p57Kip2, a potent inhibitor of several cyclin/cyclin dependent kinase complexes (CDK ), is a paternally imprinted gene in both humans and mice, and here we show that pregnant mice which are heterozygous for p57Kip2 deficiency display symptoms similar to preeclampsia. p57-/+ (heterozygotes for p57Kip2 ) female mice that were mated with p57-/+ males showed hypertension, proteinuria, thrombocytopenia, decreased anti-thrombin III activity, and increased endothelin levels during late pregnancy. In their kidneys, endotheliosis of glomeruli were recognized along with fibrinoid or hyalinoid deposits. These characteristics were also observed in pregnant p57-/+ females that were mated with wild type males, but not in pregnant wild type females mated with p57-/+ males or wild type males. The pregnant p57-/+ mice had conceptuses both with and without p57Kip2 expression. The conceptuses without p57Kip2 expression showed trophoblastic hyperplasia, which mimics the hallmark proliferation of intermediate trophoblasts in clinical preeclampsia. It is suggested that the preeclampsia-like symptoms of the pregnant p57-/+ mice might have been induced by the conceptus(es) without p57Kip2 expression. In addition, pregnant p57-/+ mice might serve as a new animal model for preeclampsia characterized by trophoblastic hyperplasia.

The aim of the present study was to investigate the relationship between assisted reproductive technology procedures, the morphology of the basal plate of placentas, and amount of bleeding in deliveries. Fifty-five whole placentas (fresh-embryo transfer in the in vitro fertilization cycle [n = 6], frozen-thawed embryo transfer in the natural cycle [n = 13] or in the hormonal cycle [n = 10], and age-matched spontaneously conceived pregnancies [n = 26]) were retrospectively enrolled and histologically analyzed. The whole placentas were stored in our pathological division among 512 singleton pregnancies with vaginal deliveries (34-41 weeks of gestation) at Hamamatsu University Hospital. The morphology of the placental basal plate was examined using Azan staining. A total of 20 digital images (each 0.53 mm(2)) of microscopic fields were analyzed per placenta to measure the mean values of the vertical maximum thickness of Rohr and Nitabuch fibrinoid layers and % loss of decidua. The thickness of Rohr fibrinoid layer and % loss of decidua were significantly higher in the frozen-thawed embryo transfer in the hormonal cycle group than in the frozen-thawed embryo transfer in the natural cycle and spontaneously conceived pregnancy groups (each P < .01). The z scores for both the thickness of Rohr fibrinoid layer and % loss of decidua positively correlated with those for the amount of bleeding in deliveries (P < .05 each). Assisted reproductive technology procedures changed the morphology of the placental basal plate, suggesting a possible association with an increase in the amount of bleeding in deliveries.

Factor XII (FXII) is an important protease that plays a major role in the initiation of the intrinsic pathway of blood coagulation. Although congenital FXII deficiency is not associated with a clinical bleeding tendency, it can be identified on a routine coagulation test, such as a prolonged activated partial thromboplastin time. This deficiency is a rare autosomal recessive disorder. It is still unclear whether FXII deficiency causes any disorders during pregnancy. Recurrent miscarriages and placental abruption were reported in cases with FXII deficiency. We successfully treated a woman whose pregnancy was complicated by congenital FXII deficiency. We report her clinical courses of gestation, delivery, and puerperium and discuss the role of maternal FXII associated with pregnancy. In our case, courses of gestation and delivery were normal. Postpartum uterine bleeding was, however, prolonged due to a subinvolution of the puerperal uterus. Our results indicate that, except for postpartum uterine contraction, FXII does not play a major role in gestation and delivery. We suggest that FXII deficiency is not associated with recurrent miscarriage and that normal gestation and vaginal delivery are possible even in cases with congenital FXII deficiency. We assert that the possible correlation of FXII deficiency with recurrent miscarriage merits reevaluation.

Mature oocyte retrieval followed by natural rather than stimulated in vitro fertilization might be a potential treatment for patients of advanced age when stimulated in vitro fertilization has been repeatedly unsuccessful.

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