Leukaemia Inhibitory Factor (<i>LIF</i>) Gene Mutations in Women Diagnosed with Unexplained Infertility and Endometriosis Have a Negative Impact on the IVF Outcome A Pilot Study

Novotný, Z.; Křížan, J.; Šíma, R.; Šíma, P.; Uher, P.; Zech, N.; Hüttelová, R.; Baborová, P.; Ulčová-Gallová, Z.; Šubrt, I.; Ulmanová, E.; Houdek, Z.; Rokyta, Z.; Babuška, V.; Králíčková, Milena

doi:10.14712/fb2009055030092

Folia Biologica > Archive > 2009, Vol. 55 > Issue 3 > Leukaemia Inhibitory Factor (LIF)…

Fol. Biol. 2009, 55, 92-97

https://doi.org/10.14712/fb2009055030092

Leukaemia Inhibitory Factor (LIF) Gene Mutations in Women Diagnosed with Unexplained Infertility and Endometriosis Have a Negative Impact on the IVF Outcome A Pilot Study

Z. Novotný¹, J. Křížan², R. Šíma³, P. Šíma², P. Uher^1,4, N. Zech^5,6, R. Hüttelová⁴, P. Baborová⁴, Z. Ulčová-Gallová¹, I. Šubrt⁷, E. Ulmanová⁴, Z. Houdek⁴, Z. Rokyta¹, V. Babuška⁸, Milena Králíčková^1,4

¹Charles University in Prague, Faculty of Medicine in Pilsen and University Hospital, Department of Obstetrics and Gynecology, Pilsen, Czech Republic
²Department of Immunology and Gnotobiology, Institute of Microbiology v. v. i., Academy of Sciences of the Czech Republic, Prague, Czech Republic
³Charles University in Prague, Faculty of Medicine in Pilsen and University Hospital, Department of Pathology, Pilsen, Czech Republic
⁴Institute of Reproductive Medicine and Endocrinology, Pilsen, Czech Republic
⁵Department of Obstetrics and Gynecology, University Hospital Zurich, Zurich, Switzerland
⁶Reproductive Genetics Institute, Chicago, Illinois, USA
⁷Charles University in Prague, Faculty of Medicine in Pilsen and University Hospital, Department of Genetics, Pilsen, Czech Republic
⁸Charles University in Prague, Faculty of Medicine in Pilsen and University Hospital, Department of Biochemistry, Pilsen, Czech Republic

Received September 2008
Accepted March 2009

The frequency of functionally relevant mutations of the leukaemia inhibitory factor (LIF) gene in infertile women is significantly enhanced in comparison with fertile controls. The objective of this retrospective cohort study was to evaluate the impact of LIF gene mutations on the outcome of the treatment in women with various causes of infertility. Fifteen infertile women with the G to A transition at position 3400 leading to the valine to methionine exchange at codon 64 were analysed. Group A was made up of women with diagnoses that are frequently accompanied by changes in humoral as well as cell-mediated immunity – idiopathic infertility and endometriosis (N = 7). Group B consisted of patients with polycystic ovary syndrome (PCOS), andrological factor, tubal factor and hyperprolactinaemia (N = 8). The control group comprised 136 infertile women with no LIF gene mutation diagnosed with idiopathic infertility and endometriosis (N = 37) (group C) and patients with PCOS, tubal and andrological factor (N = 99) (group D). Seven of the mutation-positive patients were successfully treated by in vitro fertilization (IVF), but nobody in this group was diagnosed with idiopathic infertility and only one with endometriosis, which means that there is a statistically significant difference in the pregnancy rates between groups A and B (P = 0.01, Fisher’s 2 by 2 exact test) but no statistically significant difference when comparing patients with the LIF gene mutation (group A+B) to no LIF gene mutation (group C+D). The results suggest that in mutation-positive women the idiopathic infertility and endometriosis have a negative impact on the outcome of IVF treatment.

Keywords

leukaemia inhibitory factor (LIF), mutation, infertility, in vitro fertilization.

Funding

This study was supported by the Internal Grant Agency of the Ministry of Health IGA MZd NR/ 9135-3 (M. Králíčková), by the Institutional Research Concept AV 0Z 50200510 (P. Šíma) and MSM 0021620812 (Z. Ulčová-Gallová).