Clinical manifestations and treatment of dysfunctional uterine bleeding.

Dysfunctional uterine bleeding is a common gynecologic disorder that can affect any woman during her reproductive years. It is a diagnosis of exclusion, and the clinician must proceed through a logical stepwise evaluation to rule out all other causes of the abnormal bleeding. In most cases dysfunctional uterine bleeding is associated with anovulation. During the pubertal and perimenopausal periods, anovulatory bleeding is a common occurrence. During these transitional states, the abnormal bleeding has a physiological basis and is secondary to an estrogen withdrawal. Anovulatory bleeding can also be associated with chronic anovulation. The chronic unopposed estrogen that characterizes this disorder causes a continuous proliferation of the endometrium; this can result in abnormal bleeding and place the patient at risk for endometrial cancer. The goals of treatment for anovulatory bleeding are to stop the acute bleeding, avert future episodes, and prevent long-term complications. In some cases surgical intervention is indicated, but the foundation of treatment has been a medical approach. Several progestational agents have demonstrated effectiveness and can be administered either orally or by intramuscular injection. If the patient fails to have resolution of the bleeding with medical therapy, another cause of the bleeding must be suspected, and reevaluation is necessary.

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.

Rapid identification of deoxyribonucleic acid sequence differences in cytochrome P-450 21-hydroxylase (CYP21) genes with denaturing gradient gel blots.

Denaturing gradient gel electrophoresis was used to identify single-base differences in the cytochrome P-450 21-hydroxylase (CYP21) genes of 132 unrelated control individuals and family members of three unrelated patients with 21-hydroxylase deficiency. The salt-wasting variety was caused by gene deletion and gene conversion/deletion mutations in affected members of two families studied. The simple virilizing form, present in the third family, was caused by an apparent point mutation not detectable by routine Southern blots. We have detected many restriction fragment melting polymorphisms in the CYP21 genes of the members of both salt-wasting families and normal individuals with denaturing gradient gel electrophoresis. We also identified a restriction fragment melting polymorphism specific for the simple virilizing patient in the third family. The data demonstrate that the CYP21 genes are highly polymorphic and that denaturing gradient gel electrophoresis is useful for genomic deoxyribonucleic acid analysis of patients with 21-hydroxylase deficiency.

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.

Spectrophotometric analysis of follicular fluid related to oocyte fertilization, embryo cleavage, and follicular fluid protein and hormone content.

Spectrophotometric absorbance patterns of follicular fluids (FF) obtained from in vitro fertilization patients were analyzed and compared with oocyte fertilization and embryo cleavage rates. Each absorbance pattern was resolved into three components: delta OD360, delta OD415, and delta OD455. A positive correlation was found between fertilization outcome and delta OD455. The absorbances were not related to embryo cleavage rates. We confirmed the presence of bilirubin and beta-carotene in FF: these pigments absorb at 455 nm and are most likely serum-derived. To explain the association between delta OD455 and fertilization, we hypothesized that the FF delta OD455 is a marker of the degree of vascularization of the follicle that could be assessed by FF protein and hormone concentrations. However, no correlation was found between the delta OD455 and these FF parameters, suggesting an alternative explanation for this association.

The effect of endometriomas on in vitro fertilization outcome.

To determine the effect of ovarian endometriomas on in vitro fertilization (IVF) outcome, two groups of patients were studied. Group I consisted of seven patients with ovarian endometriomas and severe pelvic adhesions treated for a total of 12 cycles. Group II patients consisted of eight patients with hydrosalpinges and comparable pelvic adhesions treated for a total of 27 cycles. There were no differences in the number of days required for stimulation or in the serum estradiol levels attained between the two groups. Group I patients were noted to have significantly fewer preovulatory follicles (1.42 vs 3.33, P less than 0.005), cycles with fertilization (28 vs 84%, P less than 0.005), and embryos transferred (0.78 vs 2.56, P = 0.01) than Group II patients. Three pregnancies occurred in Group II, while there were no conceptions among Group I patients. This study suggests that the presence of an ovarian endometrioma(s) has an adverse effect on IVF outcome and suggests that patients with ovarian endometriomas should have them removed prior to undergoing IVF.

Spectrophotometric absorbance of follicular fluid: a predictor of oocyte fertilizing capability.

Follicular fluid volume, scoring of the oocyte-cumulus-corona-complex (OCCC), and spectrophotometric absorbance of the follicular fluid were separately compared between a group of fertilized (n = 53) and unfertilized oocytes (n = 35). Scoring of the OCCC and follicular fluid volumes was not found to be statistically different between the two groups. Spectrophotometric analysis of the follicular fluid in the visible spectrum demonstrated two peaks of maximum absorbance at 415 nm and 455 nm. The group of oocytes that fertilized was associated with follicular fluids that had significantly higher absorbances at 415 nm and 455 nm. In conclusion, follicular fluid volume and scoring of the OCCC were poor predictors of fertilizing capability; however, spectrophotometric absorbance, particularly at 455 nm, was positively correlated with oocyte fertilization.

Efficacy of danazol treatment for minimal endometriosis in infertile women. A prospective, randomized study.

We compared pregnancy rates between a danazol-treated and an untreated group of infertile women with minimal endometriosis. After completion of a basic infertility workup and laparoscopy, women with minimal endometriosis were entered into the study and randomly selected to receive either a six-month course of danazol or no treatment at all. Those patients with other infertility factors were included in the study only if the factors were correctable and ultimately determined to be noncontributory. Life-table analysis was used to compare pregnancy rates between the two groups over a 12-month period that started immediately after laparoscopy in the untreated group and after completion of danazol therapy in the treated group. The cumulative pregnancy rate (+/- SEM) was 37.2 +/- 8.4% in the danazol group (n = 37) and 57.4 +/- 10.4% in the untreated group (n = 36) (NS, P greater than .10). This prospective, randomized study showed danazol to be ineffective in improving pregnancy rates over doing nothing at all in patients with minimal endometriosis.