Jeanne A. Epstein

Clomiphene treatment in oligospermic infertile males.

This study of the effects of long-term clomiphene administration on semen analyses of oligospermic infertile males once again points to the potential therapeutic efficacy of clomiphene in certain subjects. Although the group of 16 subjects was small, all were men with long-standing infertility that had been refractory to previous treatments such as exogenous injections of human chorionic gonadotropin and varicocelectomy; 10 of the 16 men (62.5%) showed improvement in sperm counts within 2 to 5 months of starting clomiphene. Sperm motility improved moderately when counts improved; no effects on sperm morphology were noted. Of the 10 men classified as semen responders to clomiphene, 5 (50%) were successful in impregnating their wives within 2 to 8 months of starting treatment. These results approach the therapeutic efficacy seen with clomiphene in appropriately selected females with ovulatory disturbances. We have been unable to predict or characterize the patient who might be expected to show a semen response to clomiphene by history, physical examination response to previous treatment, or changes in blood testosterone levels while taking clomiphene.

Variations in Seminal Plasma Constituents from Fertile, Subfertile, and Vasectomized Azoospermic Men

Freshly ejaculated semen specimens from 20 normal fertile, 11 subfertile, and 20 vasectomized men whose semen analyses had reached complete azoospermia were compared. The mean levels of seminal acid phosphatase were significantly higher in the vasectomized men. The mean values of sialic acid in normal and postvasectomy seminal plasmas were similar, in contrast to the lower values in oligospermic men. No significant differences were observed in seminal plasma proteins, alkaline phosphatase, and fructose levels. No correlation was found between seminal alkaline phosphatase and fructose levels and sperm concentration. Azoospermia occurring after vas ligation was attributed to high phosphatase values.

Sperm-agglutinating antibodies in 236 infertile couples.

19 wives of 236 couples had positive sperm agglutination tests. (SPAT) 6 of the 19 belonged to the 70 couples (9.4%) with no no known cause for infertility; 11 belonged to the group of 154 couples (7.1%) with a known cause; and 2 to the 12 couples inadequately investigated (15.7%). 6 of these 19 women (31.6%) became pregnant without condon therapy; of these 6, 3 had no known cause for infertility and 3 had a known cause. 11 husbands had positive sperm aggluatination tests. 4 of these 11 were among the 70 couples (5.6%) with no known cause for infertility, while the other 7 were among the 154 couples (4.5%) with a known cause. 5 of their wives (45.5%) became pregnant without any treatment. Outcomes of 8 of 11 pregnancies were normal deliveries and no abortioons, which showed that positive SPAT had no apparent effect on the pregnancies. There was no relationship between postitive SPAT and history of venereal disease, allergy, autoimmune disease, abortioon, postcoital tests, or ABO imcompatability.

Cervical Mucus Amylase Levels in Normal Menstrual Cycles

A clinical study was undertaken to assess the levels of cervical mucus amylase in women during normal menstrual cycles. Multiple cervical mucus samples were taken throughout the menstrual cycle in 15 ovulatory women and random samples taken in an additional 7 ovulatory women; all these women and their husbands had undergone evaluations for infertility etiology. The level of cervical mucus amylase was found to decrease during the ovulatory cycles at the time when the thermal shift in BBT (basal body temperature) cornification peak in vaginal cytology and the highest mucus scores also occurred. A secondary drop in the amylase level was observed in some cases coincidental with the midluteal estrogen surge. The results of the study indicate that mucus amylase levels are inversely related to estrogen output rather than to water content of the mucus. The presence of amylase does not seem to be related to infertility etiology.

COMPARATIVE PHARMACOLOGICAL AND CLINICAL ACTIVITY OF 19‐NORTESTOSTERONE AND 17‐HYDROXYPROGESTERONE DERIVATIVES IN MAN

Studies on a comparison of the biological activity of 19-nortestosterone and 17-hydroxyprogesterone derivatives were presented. Pituitary inhibiting androgenic and anabolic effects induced by progestational steroids in parabiotic rats were presented. Initial studies with parabiotic rats showed that these compounds produce hypertrophy of secondary male sex glands and an increase in levator ani muscle weight. The female parabiont underwent marked precocious sexual maturation. In comparing levator ani weights the 17-ethyl and 17-methyl nortestosterones were the only compounds with marked anabolic activity. Progestational steroids were rated as good to excellent in inhibition of human ovulation and in the treatment of dysmenorrhea. It was found that 17-methyl-19-nortestosterone appeared to be undesirably androgenic in many women while 17-ethyl-19-nortestosterone showed good anabolic activity with minimal androgenic effects.

Induction of ovulation in the human: therapeutic and diagnostic importance.

Abstract 1.1. In anovulatory women, with normal or medically corrected thyroid and adrenal function, ovulation may be induced by triggering the release of LH with a single large intravenous dose of conjugated estrogens (equine). 2.2. The early diagnosis of surgically correctable ovulation defects may be made on the basis of absence of an ovulatory response to this therapy.

Leukocyte alkaline phosphatase activity in symptomatic users of intrauterine contraceptive devices

Abstract Leukocyte alkaline phosphatase activity (LAPA) scores in 55 symptomatic users of intrauterine contraceptive devices (IUDs) proved to be high in 47 (85 per cent), and corroborative abnormal findings in the endometrial biopsy were found in 33 (60 per cent). In a control group of asymptomatic IUD users, LAPA was high in 34 (56 per cent) of the 61 women, and biopsy was abnormal in 21 of these, as well as in 5 others, or 43 per cent of the group. The delicate sensitivity of LAPA to body distress reacted earlier and more consistently than the other variables studied and often before clinical findings were present in cases in which biopsy confirmed endometritis.

Isolated follicle-stimulating hormone deficiency in a woman with X chromosomal mosaicism

Primary amenorrhea was observed in a 40-year-old woman with a proportionate female habitus. Serum levels of luteinizing hormone (LH) (71 to 97 mIU/ml) and estradiol (less than 10 pg/ml) were in the postmenopausal range, while follicle-stimulating hormone (FSH) remained at the lower limit of detection (1 to 6 mIU/ml). LH was found to be biologically active in a mouse Leydig cell testosterone production assay. Chromosomal analysis revealed three major cell lines: 5% 45,X; 83% 46,XX; and 3% 47,XXX. The remaining cells showed apparently random aneuploidy and chromosome rearrangements. Intravenous administration of 150 micrograms of gonadotropin-releasing hormone produced a threefold elevation in LH but did not alter FSH levels. Review of ovarian biopsies performed at age 22 revealed a multitude of primordial follicles and one follicle with antrum formation. There was no evidence of recent or past ovulation. An insulin tolerance test evoked normal responses in serum growth hormone, prolactin, and cortisol. This is the first reported case of an isolated deficiency of FSH associated with mosaicism of the X chromosome. This coexistence of functional and genetic aberrations suggests that the differential secretion of LH and FSH may be related to specific independent loci on the X chromosome.

The comparative effects of estrogens on amylase levels of cervical mucus.

The influence of equine conjugated estrogens estriol and the 3-cyclopentyl ether of ethinyl estradiol (EECPE) on cervical mucus amylase secretion was studied both in patients with normal ovarian function and with premature ovarian failure. Conjugated estrogens produced an essentially normal pattern of cervical mucous amylase levels. No biologic estrogenic effects could be detected in either type of patient under the influence of oral estriol at the dosages used. EECPE when given to patients with normal ovarian function produced a fluctuating amylase pattern during the proliferative phase when ovulation was delayed or suppressed. Cervical mucous amylase levels were low and no fluctuations occurred in patients with ovarian failure treated with this long-acting estrogen. Under the influence of endogenous estrogen production stimulated with human menopausal gonadotropin (HMG) the amylase secretion levels were low. After HMG- human chorionic gonadotropin (HCG)-induced ovulations a directly proportional quantitative relationship between cervical mucous amylase and urinary pregnanediol levels was found.

Diagnosis and results of therapy of ovarian tunica fibrosa with cystic changes

Abstract Follow-up results are presented on a series of 20 patients who had essentially normal pelvic findings and normal thyroid and adrenal function, but who were anovulatory with problems of infertility. These patients all showed a persistent failure of response to three or more attempts at induction of ovulation with 20 mg. of intravenous estrogen, equine, given 14 or more days after the preceding catamenia. It was this persistent failure of ovulation which prompted recommendations for ovarian wedge resection in all of these otherwise clinically normal, married, but infertile women. The preoperative diagnosis of tunica fibrosa of the ovaries with cystic changes has been confirmed grossly and by microscopic sections of the resected tissue in 18 of the 19 operated cases. In the seventeenth case, the ovarian surgical pathology was primarily that of subacute, marked pelvic inflammatory disease although there were also areas suggestive of a thickened fibrotic ovarian capsule. Only 2 of the other 18 patients who have had operations and who have been followed for a sufficient length of time have failed to ovulate postoperatively, and both of these cases were unusual in that the patient showed marked hypoplasia of the internal genitals, as contrasted with the other 16 cases where ovaries, uterus, and Fallopian tubes were normal in size. It is suggested that this condition accompanied by internal genital hypoplasia may represent a variant which bears a poor prognosis for eventual fertility. There has been as yet no satisfactory technique for preoperative differentiation of the two types of ovarian tunica fibrosa.