Richard E. Blackwell

Prostate-specific antigen in vaginal fluid as a biologic marker of condom failure

Forty women participated in three clinic visits during which they were exposed to their partners semen (10 microL, 100 microL, and 1 mL). At each visit they took vaginal fluid samples before exposure to their partners semen, immediately after, and at 1, 24, and 48 h after exposure. PSA was measured with an enzyme-linked immunoassay. The mean PSA level for preexposure swabs ranged between 0.43 and 0.88 ng/mL. The mean PSA levels were 193 immediately after exposure to 10 microL, 472 after 100 microL, and 19,098 after 1 mL. The PSA levels declined within 1 h, and returned to background at 48 h. The findings confirm that our procedure is a sensitive and specific method for detecting recent semen exposure, and indicate that PSA levels depend on exposure intensity and time since exposure. Application of this method in condom efficacy studies provides objective evidence of condom failure that enhances the interpretation of self-report.

Hormonal treatment of functional ovarian cysts: a randomized, prospective study *

Estrogen (E)/progestin therapy for functional ovarian cysts is widely used in clinical practice, but the efficacy of this treatment has not been determined in controlled trials. In this study, we examined the effect of E/progestin administration in a group of infertility patients enrolled in a program of ovulation induction who had cysts identified by transvaginal sonography. Patients were randomized to receive either norethindrone 1 mg/mestranol 0.05 mg/d (group A, n = 24) or no treatment (group B, n = 24) for up to 6 weeks. Patients were re-evaluated by sonography at 3, 6, and 9 weeks after entry into the protocol. The ages, mean cyst diameters, and proportions of patients having received gonadotropins in the previous menstrual cycle were not significantly different among the two groups. All patients who had a sonographic abnormality persisting for 9 weeks were surgically explored and found to have pathological cysts. The rate of disappearance of functional ovarian cysts was not affected by E/progestin treatment.

Diagnosis and management of prolactinomas

Prolactin secreting tumors account for ten to twenty percent of all intracranial lesions. The patients harboring these tumors present with amenorrhea, galactorrhea, other ovulatory disorders, infertility, delays in puberty and mixed polyendocrinopathy. These tumors are diagnosed by the measurement of serum prolactin levels, Goldmann-Bowl perimetry, and either computed axial tomography or magnetic resonance imaging. Protein secreting tumors are usually benign lesions and historically have been treated by partial or total hypophysectomy or radiation therapy. Surgical resection of the lesion often is followed by recurrence and administration of proton beam radiation therapy results in the development of a panhypopituitary state. Growth of pituitary tumors is controlled with the administration of dopamine agonists such as bromocriptine and prospective studies have suggested that these drugs are now the preferred method of treatment for primary lesions and recurrences.

Self-reported mechanical problems during condom use and semen exposure : Comparison of two randomized trials in the United States of America and Brazil

Objectives/Goal: To compare self-reported condom use problems and objectively determined semen exposure in 2 populations. Study Design: Two randomized crossover trials in the United States and Brazil compared the failure rates of the female condom (FC) and male condom (MC). Participants used both condom types, completed condom-specific questionnaires to report problems, and collected precoital and postcoital samples of vaginal fluid. Prostate-specific antigen (PSA) was detected by immunoassay. Results: Problems with condom use were reported less frequently in the Brazilian study (rate difference: FC = 24%, P <0.0001, MC = 5%, P = 0.003). By contrast, the PSA detection rates were similar for both the FC and the MC (rate difference: FC = 2%, MC = 1%, not significant). These results suggest that the PSA detection rate was similar in the 2 study groups and that self-reported problems may be a less reliable measure of condom failure. Conclusions: Use of biomarkers of condom failure like PSA may help to strengthen the validity of studies promoting behavior change for the prevention of sexually transmitted diseases.

Performance anxiety during infertility treatment: effect on semen quality

The requirement to obtain a semen sample at a specific time for an infertility treatment procedure has potential to produce considerable performance anxiety. This study was designed to evaluate the semen quality of men participating in infertility treatments associated with heightened performance anxiety. The most recent pretreatment semen analysis and the infertility treatment semen analysis, as well as the first and last procedure semen analyses, were compared using paired t-tests for 77 patients undergoing assisted reproductive technology procedures and 121 patients undergoing intrauterine insemination. No significant differences were noted in either of these groups of patients. However, in men with total motile sperm counts of less than 40 million, semen parameters improved significantly in the procedure semen analyses. Thus, participation in infertility treatments associated with performance anxiety does not appear to be detrimental to semen quality, and in certain groups of patients semen quality may improve.

Peripheral progesterone (P) levels and endometrial response to various dosages of vaginally administered P in estrogen-primed women

OBJECTIVE To compare the pharmacokinetics and pharmacodynamics of 100 mg/d, 200 mg/d, and 400 mg/d (200 mg two times per day) of P administered vaginally for 14 days to estrogen-primed postmenopausal women. DESIGN Randomized, open-label, three-way crossover study. SETTING Two university-based investigative sites. PATIENT(S) Twenty healthy postmenopausal women with histologically normal endometria. INTERVENTION(S) Oral 17 beta-E2 was given each day of a 28-day cycle; a P vaginal suppository was inserted daily according to the randomization schedule during days 15-28 of each cycle; blood samples were collected; an endometrial biopsy was obtained on day 25; and patients were crossed over to the next treatment cycle after a washout period of at least 30 days. MAIN OUTCOME MEASURE(S) Mean P blood levels, endometrial dating/conversion. RESULT(S) There was good vaginal absorption of P for all dosages. Endometrial conversion occurred in all 200- and 400-mg/d P-dosed cycles, whereas the 100-mg/d dosage failed to convert primed endometria consistently. There also was a significantly increased tendency for earlier bleeding and spotting with the 100-mg/d dosage. CONCLUSION(S) Both the 200- and 400-mg/d dosage regimens consistently convert an estrogen-primed endometrium, and yield appropriate endometrial dating and bleeding patterns. However, the 400-mg/d dosage attains the highest sustained blood levels and may be the best dosage regimen for further study.

Regulation of human prolactin secretion by gonadotropin-releasing hormone in vitro *

The regulation of human prolactin (PRL) secretion by gonadotropin-releasing hormone (GnRH) was evaluated with human pituitary monolayer cell cultures. Synthetic GnRH stimulated PRL secretion when exposed to cells in an estrogen-depleted environment. This response was inhibited by pretreatment of the cells with 17 beta-estradiol (E2). A 10(-5) M GnRH antagonist inhibited luteinizing hormone (LH) but not PRL secretion when cells were maintained in an estrogen-depleted environment. However, the GnRH antagonist inhibited basal PRL secretion when cells were maintained in medium containing 10(-8) M E2. The 10(-5) M GnRH antagonist, when coincubated with 10(-5) M GnRH inhibited the release of PRL in an estrogen-depleted environment. However, coincubation of the 10(-5) M GnRH antagonist with 10(-5) M thyrotropin-releasing hormone (TRH) failed to inhibit PRL secretion. Incubation of 10(-8) M TRH and 10(-8) M GnRH produced a synergistic release of PRL in an estrogen-depleted environment. These observations led us to conclude that GnRH stimulates PRL secretion by direct action on human pituitary cells and that GnRH acts either via the gonadotrope or through receptors on the galactotrope other than that acted upon by TRH to release PRL.

Hidden costs of infertility treatment in employee health benefits plans.

OBJECTIVES Many employers exclude infertility treatment from coverage under their health benefits plans. However, infertility treatment is often provided under other diagnoses or in association with therapy rendered for other disease processes. This study attempted to estimate those hidden costs and to determine what the impact would be of providing coverage for infertility treatment. STUDY DESIGN A 1-year retrospective analysis was carried out to isolate the hidden costs of infertility treatment from specific medical claims data gathered from a large representative employer with no infertility benefit provided. Data were analyzed in the context of the claims experience of a health plan covering approximately 28,000 employees. Infertility treatment was excluded under this plan. Medical claims for specific procedures and diagnoses in 1996 were analyzed by using Current Procedural Terminology codes in conjunction with International Classification of Diseases, Ninth Revision codes to estimate the hidden costs of infertility treatment. Forty-one Current Procedural Terminology codes and 68 International Classification of Diseases, Ninth Revision codes were used for the analysis. Clinical practice experience was used to set boundaries (conservative and moderate estimate) regarding the likelihood of a given treatment being associated with infertility. This was compared with 100% covered charges to generate claims per employee per month. Procedures covered operative, diagnostic, and laboratory services. These figures were used to compute a range of cost for infertility treatment per member per month. RESULTS Forty-one Current Procedural Terminology codes were identified that indicated possible infertility treatment. These covered the areas of laparoscopic and hysteroscopic surgery, lysis of adhesions, neosalpingostomy, cyst drainage, oocyte retrieval or embryo transfer, echography, and various hormonal analyses. Sixty-eight International Classification of Diseases, Ninth Revision codes indicated the possibility of infertility treatment. These included endocrine disorders, various uterine pathologic conditions, pelvic pain, endometriosis, pregnancy loss, irregular menses, and various ovulatory dysfunctions. The retrospective analysis found that 35 Current Procedural Terminology codes were involved in claims highly indicative of infertility services, such as 56353, hysteroscopic division of uterine septum, and 58345, transcervical fallopian tube catheterization. According to the 35 Current Procedural Terminology codes,

Long-term monolayer culture of human anterior pituitary cells: functional validation of a method *

603,807.95 would have been paid if 100% of the charges had been covered; this would have resulted in a claim per employee per month of

Participant characteristics associated with withdrawal from a large randomized trial of spermicide effectiveness

1.12 by conservative estimate to