Effects of a single 20 mg dose of letrozole on ovarian function post dominant follicle selection: an exploratory randomized controlled trial.

BACKGROUND: Our objective was to explore the impact of a single dose of an aromatase inhibitor (letrozole) administered at defined times of the follicular phase or immediately after ovulation on dominant follicle development, luteogenesis and new follicle wave emergence. METHODS: A prospective pilot study using a randomized complete block, controlled, open label design was conducted at an academic clinical research center. Forty-five healthy, female volunteers (25.5 ± 0.9 years, BMI 25.0 ± 0.6 kg/m2) who had not taken hormonal contraceptives for a minimum of 2 months were recruited. A 20 mg dose of Letrozole was administered once orally in each of 3 groups when the dominant follicle reached a diameter of 1) 12 mm, 2) 18 mm, 3) the first day following ovulation (post-ovulation), or 4) treatment was withheld (control). Serial ultrasonography and phlebotomy began on day 4 of the menstrual cycle and continued for 1.5 menstrual cycles. Participants recorded menses and daily events in a life events calendar for the duration of the study. Demographic and single point measurements were compared among groups by ANOVA. Changes in hormone concentrations over time were compared among groups by repeated measures ANOVA. Kruskal-Wallis tests were used for non-normally distributed data. RESULTS: The dominant follicle in all treatment groups ovulated. There were no differences among experimental groups in peak follicle diameter, follicular growth rate, endometrial thickness at ovulation or inter-ovulatory interval. Plasma concentrations of estradiol dropped, while FSH and LH concentrations rose following treatment in all treatment groups. Plasma FSH and LH concentrations were higher in the 18 mm group compared to the 12 mm and post-ovulation groups (P < 0.02). CONCLUSION: Administration of a single 20 mg dose of Letrozole at the times of the menstrual cycle we examined did not induce dominant follicle regression or failure of corpus luteum formation. Letrozole-induced suppression of estradiol synthesis by the dominant follicle was not detrimental to follicle growth or ovulation following follicle selection, likely due to increased circulating concentrations of FSH and LH resulting from a lack of estradiol-induced suppression of the hypothalamic-pituitary-ovarian axis. TRIALS REGISTRATION NUMBER: Clinical trials registration number NCT01046578 .

Development of morphologically dominant follicles is associated with fewer metabolic disturbances in amenorrheic women with polycystic ovary syndrome: a pilot study.

OBJECTIVES: To determine if amenorrheic women with polycystic ovary syndrome (PCOS) demonstrate ultrasonographically detectable changes in follicle population. METHODS: Sixteen women with PCOS reporting the absence of menses for more than 3 months were enrolled in the study. Subjects had a physical examination, fasting blood tests and two transvaginal ultrasound scans spaced 1 month apart. In cases where evidence of a morphologically dominant follicle (≥ 10 mm in diameter) occurred, subsequent ultrasound scans were performed to determine the fate of the dominant follicle. Differences in total follicle population, maximum follicle diameter and clinical, hormonal and metabolic features were determined. RESULTS: Forty-four percent of subjects showed changes in follicle population of 6-10 follicles and 37% showed changes in follicle population of > 10. Maximum follicle diameters ranged between 5.4 and 33.0 mm. Four subjects demonstrated follicle diameters ≥ 10 mm. Of those who developed dominant follicles, two subjects ovulated, one subject developed a persistent anovulatory follicle and the dominant follicle regressed in the remaining subject. Diagnostic criteria for PCOS were similar among women that did or did not develop dominant follicles (menstrual cycle length, P = 0.880; hirsutism score, P = 0.809; free androgen index, P = 0.991; total follicle count, P = 0.199). However, lower glycosylated hemoglobin (P = 0.047) and insulin levels (P = 0.049) and better insulin sensitivity (P = 0.048) were noted in women who attained dominant follicles. CONCLUSION: Amenorrheic women with PCOS demonstrate changes in follicle population that are consistent with active follicle growth and regression despite prolonged periods of anovulation. Morphologic selection occurs in amenorrheic women and attainment of dominant follicles is associated with improved metabolic status.

Screening of potential semen donors for sexual transmitted diseases.

BACKGROUND AND OBJECTIVES: The risk of infection with sexually transmitted diseases (STDs) is of great concern to couples undergoing therapeutic donor insemination. GOAL OF STUDY: We sought to determine the prevalence of STDs in potential semen donors and assess the rate of acquisition of new infection during the follow-up period. STUDY DESIGN: 29 potential semen donors were screened for common STDs. RESULTS: The study population had a prevalence of the following STDs: 27.5% ureaplasma, 13.8% mycoplasma, 6.9% cytomegalovirus 6.9% group B streptococcus, and 3.4% human papillomavirus infection. No participant tested positive for gonoccoccal or HIV infection. Over all, evidence of STD was present in 10 of 29 (34.5%) prospective donors. A follow-up infection rate of 22.2% (6 of 27 enrolled donors) was found and 3 (11.1%) of these were excluded from semen donation. CONCLUSION: A high prevalence of sexually transmissible infections is present in potential semen donors. New infections are also common during the follow-up period.

Spontaneous ovarian hyperstimulation syndrome in four consecutive pregnancies.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is almost exclusively associated with ovulation induction with gonadotropins or occasionally, clomiphene citrate. Severe ovarian hyperstimulation associated with a spontaneously conceived pregnancy is rare with only two previous reports. Misdiagnosis as a neoplastic process may result in inappropriate intervention. CASE: A patient with polycystic ovarian disease experienced severe spontaneous OHSS in four consecutive singleton pregnancies. Serial color and pulsed Doppler ultrasonographic imaging facilitated adequate evaluation of the patient and permitted conservative therapy. She achieved live births in two of the pregnancies. This is the third reported case of spontaneous OHSS associated with pregnancy and the first to result in live births. In one previous report, misdiagnosis resulted in inadvertent castration. CONCLUSIONS: Spontaneous ovarian hyperstimulation syndrome and pregnancy may occur in patients with polycystic ovarian disease. Color Doppler ultrasonography is a useful aid in the diagnosis and management of this rare complication, and in avoiding inappropriate intervention.

Characteristics of follicular evacuation during human ovulation.

Our objectives were to determine the rate and extent of follicular evacuation during human ovulation. Female volunteers were given 5000 or 10,000 IU human chorionic gonadotropin to induce ovulation when a follicle reached 18-20 mm. Ovulations were observed via transvaginal ultrasonography and recorded. Images were digitized for computer-assisted analysis. Areas of the follicles, taken to reflect follicular volume, were measured at specific time intervals from the moment of the first leakage of fluid until complete follicular evacuation. Twenty-five ovulations were visualized. In 23 cases (92%) all of the follicular fluid was expelled, but in two cases the follicle failed to empty completely. In all complete ovulations the initial fluid loss was rapid. The time to reach 70% evacuation was 0.9 +/- 0.3 min (+/- SEM). The remaining fluid leaked out more slowly; the mean time to complete follicular evacuation was 6.1 +/- 1.1 min. There was considerable variability in the rates of ovulation (range 6 s to 18.5 min). An association was observed between the type of stigma formed prior to ovulation and the initial rate of fluid loss. The data provide evidence of variability during follicular evacuation, which may in turn influence the successful expulsion of the oocyte from the follicle.