Top

Journal of Assisted Reproduction and Genetics

Published in:

01-04-2013 | Genetics

Do estrogen receptor alpha polymorphisms have any impact on the outcome in an ART program?

Authors: Elli Anagnostou, Fotodotis Malamas, Despina Mavrogianni, Vasiliki Dinopoulou, Peter Drakakis, Konstantinos Kallianidis, Dimitris Loutradis

Published in: Journal of Assisted Reproduction and Genetics | Issue 4/2013

Abstract

Purpose

To investigate two of the most studied estrogen receptor alpha polymorphisms (PvuII and XbaI) in combination, in order to evaluate their impact on an ART program outcome.

Methods

203 normally ovulating women who underwent IVF or ICSI treatment were genotyped for PvuII and XbaI polymorphisms in ESR1 intron 1 using Real-Time PCR. The relationship between the presence of polymorphic alleles and the ovulation induction parameters and outcome was examined.

Results

Women were grouped according to the number of polymorphic alleles they carried in two groups (0–2 versus 3–4 polymorphic alleles). The presence of 3 or more polymorphic alleles was associated with significantly lower E2 levels on the day of hCG administration and a significantly lower rate of good quality embryos.

Conclusion

There is an association between ESR1 polymorphisms and some ART parameters such as the level of E2 on the day of hCG administration and the quality of the embryos. These results underline the importance of ESR1 as a candidate gene for the prediction of ovarian response to IVF/ICSI protocols. Future research work concerning several more genes is necessary for a better evaluation of patients before entering an IVF/ICSI program.

Altmäe S, Haller K, Peters M, et al. Allelic estrogen receptor 1 (ESR1) gene variants predict the outcome of ovarian stimulation in in vitro fertilization. Mol Hum Reprod. 2007;13:521–6.PubMedCrossRef

Anagnostou E, Mavrogianni D, Theofanakis C, et al. ESR1, ESR2 and FSH receptor gene polymorphisms in combination: a useful genetic tool for the prediction of poor responders. Curr Pharm Biotechnol. 2012;13:426–34.PubMedCrossRef

Ayvaz OU, Ekmekçi A, Baltaci V, Onen HI, Unsal E. Evaluation of in vitro fertilization parameters and estrogen receptor alpha gene polymorphisms for women with unexplained infertility. J Assist Reprod Genet. 2009;26:503–10.PubMedCrossRef

Corbo RM, Ulizzi L, Piombo L, et al. Estrogen receptor alpha polymorphisms and fertility in populations with different reproductive patterns. Mol Hum Reprod. 2007;13:537–40.PubMedCrossRef

de Castro F, Moron FJ, Montoro L, et al. Human controlled ovarian hyperstimulation outcome is a polygenic trait. Pharmacogenetics. 2004;14:285–93.PubMedCrossRef

Delvigne A, Rozenberg S. Epidemiology and prevention of ovarian hyperstimulation syndrome (OHSS): a review. Hum Reprod Update. 2002;8:559–77.PubMedCrossRef

Drummond AE. The role of steroids in follicular growth. Reprod Biol Endocrinol. 2006;4:16.PubMedCrossRef

Fauser BCJM, Diedrich K, Devroey P, Evian Annual Reproduction Workshop Group 2007. Predictors of ovarian response: progress towards individualized treatment in ovulation induction and ovarian stimulation. Hum Reprod Update. 2008;14:1–14.PubMedCrossRef

Freour T, Masson D, Mirallie S, et al. Active smoking compromises IVF outcome and affects ovarian reserve. Reprod Biomed Online. 2008;16:96–102.PubMedCrossRef

10.

Gearhart J, Coutifaris C. In vitro fertilization, the Nobel Prize, and human embryonic stem cells. Cell Stem Cell. 2011;8:12–5.PubMedCrossRef

11.

Georgiou I, Konstantelli M, Syrrou M, Messinis IE, Lolis DE. Oestrogen receptor gene polymorphisms and ovarian stimulation for in-vitro fertilization. Hum Reprod. 1997;12:1430–3.PubMedCrossRef

12.

Gonzalez-Gomez F, Vergara F, Fernandez A, et al. Detection of pvull polymorphism within intron 1 of ESR1 gene by real-time PCR. Clin Chem Lab Med. 2003;41:392–3.PubMedCrossRef

13.

Kligman I, Rosenwaks Z. Differentiating clinical profiles: predicting good responders, poor responders, and hyperresponders. Fertil Steril. 2001;76:1185–90.PubMedCrossRef

14.

Kolibianakis EM, Papanikolaou EG, Fatemi HM, Devroey P. Estrogen and folliculogenesis: is one necessary for the other? Curr Opin Obstet Gynecol. 2005;17:249–53.PubMedCrossRef

15.

Kolibianakis EM, Venetis CA, Tarlatzis BC. Role of the endocrine profile for the achievement of pregnancy with IVF. Reprod Biomed Online. 2009;18 Suppl 2:37–43.PubMedCrossRef

16.

Kupesic S, Kurjak A. Predictors of IVF outcome by three-dimensional ultrasound. Hum Reprod. 2002;17:950–5.PubMedCrossRef

17.

Le Hir H, Nott A, Moore MJ. How introns influence and enhance eukaryotic gene expression. Trends Biochem Sci. 2003;28:215–20.PubMedCrossRef

18.

Licciardi FL, Liu HC, Rosenwaks Z. Day 3 estradiol serum concentrations as prognosticators of ovarian stimulation response and pregnancy outcome in patients undergoing in vitro fertilization. Fertil Steril. 1995;64:991–4.PubMed

19.

Loutradis D, Drakakis P, Kallianidis K, et al. Oocyte morphology correlates with embryo quality and pregnancy rate after intracytoplasmic sperm injection. Fertil Steril. 1999;72:240–4.PubMedCrossRef

20.

Loutradis D, Drakakis P, Milingos S, Stefanidis K, Michalas S. Alternative approaches in the management of poor response in controlled ovarian hyperstimulation (COH). Ann N Y Acad Sci. 2003;997:112–9.PubMedCrossRef

21.

Loutradis D, Patsoula E, Minas V, et al. FSH receptor gene polymorphisms have a role for different ovarian response to stimulation in patients entering IVF/ICSI-ET programs. J Assist Reprod Genet. 2006;23:177–84.PubMedCrossRef

22.

Maruyama H, Toji H, Harrington CR, et al. Lack of an association of estrogen receptor alpha gene polymorphisms and transcriptional activity with Alzheimer disease. Arch Neurol. 2000;57:236–40.PubMedCrossRef

23.

M'Rabet N, Moffat R, Helbling S, et al. The CC-allele of the PvuII polymorphic variant in intron 1 of the alpha-estrogen receptor gene is significantly more prevalent among infertile women at risk of premature ovarian aging. Fertil Steril. 2012;98:965–972.e1-5.PubMedCrossRef

24.

Muttukrishna S, McGarrigle H, Wakim R, et al. Antral follicle count, anti-mullerian hormone and inhibin B: predictors of ovarian response in assisted reproductive technology? BJOG. 2005;112:1384–90.PubMedCrossRef

25.

Nardo LG, Gelbaya TA, Wilkinson H, et al. Circulating basal anti-Mullerian hormone levels as predictor of ovarian response in women undergoing ovarian stimulation for in vitro fertilization. Fertil Steril. 2009;92:1586–93.PubMedCrossRef

26.

Nott A, Meislin SH, Moore MJ. A quantitative analysis of intron effects on mammalian gene expression. RNA. 2003;9:607–17.PubMedCrossRef

27.

Pelletier G, El-Alfy M. Immunocytochemical localization of estrogen receptors alpha and beta in the human reproductive organs. J Clin Endocrinol Metab. 2000;85:4835–40.PubMedCrossRef

28.

Salha O, Abusheikha N, Sharma V. Dynamics of human follicular growth and in-vitro oocyte maturation. Hum Reprod Update. 1998;4:816–32.PubMedCrossRef

29.

Scott RT, Toner JP, Muasher SJ, et al. Follicle-stimulating hormone levels on cycle day 3 are predictive of in vitro fertilization outcome. Fertil Steril. 1989;51:651–4.PubMed

30.

Sundarrajan C, Liao W, Roy AC, Ng SC. Association of oestrogen receptor gene polymorphisms with outcome of ovarian stimulation in patients undergoing IVF. Mol Hum Reprod. 1999;5:797–802.PubMedCrossRef

31.

Sundermann EE, Maki PM, Bishop JR. A review of estrogen receptor alpha gene (ESR1) polymorphisms, mood, and cognition. Menopause. 2010;17:874–86.PubMedCrossRef

32.

Syrop CH, Dawson JD, Husman KJ, Sparks AE, Van Voorhis BJ. Ovarian volume may predict assisted reproductive outcomes better than follicle stimulating hormone concentration on day 3. Hum Reprod. 1999;14:1752–6.PubMedCrossRef

33.

Tomas C, Nuojua-Huttunen S, Martikainen H. Pretreatment transvaginal ultrasound examination predicts ovarian responsiveness to gonadotrophins in in-vitro fertilization. Hum Reprod. 1997;12:220–3.PubMedCrossRef

34.

van Disseldorp J, Franke L, Eijkemans R, et al. Genome-wide analysis shows no genomic predictors of ovarian response to stimulation by exogenous FSH for IVF. Reprod Biomed Online. 2011;22:382–8.PubMedCrossRef

35.

Weickert CS, Miranda-Angulo AL, Wong J, et al. Variants in the estrogen receptor alpha gene and its mRNA contribute to risk for schizophrenia. Hum Mol Genet. 2008;17:2293–309.PubMedCrossRef

36.

Yaich L, Dupont WD, Cavener DR, Parl FF. Analysis of the PvuII restriction fragment-length polymorphism and exon structure of the estrogen receptor gene in breast cancer and peripheral blood. Cancer Res. 1992;52:77–83.PubMed

37.

Ziebe S, Loft A, Petersen JH, et al. Embryo quality and developmental potential is compromised by age. Acta Obstet Gynecol Scand. 2001;80:169–74.PubMedCrossRef

Title: Do estrogen receptor alpha polymorphisms have any impact on the outcome in an ART program?
Authors: Elli Anagnostou
Fotodotis Malamas
Despina Mavrogianni
Vasiliki Dinopoulou
Peter Drakakis
Konstantinos Kallianidis
Dimitris Loutradis
Publication date: 01-04-2013
Publisher: Springer US
Published in: Journal of Assisted Reproduction and Genetics / Issue 4/2013
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI: https://doi.org/10.1007/s10815-013-9971-7

At a glance: The STEP trials

Springer Medicine

Do estrogen receptor alpha polymorphisms have any impact on the outcome in an ART program?

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 4/2013

Greater prevalence of Y chromosome Q1a3a haplogroup in Y-microdeleted Chilean men: a case–control study

Seminal plasma insemination during ovum-pickup—a method to increase pregnancy rate in IVF/ICSI procedure. A pilot randomized trial

Failure of GnRH agonist-triggered oocyte maturation: its cause and management

The expression and distribution of aquaporin 3 in mouse embryos before and after vitrification

Characterization of 3-hydroxyisobutyrate dehydrogenase, HIBADH, as a sperm-motility marker

Lower sperm DNA fragmentation after r-FSH administration in functional hypogonadotropic hypogonadism