Jehn-Hsiahn Yang

Relationship Between Androgen Levels and Blood Pressure in Young Women With Polycystic Ovary Syndrome

The role of testosterone on the development of hypertension is controversial, especially in women with polycystic ovary syndrome (PCOS) who have higher prevalence of obesity and insulin resistance than women without PCOS. Little is known about the association between serum testosterone level and blood pressure in young women with PCOS. In the 151 young Taiwanese women with PCOS enrolled in this cross-sectional study, we measured the body mass index, waist circumference, blood pressure, fasting glucose, fasting insulin, lipid profile, and hormone profiles. The free androgen index, total testosterone, and sex hormone-binding globulin, but not the level of dehydroepiandrosterone sulfate, significantly correlated with both systolic blood pressure (SBP) and diastolic blood pressure (DBP). In multiple linear regression models adjusted for age, body mass index, and other anthropometric, metabolic, and hormonal variables, the level of serum free androgen index or total testosterone, but not the sex hormone-binding globulin, were independently related to SBP and DBP. The age- and body mass index–adjusted least-square mean of serum-free androgen index levels were significantly different between the highest quartile and other quartiles of the SBP and DBP levels. The high bioavailable testosterone levels (free androgen index: ≥19%) in women with PCOS increased the risk of elevated blood pressure (SBP ≥130 mm Hg and/or DBP ≥85 mm Hg) with an odds ratio of 3.817 (P=0.029; 95% CI: 1.14 to 12.74) after adjustment for age, anthropometric measures, and metabolic profiles. Our results suggest that the characteristic hyperandrogenemia in young women with PCOS was associated with an elevated SBP and DBP independent of age, insulin resistance, obesity, or dyslipidemia.

Fused has evolved divergent roles in vertebrate Hedgehog signalling and motile ciliogenesis

Hedgehog (Hh) signalling is essential for several aspects of embryogenesis. In Drosophila, Hh transduction is mediated by a cytoplasmic signalling complex that includes the putative serine-threonine kinase Fused (Fu) and the kinesin Costal 2 (Cos2, also known as Cos), yet Fu does not have a conserved role in Hh signalling in mammals. Mouse Fu (also known as Stk36) mutants are viable and seem to respond normally to Hh signalling. Here we show that mouse Fu is essential for construction of the central pair apparatus of motile, 9+2 cilia and offers a new model of human primary ciliary dyskinesia. We found that mouse Fu physically interacts with Kif27, a mammalian Cos2 orthologue, and linked Fu to known structural components of the central pair apparatus, providing evidence for the first regulatory component involved in central pair construction. We also demonstrated that zebrafish Fu is required both for Hh signalling and cilia biogenesis in Kupffer’s vesicle. Mouse Fu rescued both Hh-dependent and -independent defects in zebrafish. Our results delineate a new pathway for central pair apparatus assembly, identify common regulators of Hh signalling and motile ciliogenesis, and provide insights into the evolution of the Hh cascade.

Increase in the expression of killer cell inhibitory receptors on peritoneal natural killer cells in women with endometriosis

OBJECTIVE Malfunction of peritoneal natural killer cells (NK) may result in endometriosis. The present study was designed to determine whether the decrease in NK cytotoxicity occurs at early and advanced stages of endometriosis and is due to the increase in the NK inhibition receptors. DESIGN A case control study. SETTING A tertiary-care infertility center . PATIENT(S) A total of 44 women (controls, n = 11; women with early-stage endometriosis, n = 11; and women with advanced-stage endometriosis, n = 22) were included in this study. INTERVENTION(S) Laparoscopic examination. MAIN OUTCOME MEASURE(S) NK cytotoxicity was determined by assay of (51)Cr release against K562 cells, and the expression of killer cell inhibitory receptors (KIR, including NKB1, GL183, and EB6) in NK cells was examined by flow cytometry. RESULT(S) Women with endometriosis showed a decrease in peritoneal NK cytotoxicities against K562 at early and advanced stages of endometriosis. The expression of KIR (NKB1 and EB6) was significantly elevated in the peritoneal NK cells of women with advanced-stage endometriosis compared with controls. KIR (NKB1) was also significantly increased in peritoneal NK cells of women with advanced-stage endometriosis, compared with those of women with early-stage endometriosis. CONCLUSION(S) The results of this study suggest that the decrease in peritoneal NK cytotoxicities against K562 is observed and that this disease may be partially due to the increased expression of KIR on these NK cells.

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.

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.

Changes in Myometrial Thickness during Hysteroscopic Resection of Deeply Invasive Submucous Myomas

STUDY OBJECTIVE To evaluate the efficacy of hysteroscopy in resecting submucous myomas with deep intramural invasion. DESIGN Prospective, observational study (Canadian Task Force classification II-2). SETTING Department of gynecology at a general hospital. PATIENTS Sixteen women with a solitary submucous myoma, in which myometrial thickness between the outer edge of the myoma and inner edge of the serosa was between 5 and 10 mm. INTERVENTION One-step hysteroscopic myomectomy. MEASUREMENTS AND MAIN RESULTS Median myoma diameter and weight were 3.3 cm and 30 g, respectively. Myometrial thickness between the myoma and serosa increased gradually and significantly from 6.7 mm before, to 8.9 mm during, to 16.1 mm immediately after hysteroscopic myomectomy (p <0.001). The thickness of the opposite uterine wall increased from 10.1 mm before, to 11.4 mm during, to 18.8 mm after operation (p <0.001). CONCLUSION One-step hysteroscopic myomectomy may be performed to remove deeply infiltrating submucous myomas when myometrial thickness at the implantation site is as thin as 5 mm.

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.

High serum dehydroepiandrosterone sulfate is associated with phenotypic acne and a reduced risk of abdominal obesity in women with polycystic ovary syndrome

BACKGROUND Women with polycystic ovary syndrome (PCOS) are known to have high prevalence of acne and elevated androgen levels. The current study aims to determine if dehydroepiandrosterone sulfate (DHEAS) level is associated with the presence of acne and reduced risk of abdominal obesity in women with PCOS, after considering the concurrent high testosterone level and insulin resistance (IR). METHODS Three hundred and eighteen untreated consecutive Taiwanese women with PCOS were enrolled. Phenotypic hyperandrogenism was recorded, and BMI, waist circumference, waist-to-hip ratio, lipid profiles, fasting glucose and insulin levels and hormone profiles were measured. RESULTS Women with acne were younger, had higher serum DHEAS levels (6.01 ± 3.45 versus 4.87 ± 2.49 μmol/l, P = 0.002) and a lower BMI (P = 0.0006), but comparable serum testosterone levels, in comparison with women without acne. The aggravating effect of elevated DHEAS on the risk of acne (odds ratio = 2.15, 95% confidence interval: 1.25-3.68, P = 0.005 for DHEAS cut-off of 6.68 μmol/l) still exited after adjustment for age and BMI. The DHEAS level was positively correlated with the testosterone level, but inversely related to waist circumference, waist-to-hip ratio, BMI, IR index, low-density lipoprotein-cholesterol and triglycerides. Women with PCOS in the highest quartile of DHEAS had the lowest risk of abdominal obesity after adjustment for age, IR, dyslipidemia, testosterone and estradiol levels. CONCLUSIONS Our results demonstrated the high serum DHEAS in women with PCOS was associated with the presence of acne and a significantly reduced risk of abdominal obesity, independent of serum testosterone concentration and IR.

Comparison of coasting and intravenous albumin in the prevention of ovarian hyperstimulation syndrome

OBJECTIVE To compare the efficacy of coasting to prevent ovarian hyperstimulation syndrome (OHSS) with i.v. albumin and to determine if different timing of gonadotropin coasting would affect the IVF outcomes. DESIGN Retrospective study. SETTING University hospital-based IVF program. PATIENT(S) One hundred sixty-two women undergoing IVF treatment cycles who were considered to be at high risk for developing OHSS. INTERVENTION(S) Gonadotropin administration was withheld in 60 patients: either coasting occurred before follicular maturation (early coasting subset, n = 28) or follicular maturity was attained before coasting (late coasting subset, n = 32). Outcomes were compared in 102 patients at risk for OHSS who received i.v. albumin on the day of oocyte retrieval. MAIN OUTCOME MEASURE(S) Incidence of OHSS and outcome parameters. RESULT(S) Although the fertilization rates and the incidence of OHSS did not differ significantly between the coasting and i.v. albumin groups, the mean number of oocytes retrieved, the pregnancy rates, and implantation rates were significantly lower in the coasting group. There is no statistical difference in the entire outcome examined and the incidence of OHSS between the early and late coasting subsets. CONCLUSION(S) Coasting is as effective as i.v. albumin in preventing OHSS in high-risk patients but yields inferior pregnancy rates. Early coasting is as successful as late coasting in preventing OHSS with similar IVF outcome.