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Implantation factors, fertility and IVF
Summary
The failure of a human embryo to implant in an adequately prepared maternal endometrium (receptive endometrium) results in infertility. There is currently no way of diagnosing endometrial infertility. We have identified critical factors that prepare the endometrium for implantation and are now investigating precisely how these proteins regulate endometrial receptivity.
Description
Implantation failure results in infertility which affects 10% of couples worldwide.
For 25% of all couples experiencing infertility this remains ‘unexplained'. However it is known that during IVF about 75% of the embryos transferred fail to implant and develop.
Currently there is no practical means of determining whether the endometrium is optimally prepared or receptive for implantation due to the lack of reliable biomarkers; identifying such biomarkers is essential.
While numerous genes have been associated with receptivity their importance in human implantation remains to be determined.
We have identified two cytokines, interleukin 11 (IL-11) and leukemia inhibitory factor (LIF) that have critical roles in receptivity.
We will determine how these cytokines regulate receptivity and whether they are abnormal in endometrium of women who are infertile for unknown reasons or who are unsuccessful following IVF.
This project will utilise our state-of-the-art proteomics facility and a range of relevant in vitro models and in vivo models where appropriate, and will also determine whether the identified factors are abnormal in women with infertility.
Funding
National Health and Medical Research Council
Contraceptive Research and Development Agency (CONRAD), USA
Outcomes
This research has shown that:
IL-11 and LIF are abnormal in the endometrium of women with infertility and endometriosis.
IL-11 is abnormal in the endometrium in cases of unexplained infertility.
IL-11 and LIF regulate endometrial cell function that is important for embryo implantation.
Selected Publications
Marwood E, Visser K, LA Salamonsen, E Dimitriadis (2009) Interleukin 11 and leukemia inhibitory factor regulate the adhesion of endometrial epithelial cells: implications in fertility regulation. Endocrinology, 150:2915-23
White CA, Zhang J-G, Salamonsen LA, Baca M, Fairlie WD, Metcalf D, Nicola NA, Robb L, Dimitriadis E (2007) Blocking leukemia inhibitory factor action in the uterus using a novel PEGylated antagonist prevents implantation: a new non-hormonal contraceptive strategy. Proc Natl Acad Sci USA 104:19357-62. (Work included in an Editorial in Science, 318: 1835 (2007) and PNAS cover feature).
Dimitriadis E, Stoikos C, Stafford-Bell M, Clark I, Paiva P, Kovacs G, Salamonsen LA (2006) Interleukin-11, IL-11 receptor alpha and leukemia inhibitory factor are dysregulated in endometrium of infertile women with endometriosis during the implantation window. Journal of Reproductive Immunology. 69:53-64.
Dimitriadis E, Sharkey AM, Tan YL, Sherwin JR (2007) Immunolocalisation of phosphorylated STAT3, interleukin 11 and leukaemia inhibitory factor in endometrium of women with unexplained infertility during the implantation window. Reprod Biol Endocrinol 5(1):44.