Endometrial Gene Expression Profiles During Ovarian Stimulation With Recombinant FSH With or Without the Addition of Recombinant LH in Genuine Poor Responders
Overview
- Phase
- Phase 4
- Intervention
- Follitropin alfa
- Conditions
- Poor Response to Ovulation Induction
- Sponsor
- CRG UZ Brussel
- Primary Endpoint
- endometrial gene expression
- Status
- Withdrawn
- Last Updated
- 2 years ago
Overview
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.
Investigators
Liese Boudry
Principal investigator
CRG UZ Brussel
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
Arms & Interventions
Control arm
In the control group, 225 IU of recombinant FSH will be administered in a fixed antagonist protocol.
Intervention: Follitropin alfa
Control arm
In the control group, 225 IU of recombinant FSH will be administered in a fixed antagonist protocol.
Intervention: Endometrial biopsy
Study arm
In the study group, 225 IU of recombinant FSH plus 112,5 IU of recombinant LH will be administered.
Intervention: Lutropin alfa
Study arm
In the study group, 225 IU of recombinant FSH plus 112,5 IU of recombinant LH will be administered.
Intervention: Follitropin alfa
Study arm
In the study group, 225 IU of recombinant FSH plus 112,5 IU of recombinant LH will be administered.
Intervention: Endometrial biopsy
Outcomes
Primary Outcomes
endometrial gene expression
Time Frame: 7 days after finale oocyte maturation trigger
gene expression profile of the endometrium
Secondary Outcomes
- 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)