Kenneth A. Ginsburg

Vaginal-Associated Immunity in Women with Recurrent Vulvovaginal Candidiasis: Evidence for Vaginal Th1-Type Responses following Intravaginal Challenge with Candida Antigen

Studies from women with recurrent vulvovaginal candidiasis (RVVC) and from an animal model of experimental vaginitis suggest that deficiencies in immune function should be examined at the local rather than systemic level. Evidence of vaginal cell-mediated immunity (CMI) was evaluated for the first time in cervicovaginal lavage (CVL) fluid from RVVC patients. Results showed that although constitutive Th1- and Th2-type cytokine expression was detectable in CVL fluid from normal women, and differences in cytokines were observed in RVVC patients, limitations in experimental design of such de novo analyses urged caution in interpretation. Alternatively, attempts were made to establish conditions in control subjects whereby vaginal immunity could be detected after intravaginal challenge with Candida antigen. Preliminary results showed that Th1-type cytokines (interleukin-2 and -12, interferon-gamma) and histamine were increased 16-18 h after intravaginal introduction of Candida skin test antigen. Intravaginal antigenic challenge represents a novel approach for studying Candida-specific vaginal CMI.

Pregnancy after medical therapy of adenomyosis with a gonadotropin-releasing hormone agonist

A patient with long-standing secondary infertility was explored for myomectomy, at which time severe adenomyosis was found. A 6-month course of nafarelin acetate resulted in resolution of dysmenorrhea and uterine enlargement. The patient conceived quickly. Although the patient spontaneously aborted, this report presents the first in which medical therapy of adenomyosis is associated with successful treatment of infertility.

The influence of chamber characteristics on the reliability of sperm concentration and movement measurements obtained by manual and videomicrographic analysis

To assess the influence of chamber design and depth on the accuracy and precision of sperm measurements, manual counting of a standardized latex bead solution and automated sperm motility measurements were made using a Makler chamber (Sefi Medical Industries, Haifa, Israel), Neubauer hemocytometer (American Optical Company, Buffalo, NY), and a new, disposable device (Micro-Cell; Cyto Fluidics, Inc., Silver Spring, MD). Bead counts obtained with the Micro-Cell chamber or hemocytometer were not statistically different from those determined by electronic particle counting, whereas Makler chamber counts were 62% higher. Makler counts had a significantly higher standard deviation, suggesting that counts made with this device are less reproducible. Analyzing live sperm samples, the percentage of motile sperm determined using Micro-Cell and Makler chambers were similar. However, significant differences in sperm concentration and mean velocity were found. The Micro-Cell disposable chamber provided consistent and accurate data on sperm concentration, percent motility, and mean velocity. These differences in sperm measurements emphasize the importance of sampling chamber characteristics on data reliability.

Thrombosis and hormone replacement therapy in postmenopausal women.

OBJECTIVE The effects of postmenopausal hormone replacement therapy on thrombosis remain controversial. We tested the hypothesis that estrogen or progesterone has no significant effect on thrombosis by means of newly developed markers of blood clotting, specifically prothrombin fragment 1 + 2, a marker of factor Xa generation, and thrombin-antithrombin III complex, a marker of thrombin generation. STUDY DESIGN A prospective study that included 106 women, 68 postmenopausal women on hormone replacement therapy and 38 postmenopausal controls, was performed. Plasma levels of prothrombin fragment 1 + 2 and thrombin-antithrombin III complex were measured by enzyme-linked immunosorbent assay. Multivariate analysis of the covariance was used for statistical analysis, controlling for patients age because the hormone replacement therapy group was older. RESULTS There were no statistically significant differences between the hormone replacement therapy and control groups in either of the clotting parameters measured. A comparison of the levels of prothrombin fragment 1 + 2 and thrombin-antithrombin III complex in patients receiving estrogen alone or estrogen plus progestin also revealed no differences. CONCLUSIONS Current doses of postmenopausal hormone replacement therapy do not appear to enhance in vivo clotting. Thromboembolic complications among postmenopausal women receiving hormone replacement therapy may therefore be secondary to congenital or other acquired coagulation defects.

Unexplained infertility: Evaluation of the luteal phase; results of the National Center for Infertility Research at Michigan

OBJECTIVE To evaluate the luteal phase in women with rigorously defined unexplained infertility. DESIGN Prospective study. SETTING National Center for Infertility Research at Michigan. PATIENT(S) Evaluation of 1,885 women with infertility identified 12 women who met the rigorously defined criteria for unexplained infertility: [1] infertility of > or = 24 months duration, with no male factor, anatomic-functional disorders of the reproductive tract, or immunologic infertility; [2] normal body mass index (BMI); [3] ovulatory cycles ranging from 26 to 32 days; [4] normal luteal phase determined by endometrial biopsy; and [5] normal baseline hormonal profile. Controls (n = 12) were healthy, parous women with normal ovulatory cycles, normal hormonal screen, and were matched for age and BMI to patients. MAIN OUTCOME MEASURE(S) Pattern of follicular growth rate and luteal phase hormonal profile. RESULT(S) Women with unexplained infertility did not differ in menstrual cycle characteristics, follicular growth rate or mean preovulatory follicle diameter, or endometrial biopsy dating. The mean levels of P tended to be lower in the unexplained infertility group throughout the luteal phase, but only the midluteal interval reached statistical significance. Luteal phase mean integrated P or urinary PDG levels of unexplained infertility women did not differ from those of fertile controls. The ratio of integrated E2:P also was significantly greater in women with unexplained infertility than in fertile controls. CONCLUSION(S) Women with rigorously defined unexplained infertility have subtle hormonal anomalies during the luteal phase when compared with fertile controls.

Wireless Handheld Computers in the Undergraduate Medical Curriculum

Abstract Wayne State University Medical School has implemented wireless handheld computers or PocketPCs (PPCs) into all four years of the undergraduate curriculum. A transition from a passive to an interactive learning environment in the classroom, as well as administrative solutions for monitoring patient encounter data by students in their clinical rotations was fostered by this educational technology. Implementation of the wireless devices into the curriculum will be described in this report. This will include the technical specifications and justification for the required device, as well as a detailed discussion of the different applications used for educational and administrative purposes by the preclinical and clinical students. Outcomes from the educational and administrative aspects of the project will also be presented in this report.

Fibrinolytic parameters in women undergoing ovulation induction

OBJECTIVE The purpose of this study was to evaluate the effect of elevated levels of circulating estradiol on the clotting and fibrinolytic system in patients undergoing controlled ovarian hyperstimulation. STUDY DESIGN Fifty-two patients undergoing controlled ovarian hyperstimulation with human menopausal gonadotropins or urofollotropin were asked to participate. Blood for hemostasis parameters was obtained on the days that patients returned for estradiol sampling. Sample days were identified as cycle days 1 to 5 (baseline), 6 to 9, and 10 to 14. Each factor was analyzed by repeated-measures analysis of variance and correlation analysis. RESULTS A significant decline was observed for tissue plasminogen activator antigen and plasminogen activator inhibitor type 1 activity from baseline to cycle days 10 to 14. As serum estradiol levels increased throughout each phase (maximum mean estradiol 739.8 pg/ml), a significant linear decrease was observed for both tissue plasminogen activator antigen and plasminogen activator inhibitor type 1 activity, whereas thrombin-antithrombin III complexes did not change significantly. A significant positive correlation was also observed for plasminogen activator inhibitor activity and tissue plasminogen activator antigen level over all cycle days examined. CONCLUSION Down-regulation of the fibrinolytic system was observed as estradiol levels increased. However, thrombin formation did not change, thus suggesting that elevated circulating estradiol alone does not predispose to a thromboembolic event.

Flare-up of endometriosis induced by gonadotropin-releasing hormone agonist leading to bowel obstruction

OBJECTIVE To report a case of intestinal obstruction that developed shortly after preoperative administration of a GnRH analogue (GnRH-a) that caused flare-up and rapid progression of enteric endometriosis. DESIGN Case report. SETTING University tertiary reproductive endocrinology practice. PATIENT A 34-year-old nulligravid female with progressive severe symptomatic endometriosis. INTERVENTIONS Planned preoperative administration of GnRH-a for 3 months followed by extirpative surgery and hormone replacement therapy. Instead, total abdominal hysterectomy, bilateral salpingoophorectomy, resection of the obstructed ileocecal junction, and side-to-side ileo-ascending enterocolostomy was performed. RESULTS Preoperative GnRH-a administered in the midfollicular phase resulted in flare-up of preexisting ileocecal endometriosis that rapidly progressed, resulting in partial small bowel obstruction. CONCLUSION Gonadotropin-releasing hormone agonist should be used with caution when there is known or suspected enteric endometriosis. Consideration should be given to blocking the agonistic effect of GnRH-a in this setting by the prior or concomitant use of progestins or danazol.

Elevated early follicular gonadotropin levels in women with unexplained infertility do not provide evidence for disordered gonadotropin-releasing hormone secretion as assessed by luteinizing hormone pulse characteristics

OBJECTIVE To determine whether women with rigorously defined unexplained infertility demonstrated altered GnRH secretion, as reflected by serum LH secretion patterns. DESIGN Prospective observational study. SETTING National Center for Infertility Research at Michigan. PATIENT(S) Nine women with rigorously defined unexplained infertility and 11 healthy, parous age-matched control women.Gonadotropin-releasing hormone (25 ng/kg) as a bolus injection. MAIN OUTCOME MEASURE(S) Daytime pulse patterns of LH secretion measured every 10 minutes; mean serum concentrations of LH, FSH, E(2), P, PRL, and cortisol; and response to a physiologic dose of GnRH in the early follicular, late follicular, mid-luteal, and late luteal phases of the same menstrual cycle. RESULT(S) Serum LH pulse frequency and pulse amplitude and LH secretion in response to a physiologic bolus of GnRH were not significantly different in unexplained infertility patients at any phase of the cycle. Luteinizing hormone pulse frequency and amplitude, as well as response to GnRH, varied significantly across the cycle. Mean early follicular serum LH and FSH concentrations were significantly higher in unexplained infertility patients than in fertile control subjects (LH: 5.31 +/-.51 vs. 4.03 +/-.33 [mIU/mL +/- SEM]; FSH: 5.81 +/-.63 vs. 3.80 +/-.45) but were not different at any other phase of the cycle. CONCLUSION(S) These data do not support the hypothesis that unexplained infertility is caused by an abnormality in pulsatile GnRH secretion or abnormal pituitary sensitivity to GnRH. However, the results are consistent with a difference in negative feedback from the ovary to the pituitary in unexplained infertility patients that is suggestive of diminished ovarian reserve.

The effects of in vitro cocaine exposure on human sperm motility, intracellular calcium, and oocyte penetration *

Objective To determine if cocaine exposure affects human sperm motility, intracellular calcium level, and fertilizing capability. Design and Methods Human semen samples were treated with 1 to 1,000 µ M cocaine hydrochloride for up to 2hours in vitro. Sperm motion kinematics were measured by computer-assisted semen analysis (CASA). Spermatozoan intracellular calcium was determined by laser cytometry. The sperm fertilizing capability was assessed using the zona-free hamster oocyte penetration test. Results After a short exposure (15minutes) to cocaine, the sperm motion kinematic parameters, straight line velocity and linearity, were decreased in the high concentration groups. However, after a longer exposure (2hours) to cocaine, the differences were no longer significant. Cocaine treatment did not alter spermatozoa intracellular calcium levels. Most importantly, human sperm treated with cocaine at a high concentration were fully capable of penetrating zona-free hamster oocytes. Conclusion Human spermatozoa acutely exposed to high concentrations of cocaine initially demonstrate a decrease in two motion kinematics, straight line velocity and linearity. However, overall, cocaine exposure had no significant effects on sperm motility and fertilizing capability.