Authors: M. Králíčková 1,2; R. Šíma 3; P. Martínek 3; T. Vaněček 3; Z. Ulčová-Gallová 1; P. Šíma 4; J. Křižan 4; V. Kališ 1; Štěpán Jr. 1; J. Štěpán 5; Z. Rokyta 1; P. Uher 1,2; O. Hes 3 Authors‘ workplace: Gynekologicko-porodnická klinika LF UK a FN, Plzeň, přednosta doc. MUDr. Z. Rokyta, CSc. 1; Institut reprodukční medicíny a endokrinologie, Plzeň 2; Ústav patologické anatomie a histologie LF UK a FN, Plzeň 3; Oddělení imunologie a gnotobiologie, Mikrobiologický ústav AV ČR, Praha 4; Sanatorium Sanus, Hradec Králové 5 Published in: Ceska Gynekol 2007; 72(4): 293-298 Category: Original Article
Objective: The leukemia inhibitory factor (LIF) is one of the most important signaling factors in the embryo-maternal cross talk during the embryo implantation. We investigated the prevalence of the LIF gene mutations in the population of infertile women and their impact on infertility treatment.
Design: A cohort study.
Setting: Department of Obstetrics and Gynecology, Faculty of Medicine and University Hospital of Charles University, Pilsen.
Subjects and methods: The population to screen consisted of 399 infertile women. The control population was comprised of 202 healthy fertile subjects. For the mutational analysis, the temperature gradient gel electrophoresis (TGGE) followed by subsequent sequencing of the positive samples, had been used. The groups of fertile controls and infertile patients were compared for statistically significant difference using the Fisher’s 2 by 2 Exact test.
Results: Twelve potentially functional LIF gene mutations, the G to A transversion at the position 3400 leading to the valin to methionin exchange at codon 64 (V64M) were detected in the group of infertile women. No mutations were identified in the control group, which means that the frequency of functionally relevant mutations of the LIF gene in infertile women is significantly enhanced in comparison with controls (P = 0.01, Fisher’s 2 by 2 Exact test ). Seven of these patients were successfully treated by in vitro fertilization (IVF).
Conclusion: The results suggest that the LIF gene mutation, the heterozygote G to A transition on the position 3400, affects fertility but the infertility treatment can succeed. Even though LIF gene mutations occur infrequently and can be overcome by infertility treatment, their impact on molecular events during early phases of pregnancy should be further elucidated.
Key words: leukemia inhibitory factor (LIF); mutation; embryo implantation; infertility, assisted reproduction, in vitro fertilization, temperature gradient gel electrophoresis, DNA sequencing
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