Polycystic ovary syndrome is associated with endothelial dysfunction.

BACKGROUND: We recently reported endothelial dysfunction as a novel cardiovascular risk factor associated with insulin resistance/obesity. Here, we tested whether hyperandrogenic insulin-resistant women with polycystic ovary syndrome (PCOS) who are at increased risk of macrovascular disease display impaired endothelium-dependent vasodilation and whether endothelial function in PCOS is associated with particular metabolic and/or hormonal characteristics. METHODS AND RESULTS: We studied leg blood flow (LBF) responses to graded intrafemoral artery infusions of the endothelium-dependent vasodilator methacholine chloride (MCh) and to euglycemic hyperinsulinemia in 12 obese women with PCOS and in 13 healthy age- and weight-matched control subjects (OBW). LBF increments in response to MCh were 50% lower in the PCOS group than in the OBW group (P:<0.01). Euglycemic hyperinsulinemia increased LBF above baseline by 30% in the PCOS and 60% in OBW group (P:<0.05 between groups). Across all subjects, the maximal LBF response to MCh exhibited a strong inverse correlation with free testosterone levels (r=-0.52, P:<0.007). This relationship was stronger than with any other parameter, including insulin sensitivity. CONCLUSIONS: PCOS is characterized by (1) endothelial dysfunction and (2) resistance to the vasodilating action of insulin. This endothelial dysfunction appears to be associated with both elevated androgen levels and insulin resistance. Given the central vasoprotective role of endothelium, these findings could explain, at least in part, the increased risk for macrovascular disease in women with PCOS.

Double Gires-Tournois interferometer negative-dispersion mirrors for use in tunable mode-locked lasers.

We report the implementation and operation of novel superhigh-reflectivity negative-dispersion dielectric mirrors for use in tunable ultrafast laser systems. The mirror structure is divided into two distinct regions: an underlying superhigh-reflectivity dielectric quarter-wavelength stack and an overlying negative-dispersion section consisting of only a few layers and forming simple multiple Gires-Tournois interferometers. The example that we present was designed for operation from 800 to 900 nm and has a near-constant group-delay dispersion of -40 fs(2) and a peak reflectivity greater than 99.99%. We show a comparison of the predicted and the measured mirror performance and application of these mirrors in a mode-locked Ti:sapphire laser tunable from 805 to 915 nm.

Müllerian agenesis: an update.

Recently, many advances have been made in the study of sexual differentiation, including the discoveries of the gene for antimüllerian hormone as well as the gene for its receptor. However, the etiology of the clinical syndrome of müllerian agenesis remains elusive. We hypothesize that activating mutations of either the antimüllerian hormone gene or its receptor gene may cause müllerian duct regression in a genetic female during embryogenesis. This clinical commentary discusses the current management of the syndrome including the Abbe-McIndoe procedure, the most commonly used method of surgical correction, and the Frank vaginal dilation method, the most common nonsurgical method of correction.

30-fs pulses tunable across the visible with a 100-kHz Ti:sapphire regenerative amplifier.

A 100-kHz mode-locked Ti:sapphire-seeded regenerative amplifier pumping an optical parametric amplifier generates femtosecond pulses tunable from 470 to 710 nm. This output was compressed with a pair of prisms to bandwidth-limited pulses of 80- to 40-fs duration and more than 150 nJ of energy. These tunable pulses were then bandwidth expanded through self-phase modulation in bulk material and further compressed to less than 30-fs duration.

The effects of baseline ovarian cysts on cycle fecundity in controlled ovarian hyperstimulation.

Patients undergoing COH were prospectively studied in 174 cycles for the presence of baseline ovarian cysts. In 37.4% of all cycles, a baseline cyst > 10 mm mean diameter was found, but a cyst was more common in subsequent cycles than on the first (41.5% versus 15.8%). Cycle fecundity as determined by life table analysis was significantly higher if no baseline cyst were present (0.25 versus 0.06, P > 0.01). These findings suggest that baseline ovarian cysts may adversely affect the chances for pregnancy in COH not associated with IVF or GIFT.

The effects of spontaneous luteinizing hormone surges on superovulatory cycles.

OBJECTIVE: To determine the effect of a spontaneous luteinizing hormone (LH) surge on the cycle fecundity during superovulation induction. DESIGN: Superovulatory cycles of patients with various diagnoses are retrospectively compared. SETTING: Reproductive Endocrinology Outpatient Clinic. PATIENTS: A total of 1,185 superovulatory cycles from July 1, 1982 until November 1, 1991 are compared. MAIN OUTCOME MEASURE: The probability of achieving a pregnancy per treatment cycle. RESULTS: Patients with unexplained infertility and hyperprolactinemia were more likely to have a spontaneous LH surge during superovulation than patients with either endometriosis or polycystic ovarian disease. However, the cycle fecundity rate did not differ whether or not an LH surge occurred, regardless of the diagnosis. CONCLUSIONS: Spontaneous onset of an LH surge during superovulation induction does not influence the chances for pregnancy.

Partial characterization of Chlamydia trachomatis isolates resistant to multiple antibiotics.

In vitro susceptibility testing was done on urogenital isolates of Chlamydia trachomatis from five patients, four of whom were suspected treatment failures. At least one isolate from each patient was resistant to tetracycline at concentrations greater than or equal to micrograms/ml, although less than 1% of a population of organisms showed high-level resistance. Fully resistant populations selected by passage through 8 micrograms/ml tetracycline either died or lost their resistance on further passage in antibiotic-free medium. Relatively large inocula were required to demonstrate resistance, and morphology of inclusions was altered at high tetracycline concentrations. The observed resistance may be a new characteristic of the organism or merely newly recognized. Isolates resistant to tetracycline were resistant to doxycycline, erythromycin, sulfamethoxazole, and clindamycin but sensitive to rifampin, ciprofloxacin, and ofloxacin. Thus, resistance to tetracycline, erythromycin, and clindamycin occurs in C. trachomatis and may be a factor in some treatment failures.

Recovery of Chlamydia trachomatis from endometrial and fallopian tube biopsies in women with infertility of tubal origin.

In order to examine the role of chronic active chlamydial infection in tubal infertility, cultures for Chlamydia trachomatis were performed on endometrial biopsies from 38, and fallopian tube biopsies from all, of 52 women undergoing tubal surgery for infertility. C. trachomatis was recovered from one or both sites in 8 of 52 (15%). Five of 6 women with positive fallopian tube cultures had endometrial cultures performed, and of these, 4 (80%) were positive. Three culture-positive women had been treated with tetracycline or doxycycline. Multiple blind passage in tissue culture was required for recovery of all six fallopian tube and four of the six endometrial isolates. No specific anatomic lesion was associated with documented infection. Chronic active chlamydial infection is frequently associated with tubal infertility, may persist despite therapy, and often can be detected by endometrial biopsy culture.

Recovery of Chlamydia trachomatis from the endometrium of women at risk for chlamydial infection.

Chlamydia trachomatis is the most common sexually transmitted disease in Western Society today and is a major cause of salpingitis and tubal infertility. However, the frequency with which it produces upper genital tract infection in asymptomatic women has not been determined. Endometrial, endocervical, and urethral cultures for C. trachomatis were obtained from 60 women who were at risk for chlamydial infection but who did not have evidence of endometritis or salpingitis on physical examination. Chlamydia was isolated from the lower genitourinary tract in 26 (43%) and from the endometrium in 12 (20%). Thus 12 of 29 (41%) women infected with C. trachomatis had endometrial infections. Upper genital infections appear to be common in women at risk for chlamydial infection, and spread to the upper tract may occur shortly after the infection is acquired.

Assessment of follicular development by ultrasonography and total serum estrogen in human menopausal gonadotropin-stimulated cycles.

Ovarian follicular development was assessed by serial ultrasonography in infertile women being treated with human menopausal gonadotropin. Both follicular size and number of follicles correlated with serum estrogen values in most patients, and follicles increased in size 2--3 mm per day. Most patients had serum estrogen values greater than 750 pg/ml when one or more follicles larger than 18 mm were present. A comparison of conception cycles with non-conception cycles did not reveal a significant difference in size or number of follicles, or in the rate of rise or peak value of serum estrogen. When women monitored with ultrasonography were compared with patients treated with gonadotropins prior to the availability of ultrasonography, there was no significant difference in the rates of successful conception, although the number of ampules of pergonal used by the former was significantly reduced, permitting more efficient use of an expensive medication.

Fetal hemoglobin in women with normal and with hydatidiform molar pregnancy.

The quantity and the rate of synthesis of fetal hemoglobin (HbF); the level of HbF-containing erythrocytes (F cells); and the levels of progesterone, human chorionic gonadotropin (HCG), and human chorionic somatomammotropin (HCS) in serial blood samples from women at different stages of pregnancy were determined. An increase was observed in the synthesis and the quantity of maternal HbF, reaching a peak at about 9-12 weeks gestation. A major peak in F-cell level was also detected at about 9-12 weeks, with two minor peaks appearing at about 16-20 and 22-24 weeks. Levels of HCG, HCS, and progesterone also varied during pregnancy. Timing of the rise and fall of HCG levels corresponded to that of maternal HbF levels, whereas levels of HCS and progesterone did not reach their peak until later stages of gestation when HbF level had returned to normal. Similar analysis conducted on patients with hydatidiform molar pregnancy revealed that the majority (greater than 95%) of these patients showed significant increases in HbF synthesis at the time of molar evacuation, but decreased to normal levels in approximately 30 days post-evacuation. A similar profile in the levels of HCG, but not progesterone and HCS, was observed. A positive correlation between levels of HCG and HbF can be established (correlation coefficient = 0.94). These data are in agreement with the hypothesis that HCG may act as a stimulus for the enhanced HbF synthesis in adults.

Relationship of weight to successful induction of ovulation with clomiphene citrate.

Over a 6 1/2-year period, 117 patients who were anovulatory, euthyroid, and estrogen-primed were treated with clomiphene citrate. Graduated doses from 50 mg to 250 mg daily for 5 days were used to induce ovulation. Of 62 patients who completed treatment, 50 ovulated and 12 did not. Several factors, including age, duration of infertility, weight, previous menstrual history, previous pregnancy history, and previous use of oral contraceptives, were investigated to determine conditions which might influence response. Only weight was found to be significantly different between responders and nonresponders. Furthermore, there was a linear relationship between body weight and dose of clomiphene required to induce ovulation. The ovulation rate for those completing therapy was 81% with a pregnancy rate of 76% of the total and 94% of those ovulating. Population homogeneity with anovulation as the major cause of infertility appears to be the most plausible explanation for the high pregnancy rate.

Comparison of serum progesterone and endometrial biopsy for confirmation of ovulation and evaluation of luteal function.

An endometrial biopsy and a blood sample for progesterone determination obtained simultaneously in the midluteal phase of the cycles of 55 infertile women were compared for reliability for confirmation of presumptive ovulation and evaluation of luteal function. Progesterone levels of 3 ng/ml or greater were found in 90.5% of the cycles. Secretory endometrium was identified in 81% of the cycles. Thirty-three cycles yielded sufficient information to compare the two methods for evaluation of luteal function. Histology and progesterone levels were consistent with each other and the presumed time of ovulation in only 11 cycles. Histology was inconsistent with the presumed time of ovulation in 20 cycles, while progesterone was inconsistent in only two cycles. Additional samples for progesterone determinations were obtained during the biopsy cycles of 15 patients who presented adequate data for evaluation of luteal function. A single, well-timed progesterone determination appeared adequately to reflect the data obtained from serial samples in the same cycle. These results support the thesis that a single, well-timed serum progesterone determination is superior to a single endometrial biopsy as a screening method for confirmation of presumptive ovulation and for evaluation of luteal function.

PIP: An attempt to determine how accurate serum progesterone as compared with endometrial biopsy is in confirming that ovualtion has taken place, and what is the value of each method for assessing luteal function in infertile women is presented. Subjects were 55 women who were undergoing evaluation for infertility. Only patients who were presumed to be ovulatory were included. The maximum duration of infertility had been 10 years, with a mean of 3.9 years. Blood samples were obtained at the time of biopsy. Some additional blood samples were taken during the presumed luteal cycles. Progesterone serum levels of 3 ng/ml or higher were found in 90.5% of cycles. Secretory endometrium was found in 81% of cycles. There was a positive correlation between biopsy findings and serum progesteone in only 75% of cases. Only 33 cycles in 32 patients were suitable for luteal function determination. Retarded endometrial histology did not necessarily reflect insufficient progesterone secretion but low serum values during expected periods of peak progesterone secretion usually showed retarded endometrium. These findings had little prognostic value regarding future fertility. A single progesterone sample was as accurate as endometrial histology in confirming presumptive ovulation and was superior as an indication of corpus luteum function. In some cases a combination of well-timed biopsy and 3 or 4 serial progesterone values might be better to evaluate the interaction between corpus luteum function and histologic response.