Modulation of HOXA10 and other markers of endometrial receptivity by age and human chorionic gonadotropin in an endometrial explant model.

OBJECTIVE: To characterize the endometrial response to human chorionic gonadotropin (hCG), as influenced by uterine age, using endometrial receptivity markers including HOXA10, vascular endothelial growth factor (VEGF), and glycodelin in an endometrial explant culture system. DESIGN: In vitro molecular biology research. SETTING: Academic infertility clinic and molecular biology laboratory. PATIENT(S): Fourteen prospective recipients of egg donation (mean age, 44 +/- 8 years). INTERVENTION(S): Subjects received cyclical estrogen (E(2)) and progesterone (P(4)) and underwent an endometrial biopsy on day 7 of P(4). Endometrial biopsy samples were cut into 1-mm(3) pieces and cultured in Dulbecco's modified Eagle's medium/Ham's F-12 with E(2) and P(4), without (control) or with hCG (400, 4000, and 40,000 mIU/mL) on Millicell-CM inserts for 24 hours. MAIN OUTCOME MEASURE(S): Explant viability was assessed using immunohistochemistry (IHC). Semiquantitative polymerase chain reaction was performed to evaluate relative gene expression via mRNA levels of HOXA10, VEGF, and glycodelin. RESULT(S): Explant viability was confirmed on IHC by histology and Ki-67 staining, a marker of proliferation. HOXA10, VEGF, and glycodelin gene expression increased at all concentrations of hCG over those of controls. HOXA10 gene expression was inversely correlated with age (-0.08- +/- 0.03-fold decrease in gene expression/year of age). CONCLUSION(S): The endometrial explant culture system is a promising model for the study of endometrial response as it maintains interactions among the stroma, glands, and epithelium. HOXA10, VEGF, and glycodelin all demonstrated increased gene expression in response to increasing hCG concentrations, supporting the role of hCG as a candidate protein for blastocyst-endometrial communication. Statistically significant associations between age and expression of HOXA10 provide novel evidence that uterine age may play a role in endometrial response on a molecular level.

Increased insulin-like growth factor-1 after oophorectomy in postmenopausal women.

IGF-1 levels increased, and IGF-2 and IGFBP-3 levels remained unchanged, in postmenopausal women following oophorectomy. The increase in IGF-1 likely results from decreased ovarian steroidogenic precursors resulting from removal of the hormonally active ovary. This finding raises concerns, given the association between increased IGF-1 and elevated colon cancer risk, and adds to the literature suggesting a potential benefit from ovarian preservation.

Clomiphene citrate-induced follicular development in the presence of an ovarian ectopic pregnancy.

OBJECTIVE: To describe a case of a patient who had multiple follicular growth in the presence of an undiagnosed ectopic pregnancy (EP). DESIGN: Case report. SETTING: In vitro fertilization unit at a university hospital. PATIENT(S): A 34-year-old patient with secondary infertility. INTERVENTION(S): Superovulation with clomiphene citrate (CC) and IUI. MAIN OUTCOME MEASURE(S): Follicular development with CC stimulation documented by transvaginal ultrasound and beta-hCG levels. RESULT(S): Two co-dominant follicles were observed with mean diameters of 22 mm and 24 mm. The patient had unexpectedly high levels of beta-hCG at the time of missed menses and was subsequently diagnosed with an ovarian EP. CONCLUSION(S): Multiple follicular growths can occur in response to CC in spite of the presence of an ovarian EP.

Ovarian androgen production in postmenopausal women.

CONTEXT: Several studies previously reported that the postmenopausal ovary produces androgens. However, these findings have recently been questioned in a group of women with adrenal insufficiency. OBJECTIVE: We sought to use contemporary assay methodologies to investigate whether the postmenopausal ovary is hormonally active and contributes to the circulating pool of androgens. DESIGN AND PATIENTS: Serum was collected from the ovarian veins of 13 postmenopausal women undergoing total abdominal hysterectomy and bilateral oophorectomy, with sufficient quantities obtained to allow for measurement of several hormones. Serum was also analyzed from peripheral blood collected preoperatively, intraoperatively, and postoperatively. SETTING: The study took place at the Los Angeles County Women's and Children's Hospital, University of Southern California Keck School of Medicine. MAIN OUTCOME MEASURES: Testosterone (T), androstenedione (A), dehydroepiandrosterone (DHEA), estrone (E1), and estradiol (E2) were measured by RIA with preceding organic solvent extraction and Celite column chromatography. RESULTS: Statistically significant gradients were seen between the ovarian venous and peripheral samples for T, A, DHEA, E1, and E2. Postoperative levels of T and E1, but not A, DHEA, or E2, were statistically significantly lower than preoperative levels. A gradient for T between the ovarian venous and peripheral blood was present in four of five women who were menopausal for more than 10 yr. CONCLUSIONS: The postmenopausal ovary is hormonally active, contributing significantly to the circulating pool of T. Furthermore, this contribution appears to persist in women as long as 10 yr beyond the menopause.

Does St. John's wort interfere with the antiandrogenic effect of oral contraceptive pills?

BACKGROUND: St. John's wort (SJW), a commonly used herbal remedy, has been shown to compromise the efficacy of drugs, including oral contraceptive pills (OCPs), by inducing cytochrome P-450. We investigated whether the simultaneous use of SJW with OCPs resulted in elevated serum androgen levels with implications of impaired OCP treatment of hirsutism and acne. MATERIALS AND METHODS: Fifteen healthy women were treated with the low-dose OC Loestrin 1/20trade mark for 2 months and then additionally with SJW for 2 months. Androgen and sex hormone-binding globulin (SHBG) levels were measured in serum by immunoassay methods; free testosterone (fT) was calculated. Results were analyzed using the Wilcoxon signed-rank test. RESULTS: There were no statistically significant differences in androgen levels after the addition of SJW in women using Loestrin 1/20trade mark. However, there were decreases in total testosterone and fT levels (10.7% and 15.8%, respectively) along with a small increase in SHBG levels (7.0%). CONCLUSIONS: In women using OCPs and SJW simultaneously, it appears that SJW does not interfere with the antiandrogenic properties of OCPs.

Etiology of azoospermia in a large nonreferral inner-city population.

A higher proportion of nonobstructive than obstructive azoospermia, as well as an increased prevalence of hypogonadotropic hypogonadism were documented in a retrospective study characterizing azoospermia in a population of predominantly Latino, inner-city male partners of infertile couples, as compared to previous reports from relatively affluent socioeconomic status male populations.

Predictors of cervical dysplasia after the loop electrosurgical excision procedure in an inner-city population.

OBJECTIVE: To identify factors associated with persistence or clearance of cervical intraepithelial neoplasia (CIN) following loop electrosurgical excision procedure (LEEP) in high-risk patients. STUDY DESIGN: In a retrospective database review, we identified 343 patients who had 2 LEEP procedures or LEEP followed by hysterectomy for CIN at Grady Memorial Hospital. We compared margin status, endocervical curettage (ECC) at LEEP and follow-up cytology for patients characterized as having persistent or nonpersistent dysplasia. RESULTS: Seventy-nine percent (71/90) of patients with positive LEEP margins had persistent disease vs. 50% (45/90) with negative margins (odds ratio [OR]=3.7, 95% confidence interval [CI] 1.9-7.2, P<.0001). Ninety-one percent (29/32) with positive margins and positive ECC had persistent disease vs. 47% (26/55) with negative margins and negative ECC (OR=10.8, 95% CI 2.9-39.6, P<.0001). Sixty-eight percent (149/218) with at least 1 positive Pap smear following LEEP had persistent disease vs. 37% (11/30) with all negative follow-up Pap smears (OR = 3.7, 95% CI 1.7-8.3, P = .0007). CONCLUSION: Although the risk of persistent CIN increased with positive LEEP margins, ECC and cytology, these variables, when negative, offered no ensurance of a future disease-free state in this high-risk population.