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.

[Adverse effects of tamoxifen on the female genital tract].

Tamoxifen is an established adjuvant therapy for breast cancer. It exerts both estrogenic agonist and antagonist effects on target tissues. Since the use of tamoxifen is expanding, it is expected that more women will suffer from its side-effects. 3 women aged 48, 48, and 65, respectively, who were treated with tamoxifen, were referred for evaluation of possible side-effects. They had, respectively, endometrial hyperplasia, a unique sonographic appearance of the endometrium resembling neoplasia, and an ovarian cyst.

The expression of the H-19 and IGF-2 genes during human embryogenesis and placental development.

The H-19 gene in mice is maternally imprinted and its ectopic expression causes prenatal lethality. We have recently identified H-19 transcript in differentiating human placental cells and showed that its expression increases concomitantly with differentiation of cytotrophoblasts in vitro. Placental and embryonal specimens were collected from conception products derived from normal first and second trimester pregnancy terminations. We investigated the abundance of H-19 mRNA throughout placental development in vivo and compared it to the expression of other genes linked to placental differentiation. Furthermore, the expression of H-19 transcript in different organs of human fetuses, aborted during the second trimester, was examined by RNA isolation from separated fetal organs. Since IGF-2 is known to play an important role in embryogenesis, identical blots were hybridized with IGF-2 probe. H-19 expression in human placenta from the different trimesters of pregnancy remains practically constant. A high amount of H-19 gene product was found in the fetoplacental unit with the highest level measured in the adrenal gland. These findings argue that H-19 gene may play a role in human embryogenesis.

Fetal middle cerebral artery blood flow during normal active labour and in labour with variable decelerations.

OBJECTIVE: To assess the distribution of fetal blood flow impedance of the umbilical and middle cerebral artery in active uncomplicated labour and in labour complicated by variable decelerations. INTERVENTIONS: Blood flow impedance of the umbilical and fetal middle cerebral arteries was assessed by means of pulsed Doppler ultrasonography and measured by the resistance index (RI) and the systolic/diastolic ratio. SUBJECTS: 35 women at 38-40 weeks gestation admitted to, or monitored in the intrapartum unit. One group of 25 women had a normal active labour, the second group of 10 women were in active labour with moderate variable decelerations. A control group of 25 women--healthy pregnant women at term but not in active labour. All three groups were comparable for maternal age and parity. SETTING: Hospital department of obstetrics and gynaecology, Israel. DESIGN: A prospective descriptive study. RESULTS: There was a 40% reduction in middle cerebral artery blood flow impedance in the two groups of women in active labour compared with the control group. Umbilical blood flow did not differ significantly between the three groups. Fetal middle cerebral blood flow impedance in labour was not significantly different in uncomplicated labours and those complicated by fetal heart rate decelerations. CONCLUSIONS: During active labour, mechanisms that may be unrelated to low fetal blood oxygen content reduce fetal brain blood vessel impedance.

Production of 6-keto-PG F1 alpha in hyperstimulated cycles: in vivo and in vitro studies.

Prostacyclin (PG12), a potent vasodilator, is believed to be involved in increasing permeability within the wall of the preovulatory follicle. In ovarian hyperstimulation syndrome (OHSS), increased vascular permeability has been shown to lead to massive fluid accumulation in ovarian cysts and the peritoneal cavity. The objective of the in vitro and in vivo studies reported herein was to examine the production of 6-keto PGF1 alpha (a breakdown metabolite of PG12) during the luteal phase of women who develop OHSS, as well as the capacity of human granulosa luteal cells (GLC) obtained from stimulated in vitro fertilization (IVF) cycles to synthesize PGF1 alpha in vitro in long-term cultures. The in vivo results showed that during the luteal phase of women with OHSS, there is no increase in 6-keto PGF1 alpha production compared with the levels obtained from the luteal phase of normal ovulatory women. The GLC (representing early corpus luteum function) secreted significant amounts of 6-keto PGF1 alpha, but only in the first 48 hours of culture. Human chorionic gonadotropin (hCG) had no additional augmentative effect upon the production of 6-keto PGF1 alpha throughout the culture period. It is concluded that 6-keto PGF1 alpha is not produced in significant amounts during the luteal phase, and therefore PG12 probably does not play a major role in the etiology of OHSS.

Secondary biosynthetic defects in women with late-onset congenital adrenal hyperplasia.

BACKGROUND AND METHODS: Late-onset (non-classic) congenital adrenal hyperplasia is a cause of hirsutism, menstrual disorders, and infertility, but its frequency and the patterns of abnormalities in adrenal hormone secretion are not well understood. We investigated the frequency and ethnic distribution of nonclassic congenital adrenal hyperplasia due to deficiencies of 3 beta-hydroxy-delta 5-steroid dehydrogenase, 21-hydroxylase, or 11 beta-hydroxylase among 170 Israeli Jewish women with these clinical problems. All enzyme defects were identified by comparing the patients' hormonal responses to a 0.25-mg intravenous bolus dose of alpha 1-24-ACTH with those of 26 age-matched normal women. RESULTS: Twenty women (12 percent) had 3 beta-hydroxy-delta 5-steroid dehydrogenase deficiency, 18 (10 percent) 21-hydroxylase deficiency (14 homozygous), and 14 (8 percent) 11 beta-hydroxylase deficiency. All the homozygous women with 21-hydroxylase deficiency also had evidence of a partial deficiency in 11 beta-hydroxylase activity. Similarly, most of the women with 11 beta-hydroxylase deficiency also had evidence of a deficiency in 3 beta-hydroxy-delta 5-steroid dehydrogenase. Among the 118 women with no adrenal biosynthetic defect, 38 had high plasma androgen concentrations, and 80 had normal concentrations. CONCLUSIONS: About one third of Israeli Jewish women with hirsutism, menstrual disorders, or unexplained infertility had nonclassic congenital adrenal hyperplasia. Secondary adrenal biosynthetic defects were frequent in these women and were probably caused by intra-adrenal androgen excess rather than by dual inherited enzymatic deficiencies.

Prolongation of the latent period in patients with premature rupture of the membranes by avoiding digital examination.

Fifty three women with PROM between 26 and 34 weeks of gestation were examined. Twenty five women (group A) underwent one digital examination for cervical assessment while in 28 women (group B) the cervix was evaluated by speculum. No pelvic examinations were performed throughout the latent period. The latent period increased from 3.1 days in group A to 9.5 days in group B (P less than 0.005). Chorioamnionitis developed in 24% in group A and in 18% in group B (N.S.).

Sinusoidal fetal heart rate pattern due to massive feto-maternal transfusion.

A 30-year-old woman presented with mild abdominal discomfort and decreased fetal movements in the 34th week of her third pregnancy. Fetal monitoring revealed a sinusoidal heart rate pattern, and abdominal delivery was promptly performed, with the newborn having a hematocrit of 7% due to massive fetomaternal transfusion. Fetal resuscitation was followed by a favorable outcome. The sinusoidal heart rate is discussed, with emphasis on the need for proper and prompt recognition of its significance.

A single continuous suture as a possible alternative to the interrupted suture for tubal anastomosis.

A simple alternative for microsurgical anastomosis of the fallopian tube is presented. The anastomosis is composed of a single continuous suture (8-0 nylon) extending through the serosa and muscularis, avoiding the mucosa. Experimentally this technique was performed on the uterine horns of 30 female rats and compared with the conventional interrupted suture technique on 30 additional female rats. Patency was established histologically in 100% of operated horns in both groups, with an average nidation index of 0.7 in the study group as compared with 0.6 in the conventional technique group. The results indicate that this simple method of anastomosis, which reduces operative time significantly, does not affect patency or nidation index in this model as compared with the conventional interrupted suture technique. It may, therefore, be a suitable procedure for anastomosis of equal-sized segments of the fallopian tubes, especially in cases of reversal of sterilization.

Successful treatment of a viable cervical pregnancy with methotrexate.

Cervical pregnancies usually result in early spontaneous abortion, and most forms of conservative treatment are not recommended beyond 8 weeks' gestation. We present a case of a 9-week viable cervical pregnancy that is successfully managed with methotrexate.

In-vitro steroid production by human granulosa lutein cells in long-term cultures.

delta 4 and delta 5 pathway steroidogenesis by human granulosa lutein cells (GLC) in long-term cultures (6-8 days) was investigated under basal (10% serum + medium + GLC) and stimulated (human chorionic gonadotropins (hCG), 100 mIU/ml) conditions. In the delta 4 pathway, 17-hydroxyprogesterone (17-OHP) secretion increased from 160-fold at 48 hours of culture to 360-fold at 144 hours under basal conditions, when compared with the respective controls (concentrations in the 10% serum added to the medium) (p less than 0.005). HCG further augmented 17-OHP production significantly at 96, 144 and 192 hours of culture. Progesterone (P) secretion behaved similarly, and increased from 150-fold at 48 hours to 560-fold at 96 hours when compared with controls, being further stimulated by hCG. In contrast, androstenedione (A) secretion throughout the entire culture period increased only slightly (3-5-fold) under both basal and stimulated conditions, when compared with the respective controls. In the delta 5 pathway, the secretory pattern of 17-hydroxypregnenolone (17-OHPregn) and dehydroepiandrosterone (DHEA) was similar to that observed with A, and both steroids increased only slightly under basal and stimulated conditions, when compared with their respective controls. In conclusion, 17-OHP and P are secreted in very significant amounts during the entire culture period while 17-OHPregn, DHEA and A are secreted in extremely small amounts. These results demonstrate that the delta 5 pathway is inactive in long-term human GLC cultures while the delta 4 pathway is active in certain portions only.(ABSTRACT TRUNCATED AT 250 WORDS)

Radiologic evidence of a nuchal arm in the breech-presenting fetus at the onset of labor: an indication for abdominal delivery.

The occurrence of a nuchal arm during vaginal breech delivery is a potentially traumatic event associated with high perinatal morbidity and mortality. This problem usually cannot be anticipated and must be overcome immediately on diagnosis during the second stage of labor. The results of a retrospective analysis of radiologic studies of 115 cases of term singleton breech deliveries are presented here. A nuchal arm in the first stage of labor was diagnosed in five cases, an incidence of 4.35%. Of four vaginal breech deliveries, one case resulted in severe handicapping neonatal trauma. We suggest that radiologic diagnosis of a nuchal arm in the first stage of labor should indicate abdominal delivery.

Peritonitis and empyema following the use of dextran in tubal operations.

Two patients developed severe bacterial sepsis with peritonitis and pleural empyema following tubal surgery. Intraperitoneal low-molecular dextran was used in both patients and hydrocortisone was administered perioperatively. The use of dextran in tubal surgery probably increases the risk of severe postoperative infection and should be avoided in susceptible patients. Prophylactic antibiotics may be indicated when dextran is administered.

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.

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 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.

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.