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<p>Leukemia inhibitory factor (LIF) is a cytokine recognized for its various roles, including its involvement in embryo implantation and supporting the survival, proliferation, and maintenance of pluripotency in endometrial stromal cells. LIF affects the integrins present on the surface of endometrial cells, aiding the adhesion of trophoblastic cells to these endometrial cells during the process of blastocyst implantation. The objective of this study was to investigate the association between serum LIF levels and the Val64Met genetic variant concerning in vitro fertilization and embryo transfer (IVF-ET) outcomes. This case-control study included a total of 400 women, comprised of 200 infertile participants who had faced unsuccessful IVF attempts (the IVF- or recurrent implantation failure (RIF) group is typically defined as having failed at least three IVF cycles with good quality embryos transferred without resulting in a pregnancy) and 200 fertile participants with successful IVF outcomes (IVF +) serving as controls, recruited from the IVF Department at Alzahra Hospital in Rasht, Iran. Genomic DNA was extracted from peripheral blood leukocytes and analyzed via allele-specific polymerase chain reaction. Serum LIF levels were quantified using enzyme-linked immunosorbent assay. In the IVF<sup>–</sup> group, the proportions of genotypes GG, GA, and AA were 26%, 72.5%, and 1.5%, respectively, while in the IVF<sup>+</sup> group, these were 22%, 76%, and 2% (<i>P</i> = 0.61). The frequencies of the A and G alleles in the IVF<sup>–</sup> group were 37.75% and 62.25%, respectively, in contrast to 60% and 40% in the IVF+ group (<i>P</i> = 0.51). A significant reduction in serum LIF levels was observed in the IVF<sup>–</sup> group (67.41 ± 11.84&#xa0;pg/ml) compared to the IVF<sup>+</sup> group (82.43 ± 16.31&#xa0;pg/ml) (<i>P</i> &lt; 0.0001) (<i>n</i> = 200 for each group). Therefore, it can be inferred that the LIF Val64Met (rs41281637) gene variation does not appear to affect the results of IVF-ET. Nevertheless, a significant connection seems to exist between serum LIF levels and IVF-ET outcomes. In conclusion, while the LIF Val64Met (rs41281637) gene variation may not correlate with IVF-ET outcomes in the northern Iranian population, the serum concentration of LIF shows a significant relationship with IVF-ET results.</p>

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Leukemia inhibitory factor Val64Met (rs41281637) genetic variation and circulating levels in risk prediction of in vitro fertilization and embryo transfer outcome

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  • 发表日期：

    2025年9月12日

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  • Shabnam Vahdani,
  • Farhad Mashayekhi,
  • Mohammad Hadi Bahadori,
  • Zivar Salehi

摘要

Leukemia inhibitory factor (LIF) is a cytokine recognized for its various roles, including its involvement in embryo implantation and supporting the survival, proliferation, and maintenance of pluripotency in endometrial stromal cells. LIF affects the integrins present on the surface of endometrial cells, aiding the adhesion of trophoblastic cells to these endometrial cells during the process of blastocyst implantation. The objective of this study was to investigate the association between serum LIF levels and the Val64Met genetic variant concerning in vitro fertilization and embryo transfer (IVF-ET) outcomes. This case-control study included a total of 400 women, comprised of 200 infertile participants who had faced unsuccessful IVF attempts (the IVF- or recurrent implantation failure (RIF) group is typically defined as having failed at least three IVF cycles with good quality embryos transferred without resulting in a pregnancy) and 200 fertile participants with successful IVF outcomes (IVF +) serving as controls, recruited from the IVF Department at Alzahra Hospital in Rasht, Iran. Genomic DNA was extracted from peripheral blood leukocytes and analyzed via allele-specific polymerase chain reaction. Serum LIF levels were quantified using enzyme-linked immunosorbent assay. In the IVF– group, the proportions of genotypes GG, GA, and AA were 26%, 72.5%, and 1.5%, respectively, while in the IVF+ group, these were 22%, 76%, and 2% (P = 0.61). The frequencies of the A and G alleles in the IVF– group were 37.75% and 62.25%, respectively, in contrast to 60% and 40% in the IVF+ group (P = 0.51). A significant reduction in serum LIF levels was observed in the IVF– group (67.41 ± 11.84 pg/ml) compared to the IVF+ group (82.43 ± 16.31 pg/ml) (P < 0.0001) (n = 200 for each group). Therefore, it can be inferred that the LIF Val64Met (rs41281637) gene variation does not appear to affect the results of IVF-ET. Nevertheless, a significant connection seems to exist between serum LIF levels and IVF-ET outcomes. In conclusion, while the LIF Val64Met (rs41281637) gene variation may not correlate with IVF-ET outcomes in the northern Iranian population, the serum concentration of LIF shows a significant relationship with IVF-ET results.