Possibilities for noninvasive oocyte and embryo evaluation when implementing assisted reproductive technology programs for follicular-fluid growth factor mRNA expression

The selection of an embryo with a high implantation potential is one of the leading factors of successful infertility treatment with assisted reproductive technologies (ART). Moreover, the quality of the embryo depends on the state of an oocyte whose adequate interaction with the surrounding cells duringfolliculogenesis is of great importance. A bidirectional intrafollicular dialogue is mediated through a number of regulatory molecules, growth factors, among which the family of epidermal growth factors, somatomedins, and other factors to form an integrated system, whose changed balance can impair oocyte development, play a particular role. Objective. To determine the relationship between the mRNA expression of follicular fluid growth factors, such as amphiregulin (AREG), epiregulin (EREG), gremlin 1 (GREM-1), heparin-binding epidermal growth factor (HBEGF), insulin-like growth factors 1 and 2 (IGF-1, IGF-2); insulin-like growth factor-binding proteins 1, 2, 3, and 4 (IGFBP-1, IGFBP-2, IGFBP-3, and IGFBP-4), leukemia-inhibitory factor (LIF), leukemia-inhibitory factor receptor (LIFR), tumor necrosis factor-a (TNF-а), and the outcomes of infertility treatment with ART. Subject and methods. Quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to study the profile of mRNA of the AREG, EREG, GREM-1, HBEGF, IGF-1, IGF-2, IGFBP-1,2,3,4, LIF, LIFR, and TNF-а genes in 67 married couples with different results of infertility treatment by in vitro fertilization during single/double embryo transfer. Of them, the successful outcome of an IVF-embryo transfer (ET) program was seen in 24 couples; its unsuccessful outcome was in 80 couples (13 couples with spontaneous miscarriage at less than 11 weeks), 24 couples with biochemical pregnancy, and 43 couples with a negative VF-ET outcome. Results. The mRNA expression of the growth factors AREG, EREG, and LIFR was shown to be significantly increased in the biochemical pregnancy group and in the negative IVF outcome group versus the clinical pregnancy group. There was a signif icant rise in the mRNA expression of IGF-1 by 1.6 times (p = 0.028) and by 1.2 times (p = 0.04) in the biochemical pregnancy and spontaneous miscarriage groups versus the negative outcome group. The poor IVF-ET outcome groups exhibited a significant positive correlation between mRNA for somatomedin-binding proteins (IGFBP-2/IGFBP-4) and with LIF. Conclusion. The investigation of the relationship of the mRNA expression of the follicular fluid growth factors to the outcomes of ART programs is a promising area in the comprehensive assessment of oocyte quality for selective single embryo transfer. The higher expression of the AREG, EREG, and LIFR genes is associated with early reproductive losses in the IVF program.

assisted reproductive technologies (ART), growth factor mRNA, amphiregulin (AREG), epiregulin (EREG), leukemia-inhibitory factor (LIF), leukemia-inhibitory factor receptor (LIFR), quantitative RT-PCR, follicular fluid, noninvasive diagnosis, selective embryo transfer