Infertility, FemaleNCT02979886
Effects of SNP of GnRH Receptor Genes in IVF Patients
A study testing GnRH-a and Human Menopausal Gonadotropins in people with Infertility, Female, run by Miao benyu.
Trial 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… Read more about this study
- Who is it for?
- Ages 20 to 40 years, women only
- Conditions the study is for
- Infertility, Female
- What is being tested?
- GnRH-a and Human Menopausal Gonadotropins
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,500 participants
- Where
- No sites listed yet
- Study dates
- Jan 2017to Dec 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 40 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
About this study
Official title: 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.
Read the 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.
- Conditions
- Infertility, Female
- Being tested
- GnRH-a, Human Menopausal Gonadotropins
- Keywords
- single nucleotide polymorphism,GnRH receptor, IVF
- Medical subject headings
- Infertility, Female
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GnRH-aDrug
Also called triptorelin
the hormone reaction to the down regulation of the patients
Human Menopausal GonadotropinsDrug
Also called menopur
the effects on the serum LH level of day of HCG
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: Drug: GnRH-a; Drug: Human Menopausal Gonadotropins |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: two years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2016 (estimated)
- Study startJan 2017
- Primary completionJun 2019 (estimated)
- Study completionDec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Infertility, FemaleStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Screening
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1,500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Miao benyu
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Miao benyu, First Affiliated Hospital of Zhongshan Medical University
- Investigators
- benyu miao, Study director, the first affiliated hosptial of zhongshan university
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02979886
- Sponsor's protocol ID
- FirstZhongshanMU
- Status last verified
- Dec 2016
- First submitted
- 27 Nov 2016
- Last updated
- 5 Dec 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 21736917Valkenburg 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.
PubMed 19403562Caronia 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.
PubMed 21247312
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Single Nucleotide Polymorphism of GnRH Receptor Genes on Clinical Response to Pituitary Down Regulation in IVF Patients
- ClinicalTrials.gov ID
- NCT02979886
- Acronym / sponsor ID
- FirstZhongshanMU
- Conditions
- Infertility, Female
- Keywords
- single nucleotide polymorphism,GnRH receptor, IVF
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 1,500 participants (estimated)
- Lead sponsor
- Miao benyuUniversity, hospital or other
- Study start
- Jan 2017
- Primary completion
- Jun 2019 (estimated)
- Study completion
- Dec 2019 (estimated)
- First posted
- 2 Dec 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Screening
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| triptorelin | Experimental | Drug: GnRH-a, Drug: Human Menopausal GonadotropinsGnRH-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) |
Who may qualify
- Ages
- 20 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GnRH-aAlso: triptorelinthe hormone reaction to the down regulation of the patients | Drug | triptorelin |
| Human Menopausal GonadotropinsAlso: menopurthe effects on the serum LH level of day of HCG | Drug | triptorelin |
Primary outcome
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2016.
- Results publication: PubMed 21736917Noel 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.
- Results publication: PubMed 19403562Valkenburg 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.
- Results publication: PubMed 21247312Caronia 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
benyu miao study director
the first affiliated hosptial of zhongshan university
Questions about this trial
What is this clinical trial studying?
A study testing GnRH-a and Human Menopausal Gonadotropins in people with Infertility, Female, run by Miao benyu.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 5 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02979886, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2016.