Can there be a genetic background of the primary idiopathic infertility?
The leukemia-inhibitory factor gene mutations in the population of infertile
women
Z. Rokyta (1), M. Králícková (1), Z. Ulcová-Gallová (1), P. Síma
(2), T. Vanecek (3), R. Síma (3), O. Hes (3)
Department of Obstetrics and Gynecology, University Hospital, Faculty of
Medicine, Charles University, Pilsen (1); Department of Immunology and
Gnothobiology, Institute of Microbiology, Czech Academy of Sciences, Prague (2);
Department of Pathology, University Hospital, Faculty of Medicine, Charles
University, Pilsen, Czech Republic (3)
Objective: Since the first successful In Vitro Fertilization (IVF) in
human and birth of Louise Joy Brown, the world’s first testtube baby (in 1978),
the number of patients using Assisted Reproductive Technologies (ART) has
increased tremendously. But ART are still not efficient enough – approximately
half of the women who seek medical treatment for infertility never give birth to
a child. During the past decade only one in six cycles of assisted conception
has resulted successfully in a live birth. As it was shown previously, leukemia
inhibitory factor (LIF) is one of the essential cytokines in molecular crosstalk
that influences the embryo implantation. ‘Errors’ in the embryo-endometrium
communication leading to difficulties with the embryo implantation are supposed
to be one of the causes of the relatively low pregnancy rates of ART and also
one of the causes of the primary idiopathic infertility (PII). We designed a LIF
gene mutation screening method that is based on the temperature-gradient gel
electrophoresis (TGGE) and subsequent sequencing.
Design & Methods: The population to screen consists of 105
clinically characterised group of women with diagnosed infertility including a
subgroup of 40 women with idiopathic primary infertility. The control population
comprises of 55 healthy control subjects that conceived spontaneously and
delivered successfully.
Results: Four LIF gene mutations were detected. In all cases the G to
A transition at the position 3400 of the human LIF gene was identified. This
position corresponds to region of the lif protein (AB loop) that is supposed to
be highly important for the LIF and LIF-receptor interaction. All positive women
were infertile. Three of them were diagnosed with primary idiopathic infertility
and had history of at least one unsuccessful in vitro fertilisation (IVF) cycle.
One of them got pregnant once (spontaneously) but suffered by spontaneus
abortion at the 6th week of her pregnancy. No positive TGGE samples were
identified in the control group.
Conclusions: Our results suggest that LIF gene mutations can lead to
embryo implantation failure and that way to infertility and decreased pregnancy
rates in assisted reproduction techniques. We believe that better understanding
of the genetic background of infertility belongs to the holistic approach to
reproductive health.
This study was supported by:Grant Agency of the Czech Republic, Grant No.
301/02/1232, Charles University, Institutional Research Concept No. VZ
111400005(6035).
