Eberhard K. Muechler

Pregnancy induced with menotropins in a woman with polycystic ovaries, endometrial hyperplasia, and adenocarcinoma.

A 31-year-old woman is described with PCOD associated with endometrial hyperplasia and well-differentiated adenocarcinoma. Conservative treatment with ovulation induction was pursued for a total of 3 1/2 years. After CC treatment failed to achieve conception, treatment with menotropins resulted in a twin pregnancy that aborted spontaneously and a singleton term pregnancy. Hysterectomy was performed 4 1/2 years after the initial diagnosis of well-differentiated endometrial adenocarcinoma was made. Histologic examination of the endometrium showed no progression of the disease. Ovulation induction of patients with polycystic ovaries and well-differentiated and noninvasive endometrial adenocarcinoma may be justified in properly selected cases.

Serum progesterone levels in women treated with human menopausal gonadotropin and human chorionic gonadotropin for in vitro fertilization

For evaluation of the adequacy of luteal function after in vitro fertilization-embryo transfer (IVF-ET), serum progesterone (P) levels were measured on days 3, 7, and 10 after laparoscopic follicle aspiration. Fifty-six infertile patients were treated during 86 cycles with human menopausal gonadotropin-human chorionic gonadotropin (hMG-hCG) for stimulation of follicular development. Serum estradiol (E2) levels were measured daily during hMG-hCG treatment. P levels were determined in 67 cycles. The mean (+/- standard deviation [SD]) of the sums of 3 P levels was 55.63 +/- 24.13 ng/ml. There were 11 pregnancies. The mean of the sums of 3 P levels of pregnant patients was 64.45 +/- 26.23 ng/ml and of 56 nonpregnant cycles was 53.90 +/- 23.35 ng/ml. The duration of luteal phase varied from 9 days to 15 days. The mean of the sums of 3 P values of patients with different luteal phase lengths ranged from 28.8 ng/ml to 60.51 +/- 25.68 ng/ml. The mean of the sums of 3 P levels of women with normal luteal phase and that of women with luteal phase defect by endometrial biopsy study were used as controls for comparison. There was poor correlation (r = 0.3441) between E2 peak levels and P levels; the sum of 3 P levels did not indicate luteal phase inadequacy in IVF-ET patients; and the majority of the nonpregnant cycles (32/56) showed a luteal phase of 11 days or less, in spite of adequate P levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Parthenogenesis of human oocytes as a function of vacuum pressure

The effect of different vacuum pressures on the rate of parthenogenesis was studied in 109 cycles of laparoscopic follicle aspiration. A total of 388 follicles was aspirated at settings of vacuum pressure of 100, 75, and 50 mm Hg. Parthenogenesis occurred at the rates of 5.9, 7, and 1%, respectively. The difference between 100 and 50 mm Hg was statistically significant (P<0.025). We conclude that the rate of parthenogenesis is influenced by the magnitude of vacuum pressure.

Human chorionic gonadotropin, estriol and testosterone changes in two pregnancies with hyperreactio luteinalis

A case of hyperreactio luteinalis is presented with measurements of human chorionic gonadotropin, total and free testosterone, and estriol throughout two term pregnancies. Ovulation induction with menotropins resulted in one spontaneous first-trimester abortion, one singleton term pregnancy, and 1 triplet pregnancy that converted to a singleton term pregnancy after spontaneous degeneration of two fetuses in the first trimester. During the first term pregnancy, levels of human chorionic gonadotropin peaked at 34 weeks of gestation (169,000 mIU/ml) and levels of total testosterone peaked at the same time (1777 ng/dl). Free testosterone (16.6 ng/dl) and estriol (10.8 ng/ml) reached their peak at 36 weeks of gestation. During the second term pregnancy, peak values of human chorionic gonadotropin (150,900 mIU/ml) and total testosterone (870 ng/dl) occurred at 10 and 5 weeks of gestation, respectively, before two fetuses of a triplet pregnancy degenerated.

The Androgen Receptor of the Human Endometrium

Available androgen binding to soluble proteins from the cytosol of human endometrium was studied using the dextran coated charcoal adsorption method and sucrose density centrifugation analysis. Specific binding of [3H]-5 alpha-dihydrotestosterone ([3H]-DHT) was observed with both methods. The apparent dissociation constant (Kd), for DHT binding is 1.3 +/- 0.2 (SEM) nM and the binding capacity 177 +/- 42 (SEM) fmol/mg protein. Sucrose density ultracentrifugation identifies specific [3H]-DHT binding that sediments at 4S and 8S. The stability of the androgen receptor in human endometrium is increased by the addition of 10% glycerol to the homogenization buffer. The addition of trypsin or pronase and heating at 60 degrees C reduces specific binding which demonstrates that the specific [3H]-DHT binder is a protein. The uptake of [3H] DHT in endometrial tissue minces indicated that 20% of the bound radioactivity was nuclear. Steroid specificity suggests that the binding protein from the uterus is specific for androgens. These observations indicate that androgen binding protein in the human uterus has the characteristics of the androgen receptor.

Further characterization of estrogen receptors in the human oviduct

Estrogen binding in human oviducts was studied in vitro by the dextran-coated charcoal assay and sucrose density ultracentrifugation. Estrogen binds with high affinity and limited capacity to cytosol of the human oviduct. The concentration of competitive inhibitors to produce 50% reduction in estrogen binding was 8 x 10(-8) M for the antiestrogen CI-628, 8 x 10(-7) M for the progestogen norethynodrel, and 3 x 10(-6) M for the testosterone derivative danazol at the ligand concentration of 1 nM estradiol. Nuclear estrogen binding was not inhibited by a 100-fold excess of progesterone or by a 10-fold excess of norethynodrel. Estrogen-binding protein with a sedimentation coefficient of 4S was seen in oviductal cytosol of all three anatomic segments. The nuclear 4S peak of estrogen binding was demonstrated in the ampullary tubal segment.

Plasma estrogen and progesterone in quintuplet pregnancy induced with menotropins

I. =l Amp HMG gestation. The frequency of this complication ranges from IS% to 53.5%’ Several investigators have suggested that estrogen monitoring may reduce the incidence of multiple gestation. Furthermore, recent studies propose ultrasonography for measurements of follicular size and number. We have observed a case of quintuplet pregnancy after treatment with menotropins. This case is of interest because it demonstrates a possible relationship between the rate of administration of menotropins and the development of quintuplet pregnancy.

Heuristic determination of relevant diagnostic procedures in a medical expert system for gynecology

Many professions including medicine have standard operating procedures for the performance of their tasks. In the construction of expert systems, knowledge engineers have exploited this fact in devising heuristic rules that mimic the standard practice among such personnel (i.e., experts). This article suggests that the expert system designer should not stop at the level of the standard operating procedure heuristic but should instead investigate the reasons that the standard procedures have become standard. Because the experts in a field often do not understand the reasons for the standard operating procedures of their profession, this effort not only rewards the system designer but the expert as well. Because medical training does not always emphasize the logical reasoning underlying certain standard operating procedures, the ability to perform this reasoning is especially important in medicine. Further, a medical expert system for consultation or education would make a valuable impact by incorporating such knowledge and inference rules. This article investigates the development of a computerized medical expert system that applies the principles of artificial intelligence by limiting the number of questions and tests to find the solution for an ill-defined complex problem. Finally, we describe a logic program that tests the basic ideas.

HORMONAL AND CYTOGENETIC STUDIES IN PHENOTYPICALLY FEMALE PATIENTS WITH GONADAL DYSGENESIS

In 4 cases of gonadal dysgenesis the clinical, hormonal, cytogenetic, and histological findings were correlated. There were 2 patients with 46, XY karyotype, one patient with 45, X Turners syndrome and one patient with a 46,XX chromosome complement. All patients had streak gonads with ovarian stroma. In one phenotypically female 46,XY individual an involuted gonadoblastoma was found. Her testosterone was four‐fold higher in gonadal vein blood compared to peripheral blood. Cytogenetic analysis of multiple tissues in both cases with the 46,XY karyotype greatly reduced the probability of mosaicism. In the patient with 45,X Turners syndrome and in the one with 46,XX gonadal dysgenesis only peripheral blood cells were karyotyped and mosaicism was not further excluded by analysis of other tissues. The concentrations of steroid hormones in gonadal vein blood were low. The levels ranged as follows: estrone 41–98 pg/ml, estradiol 18–90 pg/ml, testosterone 37–294 ng/100 ml, dihydrotestosterone 13–22 ng/100 ml, and progesterone 0.3–1.5 ng/ml. It was concluded that gonadal streaks were similarly deficient in biosynthesis of steroid hormones despite different chromosomal complements.

Paradoxical pituitary hormone responses in a case of primary hypothyroidism and Hashimoto's thyroiditis.

A 24-year-old woman is described with irregular menstruation, anovulation, and infertility due to primary hypothyroidism and Hashimotos thyroiditis. Her baseline gonadotropins and thyroid-stimulating hormone (TSH) were increased. Microsomal and thyroglobulin antibodies were present. Stimulation of pituitary hormone release with thyrotropin-releasing hormone (TRH) resulted in appropriate responses of TSH and prolactin (PRL) as well as a substantial rise in the level of luteinizing hormone (LH). Luteinizing hormone releasing factor (LRF) markedly inhibited LH release. Bromoergocryptine led to inhibition of TSH and PRL. These results suggest that specific and nonspecific responses of pituitary glycoproteins to provocative stimuli reflect a profound disturbance of the hypothalamic-pituitary axis in this case of hypothyroidism.