Rie Kawaguchi

Subsequent pregnancy outcomes in recurrent miscarriage patients with a paternal or maternal carrier of a structural chromosome rearrangement

AbstractInformation concerning the prognosis of subsequent pregnancies in patients with reciprocal translocations is limited. This study was performed to determine the percentage success rate with first pregnancies after ascertainment of a carrier status. A total of 2,382 couples with a history of two or more consecutive miscarriages were studied in multicenters. The prevalence of an abnormal chromosome in either partner was examined, and subsequent success rates were compared between cases with and without an abnormal karyotype in either partner. A total of 129 couples (5.4%) had an abnormal karyotype in one partner excluding inversion 9 in 44 men and in 85 women. Thus, 2,253 couples had a normal karyotype in both partner. Eighty-five (3.6%) had translocations, 13 being Robertsonian translocations. Twenty-nine of the 46 cases (63.0%) who became pregnant with reciprocal translocations in either partner experienced a live birth with natural conception. In contrast, 950 of 1,207 cases (78.7%) with normal chromosomes had successful live births, the difference being significant (P = 0.019). No infant with an unbalanced translocation was found in 29 cases of successful pregnancy following recurrent miscarriage. Pregnancy prognosis was worsened with either maternal or paternal reciprocal translocations. Explanation of the success rate with natural conception should be provided before the subsequent pregnancy after ascertainment of carrier status.

Multiple injections of anti-mouse β2glycoprotein 1 antibody induce FcRγ-dependent fetal growth restriction (FGR) in mice

OBJECTIVES The antiphospholipid syndrome (APS) is characterized by the presence of circulating antiphospholipid antibodies (aPLs), is a leading cause for thromboembolic events, repeated miscarriage, fetal loss and is a major risk factor for fetal growth restriction (FGR) and preeclampsia. In human, anti-β2 glycoprotein I (aβ2GPI) antibody is one of the aPLs and considered to be a specific and important marker for APS. However, pathophysiological changes induced by aβ2GPI antibodies in FGR are largely unknown. METHODS In the present study, we developed a murine FGR model induced by multiple injections of WBCAL-1, a well-characterized mouse aβ2GPI monoclonal antibody. RESULTS Administration of WBCAL-1, but not the isotype control antibody and saline, into pregnant mice specifically decreased the size of fetuses and placentas without affecting the number of delivered pups. Also, a significant increase in urinary albumin and electron microscopic changes, such as splitting layers of basal membranes in the placental labyrinth and rearrangement of pores in glomerular endothelial cells, were observed in WBCAL-1 treated mice. WBCAL-1 injection did not induce any changes in blood pressure and typical parameters of blood thromboembolic symptoms. Furthermore, FcRγ deficiency protected the fetuses from aβ2GPI antibody-induced injuries. CONCLUSIONS Our present findings suggest that proteinuria is a symptom associated with APS-related FGR with placental and renal tissue injuries, and that FcRγ might be a molecular target for prevention of aβ2GPI antibody-mediated obstetrical pathologies.

Prenatal imaging and pathology of placental mesenchymal dysplasia: a report of three cases

Abstract Objective: Placental mesenchymal dysplasia (PMD) is a rare vascular anomaly characterized by mesenchymal stem villous hyperplasia. Accurate differential diagnosis of PMD is crucial to predict fetal outcomes associated with serious obstetrical complications. Methods: We reviewed the clinical and pathological features and immunohistochemical and imaging findings of three patients with PMD. Results: First trimester sonographic cystic findings identified molar pregnancy or PMD. However, PMD was highly suspected according to the maternal serum human chorionic gonadotropin (hCG) titers, fetal karyotypes, and imaging findings. The outcome of patient 1, in whom placental multicystic areas decreased as pregnancy progressed, was a live birth. In contrast, the babies of patients 2 and 3 were stillborn, and multicystic formations detected during the first trimester completely and consistently occupied the placentas. Pathological and immunohistochemical analyses using anti-CD34 and anti-D2-40 antibodies distinguished the cisternae from multiple small vessels in the villi. Immunohistochemical analyses using anti-CK7 and anti-Ki-67 antibodies did not detect excessive proliferation of trophoblasts. Most abnormal villi associated with PMD comprised stromal cells that did not react with an anti-p57kip2 antibody. Conclusion: In patients with PMD, if the percentage of the normal placental area decreases as pregnancy progresses, the possibility of fetal growth restriction and intrauterine fetal demise should always be considered. The immunostaining pattern of CD34 and D2-40 may represent a unique feature of PMD and can provide supporting evidence for the differential diagnosis of PMD.