Ryo Tsutsumi

Increased risk of placenta previa is associated with endometriosis and tubal factor infertility in assisted reproductive technology pregnancy

Although assisted reproductive technology (ART) is suspected to increase the risk of placenta previa, a life-threatening complication of pregnancy, the reason is poorly understood. We recruited consecutive 318 pregnancies conceived by ART in our clinic and examined relation of ten variables, i.e. maternal age, gravidity, parity, male or female fetus, previous abortion, previous cesarean delivery, endometriosis, ovulatory disorder, tubal disease, and male infertility, to placenta previa, by logistic regression analysis. As a result, we found that endometriosis (odds ratio = 15.1; 95% CI = 7.6–500.0) and tubal disease (odds ratio = 4.4; 95% CI = 1.1–26.3) were significantly associated with placenta previa. It would be preferable to take the increased risk of placenta previa into account in treating ART pregnancy with endometriosis and tubal disease.

Uterine artery pseudoaneurysm after cesarean section: case report and literature review.

Uterine artery pseudoaneurysm (UAP) occurs rarely and can develop after various gynecologic or obstetric procedures. The delayed diagnosis of this disease often results in life-threatening hemorrhage. Herein is described a case of UAP after cesarean section. The patient visited our emergency outpatient department 99 days after cesarean section because of abnormal uterine bleeding, which was diagnosed as UAP using color Doppler ultrasonography and contrast medium-enhanced computed tomography. Selective transcatheter arterial embolization was performed to resolve the lesion without complications. We also conducted a review to identify the demographic etiology of UAP. A PubMed search yielded 57 cases reported in the English literature. The most frequent cause of UAP was cesarean section, which accounted for 47.4% of all cases. The mean interval between the incident and the symptoms was approximately 2 weeks, regardless of cause. At analysis of 17 cases diagnosed within a day, it became evident that the definitive diagnosis was made at angiography (41.2%), computed tomography (29.4%), or color Doppler ultrasonography (29.4%). Almost all cases (94.1%) were conservatively treated with transcatheter uterine artery embolization. Consideration of UAP in the differential diagnosis is crucial for proper treatment before rupture and to preserve fertility.

Induction of early decidualization by cadmium, a major contaminant of cigarette smoke

To investigate the effect of cadmium (Cd) contamination on endometrial function, human endometrial stromal cells were isolated and cultured with E(2) plus P in the presence of Cd, a major contaminant in cigarette smoke, and assayed for PRL concentrations and its messenger RNA expression. Cd significantly increased PRL concentrations in the culture media and significantly up-regulated PRL messenger RNA expression of the endometrial stromal cells, suggesting that Cd stimulates decidualization of the endometrium and may disrupt endometrial environment, causing early decidualization.

Expression of retinoic acid-related orphan receptor alpha and its responsive genes in human endometrium regulated by cholesterol sulfate.

Cholesterol sulfate (CS) is a major sterol sulfate in human plasma that is detected in the uterine endometrium. CS plays a role in steroidogenesis, cellular membrane stabilization, and regulation of the skin barrier. We previously reported that CS increased in rabbit endometrium during the implantation period. Recently, CS has been reported to be a ligand of retinoic acid receptor-related orphan receptor alpha (RORA). NR1D1 is one of the genes regulated by RORA. In the present study, we investigated the regulation of RORA and NR1D1 by CS in human endometrium. We determined the association-dissociation curves for the interaction of CS with RORA and the kinetic rates by surface plasmon resonance. Immunohistochemical staining and in situ hybridization revealed that RORA and NR1D1 were expressed in human endometrial stromal and epithelial cells. CS treatment significantly induced the mRNA expression of RORA and NR1D1 mRNA in ESCs. The results of a luciferase assay showed that RORA significantly activated the human NR1D1 promoter regardless of CS. Our results suggest that CS regulates the expression of RORA responsive genes in human endometrial cells but not as a ligand for RORA.

The progesterone-responsive gene 14-3-3τ enhances the transcriptional activity of progesterone receptor in uterine cells

Members of the 14-3-3 family are intracellular dimeric phosphoserine-binding proteins that can associate with and modulate the activities of many proteins. In our efforts to isolate the genes regulated by progesterone (P(4)) using suppressive subtractive hybridization, we previously found that 14-3-3τ is one of the genes upregulated by P(4). In this study, we demonstrated by quantitative RT-PCR (qRT-PCR), western blot analyses, and immunohistochemistry that 14-3-3τ mRNA and protein levels were increased in the rat uterus after P(4) treatment. Furthermore, qRT-PCR indicated that P(4) increased 14-3-3τ mRNA levels in human endometrial epithelial cells and endometrial stromal cells (ESCs). Western blot and qRT-PCR analyses revealed that in vitro decidualization using cAMP and medroxyprogesterone 17-acetate increased levels of 14-3-3τ mRNA and protein in ESCs. We have shown by qRT-PCR and western blot analyses that P(4) increased the mRNA and protein levels of 14-3-3τ in Ishikawa cells that stably express P(4) receptor-B (PR-B). Immunocytochemistry revealed that 14-3-3τ colocalizes with PR and translocates from the cytoplasm to the nucleus in response to P(4). Moreover, by luciferase reporter assay, we demonstrated that 14-3-3τ enhances the transcriptional activity of PR-B. Taken together, we propose that 14-3-3τ is a P(4)-responsive gene in uterine cells that modulates P(4) signaling.

Clinical outcomes of assisted reproductive technology treatment by using a self-injection of recombinant human chorionic gonadotropin as the final maturation trigger

To evaluate the efficacy and safety of self‐injections of the prefilled recombinant human chorionic gonadotropin (r‐hCG) in a syringe in assisted reproductive technology (ART) treatment for the maturation trigger (MT), as compared to self‐injections of conventional hCG and intranasal administration of gonadotropin‐releasing hormone agonist (GnRH‐a).

Successful pregnancy following low-dose hCG administration in addition to hMG in a patient with hypothalamic amenorrhea due to weight loss

We describe successful ovulation induction with low-dose hCG administration in addition to hMG in a patient with refractory hypothalamic amenorrhea. A 24-year-old woman with weight loss-related amenorrhea underwent ovulation induction and intracytoplasmic sperm injection (ICSI). Administration of exogenous gonadotropins was ineffective in ovulation induction. Supplementation with low-dose hCG in order to increase luteinizing hormone (LH) activity in the late follicular phase produced late folliculogenesis and steroidogenesis, and ovulation was then successfully induced. This report reacknowledges the critical role that LH plays cooperatively with follicle-stimulating hormone in both folliculogenesis and steroidogenesis.