Effects of SNP of GnRH Receptor Genes in IVF Patients

December 1, 2016 updated by: Miao benyu

Effects of Single Nucleotide Polymorphism of GnRH Receptor Genes on Clinical Response to Pituitary Down Regulation in IVF Patients

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Short-acting GnRH-a will be administered daily since the mid-luteal phase for pituitary down-regulation. 14 days after down-regulation,serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) and E2 will be measured. Meanwhile, about 2ml of peripheral blood will be preserved for SNP analysis of the GnRH receptor genes. Once the patients are judged to achieve pituitary down-regulation, ovarian stimulation will be started. B-mode ultrasonography and determination of hormone levels will be performed regularly according to the course of follicle maturation. An appropriate dose of human menopause gonadotropin (HMG) (75~150IU) 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 human chorionic gonadotropin (HCG) 4,000~10,000 IU or Ovidrel® 250μg (equivalent to HCG 6,500IU).Oocyte retrieval guided by vaginal ultrasonography will be conducted 35~36 hours after HCG or Ovidrel®injection.Fertilization and embryo culture will be performed according to the standard IVF or intracytoplasmic sperm injection (ICSI) protocol.Embryo transfer and cryopreservation will be performed 3~5 days after oocyte retrieval. Luteal support will be provided after embryo transfer according to the Center's routine practice. Serum β-HCG level will be measured 12~14 days after embryo transfer to determine biochemical pregnancy, and transvaginal ultrasonography will be performed 4~5 weeks after embryo transfer to determine clinical pregnancy.

For data analysis, patients will be divided into two groups according to their serum LH level on day 14 after pituitary down-regulation - one group of patients with an LH level above the median of the group and another group of patients with an LH level below the median of the group.Comparisons will be made between the two groups in the following aspects: 1) age; BMI; basal levels of LH, FSH and prolactin (PRL); serum levels of FSH, LH, E2 and progesterone on the day of HCG injection; the numbers of oocytes retrieved, the number of cleavage, the number of transferrable embryos, the number of embryos transferred and the clinical pregnancy rate; and 2) genotyping results at the 11 SNP loci of the GnRH receptor genes.

Study Type

Interventional

Enrollment (Anticipated)

1500

Phase

  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 40 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Screening
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: triptorelin
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
the hormone reaction to the down regulation of the patients
Other Names:
  • triptorelin
Drug: Human Menopausal Gonadotropins
the effects on the serum LH level of day of HCG
Other Names:
  • menopur

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
Time Frame: two years
two years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Miao benyu

Investigators

  • Study Director: benyu miao, the first affiliated hosptial of zhongshan university

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2017

Primary Completion (Anticipated)

June 1, 2019

Study Completion (Anticipated)

December 1, 2019

Study Registration Dates

First Submitted

November 27, 2016

First Submitted That Met QC Criteria

November 29, 2016

First Posted (Estimate)

December 2, 2016

Study Record Updates

Last Update Posted (Estimate)

December 5, 2016

Last Update Submitted That Met QC Criteria

December 1, 2016

Last Verified

December 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FirstZhongshanMU

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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