@article{3152766,
    title = "ESR1, ESR2 and FSH Receptor Gene Polymorphisms in Combination: A Useful
Genetic Tool for the Prediction of Poor Responders",
    author = "Anagnostou, E. and Mavrogianni, D. and Theofanakis, Ch. and Drakakis, P. and and Bletsa, R. and Demirol, A. and Gurgan, T. and Antsaklis, A. and and Loutradis, D.",
    journal = "Current Pharmaceutical Biotechnology",
    year = "2012",
    volume = "13",
    number = "3",
    pages = "426-434",
    publisher = "BENTHAM SCIENCE PUBL LTD",
    issn = "1389-2010",
    doi = "10.2174/138920112799361891",
    keywords = "ESR1 gene; ESR2 gene; FSH receptor; single nucleotide polymorphisms;
ovarian stimulation outcome; poor responders; IVF/ICSI",
    abstract = "Purpose: Previous studies in humans concluded that a multigenic model
including specific FSHR, ESR1 and ESR2 genotype patterns may partially
explain the poor response to FSH. The aim of our study is to analyse
three different loci -polymorphisms in ESR1 Pvu II, ESR2 Rsa I and
Ser680Asn FSH receptor gene-in a Greek population and their involvement
in stimulation outcome and pregnancy rates. Methods: Each locus was
studied alone, and in combination with the others. We performed both
restriction fragment length polymorphism analysis and real-time
polymerase chain reaction. A total of 109 normally ovulating female
patients underwent IVF or ICSI. Results: Studying each locus alone, no
significant results were drawn for ESR1 and ESR2 genes. Concerning the
FSHR polymorphism, the women carrying the AA variant presented higher
total amount of gonadotrophins used (P=0,048) and tended to have higher
number of stimulation days (P=0,057). Considering the ESR1 and FSHR gene
polymorphisms in combination, the TC/SA combination presents the highest
number of pregnancies in poor responders group (3/4 pregnancies carried
this genotype), in good responders group (4/12 pregnancies carried this
genotype) and in the total population (10/26 pregnancies carried this
genotype). Except the CC/AA combination, all other genotype combinations
presented incidence of pregnancy, with TC/SA having the highest
incidence. The CC/AA genotype presents the worst profile of ovulation
induction, confirming a poor responder profile: the total amount of
gonadotrophins used was highest in CC/AA group (P<0,05). The peak E2,
the number of follicles and of retrieved oocytes and the pregnancy rate
were significantly lower (P<0,05). This genotype combination seems to be
over-presented in the poor responders group in a statistically
significant way (P=0,038). Women with CC/AA combination have 1,5-2,4
times more risk to be poor responders in comparison with women that do
not carry that combination. Conclusion: This study supports the
hypothesis that a multigenic model, including the well studied ESR1 and
FSHR genes is involved in the controlled ovarian stimulation outcome
indicating that the CC/AA genotype presents the worst ovulation
induction profile, while the TC/SA genotype presents the higher number
of pregnancies in our population."
}