The Study of Human Chorionic Gonadotropin (HCG) Activating the Dormant Follicles .

Phase 1

Not yet recruiting

• Conditions: Premature Ovarian Insufficiency
• Interventions: Drug: human chorionic gonadotropin

• Registration Number: NCT06754332
• Lead Sponsor: The Fourth Affiliated Hospital of Zhejiang University School of Medicine

Brief Summary

This project aims to activate dormant follicles in patients with premature ovarian insufficiency by injecting human chorionic gonadotropin (hCG) to explore the feasibility of a treatment plan that stimulates the growth of dormant follicles, not visible to the naked eye, to antral follicles visible under ultrasound, without visible follicle growth. The project also seeks to enable patients to conceive offspring carrying their own genetic material through in vitro fertilization (IVF) technology.

Detailed Description

Inclusion Criteria:

1. Females under 40 years of age with amenorrhea or oligomenorrhea for at least four months, and elevated follicle-stimulating hormone (FSH) levels \> 25 IU/l on two separate occasions (with a 4-week interval);

2. Ultrasound (B-mode) indicating no antral follicle development in both ovaries for at least 3 months prior to study participation;

3. Those who agree to participate in this study and voluntarily sign the informed consent form.

Exclusion Criteria:

1. Individuals over 40 years of age, or under 40 years of age with regular menstruation, normal ovulation, amenorrhea or oligomenorrhea for less than 4 months, and elevated follicle-stimulating hormone (FSH) levels \< 25 IU/l on two or more separate occasions (with a 4-week interval);

2. Those with contraindications to the use of injectable human chorionic gonadotropin (HCG);

3. Those with asthma, epilepsy, heart disease, migraines, renal impairment, hypertension, or other diseases;

4. Patients deemed by the researcher as otherwise unsuitable for participation in this study.

Withdrawal criteria:

1. Subjects who cannot follow up as scheduled or have poor compliance with the experimental treatment;

2. Significant safety events occur, and the investigator deems it necessary for the subject to withdraw.Study Method: A total of 60 patients with premature ovarian insufficiency who are planned to undergo in vitro fertilization (IVF) treatment at our hospital were included. Patients were divided into two groups based on their consent to receive HCG injection: the control group (those who did not agree to HCG injection) and the HCG group (those who agreed to HCG injection).

The HCG group received a single intramuscular injection of 10,000 units of HCG. One to two weeks after the injection, transvaginal ultrasound was performed to observe follicular growth, with a monitoring period of 3 months (based on the fact that it takes humans 85 days to develop from a secondary follicle to a mature follicle). If no follicular growth was observed within 3 months, the observation was abandoned. If follicular growth was observed, gonadotropins were used or not used based on follicular development to promote growth or antagonists were used to prevent premature follicular release. When the follicle reached ≥18mm and estradiol reached ≥150pg/ml, recombinant human chorionic gonadotropin (rhCG) 250ug and triptorelin 0.1mg were co-administered to trigger ovulation. Oocyte retrieval was performed 36 hours after triggering. If embryos were obtained, they were cryopreserved for later frozen-thawed embryo transfer (FET) assistance in conception.

The control group underwent transvaginal ultrasound to observe follicular growth every 1-2 weeks, with a monitoring period of 3 months. If no follicular growth was observed within 3 months, the observation was abandoned. If follicular growth was observed, gonadotropins were used or not used based on follicular development to promote growth or antagonists were used to prevent premature follicular release. When the follicle reached ≥18mm and estradiol reached ≥150pg/ml, rhCG 250ug and triptorelin 0.1mg were co-administered to trigger ovulation. Oocyte retrieval was performed 36 hours after triggering. If embryos were obtained, they were cryopreserved for later FET assistance in conception.

Follow-up Plan: ① Within 3 months after HCG administration, patients return to the center every 1-2 weeks for ultrasound and hormone testing, and return to the hospital promptly if any discomfort occurs during this period. ② After embryo transfer and pregnancy, follow-up on the outcome of childbirth, and follow-up on the offspring until one year after birth.

Study Timeline

• Study First Submitted: 2024-12-24
• Study First Submitted QC: 2024-12-24
• Study First Posted: 2024-12-31
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-11
• Last Update Posted: 2025-03-12
• Study Start: 2025-04-01
• Primary Completion: 2028-04-01
• Study Completion: 2029-08-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 60

Inclusion Criteria

1. Females under 40 years of age with amenorrhea or oligomenorrhea for at least four months, and elevated follicle-stimulating hormone (FSH) levels > 25 IU/l on two separate occasions (with a 4-week interval);
2. Ultrasound (B-mode) indicating no antral follicle development in both ovaries for at least 3 months prior to study participation;
3. Those who agree to participate in this study and voluntarily sign the informed consent form.

Exclusion Criteria

1. Individuals over 40 years of age, or under 40 years of age with regular menstruation, normal ovulation, amenorrhea or oligomenorrhea for less than 4 months, and elevated follicle-stimulating hormone (FSH) levels < 25 IU/l on two or more separate occasions (with a 4-week interval);
2. Those with contraindications to the use of injectable human chorionic gonadotropin (HCG);
3. Those with asthma, epilepsy, heart disease, migraines, renal impairment, hypertension, or other diseases;
4. Patients deemed by the researcher as otherwise unsuitable for participation in this study."

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
In vitro fertilization - Embryo transfer	human chorionic gonadotropin	Embryo vitrification and freezing were performed after fertilization of oocytes.

Primary Outcome Measures

Name	Time	Method
focilles	Interval of 1-2 weeks after HCG injection	Bilateral ovarian follicles were monitored by ultrasound

Secondary Outcome Measures

Name	Time	Method
sex hormone	Interval of 1-2 weeks after HCG injection	chemiluminescence method
Oocyte	After the egg retrieval operation, the eggs are picked up and observed	Stereo microscope
Embryo	3-5 days after In vitro fertilization	Stereo microscope
Pregnancy outcome	One month after embryo transfer	Ultrasonic
The health of the offspring	One year after birth	Telephone follow-up