Growth and sexual development before and after sex steroid therapy in patients with thalassemia major.

Growth, sexual development, and hypothalamic-pituitary-gonadal function were evaluated in 23 patients with thalassemia major (14 female and nine male) aged 13 to 29 years. Five women (group 1) with hemoglobin levels of less than 7 g/dL, which were maintained by transfusions during childhood, did not spontaneously enter puberty. They had evidence of severe hypothalamic-pituitary dysfunction. Maintaining hemoglobin levels of about 8 g/dL resulted in spontaneous onset of puberty in seven of nine female patients (group 2), but had no such ameliorative effect on the nine male patients. In the latter, peak luteinizing hormone (LH) responses to gonadotropin releasing hormone correlated with bone age. Treatment with testosterone produced inconsistent partial inhibition of LH and follicle-stimulating hormone (FSH) responses to stimulation. After discontinuation of testosterone treatment, a rebound of basal testosterone, LH, and FSH levels was observed, but this was not sustained. These findings are compatible either with dysfunction of hypothalamic maturation or with partial pituitary dysfunction. Four of the group 1 females and six of the males treated with appropriate sex hormones showed satisfactory pubertal progression. Acceleration in linear growth was observed in four of the male patients whose epiphyses were still open. Treatment was well tolerated in all patients.

Glycogen metabolism of the human endometrium.

The glycogen concentration and the activities of glycogen synthetase and phosphorylase were assayed in endometrial tissue obtained during curettage. Tissues were obtained during different phases of the menstrual cycle from women investigated because of menometrorrhagia or sterility. The glycogen concentration was less than 2 mg/g wet wt in specimens from days 1-15 and increased 10-fold during the early secretory phase. The total activities of glycogen synthetase and phosphorylase were increased 1.5- and 2-fold, respectively, during the secretory phase compared to those during the first half of the cycle. The activities of the active forms (a form) of these enzymes did not show significant changes during the menstrual cycle. The largest difference between the proliferative and secretory phases was in the activity of glycogen synthetase phosphatase, which was virtually inactive in tissues obtained on days 1-15 and increased almost 20-fold during the secretory part of the cycle. In tissues obtained from cases of sterility, the activities of glycogen synthetase and phosphorylase were significantly reduced only during the early secretory phase. Glycogen concentration throughout the menstrual cycle and enzyme activities during the midsecretory and premenstrual phase were similar in cases of sterility and other pathologies.

Amniotic fluid 3,3',5'-triiodothyronine in the detection of congenital hypothyroidism.

Amniotic fluid rT3 levels were measured during pregnancy in two women who previously gave birth to infants suffering from neonatal hypothyroidism. In the first case, hypothyroidism was strongly suspected because of repeated low levels of rT3 in the amniotic fluid (20-64 ng/dl) at 16 and 31 weeks of gestation. A normal infant was delivered. He is now 10 months old and taking no treatment; he has no clinical or laboratory signs of hypothyroidism. In the second case, amniotic rT3 levels (140-180 ng/dl) were well within the normal range for 15-19 weeks of pregnancy, but an affected hypothyroid infant was born. These data suggest that amniotic fluid rT3 levels may not be a reliable tool in diagnosing intrauterine hypothyroidism.

Prostaglandin E2-mediated suppression of human maternal lymphocyte alloreactivity by first-trimester fetal macrophages.

We examined the immunosuppressor role of the first-trimester human placental macrophages on maternal lymphocyte alloreactivity in vitro to determine whether these macrophages and their secreted mediator(s) participate in the local immunoregulation at the fetomaternal interface. These cells were tested for their effects on maternal lymphocyte proliferation when added alone (as stimulator cells) or as regulator cells in 1) a one-way mixed lymphocyte reaction for six days and 2) lymphocyte cultures in the presence of phytohemagglutinin for three days. We detected a dose-dependent inhibition of phytohemagglutinin-induced proliferation with 48-hour macrophage culture supernatants. Placental macrophages, when used alone as stimulator cells in the mixed lymphocyte reaction, were stimulatory only at a concentration of 1-2%; the stimulation was abolished at a concentration of 10%. When used as regulator cells, they showed a strong inhibition of mixed lymphocyte reaction and phytohemagglutinin-induced proliferation at a concentration of 10%; no effect was observed at a concentration of 1-2%. The major class of the molecules mediating the suppression was identified as prostaglandins, primarily prostaglandin E2 (PGE2), based on the findings that the presence of indomethacin (10(-5) M) or various dilutions of an anti-PGE2 antibody abrogated suppression substantially or completely. Prostaglandin E2 levels measured in the mixed leukocyte culture wells containing placental macrophages as regulator cells correlated positively with the macrophage dose and its suppressive effect.

Chorionic gonadotropin and progesterone levels in ectopic pregnancy.

It is assumed that one function of hCG is to preserve the developing corpus luteum and maintain pregnancy by producing progesterone and thus preventing menstrual shedding. In 8 of 17 cases of ectopic pregnancy, progesterone values were in the range of the proliferative phase of a normal cycle (0.1-1ng/ml), whereas the levels of hCG were 299-1600 mIU/ml. In 8 cases the progesterone levels were in the range of the secretory phase (2.3-6.9 ng/ml), and the hCG level was 182-5500 mIU/ml. In 1 case only was the progesterone level 15.0 ng/ml with an hCG level of 325 mIU/ml. In normal pregnancies of the same gestational age, the values of progesterone were 3.8-18.7 ng/ml, and the levels of hCG were 260-1300 mIU/ml. It seems that in addition to the level of hCG, a normal fetoplacental unit is needed for the preservation of the function of the corpus luteum.

Human chorionic gonadotropin (beta-subunit) in the early diagnosis of ectopic pregnancy.

In 15 women with suspected ectopic pregnancy considerable amounts of beta-subunit of human chorionic gonadotropin (hCG) were detected in the serum by the radioimmunoassay technique. The diagnosis was proved by laparotomy. In another 25 suspected cases beta-hCG values were less than 1 mU/ml, and in those cases the diagnosis was excluded. The detection of the beta-subunit of hCG in the serum was found to be an excellent tool for the early diagnosis of ectopic pregnancy, thus helping to prevent the dangerous sequelae which follow in the late diagnosis of this condition. The advantage of detecting the beta-subunit of hCG rather than hCG is discussed.

The management of persistent clear pelvic cysts diagnosed by ultrasonography.

Between December 1981 and June 1986, 52 women examined by ultrasonography were found to have clear pelvic cysts more than 5 cm in average diameter, without septa or solid areas. The cysts were persistent and did not respond to contraceptive pills for four to eight weeks. In all cases, there were histologic or cytologic results from surgical specimens or fluid aspirated from the cysts. In 15 women, the cysts were aspirated and revealed no malignant cells. Thirty-seven women underwent laparotomy, of whom 11 (29%) were found to have benign ovarian neoplasms (nine cystadenomas and two dermoid cysts). Because benign ovarian neoplasms are potentially malignant, and because a large number was found in our study, we recommend removal of the cysts by excision rather than aspiration.

Increased prolactin response to thyrotropin-releasing hormone in primary ovarian failure.

To investigate prolactin (PRL) and thyrotropin-stimulating hormone (TSH) secretion in ovarian failure, 14 women with primary ovarian failure were challenged with luteinizing hormone-releasing hormone (LHRH) (100 micrograms) and thyrotropin-releasing hormone (TRH) (200 micrograms) given intravenously at 30-minute intervals. Responses were compared with those of 13 healthy female controls. In the patient group, basal follicle-stimulating hormone (FSH), LH, and peak gonadotropin responses to LHRH were higher and basal estrone and estradiol levels were lower than in the controls (P less than .001). Mean basal PRL levels were similar in the 2 groups. However, the mean peak and integrated PRL responses in the patients were greater than in the controls (P less than .05). Ten patients had a markedly exaggerated PRL response to TRH. The mean basal TSH levels and the peak TSH response to TRH were similar to those of the controls. Estrogens are known to stimulate PRL secretion. These subjects had increased PRL responses with low circulating estrogens. The mechanism underlying the findings is not known, but could be related to increased aromatization of androgens to estrogens in the hypothalamus. Alternatively, other factors could be responsible for the exaggerated PRL responses to TRH noted in these patients with primary ovarian failure.

Serum prolactin levels in men during retropubic prostatectomy.

Thirty-one patients who underwent retropubic prostatectomy under epidural anesthesia for benign hypertrophy of the prostate were checked for serum prolactin levels before and during operation. A significant increase in serum prolactin levels was noted during operation after the removal of the prostate, as compared with levels just prior to its removal. This difference suggests high concentration of prolactin in the prostatic tissue, part of which was released into the bloodstream during the traumatic squeezing of the prostate.

Better postcoital test for oligospermic patients using split ejaculate artificial insemination.

In 25 oligospermic patients who had negative postcoital tests, artificial inseminations were performed with the whole semen and split ejaculates. After 30 minutes, a sample of cervical mucus was obtained and examined microscopically for the presence of motile spermatozoa. There was a significant improvement of 64% using the split ejaculate, as compared with 44% using whole semen. We found a significantly higher sperm count and progressive motility in the split ejaculate (18 patients, 72%).

Serotonin and 5-hydroxyindoleacetic acid in fertile and subfertile men.

High levels of serotonin and 5-HIAA were found in the urine of a group of 102 oligospermic and azoospermic men. These levels were significantly higher than those of normal fertile men.

The hormonal response of patients with polycystic ovarian disease to subcutaneous low frequency pulsatile administration of luteinizing hormone-releasing hormone.

Four patients with oligoamenorrhea manifesting hormonal and clinical features of polycystic ovarian disease (PCOD) were selected for treatment. All patients had high luteinizing hormone (LH) levels and a basal LH/follicle-stimulating hormone (FSH) ratio of greater than 3. Three of them had high androgen levels with normal adrenal cortical function. The four patients were treated for 12 cycles by pulsatile LH-releasing hormone (LH-RH) subcutaneously. Frequency of pulses varied between once in every 120 to once in every 400 minutes in consecutive cycles, in an attempt to reverse LH/FSH ratio. The dose of LH-RH varied between 20 and 40 micrograms/pulse. Treatment was monitored hormonally by the determinations of LH, FSH, 17 beta-estradiol, prolactin, progesterone, testosterone (T) (total and free), androstenedione (delta 4A), dehydroepiandrosterone sulfate (DHEA-S), and sex hormone-binding globulin (SHBG) every 2 days. The most striking change was the lowering of the LH/FSH ratio to the normal range, due to LH decrease and FSH increase with a pulse frequency of 180 to 240 minutes. DHEA-S levels reversed to normal in two patients and were reduced in one patient. T and delta 4A levels returned to normal with elevation to normal of SHBG. These hormonal improvements did not result in ovulation as expected (2 of 12 cycles). It may be assumed that either subcutaneous administration is inadequate in PCOD patients or that the frequency of pulses needed to correct the hormonal disturbances in PCOD patients differs from that needed for ovum maturation and ovulation.

The effect of insulin on progesterone production and cellular growth in long-term cultures of human granulosa lutein cells.

The direct action of insulin on human granulosa lutein cells (GLCs) in long-term cultures obtained from in vitro fertilization (IVF) cycles was investigated. Progesterone (P) secretion by GLC increased progressively in both basal and human chorionic gonadotropin (hCG; 100 mIU/ml) stimulated conditions up to 4 days in culture, and plateaued thereafter. Insulin (0.0025 mU/ml to 2500 mU/ml) had no effect on either basal or hCG stimulation during the culture period. GLC in culture formed a monolayer and multiplied at a rate of approximately once every 3 days. Neither morphology nor cell division was affected by insulin in supraphysiologic levels (25 mU/ml). These results suggest that GLC obtained from preovulatory follicles in an IVF program are already stimulated maximally by in vivo exposure to high doses of human menopausal gonadotropin (hMG)/hCG administered to the women. Contrary to its stimulatory effect on early preovulatory granulosa cells, insulin dose not affect P production, cellular morphology, or growth rate of luteinized granulosa cells.

Observer variability in the diagnosis and management of the hysterosalpingogram.

OBJECTIVE: To determine the reproducibility of hysterosalpingogram (HSG) interpretation and clinical management recommendations among trained observers. DESIGN: Fifty HSG films were distributed to five fertility practitioners with a mean of 20 years clinical experience. Each observer evaluated components of uterine and tubal status and provided clinical recommendations for hysteroscopy and laparoscopy. SETTING: University hospital-affiliated reproductive endocrine practice. INTERVENTION(S): None MAIN OUTCOME MEASURE(s): The level of agreement among observers for each uterine and tubal category as determined by the kappa(kappa) statistic. Determinants of clinical recommendation for further diagnostic studies were assessed. RESULT(S): The level of agreement between observers as determined by kappa ranged from 0.645 in the hydrosalpinx category, indicating fair reliability, to 0.111 for pelvic adhesions, indicating poor reliability. The composite kappa for uterine status was 0.345 whereas the composite kappa for tubal status was 0.430. Agreement among observers concerning management showed marginal reproducibility with a kappa of 0.261. Overall, more than one abnormality of either the cavity or the fallopian tubes led to a diagnostic recommendation for further workup in > or = 90% of cases. CONCLUSION(S): In a group of five experienced clinicians, there was considerable variability in the interpretation as well as the clinical management of the HSG. Physicians caring for infertile couples should be aware of this discrepancy and should, if possible, review carefully both the original films as well as the report of the attending radiologist in formulating their diagnostic evaluation and management plan.

Exaggerated prolactin response to thyrotropin-releasing hormone and metoclopramide in primary testicular failure.

Twenty-eight severely oligospermic and azoospermic men aged 20 to 42 years were challenged with luteinizing hormone (LH)-releasing hormone (LHRH), thyrotrophin-releasing hormone (TRH), and the dopaminergic antagonist, metoclopramide, given at 30-minute intervals. According to basal gonadotropin levels, the patients were subdivided into three groups: those with severe testicular failure (basal LH > 20 mIU/ml and FSH > 14 mIU/ml); those with moderate testicular failure with predominant seminiferous tubule involvement (LH < 20 mIU/ml and FSH > 14 mIU/ml) and those with mild testicular failure (LH < 20 mIU/ml and FSH < 14 mIU/ml. With one exception, mean basal prolactin (PRL) levels were normal in all patients. In all three groups, however, there was an exaggerated PRL response to TRH, the response in severe and moderate testicular failure being greater than that in mild testicular failure. The response to metoclopramide was increased only in the first two groups, not in the group with mild testicular failure. When individual patients and control subjects were considered together, the peak PRL response to TRH correlated with both basal and peak gonadotropin responses to LHRH. However, the PRL responses did not correlate with 17 beta-estradiol, estrone, testosterone, or the estradiol-testosterone ratio. It is concluded that oligospermic and azoospermic subjects with the most severe testicular failure and the highest gonadotropin levels have the greatest PRL increases after TRH and metoclopramide, indicating that the PRL response is related to the degree of testicular failure.

Advice from the obstetrician and other sources: do they affect women's breast feeding practices? A study among different Jewish groups in Jerusalem.

Breast feeding practices and the sources of advice that influenced them were studied in a sample of 276 women from North East Jerusalem. They were followed-up for 4 1/2 months and interviewed on 4 occasions during that period. It was found that 89.7% started breast feeding after parturition, 62.4% were breast feeding by 6 weeks, 40.3% were breast feeding after 3 months and 27.3% were still breast feeding by 4 1/2 months postpartum. Obstetrician's advice given at the 6 weeks postpartum examination was significantly associated with duration of breast feeding (P = 0.001). Other sources of guidance were not significantly related to duration of breast feeding when controlling for social class. Analysis of variance indicated that women of higher social classes breast fed more and for a longer period of time. There was no difference in the pattern of attendance at the obstetrician's examination by social class, although a very small proportion of women belonging to the lower social classes reported getting advice on breast feeding during that visit. There was a strong relation between advice of the obstetrician and percentage of women breast feeding 4 1/2 months postpartum. Country of origin of the women also affected breast feeding practices. Women of Western origin breast fed more and longer than women of Asian or North African origin. This might be explained by social movements that attempt a return to more natural life styles which are prominent in Western societies. The differential relationship between advice of obstetrician and women belonging to different social classes is discussed and key elements in the relation between obstetrician's advice and women's breast feeding practices are considered.

Psychological variables and premature labour: a possible solution for some methodological problems.

Two studies on the relationship of psychological variables and premature labour were conducted. The first was a retrospective comparison of psychopathological tendencies, attitudes towards pregnancy, physical complaints during pregnancy and perceived marital and social support, between a group of women who had premature labour and a group of women with term deliveries without premature contractions. Data were collected a few months after deliveries to neutralize bias caused by anxiety for newborns' condition and by proximity in time to the trauma of premature delivery. The second study was a prospective one in which the target category included not only women who delivered prematurely but also women who developed premature contractions but delivered at term. In this study we examined trait and state anxiety, mothers' attitudes towards pregnancy and physical complaints during pregnancy. Results showed that psychopathological tendencies were linked to premature labour and premature contractions. No differences were found concerning perceived social support or mothers' attitudes towards pregnancy.

Fine structure of Sertoli and Leydig cells in azoospermic human testis.

Testicular biopsy specimens taken from seven patients with azoospermia were studied by electron microscopy. We considered the possibility of a relationship between the annulate lamellae in the Sertoli cells and azoospermia. In the Leydig cells, we observed intranuclear and intracytoplasmic paracrystalline inclusions and considered their relationship with the Reinke crystalloid.

PIP: Special attention was given to the ultrastructure of 2 organelles: the annulate lamellae in the Sertoli cells and the crystalloid structure visible in the Leydig cells. Materials studied were biopsy specimens from 7 31-41 year old cases of male infertility with azoospermia or severe oligospermia. All biopsy specimens were bilateral. By light microscopy tubular atrophy with fibrosis and thickening of the boundary layer was observed. changes in the tubuli were characterized by an arrest of spermatogenesis at the stage of priamry spermatocyte production. Hyperplasia of Sertoli cells was noted with many fat vacuoles in the cytoplasm. Scattered large Sertoli cells contained Reinke crystalloids. By electron microscopy, large and irregular Sertoli cells contained abundant intracytoplasmic organelles and a prominent nucleus. The subcellular structures of the cytoplasm were all observed to be present. A specific organelle, the annulate lamellae or lamellar body, was seen in tight correlation with other structures near the nucleus. Other structural details observed are noted. Photographic reproductions illustrate electron microscopic findings. Although the presence of paracrystalline material is not specific to priamry testicular failure, the prominence of this structure in azoospermic human testes could be an expression of some modifications in the male hormone metabolism. It is suggested that a local estrogenic hyperaction could be the cause of depressed spermatogenesis and thus lead to azoospermia.

Evaluating treatments for preterm labor: possible solutions for some methodological problems.

The usual evaluation procedures for labor-inhibiting therapies are criticized and a new measure is proposed. This measure (rate of pregnancy prolongation) is shown to fulfil the criteria of high sensitivity to treatment effects and of unbiasedness for the gestational age of patients. The use of analysis of covariance is proposed as a solution for the problem of confounding background variables. The advantages of the new evaluation procedure are illustrated by the analysis of a clinical trial of labor inhibition by hypnotic relaxation.

Maternal blood pressure response to the intravenous administration of pethidine-promethazine during labor.

A double blind study on the effect of an intravenous injection of a combination of 75 mg pethidine and 25 mg promethazine was conducted on 200 women during normal deliveries. Four groups of 50 women each received injections of pethidine and promethazine, promethazine alone, pethidine alone and normal saline. In the pethidine-promethazine group there was a significant elevation in blood pressure in the first 10 min following the injection as compared with the other groups. The mean (+/- S.D.) systolic blood pressure after the injection was 143.2 +/- 14.3 mmHg as compared with 118.9 +/- 8.4 mmHg before the injection, and the mean diastolic blood pressure as 96.9 +/- 8.4 mmHg after the injection as compared with 77.7 +/- 9.3 mmHg before the injection. 25 mg promethazine alone caused slight elevation in blood pressure which was further increased by combination with pethidine. The clinical significance of these observations is discussed.