Leukaemia inhibitory factor (LIF) gene mutations in women with unexplained infertility and recurrent failure of implantation after IVF and embryo transfer.
OBJECTIVE
Leukaemia inhibitory factor (LIF) plays a central role in the control of implantation. We undertook this study to investigate the prevalence of LIF gene alterations in women with unexplained infertility and with recurrent failure of implantation after in vitro fertilisation (IVF) and embryo transfer.


METHODS
Forty five women with recurrent failure of implantation after IVF (group A), 50 with unexplained infertility (group B) and 105 fertile women (controls) were screened for LIF gene mutations. Standard genomic DNA extraction, PCR amplification of the LIF gene and single-strand conformation polymorphism (SSCP) analysis were used to search for mutations which were subsequently confirmed by DNA sequencing.


RESULTS
In group A, one woman was identified as having a neutral LIF gene polymorphism in exon 3 without affecting protein conformation. In group B, one woman with a heterozygous mutation and one with a neutral polymorphism were detected. In controls, only one woman with a neutral polymorphism in the intron between exons 2 and 3 was found. The woman with a potentially functional LIF gene mutation in group B achieved an ongoing clinical pregnancy after ovarian superovulation.


CONCLUSIONS
Potentially functional mutations in the LIF gene do infrequently occur in women with unexplained infertility and may play a role in the etiology of infertility. However, routine screening for LIF mutations or polymorphisms in these women is not justified for the low prevalence of gene alterations.
Steck
Thomas
T
Department of Obstetrics and Gynecology, University of Wuerzburg, Josef-Schneider-Strasse 4, D-97080 Wuerzburg, Germany. thomas.steck@mail.uni-wuerzburg.de
Giess
Ralf
R
Suetterlin
Marc W
MW
Bolland
Monika
M
Wiest
Stephanie
S
Poehls
Uwe G
UG
Dietl
Johannes
J
D000026:Abortion, Habitual / Q000235:genetics; D000328:Adult; D015153:Blotting, Western; D016022:Case-Control Studies; D004624:Embryo Transfer; D005260:Female; D005307:Fertilization in Vitro / Q000009:adverse effects / Q000379:methods*; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007247:Infertility, Female / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D053605:Leukemia Inhibitory Factor; D008183:Luteal Phase; D009154:Mutation; D011247:Pregnancy; D011336:Probability; D011863:Radioimmunoassay; D012016:Reference Values; D018570:Risk Assessment; D012494:Sampling Studies; D018709:Statistics, Nonparametric; D017211:Treatment Failure
D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor