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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Additional hCG injection | Experimental | 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. |
|
| No additional hCG injection | Placebo Comparator | Only estrogen and dydrogesterone would be given for luteal phase support in IHH patients. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Additional hCG injection | Drug | 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. |
| 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 |
| 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 |
| 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 |
Inclusion Criteria:
Exclusion Criteria:
Women aged between 18-45 years is reproductive. IHH patients in the age have willings to get pregnant and they would seek helps in outpatient clinic of Gynecological endocrinology.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Hexia Xia, M.D. | Contact | +86 13601843476 | hexia_xia@fudan.edu.cn | |
| Wei Zhang, Ph.D.,M.D. | Contact | +86 13611691036 | zhangwei623@hotmail.com |
| Name | Affiliation | Role |
|---|---|---|
| Wei Zhang, Ph.D.,M.D. | GCP office | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| OB & GYN Hospital of Fudan University | Recruiting | Shanghai | Shanghai Municipality | 200011 | China |
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We have two cohorts in the current study and patients are randomly assigned to either cohort of additional hCG injection or not.
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In the current study, none of patients, investigators and designers is marked.
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| estrogen and dydrogesterone | Drug | estrogen and dydrogesterone |
|
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 |
| Obstetrics and Gynecology Hospital of Fudan University | Recruiting | Shanghai | Shanghai Municipality | 200011 | China |
|
| ID | Term |
|---|---|
| C562785 | Idiopathic Hypogonadotropic Hypogonadism |
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| ID | Term |
|---|---|
| D004967 | Estrogens |
| D004394 | Dydrogesterone |
| ID | Term |
|---|---|
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D045505 | Physiological Effects of Drugs |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
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