Effects of SNP of GnRH Receptor Genes in IVF Patients

NCT02979886 | Unknown

• 1 other identifier: FirstZhongshanMU
• Study Type: interventional
• Target: 1,500
• Locations: 0 countries
• Sites: N/A

Brief Summary

Gonadotropin-releasing hormone analogue (GnRH-a) "long protocol" is a protocol for pituitary down-regulation in IVF. However, it is common in clinic that some patients are hypersensitive to pituitary down-regulation and have pituitary oversuppression, resulting in prolonged ovarian stimulation and increased consumption of exogenous gonadotropin(Gn). On the other hand, some patients may have insufficient pituitary down-regulation, which can affect the synchronization of ovarian follicles and consequently reduce the number of oocytes retrievable and lower the pregnancy rate. The differences in responses to GnRH-a among patients may be associated with the SNP of their GnRH receptor genes. It has been reported that mutations in GnRH receptor genes could change their binding affinity to the ligands, thus affecting the outcome of pituitary down-regulation. So far 20 non-synonymous mutations on the GnRH receptor genes have been reported, which can affect the function of GnRH receptor and are highly associated with disorders such as endometriosis and sexual precocity. However, the correlation between the SNP of GnRH receptor genes and the outcome of pituitary down-regulation in IVF has not been reported. The purpose of this study is to analyze the correlation between single nucleotide polymorphism (SNP) of GnRH receptor genes in infertile female patients and the extent of pituitary down-regulation by short-acting GnRH-a long protocol, with the goal to achieve individual down-regulation protocols based on the patients' SNP haplotypes of GnRH receptor genes and to improve the success rate of assisted reproductive technology.

Conditions

Infertility, Female

Keywords

single nucleotide polymorphism,GnRH receptor, IVF

Outcome Measures

Primary Outcomes (1)

• the evidence of the correlation between single nucleotide polymorphism (SNP) of GnRH receptor genes in infertile female patients and the extent of pituitary down-regulation by short-acting GnRH-a long protocol

  two years

Study Arms (1)

triptorelin

EXPERIMENTAL

GnRH-a will be given everyday to the patient undergoing IVF treatment from middle luteal phase to the day of HCG. After 14 days of injection, serum FSH/LH/E2 will be checked. Then ovarian stimulation will be started by giving daily subcutaneous injection of recombinant FSH 150\~300 IU. An appropriate dose of HMG (75\~150 IU) will be added when follicles are larger than 12\~14mm in diameter. When one leading follicle is \>18mm in diameter, or two follicles are \>17mm in diameter, or three follicles are \>16mm in diameter, final ovulation will be triggered by a single injection of HCG 4,000\~10,000 IU or Ovidrel® 250μg (equivalent to HCG 6,500 IU)

Drug: GnRH-a; Drug: Human Menopausal Gonadotropins

Interventions

GnRH-a DRUG

the hormone reaction to the down regulation of the patients

Also known as: triptorelin

triptorelin

Human Menopausal Gonadotropins DRUG

the effects on the serum LH level of day of HCG

Also known as: menopur

triptorelin

Eligibility Criteria

• Age: 20 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• regular periods of spontaneous menstruation (23\~35 days)
• basal serum FSH \<12 IU/L
• use of short-acting GnRH-a long protocol for pituitary down-regulation.

You may not qualify if:

• polycystic ovary syndrome (PCOS)
• hypothalamic-pituitary lesions
• use of oral contraceptives
• treated with a GnRH-a within 3 months before the start of GnRH-a treatment for this study
• failure to sign informed consent form.

Sponsors & Collaborators

• Miao benyu: lead

Related Publications (3)

• Noel SD, Kaiser UB. G protein-coupled receptors involved in GnRH regulation: molecular insights from human disease. Mol Cell Endocrinol. 2011 Oct 22;346(1-2):91-101. doi: 10.1016/j.mce.2011.06.022. Epub 2011 Jun 29.

  PMID: 21736917 RESULT

• Valkenburg O, Uitterlinden AG, Piersma D, Hofman A, Themmen AP, de Jong FH, Fauser BC, Laven JS. Genetic polymorphisms of GnRH and gonadotrophic hormone receptors affect the phenotype of polycystic ovary syndrome. Hum Reprod. 2009 Aug;24(8):2014-22. doi: 10.1093/humrep/dep113. Epub 2009 Apr 29.

  PMID: 19403562 RESULT

• Caronia LM, Martin C, Welt CK, Sykiotis GP, Quinton R, Thambundit A, Avbelj M, Dhruvakumar S, Plummer L, Hughes VA, Seminara SB, Boepple PA, Sidis Y, Crowley WF Jr, Martin KA, Hall JE, Pitteloud N. A genetic basis for functional hypothalamic amenorrhea. N Engl J Med. 2011 Jan 20;364(3):215-25. doi: 10.1056/NEJMoa0911064.

  PMID: 21247312 RESULT

MeSH Terms

Conditions

Infertility, Female

Interventions

ricin A-GnRH conjugate; Triptorelin Pamoate; Menotropins

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Infertility

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Gonadotropins, Pituitary; Gonadotropins; Pituitary Hormones, Anterior; Pituitary Hormones; Biological Products; Complex Mixtures

Study Officials

• benyu miao

  the first affiliated hosptial of zhongshan university

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: the associated professor

Study Record Dates

• First Submitted: November 27, 2016
• First Posted: December 2, 2016
• Study Start: January 1, 2017
• Primary Completion: June 1, 2019
• Study Completion: December 1, 2019
• Last Updated: December 5, 2016

Record last verified: 2016-12

Data Sharing

• IPD Sharing: Will not share