Pulsatile Gonadotropin-releasing Hormone for Infertility in Non-obese Patients With Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) patients are often accompanied by infertility. Non-obese PCOS infertility is more difficult to treat than obese PCOS. The study included non-obese PCOS patients who had not recovered from regular menstruation after six months of metformin treatment. Half of the patients were treated with clomiphene for ovulation induction and half with GnRH pulse therapy.

Study Overview

• Status: Unknown
• Conditions: Polycystic Ovary Syndrome; Infertility; Ovulation Disorder
• Intervention / Treatment: Drug: Gonadorelin; Drug: Clomiphene

Detailed Description

To investigate whether GnRH pulse therapy of non-obese PCOS women can improve ovulation rate.The investigators plan to recruit non-obese PCOS women with abnormal GnRH pulse mode not effective of metformin treatment at childbearing age. By using GnRH pulse therapy and Clomiphene therapy. the investigators will intervent the participants for 3 months and to compare outcome in each group.

• Study Type: Interventional
• Enrollment (Anticipated): 78
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Tao Tao, MD; Phone Number: +86-13817701776; Email: taotaozhen@hotmail.com

Study Locations

• China
  • Shanghai, China, 200127
    • Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine
    • Contact: Tao Tao, Doctor; Phone Number: +86-13817701776; Email: taotaozhen@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 24 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. PCOS of childbearing age (24-45 years old);
2. non-obesity;
3. After 6 months of metformin (at least 1000-1500 mg/d) intervention, the normal menstrual cycle was still not restored.
4. No drug intervention except metformin was used in last 3 monthes:
5. There is a pregnancy plan within 1 years.
6. The pregnancy test was negative.
7. Heart and liver function is normal, thyroid function is normal, adrenal function is normal.
8. The GnRH stimulation test confirmed that the pituitary and ovarian reserve function was good.
9. Chromosome examination is normal.
10. Did not take part in other clinical trials.

Exclusion Criteria:

1. PCOS was not diagnosed.
2. Severe liver and kidney dysfunction (ALT is 2.5 times greater than normal upper limit, or Cr > 132 umol/l, or eGFR < 60 mL/min/1.73 m2), thyroid dysfunction, adrenal dysfunction, psychosis, severe infection, severe anemia, neutropenia;
3. Other serious organic heart diseases, such as congenital heart disease, rheumatic heart disease, hypertrophic or dilated cardiomyopathy, NYHA cardiac function grade (> III);
4. Kallmann syndrome, secondary hypogonadotropic hypogonadism, acquired central nervous system diseases, infertility caused by hypothalamic amenorrhea and other secondary infertility;
5. Has a history of abuse of active substances, including alcohol and a history of alcohol related diseases in the past 2 years.
6. Previous history of central nervous system and gonad-related surgery, or other central nervous system and gonad-related surgery (such as central nervous system tumor resection, ovarian chocolate cyst resection) within one year, or other non-central nervous system and gonad surgery within six months;
7. In the past five years, there have been organ system tumors (except for local cutaneous basal cell carcinomas) that have been treated or not treated, regardless of whether there is evidence of local recurrence or metastasis;
8. Hypoglycemic drugs, contraceptives (Dain, Marvelon), ovulation-promoting drugs (clomiphene, letrozole), emergency contraceptives and sex hormone drugs have been or are being used to adjust menstrual cycle and promote ovulation except metformin.
9. Pregnancy;
10. GnRH stimulation test confirmed pituitary and ovarian reserve dysfunction.
11. Abnormal chromosome detection.
12. Patients who are allergic to drugs with similar chemical structure.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pulsatile Gonadotropin-releasing Hormone; Drug: Gonadorelin. Use Gonadorelin for 3 months to treat PCOS. The pulse was administered with a hormone pump, once every 90 min, and 10ug per pulse.	Drug: Gonadorelin; Drug: Gonadotropin-releasing Hormone. Generic name: Gonadorelin. Dosage form: 600ug. Dosage: 10ug/puls. Frequency: every 90 min. Duration: 3 months
Experimental: Clomiphene; Use Clomiphene for 3 months to treat PCOS	Drug: Clomiphene; Drug: Clomiphene. Generic name: Clomiphene. Dosage form: 50mg. Dosage: 50mg. Frequency: once a day. Duration: 3 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with ovulation recovery (according to basal body temperature, progesterone levels on cycle day 21, or ultrasonography)	Number of participants with ovulation recovery (according to basal body temperature, progesterone levels on cycle day 21, or ultrasonography) after use of drugs	up to 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0. Evaluation of efficacy and safety of short-term GnRH pulse therapy for non obese PCOS	up to 12 weeks

Collaborators and Investigators

• Sponsor: RenJi Hospital
• Investigators: Principal Investigator: TAO TAO, DM, RenJi hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2019
• Primary Completion (Anticipated): December 30, 2020
• Study Completion (Anticipated): December 30, 2021

Study Registration Dates

• First Submitted: May 30, 2019
• First Submitted That Met QC Criteria: June 15, 2019
• First Posted (Actual): June 18, 2019

Study Record Updates

• Last Update Posted (Actual): June 18, 2019
• Last Update Submitted That Met QC Criteria: June 15, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Endocrine System Diseases; Disease; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Polycystic Ovary Syndrome; Syndrome; Infertility; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Estrogen Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Clomiphene; Prolactin Release-Inhibiting Factors
• Other Study ID Numbers: 18411968700

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