Ignite Creation Date:
2024-05-06 @ 7:59 AM
Last Modification Date:
2024-10-26 @ 11:54 AM
Study NCT ID:
NCT02640976
Status:
COMPLETED
Last Update Posted:
2015-12-29
First Post:
2015-12-16
Brief Title:
Poor Ovarian Stimulation Response in In Vitro Fertilization IVF Program
Sponsor:
Cairo University
Organization:
Cairo University
Study Overview
Official Title:
Assessing the Relation Between Hormone Receptors Gene Polymorphism and Ovarian Stimulation Response in In Vitro Fertilization IVF Program
Status:
COMPLETED
Status Verified Date:
2015-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The aim of this study is to assess the role of AMH in prediction of poor ovarian response as well as the relation between ESR2 1730GA rs4986938 FSHR pThr307Ala c919AG rs6165 and FSHR pAsn680Ser c2039AG rs6166 SNPs and the poor response in Egyptian women undergoing IVF procedure Discovering the genetic variants associated with ovarian response is an important step towards individualized pharmacogenetic protocols of ovarian stimulation
Detailed Description:
In-vitro fertilization treatment safety is highly challenged by the erratic individual variability to controlled ovarian hyperstimulation COH One of the diverse predictive factors is the AMH which is considered to be the most sensitive marker Nowadays practices of pharmacogenetics could predict the stimulation success and thus tailoring the treatment reaching advancement in patient care Since the efficiency of the Follicle stimulating hormone FSH dose is greatly related to the success of COH the FSHR gene is treated as the primary candidate in explaining the difference in COH resultsFurthermore the estrogen receptors are important genes for improvements in the diagnosis and treatment of infertility
Materials and Methods Starting June 2013 couples with unexplained infertility seeking the first attempt IVFICSI treatment cycle will be recruited in AL shark Al-Awsat fertility centerIn this prospective study 216 Couples fulfilling our inclusion criteria will enroll in this study after informed consent Ovarian stimulation will be performed according to the GnRH antagonist protocol with a fixed daily morning dose of Human menopausal gonadotrophin HMG Merional 75 IU ampoules IBSA institut intra-muscular injection starting on cycle day 2 Based on the patients body mass index and hormonal profile the daily dose of HMG will be adjusted to 225 IU for participants with AMH levels 15 ngml andor FSH levels 8 mIUml and to 300 IU for participants with AMH levels 15 ngml andor FSH levels 8 mIUml doses will be increased by 75 IU in cases with BMI 30 Kgm2 On day 2 of the menstrual cycle the dose of HMG will be commenced for all patients and will be maintained for 9-11 days according to each participant individual ovarian response assessed by trans-vaginal ultrasound folliculometry starting on cycle day 7 and continued every other day until the day of Human chorionic gonadotrophin hCG injection On cycle day 7 the GnRH antagonist Cetrorelix 025 mg Cetrotide 025 mg syringes Merck Serono will be introduced as daily subcutaneous injections and continued till the day of ovulation triggering Finally when at least 3 follicles will reach 17 mm in diameter ovulation will be triggered by a single intra-muscular injection of 10000 IU of hCG Choriomon 5000 IU ampoules IBSA institut 36 hours later oocyte retrieval will be performed and will be guided by transvaginal ultrasound According to our primary outcome the number of oocytes collected patients will be classified as poor responders 4 oocytes or less and will be considered as good responders if they produced 5 or more oocytes The good responders group will serve as the control group
GenotypingPeripheral blood will be collected from each patient in an EDTA-containing tube Genomic DNA will be extracted from lymphocytes of peripheral blood by fully automated system of QIAcube using QIAamp DNA Blood Mini Kit 250 plus QIAamp DNA Blood Mini Accessory Set B cat no 1043369 Detection of the polymorphisms ESR2 1730GA rs4986938 FSHR pThr307Ala c919AG rs6165 and FSHR pAsn680Ser c2039AG rs6166 SNPs will be performed using the TaqMan system by real-time polymerase chain reaction PCR Primers and probes will be provided by applied biosystem Life Technologies Assays will be performed with TaqMan Universal Master Mix
Statistical analysis Data will be statistically described in terms of mean and standard deviation for quantitative data and frequencies number of cases and relative frequencies percentages for qualitative data Hardy-Weinberg H-W Equilibrium for each polymorphism will be tested using the Chi-square test Comparison of quantitative variables will be done using unpaired t test when comparing 2 categories and one way analysis of variance ANOVA with post hoc test when comparing more than 2 categories
For comparing categorical data Chi square test will be performed Exact test will be used instead when the expected frequency is less than 5
Genotype and allele frequencies will be compared between the disease and the control groups using chi-square tests Odds ratio OR with 95 confidence intervals will be calculated A probability value P value less than 005 will be considered statistically significant All statistical calculations will be done using SPSS Statistical Package for the Social Science SPSS Inc Chicago IL USA version 22
Materials and Methods Starting June 2013 couples with unexplained infertility seeking the first attempt IVFICSI treatment cycle will be recruited in AL shark Al-Awsat fertility centerIn this prospective study 216 Couples fulfilling our inclusion criteria will enroll in this study after informed consent Ovarian stimulation will be performed according to the GnRH antagonist protocol with a fixed daily morning dose of Human menopausal gonadotrophin HMG Merional 75 IU ampoules IBSA institut intra-muscular injection starting on cycle day 2 Based on the patients body mass index and hormonal profile the daily dose of HMG will be adjusted to 225 IU for participants with AMH levels 15 ngml andor FSH levels 8 mIUml and to 300 IU for participants with AMH levels 15 ngml andor FSH levels 8 mIUml doses will be increased by 75 IU in cases with BMI 30 Kgm2 On day 2 of the menstrual cycle the dose of HMG will be commenced for all patients and will be maintained for 9-11 days according to each participant individual ovarian response assessed by trans-vaginal ultrasound folliculometry starting on cycle day 7 and continued every other day until the day of Human chorionic gonadotrophin hCG injection On cycle day 7 the GnRH antagonist Cetrorelix 025 mg Cetrotide 025 mg syringes Merck Serono will be introduced as daily subcutaneous injections and continued till the day of ovulation triggering Finally when at least 3 follicles will reach 17 mm in diameter ovulation will be triggered by a single intra-muscular injection of 10000 IU of hCG Choriomon 5000 IU ampoules IBSA institut 36 hours later oocyte retrieval will be performed and will be guided by transvaginal ultrasound According to our primary outcome the number of oocytes collected patients will be classified as poor responders 4 oocytes or less and will be considered as good responders if they produced 5 or more oocytes The good responders group will serve as the control group
GenotypingPeripheral blood will be collected from each patient in an EDTA-containing tube Genomic DNA will be extracted from lymphocytes of peripheral blood by fully automated system of QIAcube using QIAamp DNA Blood Mini Kit 250 plus QIAamp DNA Blood Mini Accessory Set B cat no 1043369 Detection of the polymorphisms ESR2 1730GA rs4986938 FSHR pThr307Ala c919AG rs6165 and FSHR pAsn680Ser c2039AG rs6166 SNPs will be performed using the TaqMan system by real-time polymerase chain reaction PCR Primers and probes will be provided by applied biosystem Life Technologies Assays will be performed with TaqMan Universal Master Mix
Statistical analysis Data will be statistically described in terms of mean and standard deviation for quantitative data and frequencies number of cases and relative frequencies percentages for qualitative data Hardy-Weinberg H-W Equilibrium for each polymorphism will be tested using the Chi-square test Comparison of quantitative variables will be done using unpaired t test when comparing 2 categories and one way analysis of variance ANOVA with post hoc test when comparing more than 2 categories
For comparing categorical data Chi square test will be performed Exact test will be used instead when the expected frequency is less than 5
Genotype and allele frequencies will be compared between the disease and the control groups using chi-square tests Odds ratio OR with 95 confidence intervals will be calculated A probability value P value less than 005 will be considered statistically significant All statistical calculations will be done using SPSS Statistical Package for the Social Science SPSS Inc Chicago IL USA version 22
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None