Osamu Tokuyama

Insulin-Lowering Agents Inhibit Synthesis of Testosterone in Ovaries of DHEA-Induced PCOS Rats

Background: Insulin-lowering agents are reported to be useful in treating polycystic ovary syndrome (PCOS) anovulation. It has been suggested that lower insulin levels secondarily affect ovarian tissue, although the direct mechanism of action has not yet been verified. Here we investigated if these agents directly affect the ovary. Methods: Thirty female Wister rats were studied. Six control rats were injected subcutaneously with 0.2 ml sesame oil, while 24 rats used as PCOS models were injected subcutaneously with dehydroepiandrosterone (DHEA) and divided into four groups. Six rats were injected with only DHEA, while the remaining 18 rats received metformin, pioglitazone or troglitazone. The ovaries were immunohistochemically stained with anti- testosterone and anti-17β-HSD antibodies, and then evaluated for morphological changes. Results: In the DHEA administration group, the number of atretic follicles significantly increased compared to that of control rats. The insulin-lowering agents did not improve the multicystic appearance. Serum testosterone concentrations significantly increased with DHEA administration, but the increase was inhibited by oral administration of insulin-lowering agents. Testosterone deposits in ovarian tissue were also reduced by feeding rats insulin-lowering agents. Conclusion: Insulin-lowering agents affected ovarian tissue by inhibiting testosterone biosynthesis in vivo.

Vascular endothelial growth factor concentrations in follicular fluid obtained from IVF-ET patients: a comparison of hMG, clomiphene citrate, and natural cycle.

AbstractPurpose: Evaluation of vascular endothelial growth factor (VEGF) concentrations of follicular fluid (FF) in accordance with an ovarian stimulation protocol and ovarian response. Methods: The subjects of this study were 38 patients undergoing IVF-ET in our hospital. They were divided into three groups according to ovarian stimulation protocols; Group 1: hMG cycles (n = 19), Group 2: clomiphene citrate cycles (n = 10), Group 3: natural cycles (n = 9). They reclassified into three groups according to the number of oocytes harvested. VEGF concentration was measured in FF, employing ELISAs. Results: Group 1 shows lower VEGF concentrations in FF than Group 2 or Group 3. Excluding high responders from Group 1, no difference was found among these three groups. As for the reclassified groups, group of highest number of oocytes havested showed lowest VEGF concentrations in FF. Conclusions: VEGF concentrations in FF might negatively correlate with the number of follicles, irrespective of the ovulation induction protocol.

Primary abdominal pregnancy associated with severe ovarian hyperstimulation syndrome

Abstract  An uncommon case of primary abdominal pregnancy that was detected after rapid resolution of OHSS is reported. A 27-years-old nulligravida woman underwent ovarian hyperstimulation with human menoposal gonadotrophin (hMG) at another clinic and was admitted to our hospital with severe OHSS. Intravenous fluid therapy, albumin supplementation, and abodminal paracentesis was performed. The patient’s massive ascites rapidly resolved, and she was discharged from our hospital. However, 4 weeks later, at about the 8th gestational week, she was readmitted to our hospital because of strong suspicion of abdominal pregnancy. Ultrasonography revealed a gestational sac (GS) and fetus with heartbeat in Douglas’ pouch and an emergency laparotomy was performed. Both fallopian tubes, both ovaries and the uterus were completely intact and the GS was found on the anterior surface of the rectum. After removing GS, the muscle layer and serosal layer of the rectum were repaired. No bowel complications developed, and the post operative course was uneventful. To our knowledge, this is the first report of this very rare variant of ectopic pregnancy complicated by OHSS.

Expression and distribution of cyclooxygenase-2 in human ovary during follicular development

Prostaglandins play important roles for oocyte maturation and follicular rupture. Cyclooxygenase-2 (COX-2), an inducible isoform of a prostaglandin metabolic enzyme, is essential for the timed production of prostaglandins in the ovary. The aim of the present study is to examine expression and distribution of COX-2 in human ovarian follicles at each of the maturation stages. Immunohistochemical staining shows that COX-2 is expressed in the granulosa cell layer of secondary and developing follicles, but is not detected in primary and Graafian follicles. Western blotting analysis revealed the existence of COX-2 in periovulatory follicular fluid at a mean concentration of 5.6 +/- 0.6 ng/ml. COX-2 might begin to be produced at the secondary follicle stage, and once a follicle reaches the Graafian follicle stage, the production of this enzyme is stopped. After exposure to luteinizing hormone (LH) surge, follicles might resume production of COX-2, and this is secreted into the follicular fluid.

A perforated sigmoid diverticulum abscess difficult to differentiate from an ovarian tumor.

We report a case of a perforated sigmoid diverticulum abscess that was difficult to differentiate from an ovarian tumor. A 53-year-old woman was diagnosed with an ovarian tumor, but laparotomy revealed a perforated sigmoid diverticulum abscess and appendicitis, with normal ovaries.