Endocrinology of the peri-implantation period

Current research suggests that the appearance of endometrial integrins and pinopode appearance signal the opening of the receptive phase of the endometrium. These integrins may be activated by the interleukin-1 system (IL-1). IL-1beta, expressed by the blastocyst, induces vascular endothelial growth factor (VEGF) which, in turn, promotes angiogenesis and integrin expression in endometrial cells. The IL-1 system also triggers the expression of gamma interferon (IFN-gamma) from T lymphocytes. Decidual natural killer (NK) lymphocytes interact with invading trophoblast to generate leukaemia inhibitory factor (LIF). LIF induces uPA and gelatinase, enzymes which play a crucial role in trophoblastic invasion. Progesterone is a potent inhibitor of LIF, while oestrogen is a potent inducer. Oestrogen in serum reflects follicular IL-1beta level and correlates with the outcome of embryo transfer after in vitro fertilization (IVF). Progesterone induces nitric oxide (NO) synthesis in the decidua, and NO promotes local vasodilatation and uterine quiescenceMeasurement of placental protein 14 (PP14, glycodelin-A) in serum may be of value as a screening test for implantation potential. However, human chorionic gonadotrophin (hCG) remains the most reliable predictor of successful implantation and pregnancy viability. An ovulation + 14 hCG level < 50 IU/l is often predictive of a non-viable outcome, while an ovulation + 21 hCG of < 200 IU/l always indicates a non-viable pregnancy. hCG secretion by invading trophoblast appears to be negatively modulated by endothelin-1 (ET-1) and prostaglandin F(2alpha)(PGF2alpha), while tissue growth factors and collagenases are positive modulators of hCG expression.ProalphaC, an inhibin pro-monomer, may have some value in monitoring corpus luteum function. Inhibin A, activin A and follistatin all rises throughout pregnancy and peak at 36 weeks of gestation. Relaxin is another ovarian hormone that may have a role in predicting implantation. Relaxin induces placental protein 14 (PP14, glycodelin-A) expression in a receptive endometrium, and measurement of serum PP14 may be of value as a screening test for implantation potential.