Molecular genetic predictors of ovarian response, oocyte and embryo qualities in assisted reproductive technology programs


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Abstract

Objective. To search for molecular genetic markers that can predict ovarian response during superovulation and the patterns of oogenesis and embryogenesis in assisted reproductive technology (ART) programs. Subjects and methods. One hundred and sixty patients referred to in vitro fertilization programs were examined during a prospective case-control study. A study group consisted of 80 patients with normal response to ovarian stimulation; Group 1 included 40 patients with poor ovarian response; Group 2 comprised 40 patients with ovarian hyper-response. Gene polymorphisms were determined by polymerase chain reaction and melting curve analysis. Results. The carriage of the G/G genotype of FSHR gene polymorphism 2039 G>A (Ser680Asn) predisposes to ovarian hyper-response (OR = 3.49 (95% CI = 1.3-11.6); р =0.021). The G/G genotype of LHCGR gene polymorphism 939A>G (Asn312Ser) and the C/C genotype of VEGFA gene polymorphism - 634 G>C increase the risk of obtaining only immature oocytes (OR = 3.41 (95% Cl = 1.05-11.1); р = 0.039 and OR = 4.09 (95% CI = 1.3-11.71); р = 0.040, respectively)). When these two poor genotypes are combined, the probability of obtaining mature oocytes was 62.5% whereas that for other genotypic combinations was 93.4% (OR = 0.12 (95% CI = 0.03- 0.52); р = 0.019). The carriage of the A/A genotype of AMHR2 gene polymorphism - 482 A>G increases the risk of obtaining immature oocytes by more than twice (OR = 2.23 (95% CI = 1.1-4.3); р = 0.025). According to the autosomal dominant model, the carriage of the G allele of ESR1 gene polymorphism -351 A>G [XBaI] increases the risk of obtaining Class C embryos (poor quality) by more than twice (OR = 2.3 (95% CI = 1.1-4.6); р = 0.022). Conclusion. The polymorphism of the FSHR 2039G>A (Ser680Asn), LHCGR 935A>G (Asn312Ser), VEGFA - 634G>C, AMHR2 - 482 A>G, ESR1 -351A>G [XBaI] genes is an independent factor that can predict the outcome of superovulation and the quality of oocytes and embryos in ART programs and supplement the arsenal of already existing markers.

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About the authors

E. A Kalinina

Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: e_kalinina@oparina4.ru
M.D., Ph.D., Head of the Department of assistive reproductive technology in the treatment of infertility

A. E Donnikov

Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: a_donnikov@oparina4.ru
PhD, senior researcher of laboratory of molecular genetic methods

I. V Vladimirova

Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: i_teterina@oparina4.ru
postgraduate of the Department of assistive reproductive technology in the treatment of infertility

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