hCG Priming in Women With Low Ovarian Reserve

Infertility, Female Clinical Trial

Official title:

Eight Weeks of Androgen Priming by hCG Before IVF/ICSI in Women With Low Ovarian Reserve

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04643925
• Other study ID #: 73908
• Status: Completed
• Phase: Phase 4
• Start date: December 27, 2020
• Est. completion date: August 31, 2021

Study information

• Verified date: August 2022
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: August 31, 2021
• Est. primary completion date: August 31, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• In Vitro Fertilization
• Infertility
• Infertility, Female
• Ovarian Reserve

Intervention

Drug:
• Ovitrelle
Ovitrelle 260 IE once daily for 8 weeks prior to IVF/ICSI

Locations

Country	Name	City	State
Denmark	Rigshospitalet	København Ø

Sponsors (1)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Follicular output rate	Follicular Output Rate (FORT: pre-ovulatory follicle count (>16 mm) at hCG trigger day/antral follicle count at baseline (2-10 mm).	Through study completion, an average of 5 months
Secondary	Antral follicle count (=10 mm) at baseline (cd 2-3)		Through study completion, an average of 5 months
Secondary	AMH at baseline (CD 2-3)		Through study completion, an average of 5 months
Secondary	Number of pre-ovulatory follicles >16 mm on trigger day		Through study completion, an average of 5 months
Secondary	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
Secondary	Number of oocytes retrieved		Through study completion, an average of 5 months
Secondary	Number of mature (MII) oocytes		Through study completion, an average of 5 months
Secondary	Number of fertilized eggs (2pn)		Through study completion, an average of 5 months
Secondary	Number of cleaved day 2 embryos		Through study completion, an average of 5 months
Secondary	Number of good quality day 2 embryos		Through study completion, an average of 5 months
Secondary	Number of top quality day 2 embryos		Through study completion, an average of 5 months
Secondary	Number of blastocysts (Gardner score 1-6)		Through study completion, an average of 5 months
Secondary	Number of good quality blastocysts day 5/6		Through study completion, an average of 5 months
Secondary	Number of vitrified embryos/blastocysts		Through study completion, an average of 5 months
Secondary	Total number of transferred or vitrified blastocysts		Through study completion, an average of 5 months
Secondary	The number of cancelled cycles and the reasons for cancellation in the two groups		Through study completion, an average of 5 months
Secondary	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
Secondary	Granulosa/cumulus cell FSH and LH receptor expression		1 year
Secondary	Cumulus/corona gene expression analysis by quantitative PCR using three predictive genes (EFNB2, SASH1, CAMK1D).		1 year