Toshihiko Matsui

Status of the coagulation and fibrinolytic systems in ovarian hyperstimulation syndrome

OBJECTIVE To elucidate characteristic changes of plasma hemostatic markers in ovarian hyperstimulation syndrome (OHSS) cycles. DESIGN Prospective study. SETTING The IVF-ET program of the Department of Obstetrics and Gynecology, The University of Akita, School of Medicine. PATIENTS Forty cycles of 40 IVF patients, including 12 cycles in which a severe form of OHSS occurred. INTERVENTIONS Blood samples were taken during IVF treatment to determine the levels of blood markers that reflect activation of the coagulation and fibrinolytic systems. MAIN OUTCOME MEASURES Thrombin-antithrombin III complexes, plasmin-alpha 2 antiplasmin complexes, and other hemostatic markers related to the coagulation and fibrinolytic system activation. RESULTS In the OHSS cycles, the levels of thrombin-antithrombin III and plasmin-alpha 2 antiplasmin complexes in the plasma began to rise within a few days after hCG administration and demonstrated significantly higher levels during the midluteal phase. In OHSS cycles with pregnancy, elevation of these markers continued for > or = 3 weeks after the onset of disease. There were some characteristic changes in OHSS cycles in other hemostatic markers, such as a decrease in the levels of antithrombin III and prekallikrein and shortened activated partial thromboplastin time. CONCLUSION These data demonstrate the status of the coagulation and fibrinolytic systems in OHSS cycles and provide insight into the mechanism of activation in the hemostatic system.

Characteristics of blood hemostatic markers in a patient with ovarian hyperstimulation syndrome who actually developed thromboembolism.

OBJECTIVE To investigate whether a patient with ovarian hyperstimulation syndrome (OHSS) demonstrated characteristic changes in the blood hemostatic markers before she developed thromboembolism. DESIGN Patients with OHSS had blood drawn to determine hemostatic markers and related factors. PATIENTS Twenty-three OHSS patients, including a case complicated with thromboembolism. SETTING The IVF-ET program of the Department of Obstetrics and Gynecology, The University of Akita, School of Medicine. MAIN OUTCOME MEASURES Blood hemostatic markers and related factors. RESULTS The patient with thromboembolism demonstrated marked leukocytosis and higher levels of activation in the blood markers related to fibrinolytic system, such as alpha 2 plasmin inhibitor, plasmin-alpha 2 antiplasmin complexes, and D-dimers, before the onset of this episode. CONCLUSION Marked leukocytosis and higher levels of activation of the fibrinolytic system may be the signs of imminent thromboembolism in OHSS patients.

Benefit of in vitro fertilization treatment for endometriosis-associated infertility

OBJECTIVE To evaluate the effectiveness of IVF treatment in endometriosis-associated infertility. DESIGN Nonrandom retrospective study. SETTING Department of Gynecology and Obstetrics, Akita University School of Medicine. MAIN OUTCOME MEASURE(S) Cumulative pregnancy rate. PATIENT(S) One hundred eighteen infertile patients in whom diagnosis of endometriosis was established by laparoscopic examination. INTERVENTION(S) The prognoses of 60 patients (IVF group) who started IVF treatment within 6 months after laparoscopy were compared with those of 58 patients who were managed expectantly without IVF treatment during the same period. RESULT(S) The cumulative conception rates at 36 months after laparoscopy were 62% in the IVF group and 43% in the control group, and the difference was not significant (a log-rank test). For patients > or = 32 years of age, the conception rates were significantly higher in the IVF group (59% versus 29%). A relatively large but nonsignificant difference in the conception rate between the two groups was observed in patients with endometriosis at stages III or IV (52% versus 27%). CONCLUSION(S) In vitro fertilization treatment provides better prognosis in patients > or = 32 years of age and is recommended for such patients. The benefits of treatment appear to be greater in patients with more advanced stages of endometriosis.

Sperm immobilization antibodies in infertile male sera decrease the acrosome reaction: A possible mechanism for immunologic infertility

AbstractObjective: To study the effect of sperm-immobilizing antibodies from male sera on spontaneous and A23187-induced acrosome reactions (AR). Design: Swim-up spermatozoa obtained from three fertile donors were incubated with 13 sera with sperm-immobilizing antibodies obtained from infertile men and three control sera obtained from healthy fertile males. Sperm acrosomes were examined by staining with pisum sativum agglutinin labeled with fluorescein isothiocyanate (30 µg/ml; Sigma Chemical Co., St. Louis, MO) as spontaneous and A23187 (used at a final concentration of 10 µM; Sigma Chemical Co.) induced. Results: The incidence of spontaneous AR of spermatozoa incubated with antisperm antibody positive male sera (6.2±0.7) was significantly (P<0.001) lower than that of spermatozoa incubated with control sera (10.7±0.5). And the incidence of A23187-induced and -inducible (incidence of induced minus spontaneous) ARs of spermatozoa incubated with sperm antibody-positive male sera (12.4±1.9 and 6.2±1.9) was significantly lower (P<0.001) than that of spermatozoa incubated with control sera (31.0±0.5 and 20.3±0.9). Sperm-immobilizing antibody-positive sera decreased spontaneous, A23187-induced, and inducible ARs. Conclusions: Sperm-immobilizing antibodies from male sera interfere with fertilization by inhibiting the AR.

In vitro Fertilization of in vitro Matured Oocytes Obtained from the Follicles without hCG Exposure for Prevention of Severe Ovarian Hyperstimulation Syndrome: A Case Report

We aspirated ovarian follicles of an infertile patient who encountered a great risk of ovarian hyperstimulation (OHSS) during her ovulation‐induction cycle, which had been stimulated with gonadotropins, in order to avoid OHSS without interrupting the treatment. If this action were to yield a considerable number of immature oocytes, some of which were to achieve in vitro maturation and subsequent fertilization, this method could be an alternative to conventional ovulation‐induction methods for patients who repeatedly present imminent signs of hyperstimulation. However, the number of oocytes collected from the patient was disappointingly low, even though a large number of follicles were thoroughly aspirated. One of these oocytes was matured in vitro in a medium containing 30% follicular fluid and granulosa cells of mature follicles, fertilized, cryopreserved, and transferred in a later artificial cycle; but pregnancy was not achieved. A low number of recovered oocytes from patients in this situation might be a factor that greatly limits the clinical applications of this method.

Effect of danazol on the immunocompetent cells in the eutopic endometrium in patients with endometriosis: a multicenter cooperative study*†*Presented at the 15th Annual Meeting of the Study for Endometriosis, Osaka, Japan, January 28 to 29, 1994.†Supported by an educational grant from Tokyo Tanabe Pharmaceutical Co. Ltd., Tokyo, Japan.

OBJECTIVE To assess the effects of danazol on immunocompetent cells, human leukocyte antigen (HLA) expression, and adhesion molecules in the eutopic endometrium of patients with endometriosis. DESIGN Antigens were localized immunohistochemically in the endometria, before treatment and during treatment (2 months later). PARTICIPANTS Ten patients with laparoscopically proven endometriosis who consented to participate in this study were treated with 400 mg/d of danazol for 4 months. Forty-two infertile patients without endometriosis or adenomyosis served as controls. RESULTS Immunohistochemical analysis revealed significantly increased expression of the T cell subsets, macrophages, adhesion molecules, and HLA antigens in eutopic endometrium in patients with endometriosis compared with the infertile group. Treatment with danazol reduced the number of cells in T cell subsets, adhesion molecules, or HLA antigen expression, especially of gamma delta T cells, to 39.5% of the pretreatment value in patients with endometriosis. CONCLUSIONS Danazol had an immunomodulatory effect on the autoimmune response in endometrium associated with endometriosis.