Steven H. Brenner

Pregnancy during long-term gonadotropin-releasing hormone agonist therapy associated with clinical pseudomenopause

A case of pregnancy occurring with escape of suppression from GnRH-a therapy is described. Clinical pseudomenopause had been established, and the pregnancy was exposed to depot GnRH-a for 8 weeks. Normal pregnancy outcome demonstrated that successful implantation may occur in the first escaped ovulatory cycle.

The effect of in vivo progesterone administration on relaxin-inhibited rat uterine contractions

Progesterone pretreatment in vitro was previously shown to sensitize myometrium to the inhibiting effect of relaxin. The following experiments were performed to control for possible artifacts of the in vitro system and to place these studies on a more physiologic basis. Immature rats were treated with estrogen and either progesterone or vehicle only. Uterine horn segments were isolated and mounted in a muscle bath. After a baseline contraction pattern was established by means of electrical stimulation, porcine relaxin was added to the bath. At all dose levels of relaxin, greater inhibition of contraction amplitude occurred in uterine segments of progesterone-treated animals. Since both progesterone and relaxin are present in the circulation from the time of the missed menses in human pregnancy, this interaction suggests a physiologic synergism in the maintenance of early human pregnancy.

A second thought on second look laparotomy

Between 1982 and 1987, 43 patients with epithelial ovarian carcinoma, identified as International Federation of Gynaecology and Obstetrics Stages I‐IV, underwent second‐look laparotomy as a part of their treatment protocol. Twenty‐nine patients (67%) had no evidence of residual disease, five (11.6%) had residual disease 1 cm, and nine patients (20%) had residual disease 1 cm at re‐exploration. Persistent disease at the second operation was positively correlated with the initial clinical stage, and negatively correlated with the extent of the original cytoreductive surgery. Fifteen of 29 patients with negative findings (52%) developed recurrent disease within two years. All recurrences were limited to the abdominal cavity only. Three and five years survival, for the patients with negative findings, was 62% and 48% respectively. No documented benefit to the patients could be demonstrated by adopting second‐look laparotomy as a routine procedure in the management of patients with epithelial ovarian carcinoma. In view of our data, as well as that of others, such operations cannot be considered a valuable routine procedure. At this point, second‐look laparotomy may have a role in evaluating the efficacy of a post‐surgical new chemotherapy treatment regimen.

The use of voided urine temperature in the determination of basal body temperature

The temperature of freshly voided urine has been shown to be a reliable predictor of body temperature. This relationship was confirmed for the measurement of BBT. A method was described for patients to obtain their BBT in a way that they may find more convenient than obtaining either oral or rectal temperature. The BBT graph patterns generated from the temperature of freshly voided urine closely paralleled those generated by oral temperature.

Ketoconazole use in the treatment of ovarian hyperandrogenism**Presented at the 71st Annual Meeting of the Endocrine Society, Seattle, Washington, June 21 to 24, 1989.

Ovarian hyperandrogenism is a common disorder of women of reproductive age. The therapies that are presently available to treat this disorder are not uniformly effective or free of adverse effects. We conducted a prospective study of eight women receiving ketoconazole for a mean duration of 44 +/- 15 (SEM) weeks, as therapy of ovarian hyperandrogenism. Serum testosterone and hair growth rate declined in patients while on 600 to 1,000 mg ketoconazole daily. Menses normalized in seven of eight subjects during treatment. Ketoconazole therapy was not associated with a change in basal or postgonadotropin-releasing hormone stimulation gonadotropin levels. Basal cortisol levels were also unchanged on ketoconazole though responsiveness of cortisol to adrenocorticotropic hormone stimulation tended to be reduced. We conclude that ketoconazole can effectively reverse the biochemical and clinical abnormalities of ovarian hyperandrogenism. Until the issue of its safety is resolved, ketoconazole therapy is best limited to select individuals who agree to careful monitoring and the use of reliable birth control methods during treatment.

Human semen relaxin and its correlation with the parameters of semen analysis**Supported by National Institute of Health grant HD 12395 and a grant from the Mellon Foundation.

The relaxin content of 92 normal semen samples and 85 semen samples selected at random was correlated to the parameters measured on routine semen analysis in those samples. The concentration of immunoactive relaxin in a sample of semen plasma did not correlate with any of the parameters commonly used for semen analysis: count, percent motility, grade of forward progression, volume, and morphology.

The effect of relaxin on the motility of sperm in freshly thawed human semen**Supported by National Institutes of Health grant HD-12395 and by a grant from the Mellon Foundation.

In an attempt to improve the motility of thawed spermatozoa after 1 week of its being frozen, we treated ten normal semen samples with 16.7 nmol relaxin and 6 mmol caffeine. Motility and grade of forward progression were examined after thawing. Caffeine significantly improved motility of spermatozoa. Relaxin, when added to semen at the time of thawing, improved motility and grade of forward progression significantly. This effect was not seen if relaxin was added before freezing. These results suggest that the biologic activity of relaxin is adversely affected by freezing and thawing in seminal plasma. These observations may have clinical importance for the improvement of motility of frozen spermatozoan samples at the time of artificial insemination and for the possible improvement of pregnancy rates.

Stimulation of human sperm cervical mucus penetration in vitro by relaxin**Supported by NIH grant HD 12395 and a grant from the Mellon Foundation.

The effect of relaxin, a peptide hormone present in seminal plasma, on the penetration of cervical mucus by washed human sperm in vitro was studied. Penetration was analyzed by two methods. The total number of sperm per 100 X field at the 10-mm, 20-mm, and 30-mm points along a mucus-filled capillary tube was counted and the farthest distance 100 sperm and 5 sperm/100 X field penetrated the capillary tube was measured. These measurements were made at 30, 60, and 90 minutes. Treating washed sperm with physiologic concentrations of relaxin resulted in significantly increased sperm penetration as compared with sperm treated with albumin or buffer. Replacing seminal plasma to washed sperm resulted in equivalently increased penetration. The findings strongly suggest that relaxin is necessary for proper penetration of cervical mucus by human sperm.

The effect of an anti-insulin antiserum on human sperm motility**Supported by NIH grant HD-12395 and a grant from the Mellon Foundation.

Inhibition of sperm motility by anti-relaxin antiserum has been previously reported. This effect may be secondary to a nonspecific effect of immunoglobulins binding to sperm or to a specific inhibition of relaxin activity at the sperm surface. The current investigation demonstrates that an anti-insulin antiserum does not inhibit sperm motility in the same system in which an anti-relaxin antiserum results in inhibition. This supports the hypothesis that the anti-relaxin antiserum effect is specific.