Koji Kugu

Role of Laparoscopy in the Treatment of Endometriosis-Associated Infertility

Endometriosis is assumed to be one of the causative factors of infertility, although the mechanism remains to be elucidated. Mechanical factors distorting the pelvic anatomy and/or changes in the biochemical and cellular environment in the peritoneal cavity are possible contributing factors impairing fertility. Laparoscopy is a widely used diagnostic and therapeutic means of treating endometriosis-associated infertility. However, pregnancy outcome after laparoscopy varies depending on preexisting tubal adhesions and endometriosis. Without tubal adhesions, the pregnancy rate is essentially the same irrespective of the presence or stages of endoemetriosis. Minimal/mild endometriosis benefited the most from laparoscopic manipulation when tubal adhesions were present. On the other hand, IVF-ET outcome of patients who previously underwent laparoscopy was not influenced by preexisiting tubal adhesions and endometriosis.

Concentrations of interferon-gamma-induced protein-10 (IP-10), an antiangiogenic substance, are decreased in peritoneal fluid of women with advanced endometriosis.

Problem:  To assess whether interferon‐γ‐induced protein‐10 (IP‐10), a chemokine that has antiangiogenic activities, may be involved in the pathogenesis of endometriosis.

Regulation of Nitric Oxide Synthase to Promote Cytostasis in Ovarian Follicular Development

Abstract Our own recent studies have demonstrated that inducible nitric oxide synthase (iNOS) is predominantly localized in granulosa cells of healthy immature follicles in the rat ovary, whereas granulosa cells of either healthy mature follicles or follicles destined to be atretic are devoid of iNOS. These findings suggest that iNOS is pivotal for immature follicles to remain dormant. To test this hypothesis, we examined the effects of a GnRH agonist (buserelin), a proapoptotic substance, and epidermal growth factor (EGF), a mitogenic and, consequently, antiapoptotic factor, on the amount of iNOS mRNA in rat granulosa cells. Administration of buserelin in immature female rats transiently diminished iNOS mRNA levels in the ovaries as determined by Northern blot analysis. In cultured rat granulosa cells, buserelin and EGF increased the incidence of apoptosis and DNA synthesis, respectively, whereas both reduced iNOS mRNA levels as determined by reverse transcription-coupled polymerase chain reaction. The concomitant addition of S-nitroso-N-acetyl-dl-penicillamine, an NO donor, together with buserelin or EGF eliminated the observed effects of these substances (i.e., induction of apoptosis and stimulation of DNA synthesis, respectively). These results suggest that the changes in developmental status of immature follicles either into development or atresia are associated with reduced iNOS levels in granulosa cells, thus reinforcing the notion of NO as a cytostatic factor in ovarian follicles.

Human Chorionic Gonadotropin Combined with Progesterone for Luteal Support Improves Pregnancy Rate in Patients with Low Late-Midluteal Estradiol Levels in IVF Cycles

AbstractPurpose: To investigate how late-midluteal estradiol levels relate to the pregnancy outcome in IVF cycles, and to assess whether human chorionic gonadotropin (hCG) for luteal support benefits the pregnancy outcome of patients with low late-midluteal estradiol levels. Methods: The pregnancy rate of 436 women undergoing first IVF cycles with long protocol and luteal support with progesterone alone were analyzed. Unsuccessful women with low late-midluteal estradiol levels (<100 pg/mL) proceeded with the exploratory second IVF cycles where they were randomly given with either progesterone alone (P protocol) or hCG +progesterone (P+hCG protocol) for luteal support. Results: Pregnancy rate in women with low late-midluteal estradiol levels was significantly lower compared to that with medium (100–500 pg/mL) and high (>500 pg/mL) levels (13.3, 26.8, and 36.3%, respectively). P+hCG protocol increased late-midluteal estradiol levels and produced a significantly higher pregnancy rate (31.7%) than P protocol (13.7%). Conclusions: hCG in combination with progesterone for luteal support was suggested to benefit women undergoing IVF with low late-midluteal estradiol levels.

Upregulation of Interleukin-8 by Hypoxia in Human Ovaries

Problem: To evaluate the effect of hypoxia on interleukin (IL)‐8 expression in human ovarian follicles.

Preoperative diagnosis of colouterine fistula secondary to diverticulitis by sonohysterography with contrast medium

Colouterine fistulae secondary to sigmoid diverticulitis are unusual. Methods for diagnosis remain to be established. We report a case with a colouterine fistula in which sonohysterography detected the flow of ultrasound contrast medium between the uterine cavity and the sigmoid colon through the posterior uterine wall, thus confirming the diagnosis. The diagnosis was further substantiated by a charcoal challenge test. The patient underwent en bloc resection of the uterus, Fallopian tubes, ovaries and sigmoid colon, the organs involved with diverticulitis. This is the first report to describe a colouterine fistula successfully diagnosed by sonohysterography using ultrasound contrast medium. Copyright

Abnormal Fhit expression is an independent poor prognostic factor for cervical cancer

We analysed the expression of the fragile histidine triad (FHIT) gene in cervical cancer to evaluate its clinical relevance in relation to human papillomavirus (HPV) infection. A total of 73 women with cervical cancer of stage Ib or more advanced (67 squamous cell carcionomas, four adenocarcinomas, two adenosquamous carcinomas) were examined for Fhit expression by immunohistochemistry. They were further analysed for the presence of HPV and its subtype. Abnormal expression of Fhit (absent or reduced Fhit expression) was observed in 52 cases (71.2%). The high-risk HPV DNAs for cervical cancer, including type 16, 18, 31, 33, 51, 52, 58, 68, were identified in 63 cases (86%). The abnormal Fhit expression was not related to the clinicopathological factors including histology, tumour stage, and HPV type. Notably, the 5-year survival of patients showing the abnormal Fhit expression was significantly poorer than those showing normal Fhit expression (64 versus 87%, P=0.035). Interestingly, the mean age of the patients with the abnormal Fhit expression was significantly less than those with the normal Fhit expression (51.6 versus 58.7 years of age, P=0.027, students t-test). These data imply that the aberrant Fhit expression could be a poor prognostic factor independent of HPV. In the light of a high incidence of abnormal Fhit expression in younger patients and HPV as a key player in cervical carcinogenesis, abnormal Fhit expression may accelerate carcinogenesis in concert with HPV.

Exaggerated prolactin response to thyrotropin-releasing hormone in infertile women with the luteinized unruptured follicle syndrome.

SummaryTen cases of luteinized unruptured follicle (LUF) syndrome out of 250 women with unexplained infertility were detected on ultrasonography, giving a frequency of 4%. Hormonal analysis revealed lower serum progesterone levels at mid-luteal phase in LUF cases, suggesting a link between LUF syndrome and inadequate luteal phase. Prolactin response to thyrotropin-releasing hormone was exaggerated in LUF cases as compared with ovulatory cases. Aberrant prolactin release may be a contributory factor in the pathophysiology of the LUF syndrome.

Assisted reproductive technology in Japan: a summary report of 1992–2014 by the Ethics Committee, Japan Society of Obstetrics and Gynecology

The Japan Society of Obstetrics and Gynecology implemented a registry report system for the clinical practice of assisted reproductive technology in 1986. The aggregated results from 1992 to 2014 are reported herein.

Inhibition of human epithelial ovarian cancer cell growth in vitro by somatostatin analog RC-160

In this study, we investigated the effects of somatostatin analog RC-160 on the growth of the OV-1063 human epithelial ovarian cancer cell line in vitro. RC-160 inhibited cell proliferation, as measured by cell number, and [3H]thymidine incorporation into DNA at 10–9–10–5M. In OV-1063 cells, 125I-labeled RC-160 was bound to one class of specific, saturable binding sites with high affinity (Kd = 0.2 ± 0.03 nM) and low capacity (5,500 binding sites per cell). 125I-labeled RC-160 could be displaced by unlabeled RC-160. Ligand binding was dependent on time and temperature. Receptor internalization assay showed that the ligand-receptor complex was internalized at 37°C, which indicates the presence of biologically active somatostatin receptors on OV-1063 cells. These results suggest that somatostatin analog RC-160 can suppress the growth of OV-1063 human epithelial ovarian cancer cells by a direct action and that the inhibitory effect of somatostatin analog is mediated through the high-affinity somatostatin receptors.