Further study and characterization of the yellow pigments in follicular fluid that are related to oocyte quality.

OBJECTIVE: To characterize the 455-nm (yellow) absorbing pigments in human follicular fluid (FF). DESIGN: Serum and FF samples obtained from patients undergoing in vitro fertilization were analyzed for carotenoids, bilirubin, and beta-glucuronidase concentrations. Spectrophotometric analysis in the visible spectrum was performed on FF samples, and the delta OD455 absorbance was calculated. RESULTS: Thin-layer chromatography confirmed the presence of beta-carotene and bilirubin in FF. The mean (+/- SD) contribution of bilirubin and carotenoids to the FF delta OD455 absorbance was 64% +/- 9.6% and 22.7% +/- 12.1%, respectively. Bilirubin fractions in serum and FF samples were then compared. The median unconjugated bilirubin concentration in FF was lower than that in the serum (0.130 versus 0.288 mg/dL; P < 0.0001). The median conjugated bilirubin concentration was higher in the FF when compared with the serum (0.129 versus 0.101 mg/dL; P = 0.0018). beta-Glucuronidase levels in the FF were significantly lower when compared with serum concentrations. CONCLUSIONS: Bilirubin is the major contributor to the FF 455-nm spectrophotometric peak. The higher levels of conjugated bilirubin noted in the FF could in part be explained by the lower levels of beta-glucuronidase.

Rubella susceptibility of an infertile population.

The recent trend reported by the CDC reaffirms that rubella continues to be a health care issue and should be a concern particularly for those who care for women in the childbearing age group. Immunization of all susceptible women will not only offer them protection but reduce the pool of susceptible individuals that can transmit the disease.

Vulvar vestibulitis--subgroup with Bartholin gland duct inflammation.

Some women with vulvar vestibulitis have tenderness at the Bartholin gland duct opening and associated dyspareunia. Forty-four patients with severe incapacitating dyspareunia of up to 5 years' duration were studied. Microscopic examination revealed a chronic inflammation located near the Bartholin gland duct opening. No etiologic agent was evident. Of 30 women treated initially with laser vaporization of inflamed areas, 13 (43%) showed significant improvement. Sixteen patients were treated with perineoplasty and all improved significantly; all became functional sexually although eight had previously failed laser therapy. Women with vulvar vestibulitis can be identified easily with a simple Q-tip touch technique directed at the duct opening. This diagnosis should be considered in the evaluation of women with obscure etiologies of dyspareunia.

Evaluation of oral medroxyprogesterone acetate in the treatment of endometriosis.

Medroxyprogesterone acetate was administered orally at the daily dose of 50 mg for four months to 21 symptomatic women with moderate to severe endometriosis, staged according to the American Fertility Society classification. The efficacy of the therapy was evaluated prospectively by the patients' symptomatology, monthly pelvic examinations, and by restaging the disease at second-look laparoscopy during the last week of treatment. The effects of therapy on the serum gonadotropin and ovarian steroid levels and on the endometrium and the implants of endometriosis were also evaluated. Improvement of symptoms, pelvic nodularity, and tenderness occurred in 80% of the patients. The mean stage score of disease by the American Fertility Society classification decreased from 18.2 +/- 2 before therapy to 5.9 +/- 1 after therapy (P less than .005). Amenorrhea, breakthrough bleeding, and persistent cyclic bleeding occurred in 75, 20, and 10% of the patients, respectively. Ovulation was inhibited in all patients, but serum hormone changes were statistically significant only for LH, which decreased from 9.5 +/- 4 to 5.2 +/- 2 IU/L (P less than .001), and estradiol (E2), which decreased from 80 +/- 30 to 46 +/- 26 pg/mL (P less than .02). Atrophic changes and pseudodecidualized reaction occurred in both the endometrium and the implants of endometriosis. In summary, oral medroxyprogesterone acetate is effective in relieving symptoms and objectively improving endometriosis. Besides inducing a pseudodecidualized reaction and atrophic changes in the endometrium and ectopic implants, medroxyprogesterone acetate also suppresses ovulation and the serum levels of both LH and E2.

Clinical and metabolic responses of menopausal women to sequential versus continuous estrogen and progestin replacement therapy.

To minimize the cyclic menstrual bleeding associated with the sequential administration of estrogen and progestin in menopausal women, medroxyprogesterone acetate at the daily dose of 10 mg orally was administered, either sequentially for ten days of each 25-day treatment cycle or continuously with conjugated equine estrogen for three months. Cyclic menstrual bleeding occurred in all ten patients on sequential therapy; their endometrial histology was secretory in six, proliferative in two, and adenomatous hyperplasia in one. Of the ten patients on continuous therapy, four were amenorrheic and six experienced acyclic bleeding, but the endometrial histology was atrophic or inactive in all ten. The continuous treatment group experienced a statistically significant decrease in the mean serum levels of total cholesterol, whereas the serum levels of both low- and high-density cholesterol fractions decreased slightly. However, the sequential group experienced no change in serum levels of total cholesterol, a slight rise in high-density lipoprotein, and a significant decrease in low-density lipoprotein cholesterol fractions. Our data suggest that the combined and continuous use of conjugated equine estrogen and medroxyprogesterone acetate effectively relieves menopausal symptoms, decreases the frequency of uterine bleeding, induces endometrial atrophy, and significantly decreases serum levels of total cholesterol.

Familial premature ovarian failure due to an interstitial deletion of the long arm of the X chromosome.

We describe a family in which four women had menstrual irregularities and a partial deletion of the long arm of the X chromosome (Xq). Three of the four women had premature ovarian failure (at the ages of 24 to 37 years). Chromosome-banding studies initially suggested that a terminal portion of Xq was deleted. However, DNA-hybridization studies showed that an interstitial portion of Xq was deleted and that the affected women had a 46,XX,del(X)(pter-q21.3::q27-qter) karyotype. These findings help clarify the role of Xq in ovarian function and indicate that the accurate description of such abnormalities requires a combination of cytogenetic and DNA-hybridization analysis.

Diet and bone status in amenorrheic runners.

Our purpose was to determine the relationship of diet, exercise, and amenorrhea with bone mineral status in trained young women. Bone mineral density of the lumbar spine was significantly lower in amenorrheic compared to normally menstruating runners. Circulating estradiol was also significantly lower. No significant differences between the two groups were found in body composition, maximum aerobic power, or amount of training per week. A 3-day dietary record showed that the amenorrheic women reported a significantly lower daily energy intake, but no difference in the calcium intake. Protein intake was less than the US Recommended Dietary Allowance in 82% of amenorrheic women and 35% of eumenorrheic women. Abnormal eating behaviors may be associated with the development of amenorrhea. Our results show that when weight-bearing exercise and a low energy intake are associated with amenorrhea, the accretion of a large bone mass in young trained women is not favored.

Bone mineral content and levels of gonadotropins and estrogens in amenorrheic running women.

Serum gonadotropin and estrogen levels and their relationship to bone mineral content in exercise-related amenorrhea were studied in 11 amenorrheic women and 24 eumenorrheic women, all of whom were runners. Serum estradiol, LH, FSH, estrone, and testosterone were measured in serial blood samples obtained at 15-min intervals for 4 h. The amenorrheic women had lower estradiol, LH, FSH; and estrone levels as well as a higher estrone-estradiol ratio than did the eumenorrheic women. There was no difference in testosterone levels. The amenorrheic women had lower LH pulse amplitudes, whereas no differences were found in FSH pulse amplitudes. LH and FSH pulse frequencies did not differ between the two groups. Bone mineral content of the lumbar spine was lower in amenorrheic women and was positively correlated with estradiol levels in all women. There was no difference in bone mineral content of the radius. These data suggest that, in exercise-related amenorrhea, low serum LH, FSH, and estrogen levels reflect an alteration in the hypothalamic control of gonadotropin release. Reduced circulating estrogen levels in amenorrheic running women may be a cause of low mineral content of the spine.

Preliminary observations on danazol therapy of systemic lupus erythematosus: effects on DNA antibodies, thrombocytopenia and complement.

Seven patients with systemic lupus erythematosus (SLE) were treated with Danazol in a controlled study. Phenomena observed in some patients treated with Danazol were: 1) decrease in immunoglobulins and antibodies to native DNA; 2) increases in serum complement and platelets; and 3) clinical improvement. Ineffective drug trials were associated with increasing disease activity. Drug side effects were minimal. It appears that the drug may have an ameliorative effect on mildly active SLE patients and sometimes a marked effect on thrombocytopenia. Further evaluation of Danazol appears to be warranted for these types of patients but not for treatment of acute or severe forms of the disease.

Complete duplication of the uterus and cervix with a unilaterally imperforate vagina.

Complete duplication of the uterus and cervix with a unilaterally imperforate vagina must be suspected when a unilateral pelvic mass terminates in a purpuric bulge of the lateral vaginal wall in a young woman with severely progressive dysmenorrhea. Intravenous pyelography will reveal renal agenesis ipsilateral to the imperforate vagina. The prompt and accurate diagnosis of this unusual anomaly should lead to transvaginal drainage of the retained menstrual fluids prior to irreversible damage of the pelvic viscera from chronic cryptomenorrhea.

Partial vaginal agenesis with a urinary-vaginal fistula.

A patient with partial vaginal agenesis and a urinary-vaginal fistula is presented together with a review of the 12 cases reported previously. This unusual anomaly presents with cyclically recurrent hematuria; hypothetically, it results from failure of formation or canalization of the primitive vaginal plate together with partial persistence of the urogenital sinus. Surgical correction, ideally performed after puberty, requires resection of the fistula and mobilization of the apical vaginal segment for its anastomosis to the inferior vaginal pouch.

Asymmetric hyperthecosis ovarii.

Testosterone and delta4-androstenedione concentrations, in venous blood obtained by percutaneous retrograde femoral catheterization of the ovarian and adrenal veins bilaterally, demonstrated the left ovary to be the predominant secretory source of androgens in an 18-year-old virilized female. Histologic examination of the excised ovarian tissue revealed asymmetric hyperthecosis ovarii and confirmed the biochemical data. This study demonstrates the accuracy of the venous catheterization method in locating preoperatively the hypersecretory source of androgens in virilized women. The favorable postoperative clinical result emphasizes the importance of an accurate preoperative diagnosis in virilized women even in the absence of ovarian neoplasia.

Diagnostic and therapeutic modalities in women with galactorrhea.

Prolactin response to various pharmacologic agents was tested and hypocycloidal polytomograms of pituitary sellae were performed in 77 women with galactorrhea. Polytomographic findings of pituitary sellae and the results of hypothalamic-pituitary tests were analyzed retrospectively in 18 patients with pituitary adenoma. Of the patients with pituitary tumor, 94% had abnormal polytomograms of sellae turcica, 89% had serum prolactin levels greater than 160 ng/ml (range, 170 to 264 ng/ml), and 78% showed abnormal response to thyrotropin-releasing hormone (TRH) stimulation test. Transsphenoidal excision of the tumor was complete in all 14 patients with microadenoma (10 mm or less in diameter) but was incomplete in 4 patients with macroadenoma and evidence of extrasellar extension. Galactorrhea ceased and normal ovulatory menses resumed after surgery in all patients with microadenoma. Twenty-five patients received bromocriptine. Twenty-three of them had hyperprolactinemia and 21 had normal sellar polytomograms. Galactorrhea ceased and normal menses occurred in 18; 6 patients conceived. Two patients with abnormal polytomography and euprolactinemia responded to bromocriptine treatment and 1 of them conceived. The findings suggest that serial prolactin levels and hypocycloidal polytomography of sella turcica are helpful in diagnosis of pituitary prolactinomas. The TRH stimulation test is also useful in evaluating these patients. Because the natural course of the prolactinomas and the long-term results of the surgical and pharmacologic treatments are unknown, ideal management has yet to be established.

Diagnostic evaluation of hirsutism in women by selective bilateral adrenal and ovarian venous catheterization.

To determine the most significant secretory source of their androgens, 13 hirsute nonvirilized women underwent selective bilateral adrenal and ovarian venous catheterization to obtain effluent blood for the assay of testosterone and delta4-androstenedione. In three patients the testosterone and delta4-androstenedione gradients were significantly greater in the adrenal venous effluents. Testosterone and delta4-androstenedione gradients were significantly greater in the ovarian venous effluents in four patients. In six patients there were no significant differences in the testosterone gradients between the adrenal and ovarian venous effluents. The delta4-androstenedione gradients were greater in the adrenal venous effluents in three of these patients, greater in the ovarian venous effluents in one, and not significantly different in two of these patients. The fact that the measurement of urinary 17-ketosteroid excretion, the suppressibility of peripheral plasma androgens with dexamethasone, and the stimulation of peripheral plasma androgens with human chorionic gonadotropin correlated poorly with the selective catheterization data suggests that the former modalities are imprecise in the diagnostic evaluation of hirsutism in women.

Response of amenorrheic patients with normal serum prolactin to chlorpromazine during administration of human menopausal gonadotropin.

To study the effects of graded amounts of estrogens on prolactin (PRL) secretion, PRL response to chlorpromazine (CPZ) during administration of human menopausal gonadotropin (hMG) was determined. A control CPZ test was done prior to initiation of hMG therapy and the test was repeated when endogenous estrogen secretion reached the physiologic range (350 to 400 pg. per milliliter) which stimulates luteinizing hormone surge in the normal ovulatory menstrual cycle. Six euprolactinemic women with secondary amenorrhea were studied. Studies showed that there was no significant change in the mean serum prolactin concentrations during control and repeat CPZ testing procedure (5.8 +/- 2 and 10.8 +/- 2 ng. per milliliter, p less than 0.1). The maximal response of PRL to CPZ was significantly higher during hMG-induced high estrogenic state than during control testing (69.9 and 32.3 ng. per milliliter, p less than 0.01). This findings suggests that endogenous estrogen may play a role in the regulation of serum prolactin concentration during the menstrual cycle.