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Objective: While immune cells were originally thought to only play a role in maternal tolerance of the semiallogenic fetus, an active role in pregnancy establishment is becoming increasingly apparent. Uterine natural killer (uNK) cells are of specific interest because of their cyclic increase in number during the window of implantation. As a distinct entity from their peripheral blood counterparts, understanding the biology and function of uNK cells will provide the framework for understanding their role in early pregnancy establishment and adverse pregnancy outcomes. Evidence Review: This review discusses unique uNK cell characteristics and presents clinical implications resulting from their dysfunction. We also systematically present existing knowledge about uNK cell function in three processes critical for successful human embryo implantation and placentation: stromal cell decidualization, spiral artery remodeling, and extravillous trophoblast invasion. Finally, we review the features of uNK cells that could help guide future investigations. Results: It is clear the uNK cells are intimately involved in multiple facets of early pregnancy. This is accomplished directly, through the secretion of factors that regulate stromal cells and trophoblast function; and indirectly, via interaction with other maternal cell types present at the maternal-fetal interface. Current work also suggests that uNK cells are a heterogenous population, with subsets that potentially accomplish different functions. Conclusion: Establishment of pregnancy through successful embryo implantation and placentation requires crosstalk between multiple maternal cell types and invading fetal trophoblast cells. Defects in this process have been associated with multiple adverse perinatal outcomes including hypertensive disorders of pregnancy, placenta accreta, and recurrent miscarriage though the mechanism underlying development of these defects remain unclear. Abnormalities in NK cell number and function which would disrupt physiological maternal-fetal crosstalk, could play a critical role in abnormal implantation and placentation. It is therefore imperative to dissect the unique physiological role of uNK cells in pregnancy and use this knowledge to inform clinical practice by determining how uNK cell dysfunction could lead to reproductive failure.
RESUMO
OBJECTIVE: To evaluate trends of monozygotic twinning after single embryo transfer and its association with patient and treatment factors. METHODS: Our retrospective cohort study included 28,596 pregnancies after fresh, nondonor single embryo transfer during 2003-2012 reported to the National ART Surveillance System. We examined trends of monozygotic twin pregnancies (number of fetal heart tones on first-trimester ultrasonography more than one or number of neonates born more than one) and assessed patient and treatment factors for monozygotic twin compared with singleton pregnancies. Modified Poisson regression models were used to estimate adjusted risk ratios (RRs) and 95% confidence intervals (CIs) for association between monozygotic twinning and selected factors stratified by day 2-3 and day 5-6 transfer. RESULTS: During 2003-2012, the incidence of monozygotic twinning after single embryo transfer was lower for day 2-3 transfers than for day 5-6 transfers (1.71%, 95% CI 1.45-1.98, n=162 compared with 2.50%, 95% CI 2.28-2.73, n=472); the incidence did not change significantly over the study period. Among day 2-3 transfers, assisted hatching increased the risk for monozygotic twinning compared with singletons (adjusted RR 2.16, 95% CI 1.53-3.06); use of intracytoplasmic sperm injection decreased the risk (adjusted RR 0.60, 95% CI 0.42-0.85). Having one or more prior pregnancies increased the risk for monozygotic twinning among day 5-6 transfers (adjusted RR 1.26, 95% CI 1.03-1.53). CONCLUSION: Monozygotic twinning after single embryo transfers was more common among day 5-6 embryo transfers than day 2-3 transfers. Use of assisted hatching was associated with increased risk for monozygotic twinning for day 2-3 transfers. LEVEL OF EVIDENCE: II.
