[Assisted reproductive technologies reported in the National Registry of Israel 1995-1996].

National registration of the results of assisted reproductive technology (ART) is maintained by many countries. The Israel Committee for Registry of ART asked 19 in-vitro fertilization (IVF) units in 1995 and 20 in 1996 to report on their activities and results. Data were collected by questionnaires and analyzed by computer. The most common ovarian stimulation was the combination of GnRH agonist and gonadotropins. There were 10.89 treatment cycles in 1995, of which 45% were with intracytoplasmic sperm injection (ICSI). In 1996, of 12.72 cycles, 54% were with the ICSI procedure. Embryos were transferred into the uterine cavity in 90% of the conventional IVF cycles and in 95% of the ICSI cycles. The overall pregnancy rate was 22% per embryo transfer in the conventional IVF and ICSI cycles. The delivery rate was 13.7% and 15.4% per embryo transfer in the conventional IVF and ICSI cycles, respectively. The rates for abortion and tubal pregnancy were 24% and 1.3%, respectively. These results are better than in previous years and are comparable with results in some western European countries. Efforts are being made to convert the registry into a real-time computerized system.

Estrogen, progesterone and testosterone receptors in human fetal cartilaginous tissue: immunohistochemical studies.

Computerized image analysis was used to study the distribution in cartilage of receptors to estrogen, progesterone, and testosterone during human fetal development. We have examined three histologically distinct cell groups (hypertrophic, proliferating, and reserve zones) in long bones, vertebrae, and trachea from 19 fetuses. Comparisons were made across gender and gestational age. Contrasting with controls, we examined the density of receptors, the size of the nuclear area in which the receptors were detected, the number of hormone receptor-bearing cells, and the total receptor quantity per sample. We found that estrogen, progesterone, and testosterone receptors were detected in the nuclei of all cell types, in both female and male embryonic cartilaginous tissue. Gender differences were small and inconsistent. Changes associated with gestational age depicted a pattern of hormone receptor manifestation, shifting from the immature cell types to more differentiated cells. This was evident from the receptor densities and from the cellular area in which receptors were sighted. These dynamics are accompanied by a general increase in receptor content per sample, brought about by the concomitant increase in receptor containing area size and cell number. The increase in receptor levels seems to reflect the maturation and growth of the fetal skeleton.

Reproductive outcome following hysteroscopic adhesiolysis in Asherman's syndrome.

OBJECTIVE: To determine whether hysteroscopic adhesiolysis improves reproductive outcome in women with Asherman's syndrome and pregnancy failure. SUBJECTS: Ninety consecutive women who had undergone hysteroscopic adhesiolysis of intrauterine adhesions during a 5-year period. Only women in whom at least two previous pregnancies had ended with either a spontaneous abortion or a premature delivery accompanied by fetal or neonatal mortality and a hysteroscopic diagnosis of intrauterine adhesions were enrolled. RESULTS: Whereas pregnancy outcome prior to the operation was 18.3% term deliveries, 3.3% premature deliveries, 62.4% first-trimester abortions, and 16.0% late abortions, after hysteroscopic adhesiolysis pregnancy outcome was 68.6% term deliveries, 9.3% premature deliveries, 17.4% first-trimester abortions, and 4.7% late abortions. In women with two previous unsuccessful pregnancies, the operative success rate measured by delivering a healthy newborn improved from 18.3% preoperatively to 64% postoperatively. In women with three or more unsuccessful pregnancies the success rate improved from 18.3% to 75%. Successful outcome of adhesiolysis was observed in 61.9% of mild (stage I) and in 70.6% of moderate to severe cases (stages II and III) of intrauterine adhesions. CONCLUSION: Hysteroscopic adhesiolysis in women with Asherman's syndrome and poor reproductive performance contributes significantly to a successful reproductive outcome.

Recombinant technique and gonadotropins production: new era in reproductive medicine.

OBJECTIVE: To review current knowledge regarding recombinant DNA technology and its safety and efficacy in relation to recombinant gonadotropin production. DATA IDENTIFICATION AND SELECTION: Studies that relate specifically to recombinant DNA technology, method of laboratory production, and the clinical aspects of using recombinant gonadotropins were identified through literature and Medline searches. RESULTS: Recent developments in recombinant DNA technology have resulted in a rapidly expanding range of new diagnostic and therapeutic opportunities. This technology paves the way to the identification, isolation, cloning, and production of specific proteins. Recently, recombinant human gonadotropins became available for clinical use. The pharmacokinetics, receptor availability, pharmacodynamics, and safety were studied extensively and the drugs were found to be identical if not superior to urinary gonadotropins that have been used in reproductive medicine for the last 30 years. It is clear today that the use of recombinant human gonadotropins is expected to provide better batch-to-batch consistency, steady supply, and most importantly, a purified compound with high specific activity, which accounts for >99% of the preparation's protein content, allowing SC administration. CONCLUSION: There is no doubt that recombinant gonadotropins produced by genetic engineering technology are here to stay and will represent an important treatment modality in various fertility disturbances.

Induction of labor at 38 to 39 weeks of gestation reduces the incidence of shoulder dystocia in gestational diabetic patients class A2.

The purpose of this study was to test the hypothesis that the incidence of shoulder dystocia could be reduced in insulin-requiring diabetic women by elective induction of labor at 38 to 39 weeks of gestation. A prospective study protocol in which labor was induced at 38 to 39 weeks of gestation in insulin-requiring diabetic women was executed between January 1, 1990, and July 31, 1994 (n = 96). The outcome was compared to the results of a previous protocol (years 1983 to 1989) in which the pregnancies were allowed to progress to spontaneous labor, unless fetal health became compromised (n = 164). The incidence of shoulder dystocia in patients in whom labor was electively induced at 38 to 39 weeks of gestation was 1.4% as compared to 10.2% in patients who delivered beyond 40 weeks' gestation (p < 0.05). No increase in cesarean section rate was demonstrated. We conclude that elective induction of labor is suggested for insulin-requiring diabetic women in order to reduce the incidence of shoulder dystocia.

Expression of Ad4-BP/cytochrome P450 side chain cleavage enzyme and induction of cell death in long-term cultures of human granulosa cells.

Freshly isolated granulosa cells obtained from women undergoing in-vitro fertilization (IVF) become refractory to further gonadotrophin stimulation in culture due to their previous hormonal treatment. However, when precultured for 7 days in gonadotrophin-free medium they regain their response to both human chorionic gonadotrophin (HCG) and follicle stimulating hormone (FSH) with a 10-fold and 5-fold increase in progesterone production respectively, within an additional 7 days of culture. Forskolin, a direct activator of adenylate cyclase, increased progesterone levels 12-fold compared with non-stimulated cultures. Oestradiol formation was also significantly elevated (P < 0.005) following 48 h stimulation with luteinizing hormone (LH), FSH or forskolin. Intracellular cAMP levels rose 1.5-fold, 10-fold and 15-fold after 1 h of FSH, HCG or forskolin treatment. Expression of both cytochrome P450 side chain cleavage enzyme (SCC) and the steroidogenic transcription factor SF1/Ad4BP could be demonstrated by Western blotting. However, elevation of P450 SCC alone was evident following FSH and HCG stimulation. In the presence of serum, the ultrastructure of these cultured cells displayed numerous lipid droplets and well-developed mitochondria, characteristic of highly steroidogenic cells. The proportion of apoptotic nuclei in these cultures was < 30%. Removal of the serum increased apoptotic incidence to 40%, whereas addition of FSH prevented cell death significantly (P < 0.01). HCG and forskolin increased apoptosis to approximately 50%, while treatment with 8Br-cAMP led to 80% cell death. Our data suggest that, after prolonged culture, human granulosa cells can regain cAMP and steroidogenic response to gonadotrophin stimulation. Moreover, our experiments indicate that apoptosis and steroidogenesis can coexist in the same cell population while the interrelationship between these processes can be determined by the intracellular levels of cAMP.

Sonographically guided aspiration of ovarian cyst with simple appearance.

The objective of this study was to evaluate the role of sonographically guided aspiration of simple ovarian cysts. During the period from 1985 through 1992, 107 ultrasonographically guided punctures of apparently simple ovarian cysts were performed. The group included 76 premenopausal and 31 postmenopausal women who were followed for 1 to 6 years (mean, 2.7 years) after initial cyst puncture. In 42 cases, cyst aspiration constituted the definitive therapy. In 65 cases the cyst recurred and in this group, 38 women (with complete recurrence) were operated on whereas 27 women with a cyst less than 5 cm (incomplete recurrence) were allocated to a follow-up group. Overall, in 69 cases (65%) surgery was avoided. No major complications were encountered. In our experience, aspiration of simple ovarian cysts is a suitable alternative in the management of this problem. Close follow-up is necessary to detect recurrence and perform surgical intervention when indicated.

Uriscreen, a rapid enzymatic urine screening test: useful predictor of significant bacteriuria in pregnancy.

OBJECTIVE: To establish the reliability of a new rapid enzymatic screening test, the Uriscreen, in the detection of significant bacteriuria in pregnancy. METHODS: During a 6-month period, from July 1 to December 30, 1993, 313 consecutive pregnant patients were evaluated. Randomly voided, midstream, clean-catch urine specimens were used. Each sample was tested by routine laboratory culture and four rapid screening tests: the nitrite and leukocyte esterase dipstick, microscopic examination for pyuria, and the Uriscreen test. Results of the four rapid tests were compared with those of the urine culture. RESULTS: Twenty-four women (7.6%) had urine culture results indicating significant bacteriuria. The sensitivity of the nitrite test, the leukocyte esterase test, and a microscopic examination for pyuria was low (37, 52, and 56%, respectively). The Uriscreen test showed very high sensitivity (100%), lower specificity (81%), a high predictive value of negative results (100%), and a low positive predictive value (30%). CONCLUSIONS: The Uriscreen test is a reliable alternative to culture screening of all pregnant patients. A policy of performing a urine culture during pregnancy only on patients with a positive Uriscreen test will save as much as 80% of unnecessary cultures.

Beneficial effect of hysteroscopic metroplasty on the reproductive outcome in a 'T-shaped' uterus.

Eight women (aged 27-43) with reproductive dysfunction who were diagnosed by hysterosalpingogram and hysteroscopy as having a 'T-shaped' uterus were operated on using fiberoptic hysteroscopic guidance; the uterine side walls were incised until a normal uterine cavity was achieved. The women's gynecologic and obstetric records were compared before and after the operation. In all the 8 women the operation was without complications and resulted in a satisfactory uterine cavity. Before the operative procedure, the women had had 10 spontaneous abortions and 1 ectopic pregnancy. The postoperative performance available for 7 of the 8 women showed 4 term pregnancies in 3 women, 1 ectopic pregnancy, and no abortions. Our study suggests that hysteroscopic metroplasty in women with a T-shaped uterus improves the reproductive outcome, mainly in women with repeated abortions. We conclude that women with a T-shaped uterus who want to improve their reproductive function should be encouraged to undergo hysteroscopic metroplasty.

Hyperestrogenemia and presence of estrogen receptors associated with an epithelial ovarian tumor of low malignant potential.

An 80-year-old woman presented with breast congestion, tenderness and pain. Mammography was normal. Circulating estradiol was markedly elevated, while LH and FSH were low. Pelvic examination and imaging revealed an ovarian mass which was extirpated during total abdominal hysterectomy and bilateral salpingo-oophorectomy. Histopathology revealed an ovarian mucinous cystadenocarcinoma of low malignant potential, stage 1. The tumor was positively stained for estrogen receptors. Estradiol levels returned to normal post-operatively, with a corresponding adjustment of LH/FSH. Possible autocrine steroid production is discussed.

The impact of external cephalic version on the rate of vaginal and cesarean breech deliveries: a 3-year cumulative experience.

The authors have reviewed the impact of their practice of external cephalic version (ECV) at term, with respect to success rate, factors associated with successful version and the effect of this protocol on the overall breech and cesarean breech rate. Two hundred and forty-nine parturients identified as having a breech presenting fetus after the 36th gestational week over a 3-year period, after excluding contraindicated cases, were offered a trial of ECV, with the use of ritodrine tocolysis. ECV was effected by one operator, using the minimally effective force necessary. Successful ECV was achieved in 196 attempts (78.7%). No deleterious effects in fetuses or mothers were noted. Of successfully turned fetuses, 78% eventually had a vaginal vertex delivery. Parity, birthweight and amount of amniotic fluid were found to have a significant effect on the success rate of ECV, whereas gestational age at version or placental location were not found to have a significant effect on success rate. Introduction of the ECV protocol effected a significant decrease in breech presentation at term, from 3.9 to 2.4% (P < 0.01), which can be translated into a decrease of 5.5% in the overall cesarean section rate. The authors conclude that ECV is a safe and effective procedure, in properly selected cases. Institution of a screening protocol to identify breech presentation after 36 weeks, and utilizing ECV where possible, may lead to a significant reduction in the breech delivery rate, and may prevent serious infant morbidity.

Adnexal torsion in adolescents: prompt diagnosis and treatment may save the adnexa.

Adnexal torsion, although infrequent, may have a devastating effect on the future reproductive performance of adolescents and young women. However, clear variables predicting a favorable operative outcome have not yet been identified. In this retrospective study the authors analyzed the charts of 72 adolescent girls hospitalized for acute lower abdominal pain. In 13 cases (18%) torsion of the adnexa was found and six of them ended with reproductive compromise expressed by either adnexectomy or salpingectomy. We have found that in the cases of adnexal torsion, the time factor, from admission until final diagnosis and treatment, was the only significant variable affecting the operative results. A shorter time until the operation, resulted in less harm to the reproductive organs involved. Therefore, we conclude that whenever an adnexal torsion is suspected, a quick diagnostic laparoscopy followed by an operative procedure when needed, may contribute to better reproductive performance in the future.

Recurrent spontaneous ovarian hyperstimulation syndrome associated with polycystic ovary syndrome.

Ovarian hyperstimulation syndrome (OHSS) is the most serious potentially life-threatening iatrogenic complication of ovulation induction. Presented here is the first reported case of recurrent severe OHSS which developed spontaneously in a women with polycystic ovary syndrome, diagnosed early in her second pregnancy, and necessitated intensive fluid and colloid therapy.

Menopause is associated with a significant increase in blood monocyte number and a relative decrease in the expression of estrogen receptors in human peripheral monocytes.

PROBLEM: The clinical significance of the differential expression of estrogen receptor (ER) in human monocytes was evaluated. METHOD: Two color flow cytometry analysis was used on peripheral blood samples of young and postmenopausal females and postmenopausal females treated with estrogen replacement therapy. In addition, the monocyte and lymphocyte counts and the blood estrogen levels of each patient were determine. RESULTS: During menopause there is a significant decrease in the percentage of ER positive monocytes, and an increase in blood monocyte number, which declines following estrogen replacement therapy to values of the young. CONCLUSIONS: These findings suggest that estrogen modulates the monocyte numbers and its effects may be mediated through the ER in the monocytes.

The role of sonography in the detection of vaginal foreign bodies in young girls: the bladder indentation sign.

The cases of four young girls with vaginal foreign bodies, successfully diagnosed by ultrasound, are presented. The sonographic signs include varying echogenicity and acoustic shadowing, but always an indentation of the posterior bladder wall was clearly observed. Sonography should be considered as the first step in the evaluation of suspected vaginal foreign bodies in young girls.