipelle de cornier biopsy

Sponsors

Merck KGaA, Darmstadt, Germany
CollaboratorINDUSTRY
CRG UZ Brussel
Lead SponsorOTHER

Study design

Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DIAGNOSTIC
Masking
NONE

Intervention model description

prospective randomized open-label cross-over study

Eligibility

Sex/Gender
FEMALE
Age
35 Years to 40 Years
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
endometrial gene expression7 days after finale oocyte maturation triggergene expression profile of the endometrium

Secondary

MeasureTime frame
endometrial histologic analysis based on Noyes' classification system3-6 months
progesterone level at oocyte triggering3-6 months
follicular fluid (FF) hormonal analysis3-6 months
number of preovulatory follicles3-6 months
number of MII oocytes3-6 months
number of oocytes fertilized3-6 months
cumulus cell gene expression3-6 months
total dose of gonadotropins administered3-6 months
duration of stimulation3-6 months
endometrial thickness at the day of endometrial biopsy3-6 months
implantation rate6-12 months
clinical pregnancy rate6-12 months
live birth rate20 months
number of good quality embryos3-6 months

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026