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.
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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
addition of recombinant luteinizing hormone
recombinant follicle stimulating hormone (FSH)
pipelle de cornier biopsy
endometrial gene expression
gene expression profile of the endometrium
Time frame: 7 days after finale oocyte maturation trigger
cumulus cell gene expression
Time frame: 3-6 months
endometrial histologic analysis based on Noyes' classification system
Time frame: 3-6 months
progesterone level at oocyte triggering
Time frame: 3-6 months
follicular fluid (FF) hormonal analysis
Time frame: 3-6 months
number of preovulatory follicles
Time frame: 3-6 months
number of MII oocytes
Time frame: 3-6 months
number of oocytes fertilized
Time frame: 3-6 months
number of good quality embryos
Time frame: 3-6 months
total dose of gonadotropins administered
Time frame: 3-6 months
duration of stimulation
Time frame: 3-6 months
endometrial thickness at the day of endometrial biopsy
Time frame: 3-6 months
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implantation rate
Time frame: 6-12 months
clinical pregnancy rate
Time frame: 6-12 months
live birth rate
Time frame: 20 months