An Open Labeled RCT on the Effect of Additional hCG Injection for LPS on Pregnancy Outcomes in IHH Patients (LPS-IHH)

An Open-labeled Prospective Randomized Controlled Trial on the Effect of Different Regimens for Luteal Phase Support on Pregnancy Outcomes in Patients With Idiopathic Hypogonadotropic Hypogonadism

Luteal phase deficiency (LPD) accounts for most failures of assistant artificial reproduction (ART) and early pregnancy loss for patients with idiopathic hypogonadotropic hypogonadism (IHH). Luteal phase support (LPS) is one of the indispensable interventions in ART treatments for IHH patients, which includes progestin, estrogen, human chorionic gonadotropin (hCG), and GnRH agonists (GnRHa). We aim to verify additional hCG injection 48 hours following routine hCG trigger and ovulation for LPS on the basis of supplementation of estrogen and dydrogesterone could improve clinical pregnancy rate, cumulative pregnancy rate, live birth rate and the prevalence of early pregnancy loss and ovarian hyperstimulation syndrome (OHSS) by an open labeled, prospective, and randomized clinical trial (RCT) in IHH patients in a single center.

Study Overview

• Status: Recruiting
• Conditions: Idiopathic Hypogonadotropic Hypogonadism; Luteal Phase Support; Luteal Phase Deficiency
• Intervention / Treatment: Drug: Additional hCG injection; Drug: estrogen and dydrogesterone

Detailed Description

Idiopathic hypogonadotropic hypogonadism (IHH) is a congenital disease caused by a variety of gene variants leading to dysfunction in the secretion of hypothalamic gonadotropin-releasing hormones (GnRHs), with a prevalence of 1:125 000 in females. Girls with IHH often suffer from lack of puberty onset, amenorrhea and infertility, complicated with psychological problems such as depression and anxiety, due to delayed diagnosis and inappropriate treatment. Luteal phase deficiency (LPD) accounts for most failures of assistant artificial reproduction (ART) and early pregnancy loss for IHH patients. We have reported a severe LPD during the early trimester in a case with secondary HH following craniopharyngioma resection and speculated similar LPD happen in IHH patients complicated with low clinical pregnancy rate and live birth rate. Therefore, luteal phase support (LPS) is one of the indispensable interventions in ART treatments for IHH patients, which includes progestin, estrogen, human chorionic gonadotropin (hCG), and GnRH agonists (GnRHa). We aim to verify additional hCG injection 48 hours following routine hCG trigger and ovulation for LPS on the basis of supplementation of estrogen and dydrogesterone could improve clinical pregnancy rate, cumulative pregnancy rate, live birth rate and the prevalence of early pregnancy loss and ovarian hyperstimulation syndrome (OHSS) by an open labeled, prospective, and randomized clinical trial (RCT) in IHH patients in a single center of the Obstetrics and Gynecology Hospital Affiliated to Fudan University. The onset of patients' mental and psychological diseases such as depression and anxiety rely on their reproductive needs and pregnancy outcomes, which will also be investigated in the current study. Moreover, the effect of clinical interventions to improve pregnancy outcomes and emotional disorders would be discussed.

• Study Type: Interventional
• Enrollment (Estimated): 46
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hexia Xia, M.D.; Phone Number: +86 13601843476; Email: hexia_xia@fudan.edu.cn
• Study Contact Backup: Name: Wei Zhang, Ph.D.,M.D.; Phone Number: +86 13611691036; Email: zhangwei623@hotmail.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200011
      • Recruiting
      • OB & GYN Hospital of Fudan University
      • Contact: Hexia Xia, Doctor; Phone Number: 13601843476; Email: hexia_xia@fudan.edu.cn
      • Principal Investigator: Hexia Xia, Doctor
      • Sub-Investigator: Haiyun Guan, Doctor
      • Sub-Investigator: Rongmin Wang, Master
      • Sub-Investigator: Zhijing Tang, PhD student
    • Shanghai, Shanghai, China, 200011
      • Recruiting
      • Obstetrics and Gynecology Hospital of Fudan University
      • Contact: Wei Zhang, PhD; Phone Number: +86 13611691036; Email: zhangwei623@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Clinical diagnosis of IHH (primary amenorrhea (with or without a history of hormone supplementation therapy); basic LH levels <5IU/L, FSH<5IU/L or normal; no organic lesions in the hypothalamus and pituitary MRI).
• Women of childbearing age who desire to get pregnant

Exclusion Criteria:

• Premature ovarian insufficiency or premature ovarian failure
• Primary amenorrhea due to hypothalamic/pituitary lesions
• Secondary amenorrhea

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: Additional hCG injection; An additional hCG injection of 2000-5000IU would be performed 48 hours following routine hCG trigger on the basis of supplementation of estrogen and dydrogesterone in IHH patients.	Drug: Additional hCG injection; An additional hCG injection of 2000-5000IU would be given 48 hours following routine hCG trigger and ovulation for LPS on the basis of supplementation of estrogen and dydrogesterone.; Drug: estrogen and dydrogesterone; estrogen and dydrogesterone
Placebo Comparator: No additional hCG injection; Only estrogen and dydrogesterone would be given for luteal phase support in IHH patients.	Drug: estrogen and dydrogesterone; estrogen and dydrogesterone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical pregnancy rate	Defined as the presence of a gestational sac under ultrasonography	7 weeks
Cumulative pregnancy rate	Defined as a pregnancy with a detectable heart rate at 12 weeks of gestation or beyond.	12 weeks
Live birth rate	Defined as the number of deliveries that resulted in a live born neonate, expressed per 100 pregnancies.	42 weeks or beyond

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of IHH patients ending in early pregnancy loss	Early pregnancy loss is defined as the loss of a pregnancy prior to 12 weeks gestation	12 weeks
Number of IHH patients with ovarian hyperstimulation syndrome	Ovarian hyperstimulation syndrome is defined as an exaggerated response to excess hormones. It usually occurs in women taking injectable hormone medications to stimulate the development of eggs in the ovaries. Ovarian hyperstimulation syndrome (OHSS) causes the ovaries to swell and become painful.	12 weeks or beyond

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum progesterone levels on Day 1, 7, and 14 after ovulation	Serum progesterone levels is a symbol of luteal function	7 weeks

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Wei Zhang, Ph.D.,M.D., GCP office

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: October 2, 2022
• First Submitted That Met QC Criteria: October 5, 2022
• First Posted (Actual): October 6, 2022

Study Record Updates

• Last Update Posted (Actual): August 7, 2024
• Last Update Submitted That Met QC Criteria: August 6, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Idiopathic hypogonadotropic hypogonadism; Luteal phase deficiency
• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Hypogonadism; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progestins; Dydrogesterone; Estrogens
• Other Study ID Numbers: FudanU2022-08-18

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