hCG Priming in Women With Low Ovarian Reserve
- Conditions
- Infertility, FemaleOvarian ReserveIn Vitro Fertilization
- Interventions
- Registration Number
- NCT04643925
- Lead Sponsor
- Rigshospitalet, Denmark
- Brief Summary
The aim of this trial is to examine the possible effects of hCG administration for eight weeks prior to IVF/ICSI in women with low ovarian reserve. Primary outcome is the proportion of the antral follicle count that reach the pre-ovulatory stage.
- Detailed Description
One of the fundamental goals in In Vitro Fertilisation (IVF) is obtaining a high number of good quality oocytes, in order to select and transfer embryos with the highest possible implantation potential thereby optimizing the chance of a pregnancy and ultimately a live birth. This is done by applying an individualized controlled ovarian stimulation (iCOS) protocol, primarily based on ovarian reserve markers like antral follicle count (AFC) and Anti-Müllerian hormone (AMH), when deciding the follicle stimulating hormone (FSH) stimulation dose. Certain patients, the so called "poor ovarian responders' (PORs), pose a clinical challenge because they have a poor ovarian reserve and develop a limited number of pre-ovulatory follicles in respond to ovarian stimulation despite high FSH stimulation doses, thus experiencing reduced live birth rates.
The aim of the present study is to examine the possible effects of long-term LH activity by the administration of hCG for eight weeks in between two identical IVF/ICSI cycles and compare cycle characteristics and outcome. The primary outcome is the follicular output rate (FORT) which reflects the proportion of antral follicles at the start of controlled ovarian stimulation that reaches the pre-ovulatory state. Secondary outcomes include amongst others AMH and antral follicle count at baseline (cd 2-3), number of pre-ovulatory follicles, oocytes retrieved, and embryos developed.
We hypothesize that eight weeks of androgen priming by hCG increases the proportion of antral follicles that reaches the pre-ovulatory state during controlled ovarian stimulation for IVF/ICSI in women with poor ovarian reserve.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 20
- Regular menstrual cycle (23-35 days)
- 1.-5. IVF/ICSI cycle at inclusion
- AMH < 6.29 pmol/L (Elecsys® AMH assay)
- Uterine malformations or hydrosalpinx
- Submucosal uterine myomas
- Uterine polyps
- Allergy to standard IVF/ICSI medication
- Endometriosis stage III-IV
- Severe comorbidity
- Preimplantation genetic testing
- Testicular sperm aspiration/extraction
- Tumors in the hypothalamus or pituitary gland
- Active thromboembolic disease
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description hCG priming Ovitrelle Control cycle: A standard IVF/ICSI cycle in the fixed GnRH-antagonist protocol using a daily dose of 300 IU rFSH initiated from cd 2-3 and the GnRH antagonist (Fyremadel 0.25 mg) from stimulation day 5-6 followed by blastocyst culture and a freeze-all strategy. Study cycle: hCG priming by Ovitrelle 260 IE once daily for 8 weeks followed by a standard IVF/ICSI cycle in the fixed GnRH-antagonist protocol using a daily dose of 300 IU rFSH initiated from cd 2-3 and the GnRH antagonist (Fyremadel 0.25 mg) from stimulation day 5-6 followed by a single blastocyst transfer at day 5.
- Primary Outcome Measures
Name Time Method Follicular output rate Through study completion, an average of 5 months Follicular Output Rate (FORT: pre-ovulatory follicle count (\>16 mm) at hCG trigger day/antral follicle count at baseline (2-10 mm).
- Secondary Outcome Measures
Name Time Method Antral follicle count (≤10 mm) at baseline (cd 2-3) Through study completion, an average of 5 months Number of oocytes retrieved Through study completion, an average of 5 months Number of good quality day 2 embryos Through study completion, an average of 5 months Serum and follicular fluid hormonal levels (AMH, estradiol, progesterone, 17-OH-progesterone, hCG, LH, FSH, testosterone, androstenedione and Inhibin B Through study completion, an average of 5 months Number of pre-ovulatory follicles >16 mm on trigger day Through study completion, an average of 5 months Number of blastocysts (Gardner score 1-6) Through study completion, an average of 5 months Number of good quality blastocysts day 5/6 Through study completion, an average of 5 months Granulosa/cumulus cell FSH and LH receptor expression 1 year AMH at baseline (CD 2-3) Through study completion, an average of 5 months Number of cleaved day 2 embryos Through study completion, an average of 5 months Number of top quality day 2 embryos Through study completion, an average of 5 months Number of vitrified embryos/blastocysts Through study completion, an average of 5 months Total number of transferred or vitrified blastocysts Through study completion, an average of 5 months Cumulus/corona gene expression analysis by quantitative PCR using three predictive genes (EFNB2, SASH1, CAMK1D). 1 year Number of follicles >14 mm and >12 mm, >10 mm and ≤10 mm on hCG trigger day Through study completion, an average of 5 months Number of mature (MII) oocytes Through study completion, an average of 5 months Number of fertilized eggs (2pn) Through study completion, an average of 5 months The number of cancelled cycles and the reasons for cancellation in the two groups Through study completion, an average of 5 months
Trial Locations
- Locations (1)
Rigshospitalet
🇩🇰København Ø, Denmark