Souichi Yoshida

Increased interleukin-6 levels in peritoneal fluid of infertile patients with active endometriosis.

OBJECTIVE Our purpose was to investigate the relationship between the levels of interleukin-6, interleukin-6 soluble receptor, and tumor necrosis factor-alpha in peritoneal fluid and the size and number of active red endometriotic lesions. STUDY DESIGN In a university hospital 39 women of reproductive age underwent either laparoscopy for infertility workup or laparoscopic surgery for ovarian chocolate cysts. Peritoneal fluid was collected by laparoscopy. Active lesions, such as red flamelike lesions, glandlike lesions, and red vesicles, were scored according to the revised American Fertility Society classification system according to the size and number of active lesions. Peritoneal fluid levels of interleukin-6, interleukin-6 soluble receptor, and tumor necrosis factor-alpha levels were determined by enzyme-linked immunosorbent assays. The relationship between peritoneal fluid concentrations of interleukin-6 and tumor necrosis factor-alpha and the score of active endometriosis was investigated. RESULTS Peritoneal fluid levels of interleukin-6 and tumor necrosis factor-alpha were significantly higher in patients with endometriosis compared with patients without endometriosis. The concentrations in patients with active endometriosis increased as the size and the number of active lesions increased. Cyclic variations in interleukin-6 concentrations were seen in peritoneal fluid from patients with endometriosis; the concentrations in the secretary phase were significantly higher than those in the proliferative phase. CONCLUSIONS Increased peritoneal fluid levels of interleukin-6 in patients with active red endometriosis may relate to endometriosis-associated infertility and to the pathogenesis of endometriosis.

Paracrine effects of bFGF and KGF on the process of mouse blastocyst implantation

Implantation is a complex process that requires the interaction of the blastocyst, and subsequently, that of the developing embryos with the endometrium. Several growth factors and cytokines are involved in implantation, but the details of their actions as related to the regulation of blastocyst implantation remain unclear. In the present study, the RT‐PCR method was used to determine the gene expression of basic fibroblast growth factor (bFGF), keratinocyte growth factor (KGF), FGF receptor 1 (FGFR1), FGF receptor 2 (FGFR2), and KGF receptor (KGFR) in mouse embryos and in the stromal and epithelial cells of the uterine endometrium. Basic FGF and KGF mRNA were expressed in the endometrial cells, but were not expressed in the embryos. The mRNAs of receptors for bFGF and KGF were expressed in the blastocysts and in the in vitro implanting embryos, suggesting that bFGF and KGF may exert paracrine effects on blastocyst implantation. In this mouse model of blastocyst implantation, it was found that transforming growth factor α (TGF‐α) at the concentrations of 1 ng/ml and 10 ng/ml significantly enhanced the blastocyst attachment and trophoblast spreading and increased trophoblast surface area. Relatively high concentrations of bFGF (100–500 ng/ml) significantly enhanced the rates of blastocyst attachment and of trophoblast spreading and promoted the expansion of the surface area of the implanting embryos. Unlike the rates of blastocyst attachment and trophoblast spreading, the surface area of the spreading embryos was significantly increased by addition of KGF (1–100 ng/ml). These results suggest that the bFGF and KGF derived from the endometrial cells exert paracrine effects on the process of implantation by stimulating trophoblast outgrowth through their cognate receptors. Mol. Reprod. Dev. 50:54–62, 1998.

Cervical Ureaplasma urealyticum colonization might be associated with increased incidence of preterm delivery in pregnant women without prophlogistic microorganisms on routine examination.

Aim: We examined whether the detection of Ureaplasma urealyticum DNA in the cervix is associated with preterm labor and delivery.

Immature brain injury via peroxynitrite production induced by inducible nitric oxide synthase after hypoxia-ischemia in rats.

Objective: To determine whether, and if so how, iNOS expresses and affects brain injury induced by hypoxia‐ischemia in an immature brain.

Adenomyosis in a patient with the Rokitansky-Kuster-Hauser syndrome

Endometriosis remains an enigma despite extensive clinical investigations and experience. Several theories have attempted to explain the puzzling and controversial pathogenesis of endometriosis. Sampson’s implantation theory is the most commonly accepted. Early endometriotic lesions have been found in the Douglas cavity, where retrograde menstruation was confirmed in 90% of women. These findings support Sampson’s theory. In contrast, endometriosis occurs in some patients who have no functional endometrium, such as those with the Rokitansky-Kuster-Hauser syndrome, a clinical condition that supports Iwanoff and Mayer’s coelomic metaplasia theory.

Interleukin-1beta-induced expression of IL-6 and production of human chorionic gonadotropin in human trophoblast cells via nuclear factor-kappaB activation.

Problem:  The cytokine, interleukin‐6 (IL‐6), stimulates the production of human chorionic gonadotropine (hCG) in chorionic cells. The purpose of this study was to examine the role of nuclear factor‐κB (NF‐κB) during the induction of IL‐6 by IL‐1β in human trophoblast cells.

Laparoscopic Surgery for the Management of Ovarian Endometrioma

The purpose of this study was to evaluate the effects of laparoscopic surgery on the symptoms associated with ovarian endometrioma. We also examined serum IL-6 concentrations in patients with endometrioma. Ninety-two patients who underwent laparoscopic surgery for ovarian endometrioma were enrolled in this study. The mean duration of follow-up was 27.6 months. Transvaginal ultrasound examinations revealed a recurrence of endometrioma in 13% of the cases. We evaluated the severity of dysmenorrhea using a 0–3-point verbal rating scale, and found that the dysmenorrhea score was statistically improved after the operation. Follicular growth was preserved in 94%, and the pregnancy rate was 43%. We measured serum IL-6 concentrations in 14 patients with ovarian endometrioma and 4 patients with benign gynecologic disease without endometriosis. IL-6 was significantly higher in patients with endometrioma than in those without endometriosis at the time of diagnosis. The mean serum IL-6 concentration significantly decreased after the operation. In conclusion, laparoscopic surgery is effective for alleviating pain and preserving fertility in patients with endometrioma. Measurements of serum IL-6 concentrations may be useful for the management of endometrioma.

Coasting May Reduce the Severity of the Ovarian Hyperstimulation Syndrome in Patients with Polycystic Ovary Syndrome

The aim of our study was to determine the efficacy of postponing administration of human chorionic gonadotropin while continuing daily gonadotropin-releasing hormone agonist therapy (‘coasting’) to prevent the occurrence of severe ovarian hyperstimulation syndrome (OHSS) for patients with polycystic ovary (PCO) syndrome. Five patients with PCO who had been hospitalized due to severe OHSS in previous in vitro fertilization and embryo transfer or intrauterine insemination cycles at the Tottori University Hospital were included in the study. The rates of mature oocytes and fertilization were comparable between the cycles. A singleton pregnancy was achieved in a patient during the coasting cycle, and none of the women developed severe OHSS in coasting cycles. The results suggest that coasting may be an alternative method for reducing the severity of OHSS in patients with PCO.

Expression of transforming growth factor alpha (TGF-α) gene in mouse embryonic development

Purpose: The expression of genes for TGF-α, epidermal growth factor (EGF), and the EGF receptor (EGFR) in mouse blastocysts was evaluated by the reverse transcription-polymerase chain reaction (RT-PCR). We evaluated the effects of TGF-α and EGF on the development of mouse embryo prior to implantation.Results: The results revealed the presence of transcripts of TGF-α and EGFR. However, EGF mRNA was not observed in repeated experiments. None of these growth factors influenced the rate of development from the two-cell stage to the blastocyst stage when added to the culture medium. These effects were further examined on measuring the incorporation of tritiated thymidine and leucine, providing indices of the synthesis of DNA and protein, respectively. A concentration of only 0.1 ng/ml of TGF-α, which shares a cell surface receptor with EGF, stimulated the synthesis of both DNA and protein. EGF at a concentration of 10 ng/ml stimulated the synthesis of DNA and protein by blastocysts. To explore autocrine effects of TGF-α on the rate of blastocoel expansion, TGF-α antisense oligodeoxynucleotides was used to reduce expression of the TGF-α gene. TGF-α at a concentration of 0.1 ng/ml stimulates the rate of blastocoel expansion in early cavitating mouse blastocysts. In contrast, TGF-α antisense oligonucleotides significantly reduced the rate of expansion.Conclusions: Our present observations suggest that TGF-α/EGF and the EGFR may be involved in regulating embryonic development. In particular, TGF-α may serve as an autocrine factor in the regulation of embryonic development.

Detailed multigrade evaluation of fetal disorders with the quantified actocardiogram

Abstract Aims: To evaluate fetal disorders using detailed quantitative values from the actocardiogram (ACG) involving simultaneous tracing of ultrasonic Doppler fetal movement bursts and fetal heart rate (FHR). Methods: Duration of FHR accelerations and fetal movement bursts were measured manually in 20 common fetal disorders. The severity of the fetal disorder was estimated using the FHR acceleration duration to movement burst ratio (A/B ratio) and 10–0 clinical severity ranks derived from the A/B ratio. The correlation of the A/B ratio and 1 and 5 min Apgar scores, as well as numerically expressed long-term outcomes were studied. Results: A/B ratios were significantly correlated with the 1 and 5 min Apgar scores and the numerically evaluated long-term outcomes. Controversial cases of FHR pattern were more easily understood using the A/B ratio. The 10–0 severity derived from the A/B ratio was useful in clinical fetal studies. Conclusion: Common fetal disorders were evaluated quantitatively and in more detail using the A/B ratio from the actocardiogram than when using common binary good or bad evaluation. The A/B ratio was useful in outcome estimation, where the prognostic capability of the A/B ratio was confirmed by significant correlation with 1 and 5 min Apgar scores and long-term outcomes of fetal disorders.