Mitsuhiro Tsuritani

Retrospective Evaluation of CO2 Laser Conization in Pregnant Women with Carcinoma in situ or Microinvasive Carcinoma

Background: We evaluated the safety and efficacy of CO2 laser conization in pregnant women with cervical intraepithelial neoplasia 3/carcinoma in situ (CIN3/CIS) or microinvasive carcinoma (MIC). Objectives: A total of 49 pregnant women with biopsy-proven CIN3/CIS (30 patients) or MIC (19 patients) were studied.Methods: Retrospective analysis based on clinical records. Results: Median age and median week of gestation were 31 years (range: 22–39) and 17 weeks (range: 7–33), respectively. The median length of cervix resected by conization, median duration of surgery and median blood loss were 14 mm (range: 5–23), 20 min (range: 7–35) and 78 ml (range: 10–797), respectively. One biopsy-proven CIN3/CIS patient was diagnosed with Federation of Gynecology and Obstetrics (FIGO) Ia2 and 3 biopsy-proven MIC patients were diagnosed with FIGO Ib1 based on conization specimens. A total of 35 patients could be followed until delivery, of which 27 (77.1%) patients delivered transvaginally. Although 8 patients (22.9%) had a cesarean section and 6 patients (17.1%) delivered preterm, no conization-related obstetric complications were observed. Conclusion: Since it results in few obstetric complications, CO2 laser conization within 20 mm of length can be considered a safe procedure for pregnant women.

Carbamyl phosphate synthetase deficiency and postpartum hyperammonemia

Carbamyl phosphate synthetase (CPS) is an enzyme that converts ammonia to carbamyl phosphate in the urea cycle. CPS deficiency is a genetic disorder that causes hyperammonemia because of enzyme activity deficiency. It is primarily diagnosed in neonates and infants and has a poor prognosis. We report an adult woman with CPS deficiency who developed hyperammonemia postpartum.

Successful anticoagulant therapy for two pregnant PNH patients, and prospects for the eculizumab era

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired stem cell disorder characterized by intravascular hemolysis and thrombosis. The most serious complication is thrombosis, the risk of which is augmented by the hyper-coagulable state that occurs during pregnancy; despite this risk, however, young female PNH patients often desire to have a baby. We recently experienced two successful deliveries in PNH patients, who were treated with anticoagulant therapy during their pregnancies. Meanwhile, given the potential benefit of eculizumab (Soliris), a humanized monoclonal antibody against C5, in reducing thrombosis and hemolysis, it represents a promising therapeutic option for the treatment of pregnant PNH patients in combination with, or in replacement of, anticoagulant therapy.

Case of acquired hemophilia with factor VIII inhibitor in a mother and newborn

We report a mother and newborn in the puerperium with hemorrhage secondary to factor VIII inhibitor. A 31‐year‐old gravida 1 para 1 delivered at a local clinic with a massive postpartum hemorrhage. The activated partial thromboplastin time was prolonged and factor VIII inhibitor was detected. The persistent hemorrhage improved following treatment, including transfusion, steroid therapy, and bypass therapy with factor VII formulations. After hysteroscopic removal of the retained placenta, the hemorrhage decreased. The newborn developed significant swelling of the hands after routine blood sampling and factor VIII inhibitor was detected. The inhibitor disappeared without any special treatment in the 5th month postpartum in the mother and the 4th month postpartum in the newborn. Factor VIII inhibitor may be transferred via the placenta from the mother to the fetus. Therefore, the newborn should also be carefully observed in a case of massive hemorrhage after delivery.

Exposure to ethinyl estradiol prenatally and/or after sexual maturity induces endometriotic and precancerous lesions in uteri and ovaries of mice

Unrecognizable exposure to estrogenic substance may cause estrogen‐dependent diseases, endometriosis and cancer. Pregnant mice (ICR/Jcl, CLEA) were exposed to 0.01u2009mg ethinyl estradiol (EE2)/kg per day or vehicle (olive oil) through oral intubation from day 11 to 17 of gestation. They delivered their offspring and raised them. When the experimental female F1 mice were at 8 weeks of age, they were not exposed to EE2 or to the same dose of EE2 or to vehicle twice a week until 20 weeks of age. The control female F1 mice were exposed to the same dose of EE2 or vehicle alone, similarly. All mice were killed at 28 weeks of age. The resected uteri and ovaries were processed for microscopic examinations and for determination of the aromatase mRNA levels and aromatase protein through quantitative RT‐PCR and Western blotting, respectively. Adenomyosis and adenocarcinomatous changes were significantly discernible in the EE2‐exposed uteri, and incidence of ectopic glands and serous cysts were significantly increased in the prenatally EE2‐exposed ovaries as compared with respective controls. Significant upregulation of the aromatase mRNA was seen in the prenatally EE2‐exposed uteri and in the EE2‐exposed ovaries. The aromatase protein was identified in all ovaries examined, and in EE2‐exposed uteri but not in controls and confirmed its localization in eutopic and ectopic glands, abnormally proliferated lesions and the lining of the cysts. Taken together, continuous EE2 exposure may cause endometriotic and precancerous lesions due to excessive estrogen synthesis in both target organs.

Erythropoietin is involved in hemoprotein syntheses in developing human decidua.

Before establishment of feto‐placental circulation, decidua can synthesize hemoproteins to maintain oxygen homeostasis in situ. Using the human decidua of induced abortions ranging from 5 to 8 weeks of gestation, we determined the expression levels of erythropoietin, erythropoietin receptor, cytoglobin, myoglobin, embryonic‐, fetal‐ and adult hemoglobin mRNA by quantitative RT‐PCR analysis and identified their proteins by Western blot and immunohistochemical analyses. Erythropoietin signaling was demonstrated in phosphatidylinositol‐3‐kinase/protein kinase B pathway by Western blot, and the transcriptional factors for erythroid and non‐erythroid heme synthesis were examined by RT‐PCR analysis. In decidua, erythropoietin and its receptor mRNAs, erythropoietin receptor protein and phosphatidylinositol‐3‐kinase, were expressed with a peak at 6 weeks of gestation. Moreover, the decidua during 5 to 8 weeks of gestation expressed embryonic, fetal and adult hemoglobins additionally cytoglobin and myoglobin at transcriptional and protein levels. The heme portion of these hemoproteins is considered to be synthesized by non‐erythroid δ‐aminolevulinate synthase. These hemoproteins were discernible especially in decidual cells concomitant with cytotrophoblast cells and macrophage in these developing decidua. Considering the different capacity for oxygen binding and dissociation among hemoglobins with the oxygen storage capacity for cytoglobin and myoglobin, these hemoproteins appear to play a role in oxygen demand in decidua in situ before development of feto‐placental circulation under the control of erythropoietin signaling.

Safety and efficacy of a 52‐mg levonorgestrel‐releasing intrauterine system in women with cardiovascular disease

We sought to examine the safety and efficacy of a 52‐mg levonorgestrel‐releasing intrauterine system (LNG‐IUS), and to evaluate the changes in biomarkers of infection, anemia and cardiovascular conditions after LNG‐IUS insertion in women with cardiovascular disease.

Utility of Fluid Assessment Based on the Intrathoracic Impedance Monitoring in a Peripartum Woman with Heart Disease

Recently, implantable cardioverter-defibrillators (ICD) have become capable of monitoring intrathoracic impedance to detect an increased fluid volume and heart failure. Pregnancy is a well-known cause of an increased body fluid volume; however, it is not clear whether the measurement of intrathoracic impedance by ICD is clinically useful for precisely detecting heart failure in pregnant women. We herein report the case of a 39-year-old woman with an ICD that had been implanted after an event of ventricular fibrillation due to severe aortic regurgitation with a bicuspid aortic valve. Elevated right ventricular pressure and brain natriuretic peptide levels were detected at 37 weeks of gestation and postpartum. At the same time, the ICDs stored fluid index gradually increased and exceeded the threshold on the 10th day after delivery. She was treated with diuretics and recovered from postpartum heart failure. The physiological volume changed in the perinatal period, but we were still able to detect heart failure by ICD. Intrathoracic impedance monitoring is effective in the perinatal field.

Cardiomyopathy Phenotypes and Pregnancy Outcomes with Left Ventricular Noncompaction Cardiomyopathy: Three Cases and a Literature Review

Little is known about pregnancies of left ventricular noncompaction cardiomyopathy (LVNC), much less cases in which LVNC was definitively diagnosed prepregnancy. We report the cases of three pregnant Japanese women definitively diagnosed with LVNC prepregnancy. Case 1 presented LVNC with restrictive phenotype. Her pregnancy was terminated due to exacerbated pulmonary hypertension and low output status at 30 weeks gestation. Case 2 presented isolated LVNC with nonsustained ventricle tachycardia. A cesarean section was performed at 36 weeks gestation because of placenta previa. Case 3 presented dilated LVNC. Labor induction was performed because of decreased left ventricular ejection fraction, leading to a vaginal delivery at 37 weeks gestation. In all cases, no thromboembolic event was identified during pregnancy; two patients received anticoagulants. We reviewed all English-literature cases of pregnant women definitively diagnosed with LVNC prepregnancy to analyze causes of adverse pregnancy outcomes and the necessity of anticoagulation. Four of the six pregnancies identified were terminated due to exacerbated cardiomyopathy phenotypes and not complications due to noncompaction itself, resulting in three cases preterm deliveries. No thromboembolic event was identified by maintenance of the anticoagulation strategy determined prepregnancy. In pregnancies with LVNC, the possibility of a severe cardiac event and the indications for termination of the pregnancy can depend on the cardiomyopathy phenotypes, not noncompaction itself. Anticoagulation only because of the pregnancy itself may be redundant. In the management of LVNC during pregnancy, close monitoring of the condition of different phenotypes and reassessment of the necessity of anticoagulation can contribute to the pregnancy outcome.

Changes in echocardiographic parameters and hypertensive disorders in pregnancies of women with aortic coarctation

OBJECTIVESnPregnancy can be well tolerated after the repair of aortic coarctation. However, a higher incidence of hypertensive disorders during these pregnancies was reported. We analyzed the perinatal changes in echocardiographic parameters in women with aortic coarctation and investigated the risk factors of gestational hypertension (GH).nnnMETHODSnWe retrospectively identified 15 pregnancies in nine Japanese women with aortic coarctation between 1982 and 2015. We categorized the patients according to the presence/absence of GH as the group with GH(n=3) and that without GH(n=12). The echocardiographic parameters were compared between groups.nnnRESULTSnOur analysis revealed that a pre-pregnancy Doppler-measured pressure gradient≥20mmHg and a left ventricular mass index≥95g/m2 were significant risk factors for GH. The left ventricular end-diastolic diameters at the first and the third trimesters, the left ventricular end-systolic diameters at the first trimester, and the left ventricular ejection fraction at the third trimester were also significantly higher in the pregnancies with GH. All of these findings had been obtained before the patients GH occurred.nnnCONCLUSIONSnHypertrophy of the left ventricle with a lower ejection fraction and a high pressure gradient across the coarctation were risk factors for GH in the patients with aortic coarctation. Thus, serial measurements using echocardiography are important for predicting GH in women with aortic coarctation. However, further research investigating this finding with a larger sample size is needed.