Zvi Palti

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.

Effect of viscous macromolecules on peritoneal plasminogen activator activity: A potential mechanism for their ability to reduce postoperative adhesion formation

Activity of peritoneal plasminogen activator and its regulation by dextran and other macromolecules that clinically suppress postoperative adhesions was studied. Plasminogen activator activity was assayed by a two-stage globinolytic assay that monitors formation of plasmin, as well as by cleavage of a chromogenic peptide substrate (S-2444) in the presence of aprotinin (Trasylol). Plasminogen activator activity was located on the outer surface of human peritoneum. Incubation of peritoneal tissue with buffer in vitro (conditioning) prompted release of plasminogen activator into the conditioning medium. The released plasminogen activator formed a single band on sodium dodecyl sulfate-gel electrophoresis at an apparent molecular weight of 174,000 and was markedly suppressed by antiserum raised against human melanoma tissue-type plasminogen activator. Nonspecific proteolytic activity did not accumulate in the medium during conditioning. The presence of dextran 80 during conditioning of peritoneum reversibly suppressed tissue-bound plasminogen activator activity and reduced plasminogen activator activity in the spent medium. A similar inhibition of peritoneal plasminogen activator was induced by dextran 500, methyl cellulose, and polyvinylpyrrolidone. Dextran, when added to the medium after conditioning, had no direct inhibitory effect on plasminogen activator activity. Dextran did not induce peritoneal production of inhibitor(s) of trypsin, chymotrypsin, or urokinase. On the basis of these findings, two possible mechanisms for the effect of viscous polymers in the reduction of adhesion formation are proposed. These mechanisms consider the importance of peritoneal tissue-type plasminogen activator for removal of fibrin clots and suggest that polymer coating either prevents the shedding of plasminogen activator into the abdominal cavity or reduces the access of fibrin clots to the serosal surfaces.

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.

Vitamin D3 metabolites in rat epididymis: high 24,25-dihydroxy vitamin D3 levels in the cauda region.

Normal male rats received six subcutaneous injections of 8.0 pmoles of tritiated 25-hydroxy vitamin D3 ([3H]25(OH)D3) or one intrajugular injection of 8.0 pmoles of high specific radioactivity [3H]-25(OH)D3. Lipid extracts of several tissues including the reproductive organs were subjected to sephadex LH-20 chromatography to determine the tissue distribution of the injected material and of the in vivo produced dihydroxylated cholecalciferol metabolites. The nature of the putative 25(OH)D3 and the 24,25-dihydroxy vitamin D3 (24,25(OH)2D3) from epididymis tissue was confirmed by high performance liquid chromatography (HPLC). The epididymis levels of 24,25(OH)2D3 were considerably higher in the cauda epididymis compared to kidney and caput epididymis levels. The other metabolites levels in this tissue were similar to those determined in the kidneys. The amounts of the three metabolites found in all other tissues were well below the cauda epididymis or kidney levels. The findings suggest a possible physiological role for 24,25(OH)2D3 in the epididymis, and are also consistent with data of others which indicated a possible action of 1,25-dihydroxy vitamin D3 (1,25(OH)2D3) in rat reproductive tissues.

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.

In utero ponderal index as a prognostic factor in the evaluation of intrauterine growth retardation

The in utero ponderal index has become a method of estimating fetal growth. Several methods have been used in the formulation of the in utero ponderal index. In the present study, 1040 pregnant women underwent ultrasonic examination between 24 and 41 weeks of gestation, and the in utero ponderal index was determined by dividing the estimated fetal weight by the third power of the femur length, rendering a relatively constant value of 8.345 +/- 2.5 (2 SD). Fifty-one cases were defined as intrauterine growth retardation due to an estimated fetal weight lower than the tenth percentile for gestational age. The in utero ponderal index proved to be a valuable index in the prediction of fetal outcome in those cases of intrauterine growth retardation in which the in utero ponderal index was smaller than 1 SD from the average of 8.345. Fetal and neonatal well-being was clearly compromised when intrauterine growth retardation was associated with a low in utero ponderal index.

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.

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.

The significance and importance of prenatal diagnosis of fetal cardiac malformations by Doppler echocardiography

Pulsed Doppler echocardiography is an excellent technique for cardiac diagnosis and assessment of cardiac performance in combination with M-mode and two-dimensional echocardiography. Its exact role in fetal cardiac diagnosis has not been established. We examined 67 high-risk fetuses for cardiac malformations and found cardiac abnormalities or malfunction in 15. In four fetuses pulsed Doppler echocardiography played a primary or a definitive diagnostic role: One fetus had a complete atrioventricular canal, another lacked the pulmonary valve, the third had transposition of the great vessels without ventricular septal defect, and the fourth had high cardiac output failure caused by placental chorioangioma. Pulsed Doppler echocardiography is an integral part of the ultrasonic cardiac examination in high-risk fetuses and should be used in combination with two-dimensional and M-mode echocardiography. It has an important place in the diagnosis of high-risk fetuses and may have a primary role in the diagnosis of fetuses when ultrasound resolution is poor, where cardiac circulatory hemodynamics are essential for diagnosis, and in complicated cardiac malformations in which a comprehensive and accurate diagnosis can be achieved only with pulsed Doppler echocardiography.

Severe Fetal Distress with Hydramnios due to Chorioangioma

Abstract. A case is described of antenatal detection of a placental mass by ultrasound in a patient with hydramnios due to chorioangioma and who had a sinusoidal‐like pattern and positive oxytocin challenge test (OCT). The importance of frequent fetal heart rate monitoring in cases of supected chorioangioma is emphasized.