Intrauterine device insertion after medical abortion.

BACKGROUND: Studies comparing immediate intrauterine device (IUD) insertion after first-trimester surgical abortion with interval insertion show similar efficacy and expulsion rates. However, women randomized to interval insertion of an IUD are less likely to return for device placement. An ideal time to insert intrauterine contraception may be the day a woman presents for verification of a completed medical abortion. We examined immediate insertion of IUDs after completed first-trimester medical abortion. STUDY DESIGN: This is a prospective, observational clinical study to determine expulsion rates of intrauterine contraception placed immediately after confirmed, completed first-trimester medical abortion. RESULTS: Of 118 subjects, 78 women had levonorgestrel IUDs placed, whereas 41 women received copper IUDs. Of 97 subjects who completed the study, there were 4 clinical expulsions (4.1%) during 3 months of follow-up. There were no diagnosed pelvic infections, pregnancies, or uterine perforations. The continuation rate at 3 months was 80%. CONCLUSION: Intrauterine devices inserted at the time of completed, confirmed first-trimester medical abortion have low rates of expulsion.

Relationship of intraamniotic digoxin to fetal demise.

BACKGROUND: Induced fetal demise by intraamniotic injection of digoxin is an alternative to methods using intracardiac or umbilical vein injection. This study was designed to evaluate the effectiveness of intraamniotic injection and the timing of fetal demise after injection. STUDY DESIGN: Twenty-two women had ultrasonic fetal cardiac assessments 1, 2, 4 and 20 to 24 h after intraamniotic injection of 1.5 mg digoxin. RESULTS: Fetal cardiac activity was absent in 21/21 women assessed at least 20 h after injection. One woman had agonal (40 bpm) fetal cardiac activity at 14 h. Most women had fetal cardiac activity 4 h after injection. Signs of toxicity were not seen. CONCLUSION: Intraamniotic injection of digoxin 1.5 mg is effective at causing fetal demise by 20 to 24 h. However, for most women, fetal demise is not obtained within 4 h.

Gene expression profiling of the human maternal-fetal interface reveals dramatic changes between midgestation and term.

Human placentation entails the remarkable integration of fetal and maternal cells into a single functional unit. In the basal plate region (the maternal-fetal interface) of the placenta, fetal cytotrophoblasts from the placenta invade the uterus and remodel the resident vasculature and avoid maternal immune rejection. Knowing the molecular bases for these unique cell-cell interactions is important for understanding how this specialized region functions during normal pregnancy with implications for tumor biology and transplantation immunology. Therefore, we undertook a global analysis of the gene expression profiles at the maternal-fetal interface. Basal plate biopsy specimens were obtained from 36 placentas (14-40 wk) at the conclusion of normal pregnancies. RNA was isolated, processed, and hybridized to HG-U133A&B Affymetrix GeneChips. Surprisingly, there was little change in gene expression during the 14- to 24-wk interval. In contrast, 418 genes were differentially expressed at term (37-40 wk) as compared with midgestation (14-24 wk). Subsequent analyses using quantitative PCR and immunolocalization approaches validated a portion of these results. Many of the differentially expressed genes are known in other contexts to be involved in differentiation, motility, transcription, immunity, angiogenesis, extracellular matrix dissolution, or lipid metabolism. One sixth were nonannotated or encoded hypothetical proteins. Modeling based on structural homology revealed potential functions for 31 of these proteins. These data provide a reference set for understanding the molecular components of the dialogue taking place between maternal and fetal cells in the basal plate as well as for future comparisons of alterations in this region that occur in obstetric complications.

EPHB4 regulates chemokine-evoked trophoblast responses: a mechanism for incorporating the human placenta into the maternal circulation.

In humans, fetal cytotrophoblasts leave the placenta and enter the uterine wall, where they preferentially remodel arterioles. The fundamental mechanisms that govern these processes are largely unknown. Previously, we have shown that invasive cytotrophoblasts express several chemokines, as well as the receptors with which they interact. Here, we report that these ligand-receptor interactions stimulate cytotrophoblast migration to approximately the same level as a growth factor cocktail that includes serum. Additionally, cytotrophoblast commitment to uterine invasion was accompanied by rapid downregulation of EPHB4, a transmembrane receptor associated with venous identity, and upregulation of ephrin B1. Within the uterine wall, the cells also upregulated expression of ephrin B2, an EPH transmembrane ligand that is associated with arterial identity. In vitro cytotrophoblasts avoided EPHB4-coated substrates; upon co-culture with 3T3 cells expressing this molecule, their migration was significantly inhibited. As to the mechanisms involved, cytotrophoblast interactions with EPHB4 downregulated chemokine-induced but not growth factor-stimulated migration. We propose that EPHB4/ephrin B1 interactions generate repulsive signals that direct cytotrophoblast invasion toward the uterus, where chemokines stimulate cytotrophoblast migration through the decidua. When cytotrophoblasts encounter EPHB4 expressed by venous endothelium, ephrin B-generated repulsive signals and a reduction in chemokine-mediated responses limit their interaction with veins. When they encounter ephrin B2 ligands expressed in uterine arterioles, migration is permitted. The net effect is preferential cytotrophoblast remodeling of arterioles, a hallmark of human placentation.

Human cytotrophoblasts promote endothelial survival and vascular remodeling through secretion of Ang2, PlGF, and VEGF-C.

Cytotrophoblasts are specialized epithelial cells of the human placenta that differentiate to acquire tumor-like properties that allow them to invade the uterus. Concurrently, they develop endothelial-like characteristics. This transformation allows cytotrophoblasts to replace the maternal cells that line uterine vessels, thereby diverting maternal blood to the placenta. Previously, we showed that invading cytotrophoblasts secrete VEGF-C and PlGF, factors that regulate their acquisition of an endothelial-like phenotype. Here, we examined the cells' expression of angiopoietin ligands and their Tie receptors. The data show that cytotrophoblasts predominantly expressed Ang2. We also studied the paracrine functions of Ang2 and the VEGFs by culturing uterine microvascular endothelial cells in cytotrophoblast-conditioned medium, which supported their growth. Removal of VEGF-C, PlGF, and/or Ang2 from the medium caused a marked reduction in cell number due to massive apoptosis. We also assayed the angiogenic potential of cytotrophoblast-derived factors in the chick chorioallantoic membrane assay. The results showed that they stimulated angiogenesis to a level comparable to that of basic FGF. These data suggest that invasive human cytotrophoblasts use an unusual repertoire of factors to influence the angiogenic state of maternal blood vessels and that this cross talk plays an important part in the endovascular component of uterine invasion.