Genetic polymorphisms influence the ovarian response to rFSH stimulation in patients undergoing in vitro fertilization programs with ICSI.
BACKGROUND
Obtaining an adequate number of high-quality oocytes is a major challenge in controlled ovarian hyperstimulation (COH). To date, a range of hormonal and clinical parameters have been used to optimize COH but none have significant predictive value. This variability could be due to the genetic predispositions of single-nucleotide polymorphisms (SNPs). Here, we assessed the individual and combined impacts of thirteen SNPs that reportedly influence the outcome of in vitro fertilisation (IVF) on the ovarian response to rFSH stimulation for patients undergoing intracytoplasmic sperm injection program (ICSI).


RESULTS
Univariate analysis revealed that only FSHR, ESR2 and p53 SNPs influenced the number of mature oocytes. The association was statistically significant for FSHR (p=0.0047) and ESR2 (0.0017) in the overall study population and for FSHR (p=0.0009) and p53 (p=0.0048) in subgroup that was more homogeneous in terms of clinical variables. After Bonferroni correction and a multivariate analysis, only the differences for FSHR and ESR2 polymorphisms were still statistically significant. In a multilocus analysis, only the FSHR and AMH SNP combination significantly influenced oocyte numbers in both population (p<0.01).


CONCLUSIONS
We confirmed the impact of FSHR and ESR2 polymorphisms on the IVF outcome. Furthermore, we showed for the first time that a p53 polymorphism (which is already known to impact embryo implantation) could influence the ovarian response. However, given that this result lost its statistical significance after multivariate analysis, more data are needed to draw firm conclusions. Only the FSHR and AMH polymorphism combination appears to influence mature oocyte numbers but this finding also needs to be confirmed.


METHODS
A 13 gene polymorphisms: FSHR(Asn680Ser), p53(Arg72Pro), AMH(Ile49Ser), ESR2(+1730G>A), ESR1(-397T>C), BMP15(-9C>G), MTHFR1(677C>T), MTHFR2(1298A>C), HLA-G(-725C>G), VEGF(+405G>C), TNFα(-308A>G), AMHR(-482 A>G), PAI-1 (4 G/5 G), multiplex PCR assay was designed to genotype women undergoing ICSI program. We analyzed the overall study population (n=427) and a subgroup with homogeneous characteristics (n=112).
Department of Reproductive Biology, Cytogenetics, Gynaecology and Obstetrics, Poissy Saint Germain Medical Centre, Poissy, France. boudjenahradia@yahoo.fr
Radia
R
Boudjenah
Denise
D
Molina-Gomes
Antoine
A
Torre
Marianne
M
Bergere
Marc
M
Bailly
Florence
F
Boitrelle
Stéphane
S
Taieb
Robert
R
Wainer
Mohamed
M
Benahmed
Philippe
P
de Mazancourt
Jacqueline
J
Selva
François
F
Vialard
D000367:Age Factors; D017931:DNA Primers / Q000235:genetics; D047629:Estrogen Receptor beta / Q000235:genetics*; D005260:Female; D005307:Fertilization in Vitro / Q000379:methods*; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000494:pharmacology; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D015999:Multivariate Analysis; D009865:Oocytes / Q000187:drug effects* / Q000378:metabolism; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011962:Receptors, FSH / Q000235:genetics*; D020554:Sperm Injections, Intracytoplasmic / Q000379:methods*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D044465:White People
D017931:DNA Primers; D047629:Estrogen Receptor beta; D011962:Receptors, FSH; D016159:Tumor Suppressor Protein p53; D005640:Follicle Stimulating Hormone