OBJECTIVE: Leukemia inhibitory factor (LIF) is one of the key cytokines in the embryo implantation regulation. We investigated the prevalence of the LIF gene mutations in the population of infertile women that consisted of nulligravid and secondary infertile patients. STUDY DESIGN: We designed a LIF gene mutation screening method that is based on the Temperature Gradient Gel Electrophoresis (TGGE). The population to screen consisted of 176 infertile women including group A of 147 nulligravid women and group B of 29 women with secondary infertility that had a history of either miscarriage or an ectopic pregnancy but no live births. The control population was comprised of 75 healthy fertile subjects. The groups of fertile controls and infertile patients were compared for statistically significant differences using the t-test. RESULTS: Six potentially functional LIF gene mutations, the G to A transitions at the position 3400 leading to the valin to methionin exchange at codon 64 (V64M) in the AB loop region of the LIF protein, were detected. All of the six positive women were infertile. Four of them were nulligravid and two of them had history of spontaneous conception followed by early miscarriage. No positive TGGE samples 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<0.05, t-test). CONCLUSION: The results suggest that the LIF gene mutations affect fertility. Even though they occur infrequently, their impact on molecular events during early phases of pregnancy should be further established.

Department of Obstetrics and Gynecology University Hospital Faculty of Medicine Charles University Capkovo namesti 1 Plzen CZ 326 00 Czech Republic

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Association of the leukemia inhibitory factor gene mutation and the antiphospholipid antibodies in the peripheral blood of infertile women

Role of the leukemia-inhibitory factor gene mutations in infertile women: the embryo-endometrial cytokine cross talk during implantation--a delicate homeostatic equilibrium