Effect of LH Supplementation on the Endometrial Gene Expression Profile in Poor Ovarian Responders
- Conditions
- Poor Response to Ovulation Induction
- Interventions
- Registration Number
- NCT05405686
- Lead Sponsor
- CRG UZ Brussel
- 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.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- Female
- Target Recruitment
- Not specified
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Study arm Follitropin alfa In the study group, 225 IU of recombinant FSH plus 112,5 IU of recombinant LH will be administered. Control arm Follitropin alfa In the control group, 225 IU of recombinant FSH will be administered in a fixed antagonist protocol. Study arm Lutropin alfa In the study group, 225 IU of recombinant FSH plus 112,5 IU of recombinant LH will be administered. Control arm Endometrial biopsy In the control group, 225 IU of recombinant FSH will be administered in a fixed antagonist protocol. Study arm Endometrial biopsy In the study group, 225 IU of recombinant FSH plus 112,5 IU of recombinant LH will be administered.
- Primary Outcome Measures
Name Time Method endometrial gene expression 7 days after finale oocyte maturation trigger gene expression profile of the endometrium
- Secondary Outcome Measures
Name Time Method implantation rate 6-12 months live birth rate 20 months number of preovulatory follicles 3-6 months cumulus cell gene expression 3-6 months endometrial histologic analysis based on Noyes' classification system 3-6 months follicular fluid (FF) hormonal analysis 3-6 months number of MII oocytes 3-6 months duration of stimulation 3-6 months clinical pregnancy rate 6-12 months progesterone level at oocyte triggering 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 endometrial thickness at the day of endometrial biopsy 3-6 months