Chin-Der Chen

Age is a better predictor of pregnancy potential than basal follicle-stimulating hormone levels in women undergoing in vitro fertilization

OBJECTIVE To analyze to what extent the parameters of ovarian functional reserve including female age and basal FSH levels will affect the results of ovarian hyperstimulation and IVF outcome. DESIGN Retrospective cohort study. University hospital infertility center. PATIENT(S) One thousand forty-five women undergoing their first cycle of IVF with ovarian stimulation after pituitary desensitization. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Cycle parameters, cancellation rate, implantation rate, and pregnancy rate. RESULT(S) Both increasing age and basal FSH were associated significantly with reduced numbers of oocytes collected, oocytes fertilized, and embryos transferred. The combined use of age and basal FSH significantly improves the predictive power for these parameters. Increasing age, but not basal FSH, was associated significantly with reduced implantation rate and pregnancy rate. Logistic regression analysis revealed that age, but not basal FSH, was an independent predictor of pregnancy rate. Neither age nor basal FSH had significant association with fertilization rate, miscarriage rate, or ectopic pregnancy rate. CONCLUSION(S) Both basal FSH and age contributed to the prediction of the quantitative ovarian reserve as reflected by the number of oocytes collected. However, age is a better predictor of pregnancy potential for women undergoing IVF.

Decrease in interferon gamma production and impairment of T-lymphocyte proliferation in peritoneal fluid of women with endometriosis.

OBJECTIVE Our purpose was to verify regional immune modulations and to test the effect of gonadotropin-releasing hormone agonist in women with endometriosis. STUDY DESIGN Concentrations of peritoneal cytokines, including interleukin-1 beta, interleukin-2, soluble interleukin-2 receptor, interleukin-6, granulocyte-monocyte colony-stimulating factor, interferon gamma, and tumor necrosis factor-alpha were compared in women with and without endometriosis. Peritoneal cytokine and interleukin-2 production were examined by adding various mitogens to peritoneal fluid mononuclear cells of women with advanced endometriosis before and after gonadotropin-releasing hormone agonist treatment. RESULTS A significant increase in peritoneal interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha and a decrease in interferon gamma were noted in women with endometriosis. After gonadotropin-releasing hormone agonist treatment interleukin-6 decreased and interferon gamma increased. A significant impairment of interleukin-2 production of peritoneal fluid mononuclear cells by phytohemagglutinin and pokeweed mitogen stimulation was demonstrated in endometriosis, and production could be restored after gonadotropin-releasing hormone agonist treatment. CONCLUSION These results indicate that regional immunologic dysfunction might be invoked in the disease process of endometriosis.

Torsion of the previously normal uterine adnexa. Evaluation of the correlation between the pathological changes and the clinical characteristics.

Background. Treatment of adnexal torsion remains a clinical dilemma when future fertility is wanted. The purpose of this study was to evaluate the correlation between the pathological changes and the clinical characteristics on patients having torsion of the previously normal uterine adnexa which may help us decide whether detorsion is worthwhile.

Signal mechanisms of vascular endothelial growth factor and interleukin-8 in ovarian hyperstimulation syndrome: dopamine targets their common pathways

BACKGROUND Ovarian hyperstimulation syndrome (OHSS) is a serious complication of ovarian stimulation with massive ascites, pleural effusion and hemoconcentration. The pathophysiological signal mechanisms of OHSS are still unclear and merit further investigation. METHODS Various angiogenic cytokines of follicular fluid and ascites of patients with risk of OHSS were measured, and examined for inducing endothelial permeability. These include vascular endothelial growth factor (VEGF), interleukin (IL)-6, IL-8, basic fibroblast growth factor, tumor necrosis factor-alpha, IL-1alpha, IL-1beta and platelet-derived growth factor. We explore the molecular signal pathways of major contributing cytokines in granulosa-lutein cells and endothelial cells possibly involved in OHSS. RESULTS Neutralizing antibodies of VEGF or IL-8 significantly decreased follicular fluid- and ascites-induced endothelial permeability. Human chorionic gonadotrophin induced VEGF secretion of granulosa-lutein cells through the Sp1 and CREB dependent pathways. IL-8 activated CXCR1/2 of endothelial cells leading to VEGF receptor (VEGFR)-2 transactivation. Both VEGF and IL-8 of follicular fluid enhanced endothelial permeability via VEGFR-2-mediated Rho/Rock activation, actin polymerization and phosphorylations of VE-cadherin and occludin, resulting in opening of adherens junctions and tight junctions. Dopamine (2 microM) inhibited follicular fluid-induced VEGFR-2 signals and endothelial permeability, without diminishing migration and tube formation. CONCLUSIONS Our results suggest that VEGF and IL-8 secreted from corpora luteae may play major roles in OHSS. Delineation of signal pathways would be helpful for treatment. Dopamine may block VEGF- and IL-8-induced endothelial permeability by inhibiting common VEGFR-2 dependent signals.

Optimal waiting period for subsequent fertility treatment after various hysteroscopic surgeries

OBJECTIVE To investigate the endometrial wound healing duration after a hysteroscopic surgery. DESIGN Prospective study. SETTING Tertiary university hospital. PATIENT(S) One hundred sixty-three women who underwent hysteroscopic surgeries for endometrial polyp (n = 37), submucous myoma (n = 65), uterine septum (n = 16), and intrauterine adhesion (IUA; n = 45). INTERVENTION(S) Postoperative office hysteroscopy was consecutively done until complete endometrial wound healing. If there was newly formed IUA occurring at the endometrial wounds, adhesiolysis was immediately done with the tip of the office hysteroscope. MAIN OUTCOME MEASURE(S) Office hysteroscopic inspection of endometrial wound healing and the presence of newly formed IUA. RESULT(S) Thirty-two of 37 women (86%) achieved a fully healed endometrium 1 month after polypectomy, a higher rate than those after myomectomy (18%), septal incision (19%), and adhesiolysis (67%). Postoperative office hysteroscopy revealed that 88% and 76% of the women had new IUA formation after septal incision and adhesiolysis, respectively, more than those after myomectomy (40%) and polypectomy (0%). Women with postoperative new IUA formation were less likely to achieve endometrial wound healing within 1 month compared with those who had no new IUA formation (31% vs. 61%). CONCLUSION(S) The duration of endometrial wound healing is different after various hysteroscopic surgeries. Postoperative new IUA formation is an important factor influencing endometrial wound healing.

Hormone replacement therapy reverses the decrease in natural killer cytotoxicity but does not reverse the decreases in the T-cell subpopulation or interferon-gamma production in postmenopausal women

OBJECTIVE To investigate the immunologic deviations of postmenopausal women before and after hormone replacement therapy (HRT). DESIGN Prospective study. SETTING University teaching hospital. PATIENT(S) Seventeen postmenopausal women (study group) and 17 women of reproductive age (control group). INTERVENTION(S) Continuous usage of E(2) valerate 2 mg/d and medroxyprogesterone acetate 5 mg/d in postmenopausal women in the study group. MAIN OUTCOME MEASURE(S) Immunophenotyping with flow cytometry, cytokine production with and without mitogen stimulation of the peripheral mononuclear cells, and a natural killer (NK) cell cytotoxicity test against K562 target cells by the (51)Cr-release assay were performed in the control group and in the study group before, 1 month after, and 6 months after HRT. RESULT(S) NK cytotoxicity, interferon-gamma production, and the T-cell subpopulation were significantly decreased, and the subpopulations of CD3(+)CD25(+) and CD3(+)HLA-DR(+) were increased in the study group before HRT when compared with those in the control group. After HRT was given for 6 months, however, the NK cytotoxicity increased significantly in the postmenopausal women to a value similar to that of the control group. CONCLUSION(S) Women after menopause are prone to impaired immune responses. Nevertheless, some of the impairment can be restored after HRT.

Prognostic importance of serial cytokine changes in ascites and pleural effusion in women with severe ovarian hyperstimulation syndrome

OBJECTIVE To determine the prognostic value of various cytokine levels in ascites and pleural effusion during the evolution of severe ovarian hyperstimulation syndrome (OHSS). DESIGN A longitudinal study. SETTING University teaching hospital. PATIENT(S) Twenty patients with severe OHSS who required either paracentesis or thoracentesis or both from whom ascites (n = 56) or pleural effusion (n = 12) samples were obtained. Control peritoneal fluid was obtained from 20 patients undergoing ovarian stimulation for IVF. INTERVENTION(S) Abdominal paracentesis for tense ascites and thoracentesis for massive pleural effusion. Control peritoneal fluid was obtained before oocyte retrieval. MAIN OUTCOME MEASURE(S) Levels of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), vascular endothelial growth factor (VEGF), E2, and progesterone concentrations in ascites and pleural effusion. RESULT(S) Levels of VEGF and IL-6 in ascites dropped significantly during the course of OHSS and were not correlated with E2 concentrations. Levels of VEGF were significantly correlated with levels of IL-1 beta, IL-8, and TNF-alpha, as well as progesterone concentrations, hematocrit, and white blood cell counts. None of the cytokine levels measured in pleural effusion were correlated with the course of OHSS. CONCLUSION(S) These results suggest that local cytokines might be involved in the evolution of severe OHSS and possibly serve as prognostic markers for this syndrome.

Increase in the production of interleukin-6, interleukin-10, and interleukin-12 by lipopolysaccharide-stimulated peritoneal macrophages from women with endometriosis.

PROBLEM: To verify whether the peritonea] macrophage (PM) is activated in endometriosis.

Intravenous albumin does not prevent the development of severe ovarian hyperstimulation syndrome

OBJECTIVE To determine the efficacy of IV albumin in the prevention of severe ovarian hyperstimulation syndrome (OHSS). DESIGN Prospective study group with historical control. SETTING University hospital-based IVF program. PATIENT(S) Between 1993 and 1995, 42 consecutive patients undergoing IVF-ET or tubal ET who had serum E2 levels > or = 3,600 pg/mL (conversion factor to SI unit, 3.671) on the day of hCG administration and/or > or = 20 oocytes retrieved were considered at high risk for severe OHSS and were selected as the control group. From December 1995 to October 1996, IV albumin was given to 30 consecutive patients who fulfilled these criteria. INTERVENTION(S) The treatment group received IV albumin after oocyte retrieval. MAIN OUTCOME MEASURE Occurrence of severe OHSS. RESULT(S) None of the 16 patients in the treatment group in nonconception cycles developed severe OHSS, compared with 5 (21.7%) of 23 in the control group. In conception cycles, 4 (28.6%) of 14 patients in the treatment group developed severe OHSS, compared with 9 (47.4%) of 19 in the control group. All 4 patients with multiple pregnancies in the treatment group developed severe OHSS, compared with 3 (60%) of 5 in the control group. None of the 10 patients with singleton pregnancies in the treatment group developed severe OHSS, compared with 6 (42.9%) of 14 in the control group. CONCLUSION(S) Intravenous albumin prevents severe OHSS in high-risk patients who did not conceive or who carried singleton pregnancies, but not in the patients with high-order pregnancies.

The expression of killer cell inhibitory receptors on natural killer cells and activation status of CD4+ and CD8+ T cells in the decidua of normal and abnormal early pregnancies.

The establishment of the human placenta in early pregnancy is characterized by the presence of large numbers of natural killer cells within the maternal decidua. These NK cells have an unusual phenotype, CD3- CD16- CD56(bright), distinguishing them from peripheral blood NK cells. They may control trophoblast migration and placentation. Using a panel of monoclonal antibodies to several members of the KIR family and flow cytometry, we found that KIRs are expressed on decidual NK cells. There is variation in both the percentage of cells expressing a particular receptor and the density of receptor expression between decidual NK cells from different individuals. In anembryonic pregnancy, the proportions of decidual NK cells with a particular KIRs (GL183 and EB6) decreased significantly when compared with normal pregnancy (p = 0.01 and 0.01, respectively), raising the possibility that these NK receptors may be involved in recognition of the allogeneic fetus by the mother at the implantation site. In the decidua, more CD4+ and CD8+ T cells expressed CD69 and HLA-DR than in blood, indicating that T cells are regionally activated during early pregnancy. When compared with normal pregnancy, decidual HLA-DR+CD4+CD3+, CD69+CD8+CD3+ and HLA-DR+CD8+CD3+ T lymphocytes are significantly increased in anembryonic pregnancy. The over-activation of decidual T cells during anembryonic pregnancy may thus contribute to the increased NK cytotoxicity activity.