TNFα and MFG-E8: Novel Biomarkers to Predict Implantation Failure

Question: Can implantation failure (IF) be predicted prior to in vitro fertilization (IVF)? A pilot, non-interventional, clinical study Prospective, controlled, cohort study

Sex

Female

Minimum age

21 Years

Maximum age

35 Years

Inclusion Criteria:

* women 21-35y
* with no contraindication to pregnancy
* on no hormonal contraception
* normal uterine cavity
* absence of hydrosalpinges
* normal ovarian reserve (FSH\<13 mIU/.ml or AMH\>1 ng/ml or normal antral follicular count\>10 total follicles \<10 mm in diameter, American Society for Reproductive Medicine-ASRM 2012).
* Three groups of patients will be enrolled: 10 fertile controls (C1-10: women who are participating in the donor egg program as egg donors), 10 with unexplained implantation failure (IF1-10: patients who have failed IVF cycles -failure of implantation following 2 or more cycles with transfer of embryos of good quality-at least 2 cleaving embryos with 6-8 cells, grades 1- 3 (scale 1-highest and 5-poorest morphology score), and normal uterus, and 10 with recurrent unexplained first trimester miscarriages (RM1-10: 2 consecutive miscarriages under 10 weeks, after spontaneous or IVF conceptions).

Exclusion Criteria:

* contraindication to pregnancy
* use of hormonal contraception
* abnormal uterine cavity
* hydrosalpinges
* abnormal karyotype.
* women who are pregnant or planning to get pregnant in the cycle in which they are participating in this study
* women who have had a hysterectomy (previous removal of your uterus)
* have a current medical condition, which, in the opinion of the investigator, would result in hazards to the subject, should she participate in the study or have a current medical condition which would potentially confound the study results.

• BACKGROUNDYu L, Anderson S, Oehninger S, Bocca S. Tumor necrosis factor alpha up-regulates endometrial milk fat globule-epidermal growth factor 8 protein production via nuclear factor kappaB activation, resulting in cell migration of epithelial cells. Fertil Steril. 2014 Feb;101(2):552-9. doi: 10.1016/j.fertnstert.2013.10.032. Epub 2013 Nov 18. PMID 24262600
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• BACKGROUNDSarhan et al, MFG-E8 (milk fat globule EGF factor 8 protein) is a novel endometrial epithelial glycoprotein regulated by human chorionic gonadotropin (hCG) and secreted via microparticles. J Cell Signaling and Trafficking 2013
• BACKGROUNDBocca SM, Anderson S, Amaker B, Swanson RJ, Franchi A, Lattanzio F, Oehninger S. Milk fat globule epidermal growth factor 8 (MFG-E8): a novel protein in the mammalian endometrium with putative roles in implantation and placentation. Placenta. 2012 Oct;33(10):795-802. doi: 10.1016/j.placenta.2012.06.015. Epub 2012 Jul 5. PMID 22770563
• BACKGROUNDRiggs RM, Bocca S, Anderson S, Franchi A, Rhavi BS, Oehninger S. Epithelial cell protein milk fat globule-epidermal growth factor 8 and human chorionic gonadotropin regulate stromal cell apoptosis in the human endometrium. Fertil Steril. 2012 Dec;98(6):1549-56.e3. doi: 10.1016/j.fertnstert.2012.07.1127. Epub 2012 Aug 24. PMID 22921913
• BACKGROUNDFranchi A, Bocca S, Anderson S, Riggs R, Oehninger S. Expression of milk fat globule EGF-factor 8 (MFG-E8) mRNA and protein in the human endometrium and its regulation by prolactin. Mol Hum Reprod. 2011 Jun;17(6):360-71. doi: 10.1093/molehr/gaq102. Epub 2010 Dec 21. PMID 21177637