Biomedical subjects
Publications and source records attributed to Z Ben-Rafael.
A bladder neck obstruction was suspected after ultrasound investigation at 16 weeks' gestation. Evaluation of protein content in the amniotic fluid, fetal ascites, and fluid from the overdistended bladder supported the diagnosis. Bladder outflow obstruction in the second trimester of pregnancy was not associated with raised alphafetoprotein levels in the amniotic fluid and maternal serum.
This is a retrospective study on 352 infertile women who were treated with HMG-hCG (Human Menopausal Gonadotropin/human Chorionic Gonadotropin) between 1962 and 1977. The purpose of this study was to search for hyperprolactinemia and prolactinomas in these women. Hyperprolactinemia was found in 75 women (21%). The prevalence of hyperprolactinemia increases with age. Asymptomatic pituitary tumors were found in 29 of 31 women evaluated (94%). Three women had macroadenomas and 26 had microadenomas. We were not able to demonstrate that the HMG-hCG treatment and the ensuing pregnancy had any long-term ill effects on the size of the tumor. These findings suggest that prolactinomas were slow growing. An active search for these tumors must be made in women treated for infertility in the past.
A retrospective study on the success of induction of ovulation with human menopausal gonadotropin and human chorionic gonadotropin (hMG/hCG) in 267 women was performed. Galactorrheic women had a higher pregnancy rate (55%) than nongalactorrheic women (22%). Galactorrhea was a far better indicator of the success of the treatment than hyperprolactinemia at present. The results obtained may suggest that in "bromocriptine failure" it is not mandatory to lower prolactin levels prior to induction of ovulation with hMG/hCG, and these women may be treated with menotropins alone.
The significance of the location of intrauterine contraceptive device in relation to the gestational sac on pregnancy outcome was studied in 13 pregnant women after extraction of the device. Of the seven women (group 1) who had the intrauterine contraceptive device removed after initial localization by sonography, two (28.5%) miscarried. In both cases the device was located cephalad or lateral to the gestational sac. In six women (group 2) continuous sonographic scanning was undertaken to visualize the extraction procedure. Traction on an intrauterine device located laterally (two cases) or cephalad (one case) to the gestational sac was followed by distortion of the sac configuration. Gentle intermittent traction on the contraceptive device resulted in successful extraction procedure. These preliminary observations suggest that pregnancies with an intrauterine contraceptive device located laterally or cephalad to the gestational sac are at greater risk during extraction of the device. Sonographic monitoring of the extraction procedure during pregnancy may minimize the hazards of intrauterine contraceptive device failure.
The fertility in previously sterile women who conceived at least once following hMG/hCG-induced ovulation is investigated. The study comprises 141 women. The cumulative spontaneous pregnancy rate (CSPR) was calculated using life table analysis and was found to be 30.4% after 5 years. The CSPR for subsequent pregnancies reached 91.3% after 5 years. This figure is similar to that of normal parous women, although the study group (previously infertile women) requires a larger exposure period to attain the figure. The spontaneous abortion rate in the hMG/hCG-induced pregnancies was 29%; whereas in subsequent spontaneous pregnancies this rate was 8.8%. This difference in rate was found to be statistically significant, and the possible reasons are discussed.
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A unique case of triplet pregnancy in a woman with uterus didelphys is described, with fetuses A and B in the right uterine horn and fetus C in the left horn. Missed abortion of fetus A was diagnosed in the 22nd week of gestation by real-time ultrasonography, but only in the 27th week of gestation did the right uterine horn contract, resulting in expulsion of fetus A. Fetus B was delivered by cesarean section 2 hours later. Fetus C remained in the left uterine horn until the 37th week of gestation, when a viable 2490-g female infant was delivered by cesarean section. Triplet pregnancy occurs with sufficient frequency to be unremarkable; however, triplet pregnancy in a patient with uterus didelphys and with 72 days' lapse between the delivery of the first 2 fetuses and delivery of the third is a rare occurrence.
Natural progesterone, which is devoid of androgenic activity, is widely used in assisted reproduction for luteal and pregnancy support. The vaginal route has become the most established way to deliver natural progesterone because it is easily administered, avoids liver first-pass metabolism, and has no systemic side-effects. The vagina has a large potential for absorption, and through the 'uterine first-pass effect' vaginal administration results in higher uterine progesterone concentrations. We have investigated the pharmacokinetics of natural progesterone in the form of a vaginal tablet. A single dose of 100 mg resulted in a mean C(max) of 31.53 +/- 9.15 nmol/l with a T(max) of 6.92 +/- 3.12 h. The terminal half-life was 16.39 +/- 5.25 h. The pharmacokinetic data are discussed in relation to dose, age, and estrogen priming. Single-dose pharmacokinetics of 100 mg of progesterone vaginal tablets and gelatin capsules were evaluated over 24 h. Results indicated a similar mean T(max) of 6.92 +/- 3.12 and 6.23 +/- 6.57 h, respectively. However, a significantly higher C(max) was achieved by the vaginal tablet (31.95 +/- 9.15 and 23.85 +/- 9.57 nmol/l, respectively, P < 0.05). Continuous use of vaginal progesterone did not influence the hormonal, liver, or lipid profiles evaluated. There was no case of endometrial hyperplasia. The vaginal tablet was found to be well-tolerated, safe, and easily administered. In conclusion, progesterone-containing vaginal tablets have good pharmacokinetic properties and should be used for progesterone supplementation in IVF.
OBJECTIVE: To relay the current knowledge on the interaction between cytokines, growth factors, and ovarian hyperstimulation syndrome (OHSS) and to propose a new insight into the pathogenesis of OHSS. METHODS: Major studies that have reported on the association between cytokines, growth factors, and OHSS were identified through MEDLINE searches and through the published literature. RESULTS: Several cytokines, as well as vascular endothelial growth factor, were found to have a role, either in the prediction or pathogenesis of OHSS. Moreover, intravenous immunoglobulin, which has an anticytokine nature and inhibits the secretion of various cytokines, was shown to prevent the development of OHSS. CONCLUSION: Current knowledge indicates a close interaction between cytokines, growth factors, and OHSS. Further understanding of these interactions may lead to different understanding of ovarian hyperstimulation syndrome.
The preconception and intrapregnancy parameters that are relevant to outcome in women with insulin dependent diabetes mellitus (IDDM) and diabetic nephropathy remain controversial. We analyzed the types and frequencies of maternal and neonatal complications in 24 IDDM patients with diabetic nephropathy (24 pregnancies), all with preserved to mildly impaired renal function. All patients received treatment with captopril for at least six months prior to planned pregnancy and were maintained under strict glycemic control from at least three months before pregnancy to delivery. A successful pregnancy outcome (live, healthy infant without severe handicaps two years after delivery) was observed in 87.5% of the patients. Preexisting hypertension was the only parameter found to be significantly predictive of an unsuccessful outcome (p = 0.0004). We conclude that in patients with IDDM complicated by diabetic nephropathy, pre-pregnancy captopril treatment combined with strict glycemic control offers a prolonged protective effect against possible renal deterioration and probably improves pregnancy outcome.
The aim of this study was to investigate the one-year developmental outcome of offspring of mothers with pregestational diabetes mellitus (PGDM). We prospectively evaluated 31 women with PGDM (21 with type 1 DM and 10 with type 2 DM) and 41 nondiabetic controls during pregnancy and for one year follow-up. Data showed that offspring of mothers with PGDM scored lower than controls in all aspects of development--mental, psychomotor, and exploration/orientation. Despite the good metabolic control of the mothers with PGDM, their offpsring showed a less favorable developmental outcome at one year than infants of nondiabetic mothers. MDI score and PDI score were significantly lower in the diabetic group than in the controls (91.04 vs 98.15, p<0.05 and 85.15 vs 95.54, p<0.05, respectively). In addition, the orientation/engagement score was lower in the diabetic group as compared with the nondiabetic group (41.04 vs 45.50, p<0.05). Whereas no significant difference was found between the type 1 and type 2 groups with regard to the MDI score, type 2 infants scored lower on the PDI than infants in the type 1 group (78.1 vs 89.3) but higher on the motor quality score (34.0 vs 31.3). These preliminary findings support the need for ongoing large scale developmental follow-up studies of offspring born to diabetic mothers in order to elucidate whether they have cognitive impairment later in life.
Concurrent intra and extrauterine pregnancies have always been thought to be rare with a mean annual incidence of 1:30.000. The condition has been reported more frequently in the recent literature. If the incidence is increasing it is a serious development as the condition is often undiagnosed. The paper describes 5 patients with the condition presenting between 1976-1981 an incidence of 1:4000 deliveries. In two of these five patients the intrauterine pregnancy was diagnosed first and the ectopic pregnancy was undiagnosed until much later. The presence of intrauterine pregnancy often leads us to ignore the possibility of a concurrent extrauterine pregnancy. Considering that ectopic pregnancy may still cause maternal death, we believe that the condition has to be considered more often. Certain features may suggest the diagnosis. 1) Lack of vaginal bleeding or uterus larger than 9 week size with a proven ectopic pregnancy. 2) Presence of two corpora lutea at laparoscopy. 3) Ultrasound to diagnose an adnexal mass. 4) Failure of serum hCG to return to normal after abortion. The text also discusses the natural history of the condition and the higher incidence expected in the future with the wider use of ovulation inducing agents.
The use of highly sensitive procedures for detecting human chorionic gonadotropin (hCG) has brought about an increasing occurrence of test results that are difficult to interpret. Furthermore, different results on the same serum sample can be obtained by different methods of measurement and, in extreme cases, serum hCG may be positive by one method and negative by the other. These observations are important, since patients may be hospitalized and receive unnecessary treatment as a result of confusing laboratory data. The clinical significance of slightly elevated serum hCG level is reviewed.
OBJECTIVE: To assess the frequency of menarche and menstrual disturbances among women suffering from insulin-dependent diabetes mellitus, and to evaluate their correlation to the onset of diabetes, its duration, and complications. RESEARCH DESIGN AND METHODS: Retrospective analysis of the menstrual regularity and gynecologic and fertility history of 100 women suffering from insulin-dependent diabetes mellitus. These data were compared with information obtained from the patients' medical records regarding the age at onset of diabetes, its management, control, and complications. RESULTS: The average age at menarche was 13.5 years. Delayed menarche tended to appear in girls whose diabetes was diagnosed before the age of menarche, and before the age of 10 years. Menstrual disturbances, such as oligomenorrhea, amenorrhea, and polymenorrhea, occurred in 32% of the women. A significant correlation was found between late menarche and menstrual disturbances. Furthermore, patients with diabetic complications had a higher incidence of menstrual disorders compared with uncomplicated diabetic patients. CONCLUSIONS: It appears that women with insulin-dependent diabetes mellitus who had been diagnosed prior to menarche had a higher probability of delayed menarche, and were at higher risk for development of menstrual disturbances, including amenorrhea with subsequent fertility disorders.
OBJECTIVE: To evaluate the role of fibrin sealant for embryo transfer (ET) and the effect of patient mobilization after ET on pregnancy rates. DESIGN: A prospective, randomized, controlled study. METHODS: Two hundred eleven patients who were admitted to the IVF Unit over a period of 6 months participated in the study. Patients who had three or more embryos were randomly divided into two groups: group 1 (study group), in which ET was performed using fibrin sealant, and group 2, who served as the controls. Ovulation induction was carried out using the long GnRH-a suppression protocol. RESULTS: Comparison of the results regarding the implantation and pregnancy rates and ectopic pregnancy rate revealed a nonsignificant difference between the two groups. However, analysis of the results according to the patients' age revealed a significant increase in pregnancy (P < .05) and implantation (P < .01) rate in elderly patients (aged 39-42) using fibrin sealant for ET as compared with controls. Furthermore, we found that bed rest has no advantage over patient mobilization after ET. CONCLUSION: The use of fibrin sealant for ET is advantageous in elderly women, but has no apparent effect on the success rate or ectopic pregnancy rate in younger patients. Immediate mobilization does not jeopardize the results of IVF-ET.
OBJECTIVE: To determine whether cultured human granulosa cells (GC) produce Interleukin (IL)-2 and whether this GC IL-2 production may be regulated by human chorionic gonadotropin (hCG). MATERIALS AND METHODS: Human GC derived from preovulatory follicles during in vitro fertilization (IVF) cycles were cultured in the absence or presence of hCG. Interleukin-2 was measured in tissue-culture medium by an enzyme-linked immunosorbent assay (ELISA) system. RESULTS: Cultured GCs were demonstrated to produce IL-2 in vitro. Moreover, a positive, but not statistically significant, dose-response effect was demonstrated between culture supernatant IL-2 levels and hCG concentration. CONCLUSIONS: Our data indicate that human GC produce IL-2 and that this production might be regulated by hCG. These results lend credence to the theory that IL-2 might be involved in the events leading to ovarian hyperstimulation syndrome (OHSS).