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

The Research on the Role of Human Chorionic Gonadotropin (HCG) Activation in Vivo on the Dormant Follicles in Patients With Premature Ovarian Insufficiency (POI).

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Premature Ovarian Insufficiency
• Intervention / Treatment: Drug: human chorionic gonadotropin

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 Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Xiao Chen, Master; Phone Number: 13868903230; Email: 30395478@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

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."

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Expectant treatment; The POl patients undergo transvaginal ultrasound to observe follicular growth every 1-2 weeks, with a monitoring period of 3 months.
Other: In vitro fertilization - Embryo transfer; Embryo vitrification and freezing were performed after fertilization of oocytes.	Drug: human chorionic gonadotropin; The POI patients receive a single intramuscular injection of 10,000 units of human chorionic gonadotropin.; Other Names: HCG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
focilles	Bilateral ovarian follicles were monitored by ultrasound	Interval of 1-2 weeks after HCG injection

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: The Fourth Affiliated Hospital of Zhejiang University School of Medicine
• Investigators: Principal Investigator: Xiao Chen, Master, The Fourth Affiliated Hospital Zhejiang University School of Medicine

Publications and helpful links

General Publications

• Xiao Y, Peng X, Peng Y, Zhang C, Liu W, Yang W, Dou X, Jiang Y, Wang Y, Yang S, Xiang W, Wu T, Li J. Macrophage-derived extracellular vesicles regulate follicular activation and improve ovarian function in old mice by modulating local environment. Clin Transl Med. 2022 Oct;12(10):e1071. doi: 10.1002/ctm2.1071.
• Cha KY, Chian RC. Maturation in vitro of immature human oocytes for clinical use. Hum Reprod Update. 1998 Mar-Apr;4(2):103-20. doi: 10.1093/humupd/4.2.103.
• Chian RC, Li JH, Lim JH, Yoshida H. IVM of human immature oocytes for infertility treatment and fertility preservation. Reprod Med Biol. 2023 Jul 11;22(1):e12524. doi: 10.1002/rmb2.12524. eCollection 2023 Jan-Dec.

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2025
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): August 31, 2029

Study Registration Dates

• First Submitted: December 24, 2024
• First Submitted That Met QC Criteria: December 24, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 11, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: HCG; POI; dormant follicles
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Genital Diseases, Female; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Premature Birth; Menopause, Premature; Primary Ovarian Insufficiency; Physiological Effects of Drugs; Reproductive Control Agents; Chorionic Gonadotropin
• Other Study ID Numbers: KY-2024-242

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No