Human Reproduction, Vol. 18, No. 3, 608-615,
March 2003
© 2003 European Society of Human Reproduction and Embryology
Analysis of intra-uterine cytokine concentration and matrix-metalloproteinase activity in women with recurrent failed embryo transfer
1 Reproductive Biology Unit in the Royal Women’s Hospital, 2 The Department of Obstetrics and Gynaecology, University of Melbourne, Royal Women’s Hospital, Melbourne and 3 The Pregnancy Research Centre in the Royal Women’s Hospital, Carlton, Victoria, Australia
4 Present address: Obstetrics and Gynecology, Saitama Municipal Hospital, 2460, Saitama City, Saitama Pref., Japan 336-8522
5 To whom correspondence should be addressed at: Reproductive Biology Unit, The Royal Women’s Hospital, 132, Grattan Street, Carlton, Victoria, 3053, Australia. e-mail: david.wilkinson150{at}mivf.com.au
BACKGROUND: In all IVF programmes, some patients fail to achieve an ongoing pregnancy, even after numerous embryo transfer procedures. An unfavourable environment within the uterus might be a contributory factor to such recurrent implantation failure. This question was addressed by measuring cytokine concentrations and matrix metalloproteinase activities in fluid derived from uterine irrigation of such patients. METHODS AND RESULTS: The uterine cavities of 22 patients who had previously undergone embryo transfer of at least 10 embryos without ongoing pregnancy were irrigated during the luteal phase. The resultant fluid was assayed for the concentration of interleukin (IL)-1beta, tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, leukaemia inhibitory factor (LIF), IL-10 and matrix metalloproteinase (MMP) -2 and -9 activity. The results were compared with those of a control population of women known to be previously fertile (n = 16) and also with women with recurrent spontaneous abortion (n = 13). In the recurrent implantation failure group, the MMP score and IL-1beta concentration were significantly higher than those in the control group, whereas concentrations of IFN-gamma and IL-10 were significantly lower. CONCLUSIONS: In IVF patients with recurrent implantation failure, an altered pattern of intra-uterine cytokine concentration and MMP activity was observed.
Key words: implantation failure/interleukin-1beta/interleukin-10/matrix metalloproteinase/uterine flushing
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