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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Luteal Phase Deficiency, Luteal Phase Support, Idiopathic Hypogonadotropic Hypogonadism

Intervention / Treatment
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* Drug: Additional hCG injection
* Drug: estrogen and dydrogesterone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: We have two cohorts in the current study and patients are randomly assigned to either cohort of additional hCG injection or not.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Additional hCG injection<br>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<br>* 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.<br>Drug: estrogen and dydrogesterone<br>* estrogen and dydrogesterone<br>|
| Placebo Comparator: No additional hCG injection<br>Only estrogen and dydrogesterone would be given for luteal phase support in IHH patients. | Drug: estrogen and dydrogesterone<br>* estrogen and dydrogesterone<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Luteal phase deficiency, Idiopathic hypogonadotropic hypogonadism