Clinical trial NCT04643925: hCG Priming in Women With Low Ovarian Reserve
Official title: Eight Weeks of Androgen Priming by hCG Before IVF/ICSI in Women With Low Ovarian Reserve
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Infertility, Female
Ovarian Reserve
In Vitro Fertilization
Keywords: IVF
Poor ovarian reserve
Controlled ovarian stimulation
Ovarian stimulation
hCG priming
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2020-11-25
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Women will undergo two identical consecutive IVF/ICSI treatments: a Control cycle including blastocyst culture and freeze-all and a subsequent identical Study cycle, separated by eight weeks of androgen priming by daily hCG-injections. Both IVF/ICSI cycles are performed 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.
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* Regular menstrual cycle (23-35 days)
* 1.-5. IVF/ICSI cycle at inclusion
* AMH \< 6.29 pmol/L (Elecsys® AMH assay)

Exclusion Criteria:

* 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

Primary outcomes:
measure: Follicular output rate
timeFrame: Through study completion, an average of 5 months
Secondary outcomes:
measure: Antral follicle count (≤10 mm) at baseline (cd 2-3)
timeFrame: Through study completion, an average of 5 months
measure: AMH at baseline (CD 2-3)
timeFrame: Through study completion, an average of 5 months
measure: Number of pre-ovulatory follicles >16 mm on trigger day
timeFrame: Through study completion, an average of 5 months
measure: Number of follicles >14 mm and >12 mm, >10 mm and ≤10 mm on hCG trigger day
timeFrame: Through study completion, an average of 5 months
measure: Number of oocytes retrieved
timeFrame: Through study completion, an average of 5 months
measure: Number of mature (MII) oocytes
timeFrame: Through study completion, an average of 5 months
measure: Number of fertilized eggs (2pn)
timeFrame: Through study completion, an average of 5 months
measure: Number of cleaved day 2 embryos
timeFrame: Through study completion, an average of 5 months
measure: Number of good quality day 2 embryos
timeFrame: Through study completion, an average of 5 months
measure: Number of top quality day 2 embryos
timeFrame: Through study completion, an average of 5 months
measure: Number of blastocysts (Gardner score 1-6)
timeFrame: Through study completion, an average of 5 months
measure: Number of good quality blastocysts day 5/6
timeFrame: Through study completion, an average of 5 months
measure: Number of vitrified embryos/blastocysts
timeFrame: Through study completion, an average of 5 months
measure: Total number of transferred or vitrified blastocysts
timeFrame: Through study completion, an average of 5 months
measure: The number of cancelled cycles and the reasons for cancellation in the two groups
timeFrame: Through study completion, an average of 5 months
measure: Serum and follicular fluid hormonal levels (AMH, estradiol, progesterone, 17-OH-progesterone, hCG, LH, FSH, testosterone, androstenedione and Inhibin B
timeFrame: Through study completion, an average of 5 months
measure: Granulosa/cumulus cell FSH and LH receptor expression
timeFrame: 1 year
measure: Cumulus/corona gene expression analysis by quantitative PCR using three predictive genes (EFNB2, SASH1, CAMK1D).
timeFrame: 1 year
Other outcomes:
Locations:
city: København Ø
country: Denmark
facility: Rigshospitalet
Study officials:
affiliation: The Fertility Department, Rigshospitalet
name: Anja B Pinborg, MD
role: STUDY_DIRECTOR
References: