Hideya Sakakibara

Treatment of Fetal Congenital Complete Heart Block with Maternal Administration of Beta-Sympathomimetics (Terbutaline)

We report a case of fetal congenital heart block treated with maternal administration of beta-sympathomimetics. The case was diagnosed as fetal complete heart block associated with maternal anti-Ro/SS-A antibody at 22 weeks of gestation. By fetal sonography, the ventricular rate was revealed to be 60 beats/min and mild cardiomegaly was shown. We initiated maternal administration of a sympathomimetic, specifically terbutaline, to prevent fetal heart failure. An increase in the fetal ventricular rate and an improvement in cardiac function were both achieved during the treatment. A viable infant was delivered by an elective cesarean section without complications at term. Maternal administration of the beta-adrenergic agent terbutaline is suggested to be effective for improving fetal congenital heart block in order to prevent heart failure in utero.

Regulation of human decidual function by epidermal growth factor.

In order to clarify a regulatory mechanism of epidermal growth factor (EGF) in the decidualization process, EGF gene expression, the change in EGF receptor, and the cell proliferative effect of EGF in the human endometrium/decidua were assessed in both in vivo and in vitro decidualization systems. Northern blot hybridization showed that, although no hybridized band was found in the proliferative and secretory phase endometria, a specific band of 5 kb was detected in decidua of early pregnancy as well as in in vitro medroxyprogesterone acetate-induced decidual cells. In situ hybridization revealed that prepro-EGF mRNA was observed in the stromal cells of decidua. Scatchard plot analysis of 125I-EGF-binding studies for the homogenates from these endometria/decidua revealed that its binding sites increased in accordance with the decidualization process, and its dissociation constant remained unchanged. EGF had a stimulatory action on cell proliferation in the early pregnant decidual cells. These results demonstrate that EGF production, EGF receptor, and decidual cell growth increase in accordance with the process of decidualization, suggesting that EGF may play an important role in the regulation of decidualization in human endometrium through an autocrine/paracrine system.

Health management of adults with Turner Syndrome: An attempt at multidisciplinary medical care by gynecologists in cooperation with specialists from other fields

Aim:  Since women with Turner Syndrome (TS) have various complications, they require comprehensive medical evaluation and multidisciplinary treatment. Although TS patients receive adequate care in childhood, many adults with TS do not. Since most TS adults attend gynecologists for hormone replacement therapy, we suggest gynecologists take primary responsibility for their management. In an attempt to provide TS patients with a comprehensive treatment regimen, we started multidisciplinary medical management in the Reproductive Health Clinic at Yokohama City University Hospital. To evaluate the efficacy of this medical care system, a retrospective analysis was conducted.

Breakpoint determination of X;autosome balanced translocations in four patients with premature ovarian failure.

Premature ovarian failure (POF) is a disorder characterized by amenorrhea and elevated serum gonadotropins before 40 years of age. As X chromosomal abnormalities are often recognized in POF patients, defects of X-linked gene may contribute to POF. Four cases of POF with t(X;autosome) were genetically analyzed. All the translocation breakpoints were determined at the nucleotide level. Interestingly, COL4A6 at Xq22.3 encoding collagen type IV alpha 6 was disrupted by the translocation in one case, but in the remaining three cases, breakpoints did not involve any X-linked genes. According to the breakpoint sequences, two translocations had microhomology of a few nucleotides and the other two showed insertion of 3–8 nucleotides with unknown origin, suggesting that non-homologous end-joining is related to the formation of all the translocations.

Efficacy of estrogen replacement therapy (ERT) on uterine growth and acquisition of bone mass in patients with Turner syndrome.

Estrogen replacement therapy (ERT) is necessary for uterine development and bone mass acquisition in women with Turner syndrome (TS) suffering from ovarian insufficiency. However, adequate ERT regimens have not yet been established. The aim of this study was to evaluate the efficacy of ERT for both uterine development and bone mass acquisition. One hundred TS patients from Yokohama City University Hospital (88 with primary amenorrhea (PA) and 12 patients with spontaneous menstrual cycles (MC)) were enrolled after obtaining consent. Clinical profiles, uterine length (UL) measured by ultrasonic examination, and bone mineral density (BMD) of the lumbar vertebrae (L2-4) assessed by DEXA were evaluated. At the time of the first visit, the ULs of patients in the PA group were significantly shorter than those in the MC group. After receiving ERT, there were no significant differences in UL between patients with PA and MC. Forty-seven patients for whom the ERT initiation age was known were investigated to clarify the influence on BMD. The results showed that the BMD in the late initiation (18 years or older) group at the latest visit (0.770 ± 0.107 g/cm2: n = 16) was significantly lower than that in the early initiation (under 18 years) group (0.858 ± 0.119 g/cm2: n = 21) or the MC group (0.941 ± 0.118 g/cm2: n = 10). No significant differences were seen between the early initiation and MC group. ERT was effective in increasing UL and BMD. However, early initiation of ERT is necessary to increase BMD.

Gene expression of gonadotropin-releasing hormone in early pregnant rat and steroid hormone exposed mouse uteri

While gonadotropin-releasing hormone (GnRH) or GnRH-like substance have been reported to exist in nonhypothalamic tissues such as placenta, gonads, and mammary gland, there have been no reports concerning the detection of GnRH mRNA in uterine tissue. In order to investigate the presence of GnRH in decidual tissues and its possible involvement in the regulation of placental function, we examined the gene for GnRH in the rodent uterus in early pregnancy and in nonpregnant animals treated with female sex steroids. Using RT-PCR and in situ hybridization we found GnRH mRNA transcripts in the rat uterus of 3- and 6- day gestation and in the mouse uterus treated with estrogen and progesterone. In situ hybridization revealed that GnRH mRNA was localized in the endometrial stromal cells of the 3rd and 6th day of gestation. These results suggest the existence of GnRH gene expression in uterine stromal cells and its possible paracrine effect derived from the decidual cells.

A severe vaginal hemorrhage caused by cervical endometriosis

We report a rare case in which a cystic lesion in the cervix, caused by endometriosis, resulted in a massive vaginal hemorrhage. Cervical endometriosis is relatively common and is usually considered a mild condition. However, we report a case in which a severe vaginal bleed originated from an endometrial cyst of the cervix and in which diagnosis was confused by the presence of atypical cells.

Gene expression of transforming growth factor-α in human endometrium during decidualization

AbstractPurpose: We previously reported the gene expression of epidermal growth factor (EGF) in the process of decidualization in the human endometrium. This study was undertaken to investigate the biological significance of transforming growth factor-α (TGF-α), which shares a significant sequence homology with EGF, in the regulation of decidualization. Methods: The gene encoding TGF-α was analyzed by Northern blot hybridization in nonpregnant human endometria and decidua from 6 to 8 weeks of gestation as well as in cultured stromal cells with or without medroxyprogesterone acetate. Results: No transcript was detected in proliferative and secretory endometrium, whereas a transcript of 4.8 kb, which was in agreement with the size of human prepro-TGF-α mRNA previously reported, was clearly detected in decidua. Transcript of 4.8 kb was also detected in vitroin medroxyprogesterone acetate (MPA)-induced decidual cells, while no TGF-α transcript was found in endometrial stromal cells cultured without MPA. Conclusions: These results suggest that the gene expression of TGF-α in uterine stromal cells is enhanced by stimulation from sex steroids and that TGF-α, like EGF, functions as one of the regulatory factors for decidualization in the human uterus.

Dienogest was effective in treating hemorrhagic ascites caused by endometriosis: a case report.

Hemorrhagic ascites caused by endometriosis is extremely rare, and its treatment is under discussion. We report a case of recurrent endometriosis-related ascites treated with dienogest (DNG). A 35-year-old nulliparous Japanese woman with a history of infertility presented with worsening dysmenorrhea and abdominal distention caused by massive ascites. The patient underwent exploratory laparotomy, and hemorrhagic ascites (5500 mL) was drained. She had a normal-sized uterus, and the bilateral ovaries could not be observed because of extensive adhesion in the abdominal cavity. Endometriosis was diagnosed by histopathological evaluation of the omental biopsy, and this was considered to be the cause of ascites. After laparotomy, she had recurrence of ascites. For the next 8 years, the patient was treated conservatively with gonadotropin-releasing hormone agonist therapy and drainage during the intermittent periods followed by DNG administration. She has been treated continuously with DNG for 1 year with no recurrence of ascites. DNG could be an effective treatment for recurrent ascites associated with endometriosis, especially when surgical therapy is undesirable.

Magnetic Resonance Imaging Evaluation of L5-S1 Intervertebral Disc Degeneration in Japanese Women

Study Design Retrospective case series. Purpose To calculate the prevalence of L5-S1 intervertebral disc degeneration (IDD) by evaluating gynecological disease findings, obtained by pelvic magnetic resonance imaging (MRI), and reveal the risk factors for IDD by analyzing its relationship with age, sacral structure, body mass index (BMI), number of deliveries, and intrapelvic space-occupying lesions. Overview of Literature Age, obesity, height, smoking history, occupation, and lumbosacral structure are reportedly the main factors of lumbar IDD. However, in women, the relationship of IDD with obstetric and gynecological history is unclear. Methods The presence of L5-S1 IDD was evaluated on sagittal T2-weighted pelvic MRI during gynecological evaluations in 660 Japanese women. We measured the sacral table angle (STA), sacral kyphosis angle (SKA), and intrapelvic space-occupying lesion size. Age, height, weight, BMI, number of deliveries, lumbosacral structure, size of space-occupying lesions, and presence of uterine leiomyoma based on medical records were compared between the IDD-positive and IDD-negative groups. Results Lumbosacral IDD was observed in 405 cases (61.4%), and its prevalence increased with age. Differences in age, height, weight, BMI, and number of deliveries between the IDD-positive and -negative groups were significant, but differences in STA, SKA, and presence of uterine leiomyoma and space-occupying lesion size were not. Logistic regression analysis indicated that age, BMI, and STA were risk factors for lumbosacral IDD. Conclusions Age is the biggest risk factor for lumbosacral IDD in Japanese women, with BMI and STA also contributing to its development. However, SKA and obstetric and gynecological history were not significantly involved.