Case series of labor induction in twin gestations with an Intrauterine Balloon catheter.

The efficacy and safety of labor induction using an intrauterine balloon catheter in twin pregnancies has been evaluated. During the study period (1992-1997), labor was induced at 36-42 weeks in 17 twin gestations. Labor induction was indicated for preeclampsia (n = 10), birth weight discordance (n = 3), suspected fetal distress (n = 2) and postdates (n = 2). Twin A was in vertex presentation in all cases. An intrauterine balloon catheter was inserted transcervically followed by augmentation whenever required. Vaginal delivery was achieved in 15 (88.2%) patients. The mean interval from balloon insertion to delivery was 17.05 h, with 80% deliveries occurring within 24 h of catheter insertion and 80% occurring within 12 h of catheter expulsion. Birth weight was 2,514+/-244 and 2,421+/-367 g for twin A and B, respectively. Oxytocin was required in 4 patients. Postpartum hemorrhage was noted in 1 patient. One patient with no progress of labor and 1 with suspected intrapartum fetal distress required cesarean section. All neonates had a 5-min Apgar score of 10. The data suggest that an intrauterine balloon catheter appears to be safe and effective to induce labor in twin gestations.

Acute changes in endometrial thickness after aspiration of functional ovarian cysts.

OBJECTIVE: To evaluate the influence of aspiration of functional ovarian cysts on endometrial thickness. DESIGN: Prospective study. SETTING: An IVF Unit of an academic medical center. PATIENT(S): Twenty-two patients from our IVF program, in whom administration of a gonadotropin-releasing hormone agonist preparation in the "long protocol" failed to induce pituitary desensitization, as evidenced by a serum E2 concentration of >55 pg/mL and the presence of an ovarian cyst of >20 mm in diameter. INTERVENTION(S): Transvaginal ultrasonographic-guided cyst aspiration was performed, and 2 days later, serum E2 concentration and endometrial thickness were reassessed. MAIN OUTCOME MEASURE(S): The values of serum E2 concentration and endometrial thickness before and after cyst aspiration were compared. RESULT(S): Two days after ovarian cyst aspiration, the serum E2 concentration dropped from a mean (+/-SD) of 203 +/- 93 to 37 +/- 34 pg/mL. The mean (+/-SD) endometrial thickness was 9.6 +/- 2.0 mm before cyst aspiration and decreased to 5.9 +/- 2.4 mm after the procedure. CONCLUSION(S): Within 48 hours after ovarian cyst aspiration, a significant reduction in endometrial thickness occurs concomitant with a sharp decline in serum E2 levels. The phenomenon of acute reduction in endometrial thickness in response to acute estrogen withdrawal has not been described previously. The exact mechanism and endometrial component involved in the "shrinking" process should be further investigated.

Prospective evaluation of endometrial thickness as a predictor of pituitary down-regulation after gonadotropin-releasing hormone analogue administration in an in vitro fertilization program.

OBJECTIVE: To determine whether pituitary down-regulation after gonadotropin-releasing hormone analogue (GnRH-a) administration can be accurately predicted by transvaginal ultrasonographic measurement of endometrial thickness. DESIGN: Prospective study. SETTING: An IVF unit of an academic medical center. PATIENT(S): One hundred eighty-one patients undergoing 265 IVF-ET treatment cycles using GnRH-a in the long protocol. MAIN OUTCOME MEASURE(S): Serum concentrations of E2 were determined, and endometrial thickness was measured by transvaginal sonography. The accuracy of endometrial thickness for predicting pituitary down-regulation was calculated. RESULT(S): Pituitary down-regulation, defined as a serum E2 concentration of < or = 55 pg/mL, was achieved in 77% (204 of 265) of the cycles. An endometrial thickness of < or = 6 mm was found in 92.2% (188 of 204) of cycles in which down-regulation was achieved. An estradiol level of < or = 55 pg/mL was present in 95.9% (188 of 196) of cycles with endometrial thickness of < or = 6 mm. CONCLUSION(S): A state of relative hypoestrogenism after GnRH-a administration, indicative of pituitary down-regulation, can be predicted with a high degree of accuracy by ultrasonographic measurement of endometrial thickness. Thus, routine testing for serum E2 concentration may be safely omitted. This may allow further simplification of IVF protocols and increase both cost-effectiveness and patients' convenience.

The threat of type IV Ehlers-Danlos syndrome on maternal well-being during pregnancy: early delivery may make the difference.

We describe a successful management of a pregnancy in a woman with type IV Ehlers-Danlos syndrome that included an elective caesarean section and tubal ligation at 32 weeks' gestation. We identified 26 women (including ours) who had been pregnant with well-documented characteristics of type IV Ehlers-Danlos syndrome in the literature. These 26 women had 50 pregnancies. Ten (38.5%) died during pregnancy or in the immediate postpartum period. The maternal mortality rate per pregnancy in type IV Ehlers-Danlos syndrome was therefore calculated to be 20.0%. Pregnancy, continuing pregnancy, or subsequent pregnancy are all contraindicated in patients with type IV Ehlers-Danlos syndrome. Termination of pregnancy before 16 weeks' gestation should be strongly advised. If the patient proceeds with pregnancy, restriction of physical activity at the beginning of third trimester, frequent evaluation of the patient, and an elective caesarean delivery at 32 weeks' gestation after an appropriate antenatal steroid therapy should be advised.

Sodium kinetics of Na,K-ATPase alpha isoforms in intact transfected HeLa cells.

By participating in the regulation of ion and voltage gradients, the Na-K pump (i.e., Na,K-ATPase) influences many aspects of cellular physiology. Of the four alpha isoforms of the pump, alpha1 is ubiquitous, alpha2 is predominant in skeletal muscle, and alpha3 is found in neurons and the cardiac conduction system. To determine whether the isoforms have different intracellular Na+ affinities, we used the Na+-sensitive dye sodium-binding benzofuran isophthalate (SBFI) to measure pump-mediated Na+ efflux as a function of [Na+]i in human HeLa cells stably transfected with rat Na-K pump isoforms. We Na+-loaded the cells, and then monitored the time course of the decrease in [Na+]i after removing external Na+. All transfected rat alpha subunits were highly ouabain resistant: the alpha1 isoform is naturally resistant, whereas the alpha2 and alpha3 isoforms had been mutagenized to render them resistant. Thus, the Na+ efflux mediated by endogenous and transfected pumps could be separated by studying the cells at low (1 microM) and high (4 mM) ouabain concentrations. We found that the apparent Km for Na+ efflux attributable to the native human alpha1 isoform was 12 mM, which was similar to the Km of rat alpha1. The alpha2 and alpha3 isoforms had apparent Km's of 22 and 33 mM, respectively. The cells expressing alpha3 had a high resting [Na+]i. The maximal activity of native alpha1 in the alpha3-transfected cells was only approximately 56% of native alpha1 activity in untransfected HeLa cells, suggesting that transfection with alpha3 led to a compensatory decrease in endogenous alpha1 pumps. We conclude that the apparent Km(Na+) for rat Na-K pump isoforms increases in the sequence alpha1 < alpha2 < alpha3. The alpha3 isoform may be suited for handling large Na+ loads in electrically active cells.

Congenital heart defects: natural course and in utero development.

BACKGROUND: Most congenital heart defects (CHDs) are diagnosed on targeted prenatal transvaginal (TVS) or transabdominal (TAS) ultrasonography during the early second trimester or at midgestation. Nevertheless, delayed diagnosis in some cardiac malformations still remains despite detailed echocardiographic examination. The present study was conducted to evaluate the evolution of fetal cardiac anomalies and assess their development in utero. METHODS AND RESULTS: We retrospectively reviewed 22,050 pregnant women who were divided into two groups: 6924 who had initial TVSs at 13 to 16 weeks' gestation, followed by TASs at 20 to 22 weeks, and 15,126 who had initial TASs at 20 to 22 weeks. Both groups were subsequently examined in their third trimester. All newborns were examined by certified pediatricians. CHD was diagnosed in 168 babies: 66 in group A and 102 in group B. In group A, 42 malformations (64%) were detected at the first TVS examination, and 11 (17%) were found during the subsequent TAS. Three additional anomalies (4%) were found during the third trimester, and 10 malformations (15%) were detected postnatally. In group B, 80 malformations (78%) were detected in the initial examination at midtrimester, and an additional 7 (7%) were found in the third trimester, whereas 15 (15%) were diagnosed postnatally. The 10 anomalies (group A, n=3; group B, n=7) that were detected only during the third trimester comprised aortic stenosis (n=2), cardiac rhabdomyoma (n=2), subaortic stenosis (n=1), tetralogy of Fallot (n= 1), aortic coarctation (n=1), sealed foramen ovale (n=1), ventricular septal defects (n=1), and hypertrophic cardiomyopathy (n=1). CONCLUSIONS: Although most fetal cardiac anomalies are detectable early in gestation, some may evolve in utero at different stages of pregnancy.

Decay constant of Doppler flow waveform as a possible indicator of ovarian malignancy.

The objectives of this study were to analyze the decay constant (tau) of the Doppler flow waveform in ovarian tumors; to determine if differences in this constant can discriminate between malignant and benign ovarian tumors; and to compare the decay constant to the known resistive index (RI), in order to determine its potential prognostic application. Patients with ovarian masses (46) were evaluated in a retrospective study; 13 had malignant tumors, 7 showed tumors with low malignant potential (LMP), 11 had benign masses, 4 had secondary ovarian metastases and 11 had functional ovarian masses. Doppler flow waves measured in the ovary before operation were analyzed from archival videotapes. The RI was calculated preoperatively, and the decay constant of the flow waveform was analyzed retrospectively. We approximated the decaying portion of the flow waveform from the systolic peak to the diastolic level to an exponential curve. Then, the decay constant associated with the flow signal was compared for different types of ovarian pathology. Ovaries with malignancies showed significantly higher mean values for the decay constant (89.7; 95% confidence interval 60.0-119.3) than those with benign tumors (41.8; 25.7-57.9) (p < 0.007), where tau is provided in pixels (in this study each pixel equals approximately 11.4 ms). The mean RI value for malignant tumors was 0.44 +/- 0.12 whereas, in benign tumors, it was 0.622 +/- 0.11. For the benign tumors, both tau and RI did not differ significantly from the measured indices in LMP tumors, metastases and functional ovarian findings. In addition, when the cutoff value of tau was set at 48, 92.3% of all malignancies were identifiable using only tau. This preliminary study indicates that the decay constant of the Doppler flow waveform is able to discriminate between malignant and benign masses and may, thus, provide substantial assistance as an additional parameter in the diagnosis of malignant ovarian tumors in postmenopausal patients.

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.

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.

Is intertwin birth weight discordance predictable?

OBJECTIVE: To compare the efficacies of intertwin difference in abdominal circumferences (ACs) and estimated fetal weight (EFWs) to predict birth weight discordance in twin gestations. METHODS: Ninety pairs of twins with sonographic measurements of AC and femur length, performed within 2 weeks before delivery, were included in the study. The EFW was calculated (Hadlock's formula). We used Bayes' theorem and the Mantel-Haenszel chi 2 test to calculate and compare the rates of false-positive and false-negative prediction of the cutoff values of 15, 20, and 25% intertwin birth weight discordance by the intertwin EFW difference and an intertwin AC difference of > or = 18 mm. RESULTS: There were no significant difference between the two methods to predict birth weight discordance at 15-25% discordance (p = 0.254, OR = 0.33, 95% CI = 1.45-0.24) and at > 25% discordance (p = 0.112, OR 0.18, 95% CI = 0.03-1.34). CONCLUSIONS: Both the intertwin AC difference (> or = 18 mm) and intertwin EFW difference have similar negative predictive values and the same efficacy to exclude discordant growth. Because of the relatively low positive predictive values, birth weight discordance cannot be accurately predicted by either method.

The intrauterine ponderal index in relation to birth weight discordance in twin gestations.

OBJECTIVE: To establish the relationship between the fetal ponderal index and birth weight discordance in twins. METHOD: The fetal ponderal index (estimated fetal weight divided by femur length3) was calculated in 86 pairs of twins delivered within 2 weeks of the last sonography and analyzed in relation to birth weight discordance. RESULTS: A weak but significant correlation between fetal ponderal index and birth weight (r = 0.26, P < 0.0007) but no correlation with gestational age (r = 0.035, P = 0.65) were found. Members of concordant pairs (< 15% birth weight difference) had a significantly higher fetal ponderal index compared with members of mildly (15-25%) discordant pairs (P < 0.02), but not as compared with members of severely discordant (> 25%) pairs. CONCLUSION: The characteristics of the fetal ponderal index in twins are similar to those in singletons. Fetal size seems to be diminished in severe but not in mild discordants. However, in its present form, the fetal ponderal index is a poor predictor of discordant growth and therefore should be employed cautiously in twin gestations.

Prenatal diagnosis of twin zygosity by DNA 'fingerprint' analysis.

A twin pregnancy with one hydrocephalic fetus with oligohydramnios is presented. Sonographic evaluation could not exclude monochorionicity. Before considering selective feticide, blood samples from both fetuses were examined for DNA 'fingerprint' analysis. The different banding patterns of the blood samples established dizygosity. This procedure is suggested in cases where sonography fails to determine chorionicity.

Chemotaxis and chemokinesis of human spermatozoa to follicular factors.

Human spermatozoa accumulate in vitro in diluted follicular fluids obtained from follicles from which the eggs have been fertilized. Using capillary assays under a variety of experimental conditions (ascending or descending gradients of follicular fluid, or no gradient at all) and microscopic assays in which individual spermatozoa could be followed, we found that the sperm accumulation in follicular fluid was the result of both sperm chemotaxis and chemokinesis and eventually hyperactivation-like motility. We determined the optimal conditions for sperm accumulation, which involved sperm preincubation (possibly to induce sperm capacitation) and proper dilution of follicular fluid. In all the assays, the net accumulation was low, probably reflecting the chemotactic responsiveness of only a small fraction of the sperm population at any given time. We partially fractionated follicular fluid in a Centricon microconcentrator (Amicon, Danvers, MA) and by acetone precipitation, and found that at least one of the chemotactic factors is a small (< 10-kDa) molecule that is probably nonhydrophobic. This is the first time that sperm chemotaxis and chemokinesis in response to a follicular factor(s) in mammals has been established and has been distinguished from other processes that might cause sperm accumulation. The physiological significance of these findings is discussed.

Sequential acquisition of chemotactic responsiveness by human spermatozoa.

Recent studies have indicated that human spermatozoa respond to follicular fluid by attraction to chemotactic factor(s) in the fluid, accompanied by enhancement of motility and ultimately hyperactivation. In this study, we quantified the sperm response. We exposed spermatozoa to a gradient of a chemotactically active fraction of follicular fluid (denoted as "the attractant") and separated the spermatozoa that accumulated in the attractant and those that did not. We thus obtained two subpopulations: one enriched with chemotactically responsive spermatozoa, and one deficient in such spermatozoa. The fraction of the responsive spermatozoa out of the total sperm population was 2-12% at any measured time point. With time, the responsive spermatozoa lost their ability to be attracted, while such activity was gradually acquired by the subpopulation originally deficient in responsive spermatozoa. These results indicate that the identity of responsive spermatozoa is continuously changing. If the in vitro results are representative of the physiological conditions in vivo, they imply that the role of sperm chemotaxis combined with enhanced motility may be to select capacitated spermatozoa and bring them to the egg. Such a mechanism may, over an extended period of time, increase the prospect that an egg will meet capacitated spermatozoa as soon as it ovulates.

Atrial natriuretic peptide attracts human spermatozoa in vitro.

Here we report that atrial natriuretic peptide (ANP), a known activator of particulate guanylate cyclase, induces attraction and swimming speed enhancement of human spermatozoa in vitro. Using capillary assays under a variety of experimental conditions (ascending or descending gradients of ANP, or no gradient at all) and microscopic assays in which individual spermatozoa could be followed, we found that spermatozoa followed the gradient of ANP and accumulated in it. Speed enhancement was detected in the presence of ANP without a gradient. These observations suggest either that an ANP-like substance is the physiological attractant for human spermatozoa, or, more likely, that ANP directly affects guanylate cyclase in a manner similar to that caused by the physiological attractant.

Management of chloroquine-resistant Plasmodium falciparum malaria in a pregnant Ethiopian immigrant--a case report.

Plasmodium falciparum malaria is infrequently recognized in Israel as a cause of infection during pregnancy. We expect that with increasing frequency physicians in Israel will confront patients with malaria. Special concern should be given to malaria in pregnancy because of its serious complications. Thus, prompt diagnosis and treatment are essential. While chloroquine is safe for use in pregnancy, drug resistance is common, especially with Plasmodium falciparum. There is concern about the safety of other antimalarial agents during pregnancy. We recently observed a case of chloroquine-resistant Plasmodium falciparum malaria during pregnancy in a new immigrant primigravida from Ethiopia. Malaria in patients from endemic regions is less severe than in nonimmune hosts. Therefore, we elected to follow the patient's parasitemia periodically without additional antimalarial treatment until after delivery.