Clinical trial NCT05405686: Effect of LH Supplementation on the Endometrial Gene Expression Profile in Poor Ovarian Responders
Official title: Endometrial Gene Expression Profiles During Ovarian Stimulation With Recombinant FSH With or Without the Addition of Recombinant LH in Genuine Poor Responders
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Poor Response to Ovulation Induction
Keywords: IVF
LH supplementation
endometrial gene expression
Lead sponsor: CRG UZ Brussel
Sponsor class: OTHER
Collaborators: name: Merck KGaA, Darmstadt, Germany
First posted: 2022-06-06
Enrollment: 0
Sex: FEMALE
Minimum age (years): 35
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: prospective randomized open-label cross-over study
Primary purpose: DIAGNOSTIC

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.

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

Primary outcomes:
measure: endometrial gene expression
timeFrame: 7 days after finale oocyte maturation trigger
Secondary outcomes:
measure: cumulus cell gene expression
timeFrame: 3-6 months
measure: endometrial histologic analysis based on Noyes' classification system
timeFrame: 3-6 months
measure: progesterone level at oocyte triggering
timeFrame: 3-6 months
measure: follicular fluid (FF) hormonal analysis
timeFrame: 3-6 months
measure: number of preovulatory follicles
timeFrame: 3-6 months
measure: number of MII oocytes
timeFrame: 3-6 months
measure: number of oocytes fertilized
timeFrame: 3-6 months
measure: number of good quality embryos
timeFrame: 3-6 months
measure: total dose of gonadotropins administered
timeFrame: 3-6 months
measure: duration of stimulation
timeFrame: 3-6 months
measure: endometrial thickness at the day of endometrial biopsy
timeFrame: 3-6 months
measure: implantation rate
timeFrame: 6-12 months
measure: clinical pregnancy rate
timeFrame: 6-12 months
measure: live birth rate
timeFrame: 20 months
Other outcomes:
Locations:
Study officials:
affiliation: UZ Brussels
name: Christophe Blockeel
role: PRINCIPAL_INVESTIGATOR
References: