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Acute exacerbations frequently occur after childbirth in patients with relapsing-remitting multiple sclerosis (MS). The present pilot study was initiated in an attempt to reduce the number of childbirth-associated acute exacerbations in the postpartum period. We treated nine MS patients with a history of 12 childbirth-associated acute exacerbations that had occurred 2-9 weeks after previous deliveries. The patients were administered intravenous immunoglobulin (IVIg) at a dose of 0.4 g/kg per day for 5 consecutive days during the 1st week after childbirth and at 6 and 12 weeks thereafter. None of the treated patients relapsed during the 6-month period after delivery. However, three patients had a remote relapse, two at 8 months and one at 10 months after childbirth, but these probably represented the natural course of disease and were not associated with childbirth. We conclude that IVIg treatment may prevent acute childbirth-associated exacerbations in relapsing-remitting MS patients.

The objective of the study was to explore the natural history and clinical significance of lateral neck cysts during the early second trimester of pregnancy. A survey was conducted of pregnant women at 12-15 weeks' gestation who presented at the ultrasonographic unit between January 1991 and December 1994. During the 4-year period, of the 1500 fetuses scanned, 42 fetuses with lateral neck cysts were detected by high-resolution transvaginal ultrasonography. Twenty-six of the 42 fetuses were seen to have isolated lateral neck cysts, and 16 demonstrated a combination of nuchal thickness of > or = 4 mm and lateral neck cysts. Natural history, fetal karyotype and pregnancy outcome were compared between these two groups. None of the fetuses with isolated neck cysts had an abnormal karyotype, and all cysts resolved spontaneously at 16-20 weeks. No congenital abnormalities were found among the 26 cases. Four chromosomal abnormalities (three trisomy 21 and one monosomy XO) were detected among the 16 fetuses with combined lesions, resulting in termination of pregnancy in all. Among the remaining 12 fetuses, spontaneous resolution of the neck findings occurred between 16 and 20 weeks' gestation. The finding of isolated lateral neck cysts in the early second trimester is not associated with increased risk of aneuploidy. However, the combination with nuchal thickness of > or = 4 mm should prompt genetic counselling and consideration of karyotyping, since this delay in maturation of the cervical jugular lymphatic communication may be associated with chromosomal aberrations.

The objective of this study was to assess the temporal relationships of serum oestradiol and luteinizing hormone (LH) with regard to the feedback mechanism leading to the LH surge. Daily measurements of oestradiol, LH and follicle stimulating hormone were made in 65 women with ovarian failure undergoing an evaluation of endometrial response to oral cycle stimulation. Patients received incremental oral oestradiol valerate for varying durations at the in-vitro fertilization unit of the Sheba Medical Center, Tel Hashomer, Israel. The treatment protocol involved the administration of daily oestradiol valerate, starting with 1 mg/day, followed by a daily increment of 1 mg for a total of 4, 6 and 8 days. After the last day, a daily maintenance dose of 2 mg was continued. Serum oestradiol concentrations correlated with the dose of oral oestradiol valerate. Peak oestradiol concentrations (mean +/- SEM) were 572 +/- 60, 721 +/- 42 and 797 +/- 53 pg/ml for 4, 6 and 8 days of oestradiol valerate administration respectively. Serum LH, after an initial suppression, peaked 2 days after maximal oestradiol valerate dose and 1 day after peak serum oestradiol. The magnitude of the LH peak was proportional to the duration of incremental oestradiol valerate treatment. In conclusion, the LH surge is temporally related to the cessation of serum oestradiol increase. Consequently, the occurrence of this surge can be explained by a simple negative feedback inhibition of pituitary LH release rather than by a dual negative/positive mechanism.

In humans, only a small fraction (2-12%) of a sperm population can respond by chemoattraction to follicular factors. This recent finding led to the hypothesis that chemotaxis provides a mechanism for selective recruitment of functionally mature spermatozoa (i.e., of capacitated spermatozoa, which possess the potential to undergo the acrosome reaction and fertilize the egg). This study aimed to examine this possibility. Capacitated spermatozoa were identified by their ability to undergo the acrosome reaction upon stimulation with phorbol 12-myristate 13-acetate. Under capacitating conditions, only a small portion (2-14%) of the spermatozoa were found to be capacitated. The spermatozoa were then separated according to their chemotactic activity, which resulted in a subpopulation enriched with chemotactically responsive spermatozoa and a subpopulation depleted of such spermatozoa. The level of capacitated spermatozoa in the former was approximately 13-fold higher than that in the latter. The capacitated state was temporary (50 min < life span < 240 min), and it was synchronous with the chemotactic activity. A continuous process of replacement of capacitated/chemotactic spermatozoa within a sperm population was observed. Spermatozoa that had stopped being capacitated did not become capacitated again, which indicates that the capacitated state is acquired only once in a sperm's lifetime. A total sperm population depleted of capacitated spermatozoa stopped being chemotactic. When capacitated spermatozoa reappeared, chemotactic activity was restored. These observations suggest that spermatozoa acquire their chemotactic responsiveness as part of the capacitation process and lose this responsiveness when the capacitated state is terminated. We suggest that the role of sperm chemotaxis in sperm-egg interaction in vivo may indeed be selective recruitment of capacitated spermatozoa for fertilizing the egg.

This study was conducted to estimate intrauterine growth of triplet pregnancies from liveborn birth weights. During the years 1975-92, 109 sets of triplets were born at our hospital. Ten sets were excluded because of either major fetal anomalies or fetal death of one or more of the fetuses. The remaining 99 sets of triplets consisted of 297 newborns that were weighted immediately after birth. The mean birth weight was plotted against gestational week. The estimated intrauterine growth of triplets, in contrast to singletons, exhibited neither an acceleration phase during the third trimester, nor a flattening of the growth curve during the last few weeks of the third trimester. The mean birth weight of triplets was slightly below the 10th centile for singletons at 38 weeks' gestation or later. We conclude that the growth of triplet fetuses as estimated from liveborn birth weights is slower than that of singletons. The diagnosis of intrauterine growth retardation in triplet pregnancies should be based on growth curves to be devised for triplet pregnancies.

The reproductive outcome of women with repeated abortions or infertility was assessed following treatment by operative hysteroscopy for an intrauterine septum or adhesions. A prospective follow-up study (mean +/- SD, 21.1 +/- 10.3 months) of 47 patients with an intrauterine septum (36 suffering from infertility and 11 from recurrent abortions) and 36 patients with intrauterine adhesions (24 complaining of infertility and 12 of recurrent abortions) was performed. The pregnancy rate in infertile women following hysteroscopic resection of an intrauterine septum or adhesions was 53 and 48% respectively. The pregnancy wastage in women with recurrent abortions who underwent hysteroscopic resection of an intrauterine septum or adhesions decreased postoperatively from 87.5 to 44.4% and from 86.5 to 42.8% respectively. Our results suggest that hysteroscopic resection of an intrauterine septum or adhesions may benefit patients suffering from infertility or recurrent pregnancy wastage.

The most common anomalies of the fetal ventral abdominal wall include omphalocele and gastroschisis. Umbilical cord hernia is another abdominal wall defect that is poorly defined and usually mistakenly considered as a small omphalocele. The present report describes the sonographic features and clinical significance of four cases of umbilical cord hernia identified transvaginally in the early second trimester of pregnancy. These cases seemed to present a different entity from that of simple omphalocele. The transvaginal sonographic approach provided a clear image of the midgut protruding into the umbilical cord, precise localization of cord insertion in the region of the umbilical ring. Doppler flow evaluation of the umbilical vessels and their relation to the protruding mass. Serial sonographic observations revealed a stable umbilical cord mass in three fetuses, and an enlarging mass in one. Normal karyotype was determined and no associated malformations were detected prenatally. However, in one case that underwent immediate correction of the hernia after delivery at term, the neonate was subsequently found to have pulmonic stenosis and severe neonatal seizures developed at 4 months of age. In two cases, pregnancy was terminated due to parental request. The fourth fetus was delivered vaginally at term and catastrophic division of the umbilical cord containing a loop of small intestine was avoided only by the diligent observation of the midwife. We suggest that umbilical cord hernia is a distinct anomaly originating at a different stage of embryogenesis, thereby having a unique clinical significance, unlike simple omphalocele. Umbilical cord hernia should therefore be defined and considered as a separate entity.

Most menopausal patients with breast cancer receive tamoxifen therapy. In these patients, TVS may show thickened, irregular cystic endometria. For better visualization of these patients' uterine cavities, we performed transvaginal sonohysterography. During vaginal ultrasonography, sterile saline was introduced by transcervical 8 French Foley catheter into the uterine cavity of 20 women who were referred with tamoxifen-associated cystic thickened endometria. In eight women, transvaginal sonohysterography provided the means to diagnose occult, free-floating endometrial polyps, whereas in 12 women, the fluid contrast augmented the diagnosis of an irregular cystic endometrial-myometrial junction. All 20 patients underwent diagnostic hysteroscopy: eight polyps, none of which were malignant, were confirmed and removed by hysteroscopic resection. Of the remaining 12 patients with an irregular endometrial-myometrial junction, endometrial curettage showed no significant pathologic findings. Transvaginal sonohysterography seems to enhance the differentiation between endometrial polyps that should be resected by operative hysteroscopy and an abnormal endometrial-myometrial junction that may benefit from biopsy sampling only.

In menopausal patients with breast cancer who receive tamoxifen therapy, transvaginal sonography may show an abnormal endometrium. Our objective was to evaluate the effects of prolonged tamoxifen therapy on endometrial blood flow in postmenopausal patients with breast cancer, and to correlate blood flow characteristics with the sonographic appearance of the endometrium and its pathology. Transvaginal color Doppler ultrasound examinations were performed on 45 postmenopausal women (age range 54-70 years) with breast cancer, who had been treated with tamoxifen for 1-3 years. Twenty women (Group 1) had a thick, irregular, cystic endometrium of > or = 5 mm, and 25 (Group 2) showed a thin endometrium of < 5 mm. The blood flow response was assessed by visualization of arterial waveforms in the endometrial and subendometrial regions with a transvaginal color flow imaging system. Resistance indexes (RI) were calculated for analysis and correlated with endometrial appearance and histology. The mean RI in Group 1 was 0.39 +/- 0.10 (range 0.32-0.54), while the mean RI in Group 2 was 0.79 +/- 0.10 (range 0.54-0.90; p < 0.001). On histology, 12 patients in Group 1 showed atrophic endometria confirmed by hysteroscopy, while in the remaining eight, endometrial polyps were found. In Group 2, all patients had scanty, atrophic endometria. Six of the eight patients with endometrial polyps had an RI of < 0.4 and none had malignant changes. These data suggest that tamoxifen therapy in women with postmenopausal breast cancer induces endometrial, morphological and blood flow changes, mimicking endometrial neoplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

A prospective study was carried out on 153 couples with recurrent abortions who desired pregnancy. The object was to determine the incidence of raised luteinizing hormone (LH) levels; to compare the outcome of further pregnancies in habitually aborting women with and without raised circulating LH concentrations; and to assess whether the efficacy of paternal leukocyte immunization is affected in the presence of raised LH concentrations. Of the 153 women with recurrent abortions (> 3) included in this study, 56 (36.6%) had follicular phase serum LH concentrations > 10 mIU/ml. Of the 103 pregnancies that were followed prospectively, 65 (63.1%) resulted in a birth of a live infant. There was no significant relationship between the pregnancy outcome and LH concentrations. Women who underwent immunization with paternal leukocytes had significantly more live births (75.8%) than those who were not immunized (43.6%). However, the live birth rate was lower after paternal leukocyte immunization in the presence of raised LH concentrations or a raised LH/follicle stimulating hormone (FSH) ratio.

The ultrasonographic appearance of fetal lung hyperechogenicity is most commonly associated with congenital bronchopulmonary abnormalities, such as cystic adenomatoid malformation or pulmonary lobar sequestration. Spontaneous disappearance of echogenic lung lesions has rarely been reported, mainly due to in utero resolution of cystic adenomatoid malformation. We describe four fetuses with echogenic lungs detected prenatally, none of them having been proved to have adenomatoid malformation or pulmonary sequestration of the lungs. Color Doppler sonography was used prenatally in all cases to rule out pulmonary sequestration. Three of the four fetuses showed complete resolution of the lung lesions during gestation, with normal neonatal outcome, but in one where the lesion decreased in size, intrauterine demise occurred at 28 weeks' gestation before complete resolution, and pneumonia was found at autopsy. We suggest that fetal lung hyperechogenicity may result from in utero bronchial tree obstruction with retention of mucoid fluid distal to the obstruction. With advancing gestation, in some cases the relative obstruction may be relieved, and the sonographic appearance of the lungs may return to normal. A retention of mucus in the bronchial tree should be added to the differential diagnosis of hyperechogenic lung lesions detected by antenatal ultrasound examination.

The death of one fetus in a twin pregnancy can affect both the mother and the cotwin. Thirty women with twin pregnancies in whom the death of one fetus was diagnosed during the second half of pregnancy and a matched group of 30 women with uncomplicated twin pregnancies were investigated. The mean gestational age at delivery for the study and control groups was 32.0 +/- 5.0 (mean +/- SD) weeks and 32.8 +/- 3.9, respectively. Twelve pregnancies (40%) were monochorionic. In 15 (50%) the diagnosis was made during active labor. The cesarean delivery rate was higher in the study group than in the control group (18 vs. 11, chi 2 = 5.43, P < .02). The mean neonatal weight was similar in both groups (1,586 +/- 725 g vs. 1,543 +/- 691 g). The subgroup of neonates (n = 15) whose cotwins were diagnosed as dead during labor had higher birth weight as compared to the neonates (n = 15) in whom the diagnosis was made prior to delivery and were managed expectantly (1,829 +/- 859 vs. 1,346 +/- 474 g, P < .01). The week of delivery was similar in both subgroups. Neonatal mortality was 30% and 26.6%, while neonatal morbidity was 26.6% and 21.7%, respectively (NS). All the cases of neonatal mortality were in the subgroup of twins in which the diagnosis of in utero death was made before 32 weeks' gestation. The death of one fetus from a twin pregnancy did not significantly jeopardize maternal health, and the neonatal outcome in the remaining twins was primarily a function of gestational age.(ABSTRACT TRUNCATED AT 250 WORDS)

This study was conducted to evaluate endometrial blood flow characteristics in response to estrogen replacement therapy (ERT) and tamoxifen in asymptomatic postmenopausal women, and to correlate the resistance index (RI) with plasma estradiol levels. Transvaginal color Doppler ultrasound examinations were performed in 30 asymptomatic, postmenopausal women who demonstrated thin endometria (< 0.5 cm). Ten healthy women receiving ERT and ten women with breast cancer receiving tamoxifen comprised the study groups. Ten postmenopausal women free of any hormonal treatment comprised the control group. Blood flow response was assessed by visualization of arterial waveforms in the endometrial region. Resistance indices were calculated for analysis and correlated with peripheral blood levels of estradiol. All postmenopausal women treated with tamoxifen or ERT showed continuous forward end-diastolic flow velocities, while the menopausal women without treatment demonstrated partial forward end-diastolic flow. Resistance index values of non-treated women were invariably higher (mean 0.89, range 0.85-0.91) than in those on tamoxifen (mean 0.79, range 0.54-0.90; p < 0.05), while the lowest RI was obtained in women taking ERT (mean 0.66, range 0.54-0.90; p < 0.05). The plasma concentrations of estradiol in women on ERT were found to be significantly higher than those of the tamoxifen and control groups. The observed data suggest that ERT and tamoxifen modify normal postmenopausal endometrial perfusion. Tamoxifen had a weaker estrogenic effect on the endometrial blood flow resistance, and ERT enhanced endometrial blood perfusion through vasodilatation.

A retrospective study of a series of pregnant patients with polycystic ovarian syndrome following in vitro fertilization-embryo transfer was conducted to assess the outcome after ovarian stimulation by different protocols. Forty-one pregnancies were evaluated in patients with polycystic ovarian syndrome who conceived during in vitro fertilization-embryo transfer using human menopausal gonadotropin alone (17 pregnancies), or combined with gonadotropin releasing hormone analog (24 pregnancies). The demographic data of in vitro fertilization-embryo transfer cycles and pregnancy outcome were compared with the use of Student's t-test, the Mann-Whitney U test and Fisher's exact test, where appropriate. Among the pregnancies that were initiated following treatment, the protocol of the combination of the two was not associated with a higher rate of deliveries. The rate of first-trimester abortions was not statistically different between the two groups. These results suggest that the combined use of gonadotropin releasing hormone agonist and human menopausal gonadotropin in an in vitro fertilization program may not have beneficial effects on pregnancy outcome in patients with polycystic ovarian syndrome.

Objective: Our objective was to compare the fertilization rates achieved by ICSI versus SUZI in couples with severe male infertility., Design: This was a randomized, prospective study., Setting: The study took place at the In-Vitro Fertilization-Embryo Transfer Unit, Department of Obstetrics and Gynecology, The Chaim Sheba Medical Center., Materials and Methods: Oocytes of 12 patients were randomly allocated to either ICSI or SUZI procedures. Each woman thus served as her own control. All 12 patients had undergone at least two previous in vitro fertilization cycles with no fertilization or had a very low sperm count, i.e., a total motile sperm count of less than 0.5 x 10(6)., Results: A total of 117 oocytes was obtained for fertilization. Of these oocytes, 16% (10/63) were successfully fertilized by SUZI, compared to 33% (18/54) treated by ICSI. This difference was statistically significant (P < 0.05). Of the 12 cycles, ICSI provided embryos in 10 cycles (83%), while SUZI was successful in only 6 cycles (50%). Four pregnancies were achieved: 33% per attempt, or 40% per transfer.

The decreased volume of maternal extracellular fluid in preeclamptics may result in a different rate of atrial natriuretic peptide secretion and thus affect its plasma levels. Our objectives were to determine whether there was a difference in plasma levels of atrial natriuretic peptide in the various hypertensive disorders of pregnancy. Forty-nine pregnant women in the third trimester of pregnancy were evaluated: 21 with preeclampsia, 17 with chronic hypertension during pregnancy and 11 normotensives. The atrial natriuretic peptide concentration was 13.9 +/- 5.9 pg/ml, 17.8 +/- 13.5 pg/ml and 16.7 +/- 7.4 pg/ml in the preeclamptics, chronic hypertensives and normotensives, respectively. The differences between the three groups were not statistically significant. Atrial natriuretic peptide plasma levels remained stable in the various hypertensive disorders of pregnancy.

Objective: To evaluate the endometrial blood flow response to hormone replacement therapy (HRT) in women with premature ovarian failure who plan to enter an oocyte donation program., Design: Transvaginal color Doppler ultrasound examinations were performed in women with ovarian failure before and during a cycle of standard HRT and in those with normal menstrual cycles. Blood flow response was assessed by visualization of arterial wave forms in the endometrial region. The transvaginal color flow mapping system was used. Resistance indexes were calculated for analysis and correlated with plasma E2 and P concentrations., Patients: Eighteen women with ovarian failure (study group), and 12 volunteers with normal ovarian cycles (control group)., Results: Data for resistance indexes were divided into five phases according to the day of hormonal cycle: 0, pretreatment phase; I, early follicular phase (days 5 to 7); II, late follicular phase (days 11 to 13); III, early luteal phase (days 17 to 21); and IV, late luteal phase (days 23 to 25). All women with ovarian failure demonstrated continuous forward end-diastolic flow velocities at phase I, whereas none showed this pattern during the pretreatment period (phase 0). Women with ovarian failure in the early follicular phase had a significantly higher resistance index (0.85 +/- 0.1; mean +/- SD) than that in the late follicular phase (0.57 +/- 0.1), and the resistance index in the early luteal phase (0.67 +/- 0.1) was significantly higher than that of the late follicular phase. There was no difference in the resistance index between early and late luteal phases. A similar pattern of lower resistance index around midcycle was observed in the control group. However, a comparison of the resistance indexes between ovarian failure and control patients revealed a significant difference between values in the early follicular phase only (0.85 +/- 0.1 versus 0.68 +/- 0.1). In the late follicular phase and during the entire luteal phase, the mean resistance index did not differ between the study and control groups., Conclusions: The observed data suggest that standard HRT in women with premature ovarian failure enables restoration of endometrial blood flow to normal. This may imply uterine receptivity for oocyte donation.

All cases of combined vaginal-abdominal deliveries at the Department of Obstetrics and Gynecology, Chaim Sheba Medical Center, over an eight-year period (1984-1991) were reviewed. During this period a total of 38,821 deliveries took place. Of 722 (1.9%) twin deliveries, 354 (48.8%) were by cesarean section; 19 were combined deliveries, including 5% of all twins delivered by cesarean section and 2.6% of all twins delivered. High transverse lie and prolapse of the umbilical cord were the main indications for delivery by cesarean section of the second twin. In order to diminish the number of combined deliveries and to increase obstetric skills and experience, a program or protocol for vaginal twin deliveries is indicated.

Our objective was to establish nomograms for fetal eye measurements from 12 weeks' gestation by using transvaginal and transabdominal high-resolution ultrasound techniques. A prospective cross-sectional study was performed on 450 normal singleton pregnancies between 12 and 37 weeks' gestation. Vitreous and lens circumferences were measured by transvaginal ultrasonography until 17 weeks, and by abdominal ultrasound between 18 and 37 weeks' gestation. Regression analyses were used to create nomograms, and several transformations were done to obtain linearity. Eye measurements of 12 fetuses at risk for ocular disturbances were plotted on the constructed nomograms. Linear relationships were fitted between vitreous (r2 = 0.79) and lens (r2 = 0.88) circumferences and gestational age. In addition, there was a significant correlation between these measurements and the biparietal diameter. Data of the fetuses at risk showed that disturbances in ocular growth were associated mainly with abnormal cerebral development. These normative data may be helpful in the prenatal diagnosis of suspected congenital syndromes that include, among their manifestations, ocular growth disturbances such as microphthalmos and anophthalmos.

Our objective was to review the association between fetal pleural effusion (FPE) and fetal aneuploidy. We conducted a retrospective survey of pregnant women who presented to our ultrasonographic unit between 1990 and 1991, and in whom the diagnosis of FPE was reached. All fetuses had karyotype investigation and a complete ultrasonographic search for associated anomalies. Six cases of FPE were identified. Trisomy 21 was found in 2 (33%). The English literature was reviewed and an additional 147 cases with FPE were collected, among them 6 cases of trisomy 21 and 1 of monosomy 45X. In this accumulated series the risk of aneuploidy in a fetus with an incidental finding of FPE was 5.8% (9 of 153), thus warranting a karyotype study.

A term fetus with atrial flutter and no signs of cardiac decompensation is described. A trial of pharmacologic cardioversion was unsuccessful, and induction of labor was initiated. Immediately after artificial rupture of the membranes, spontaneous conversion to normal sinus rhythm occurred. The possible mechanism of the cardioverion and the optional treatments for the term fetus with atrial flutter are discussed.

The objective of this study was to investigate the clinical utility of umbilical artery Doppler velocimetry in the management of very premature growth-retarded fetuses. The study comprised 34 fetuses between 26 and 34 weeks' gestation, diagnosed ultrasonically as suffering from intrauterine growth retardation. Based on the umbilical artery Doppler findings, patients were divided into 3 groups: group 1 (10 fetuses) with normal Doppler systolic/diastolic (S/D) ratios (within 2 SD of the mean for gestational age); group 2 (9 fetuses) with significant abnormal umbilical artery S/D ratios (above 2 SD of the mean for gestational age), and group 3 (15 fetuses) with absent or reverse end-diastolic flow. Fetal outcome was assessed in terms of neonatal mortality and morbidity, i.e. low umbilical artery pH (pH < 7.20) and Apgar scores. In group 1, all fetuses had a stable, normal S/D ratio; in group 2, 2 fetuses (22%) showed deterioration in the Doppler findings and were transferred to group 3, while in group 3, 3 of 15 fetuses (20%) showed improvement in the absence of end-diastolic flow and were thus transferred to group 2. Emergency cesarean section due to antenatal deterioration of the biophysical profile occurred in only 1 patient (10%) in group 1, compared to 33 and 87% in groups 2 and 3, respectively (p < 0.05). The other 9 patients in group 1 had normal vaginal deliveries at 36-37 weeks' gestation, with no perinatal complications. The mean expectant interval from admission to delivery in group 3 was 8.2 days, while in groups 1 and 2 it was 23.8 and 22.2, respectively (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

The objective of the study was to assess the effect of growth hormone (GH) supplementation to a combined gonadotrophin-releasing hormone agonist/human menopausal gonadotrophin (GnRHa/HMG) treatment protocol on ovarian response in 'poor responders' undergoing in-vitro fertilization (IVF). GH or a placebo were administered in a prospective randomized double-blind manner. A total of 14 poor-responder patients (oestradiol < 500 pg/ml, less than three oocytes retrieved in two previous IVF cycles) were randomly allocated to a combined treatment of either GnRHa/HMG/GH (18 IU on alternate days, total dose 72 IU) or GnRHa/HMG placebo. No difference was found between the study and control groups in the number of HMG ampoules used, the number of follicles (> 14 mm) and serum oestradiol concentrations on the day of administration of human chorionic gonadotrophin (HCG), the number of oocytes retrieved and fertilized, and the number of embryos transferred. The GH group (n = 7) did not show a better ovulatory response in the study cycles; mean +/- SD serum oestradiol on day of HCG 411 +/- 124 versus 493 +/- 291 pg/ml, aspirated oocytes 2.2 +/- 1.5 versus 1.9 +/- 2.0. Interestingly, when the above results for the placebo group were compared with their previous cycles (serum oestradiol 403 +/- 231 pg/ml; 0.4 +/- 0.5 aspirated oocytes), a non-specific effect was found. Follicular recruitment, oestradiol secretion by mature follicles and the number of oocytes retrieved in poor responders were not improved by GH supplementation.

Hypocalciuria due to reversibly enhanced tubular calcium reabsorption in preeclampsia has been previously described. As the fetus is exposed in utero to the toxemic environment, its kidney function may be similarly affected. We therefore evaluated the amniotic fluid (AF) concentrations of Ca2+, Mg2+, Zn2+, and Na+ in relation to creatinine in 12 preeclamptic women, 9 pregnant women with chronic hypertension, and 12 control pregnant women. Our data reveal an increased AF Ca2+, Mg2+, and Zn2+ to creatinine ratio in preeclampsia 451 +/- 283; 164 +/- 94; 787 +/- 124 Eq/mol, respectively) as compared with chronic hypertension (256 +/- 141; 94 +/- 46; 504 +/- 124 Eq/mol, respectively), and normal controls (274 +/- 132; 83 +/- 19; 477 +/- 124 Eq/mol, respectively; p < 0.05). Na+ concentration did not vary significantly among the three groups. It is suggested that the higher AF divalent cation concentration in preeclampsia may be due to lower maternal urinary excretion thereby increasing the fetal divalent cation load.

A case in which macroglossia was the sole unusual prenatal sonographic finding in a fetus affected with trisomy 21 is presented. The differential diagnosis of fetal macroglossia is given, emphasizing its strong relationship to fetal aneuploidy, together with the principles for evaluation and management.

This study was undertaken to report the results of microsurgical lysis of peri-adnexal adhesions and identify the patients who should be offered surgery and those who should be treated by in-vitro fertilization (IVF). In all, 19 women had filmy adhesions and 32 had dense adhesions; 68.4% of women with filmy adhesions conceived compared with 34.4% of women with dense adhesions (P = 0.02). In patients with filmy adhesions, the cumulative pregnancy rate 2 years after operation (47%) is similar to that reported after five cycles of IVF (52%), leading us to conclude that such patients should be offered surgery first. Dense adhesions are best treated by IVF. Lysis of filmy adhesions produces a similar intra-uterine pregnancy rate whether performed by laparotomy (57.9%) or laparoscopy (56.6%). As operative laparoscopy offers the greatest patient comfort, it is the treatment of choice in these patients.

The high frequency of mutations in the cystic fibrosis gene in patients with congenital bilateral absence of vas deferens (CBAVD) has raised the question whether all of them have a genital form of cystic fibrosis. We investigated 47 CBAVD patients by ultrasonography, 10 (21%) had renal malformations and 37 (79%) did not. In the former group, no cystic fibrosis mutations were found and sweat chloride concentrations were normal. In the latter group, 18 patients (49%) carried at least one cystic fibrosis mutation and sweat chloride was high in 17 of 26 tested (65%). Our findings suggest that CBAVD patients with renal malformations do not necessarily have cystic fibrosis.

Cerebral infarction due to menotropin therapy without evidence of ovarian hyperstimulation is presented. The patient was successfully treated with aspirin and anticonvulsive agents and was discharged without residual neurologic symptoms.

In this prospective study we compared transvaginal duplex Doppler ultrasound with two-dimensional imaging for the diagnosis or exclusion of ectopic pregnancies. The study group comprised 76 stable patients with serum beta-human chorionic gonadotropin (hCG) levels > 100 mIU/ml in whom ectopic pregnancy was clinically suspected. Ectopic pregnancies were verified in 42 patients (60%), intrauterine pregnancies (normal and abnormal) in 19 (27%), and possible complete abortions, either intrauterine or extrauterine, in 9 patients (13%). Based on 2-D imaging alone, the appearance of an adnexal mass separated from the ovaries, and a lack of clear intrauterine gestational sac indicated ectopic pregnancy with a sensitivity of 95%. Intrauterine sac-like structures and absence of adnexal masses excluded ectopic pregnancies with a specificity of 89%. High velocity systolic flow, and low impedance diastolic flow which characterizes trophoblastic tissue when detected outside the uterus, had a sensitivity of 48%, while the presence of trophoblastic signals in the uterus or their absence outside the uterus excluded ectopic pregnancies with a specificity of 89%. The positive predictive values were 91% for Doppler and 95% for 2-D imaging, while the negative predictive values were 89% for imaging alone and 44% for Doppler. These data suggest that transvaginal Doppler ultrasound has significant lower sensitivity and negative predictive value and does not provide more useful diagnostic information than 2-D imaging alone for stable patients with suspected ectopic pregnancies.

Purpose: This collaborative work was undertaken to assess perinatal outcome of in vivo conceived triplets to those following in vitro fertilization and assisted reproductive technologies (ART)., Methods: 151 triplets were examined; 56 delivered following ART, 55 following ovulation induction by gonadotropins (GN), 27 following clomiphene citrate (CC), and 13 conceived spontaneously., Results: Mean gestational length of triplets following ART (33.2 wks) was not different from those conceived following GN (33.4 wks) or CC (34.2 wks), but was significantly shorter compared to triplets following spontaneous conception (35.3 wks). Mean fetal birthweight following ART (1743 g) did not differ significantly from that following GN (1683 g) or CC (1863 g) but was significantly lower compared to those delivered after spontaneous conception (1963 g). Although no difference was found in the incidence of low birthweight infants between the groups studied, the incidence of very low birthweight newborns (<1500 g) following ART or GN was significantly higher than following spontaneous conceptions (30.6%, 30.3% vs 10.3%). Differences in perinatal mortality were not significantly different between the groups examined (77.9, 60.6, 111.0, 25.6/1000 for ART, GN, CC, and spontaneous conceptions respectively)., Conclusion: In conclusion, a similar perinatal outcome was shown for triplets conceived following ART and those following ovulation induction by GN, suggesting that the in vitro conditions as such were not the main contributing factor influencing the clinical outcome but rather the GN treatment. Triplets conceived spontaneously have a better outcome compared to those following ovulation induction or ART in terms of gestational length and birthweight.

To assess the maternal and neonatal risk associated with high-order cesarean sections, a case-control study was carried out in two university affiliated maternity wards. The outcome of 154 pregnancies of women undergoing cesarean section for the 4th time or more was compared with 148 women sectioned for the 2nd or 3rd time and 132 women of similar age and parity after spontaneous birth. The main outcome measures were maternal operative and postoperative morbidity and neonatal prematurity and its complications, Apgar scores, and the need for intensive care. Women undergoing multiple (> or = 4) cesarean sections had significantly more intra-abdominal adhesions (P < 0.0001) than women sectioned for the 2nd or 3rd time. However, the time interval from incision to delivery and the total duration of operation were similar. The postoperative course was not adversely affected by multiple cesarean sections. A high incidence (16.2%) of preterm cesarean deliveries was noted in the study group. This was due to non-elective repeat cesarean delivery rather than to poor timing of scheduled cesarean sections. The significantly increased (P < 0.05) need for neonatal intensive care was explained by the higher occurrence of prematurity. Low Apgar scores (< or = 7) at 1 and 5 min were significantly (P < 0.01) related to multiple cesarean sections, even after controlling for the effect of gestational age. We conclude that multiple cesarean sections pose little risk for the mother, but may be associated with increased neonatal risk, attributed mainly to preterm non-elective cesarean sections.

The object of our investigation was to evaluate the potential of transvaginal echocardiography for a complete anatomic study of the fetal heart, and for detection of congenital heart diseases in low-risk pregnant patients between 13 and 15 weeks' gestation. High-frequency (6.5 MHz and 7.5 MHz) transvaginal probes were employed for fetal echocardiographic assessment. Six hundred and sixty patients considered at low risk for congenital heart disease underwent in utero ultrasonographic studies, neonatal records, postnatal imaging studies, and pathologic examination. The four-chamber view was obtained in 100% of the fetuses, while the extended fetal heart examination was completed in 98%. Six fetuses with cardiac defects were diagnosed during the study: three had major heart defects (aortic atresia, tetralogy of Fallot, and persistent truncus arteriosus), all detected at the early transvaginal scan; three cardiac anomalies escaped our early diagnosis; two fetuses had a minor ventricular septal defect diagnosed only postnatally; and one had multiple cardiac rhabdomyoma diagnosed in the third trimester. Our results demonstrate that between 13 and 15 weeks' gestation transvaginal echocardiographic assessment of the fetal heart in the low-risk population is feasible. Moreover, some severe anomalies may be detected at such an early gestational age.

A case of gastric outlet obstruction diagnosed prenatally at 22 weeks' gestation is described. The differential diagnosis and the clinical management of this rare condition are discussed, and an updated literature review is presented.

Objective: To clarify how often infertile men should have intercourse to achieve conception, the effect of sequential ejaculation on total motile sperm counts was investigated., Design: Case-control study., Setting: Infertility and IVF unit, tertiary care center., Participants: Five hundred seventy-six men who produced two closely spaced sequential ejaculates., Main Outcome Measure: The total motile sperm counts of the second ejaculates were compared with the total motile sperm counts of the first ejaculates., Results: In normospermic men (n = 359), the total motile sperm counts decreased significantly from 93 (18 to 601) (median [minimum to maximum] x 10(6)) in the first ejaculate to 42 (1.2 to 387) in the second ejaculate, produced 24 hours later. In contrast to the normospermic men, in the asthenospermic group (24 hours difference, n = 81) and in both oligospermic groups, (1 to 4 hours difference, n = 27; and 24 hours difference, n = 45), there were no significant changes in the total motile sperm counts (24 [5.9 to 229] versus 30 [0.8 to 150], 6 [0.8 to 18] versus 3.6 [0.1 to 63] and 13 [2.5 to 32] versus 10 [0.1 to 66], respectively). Moreover, in both oligoasthenospermic groups (1 to 4 hours difference, n = 23; and 24 hours difference, n = 41) the total motile sperm counts increased significantly (3.2 [0.6 to 7.9] versus 8 [0.4 to 48] and 4 [0.2 to 13] versus 4 [0.1 to 101], respectively). In all groups, pooling sequential ejaculates significantly increased the total motile sperm counts, over and above that of the first ejaculate, by 49% in the normospermic group, 95% in the asthenospermic group, 67% and 75% in the oligospermic groups (1 to 4 hours and 24 hours difference, respectively), and 233% and 139% in the oligoasthenospermic groups (1 to 4 hours and 24 hours difference, respectively)., Conclusions: Sequential ejaculation may overcome the impaired sperm transport causing low total motile sperm counts observed in some oligospermic and/or asthenospermic men. Most of these infertile men may significantly increase their fertility potential, assessed by the total motile sperm counts, either by pooling sequential ejaculates for IUI, GIFT, and IVF, or by having intercourse every day or even twice a day, at the time of ovulation.

The dramatic increase in the number of women of childbearing age infected with human immunodeficiency virus (HIV) has led to the revelation of another terrible consequence of the human immunodeficiency virus (HIV) pandemic; maternal transmission of HIV to the fetus. Over 90 per cent of the children who are infected with HIV contract the virus from their mother. Viral transmission may occur in utero, during labor when the newborn is exposed to maternal blood and body fluids or postnatally, mainly via breast-feeding. However, the risk of infection for a baby whose mother is an HIV carrier is not yet clear. The determination of the HIV status of the newborn remains a major diagnostic problem as the routine test, which detects antibodies to HIV, is of limited value in evaluating newborns. A summary of all of the large prospective long-term follow-up studies reported to date, shows an overall transmission rate of 22.4 per cent, with a 95 per cent confidence interval of 20.5 to 24.0 per cent. However, it is difficult to refer to the wide range of reported transmission rates, from 9.1 to 55.0 per cent, as they are confounded by the differing distribution of risk factors. The risk of maternal to newborn transmission must, therefore, be determined according to the specific characteristics of each parturient population.

Cytomegalovirus is the most common cause of congenital viral infection. In utero infection is usually suspected in patients with growth-retarded fetuses or when maternal illness precipitates serological investigations. A case is presented where routine ultrasound examination at 30 weeks' gestation in an asymptomatic patient demonstrated mild fetal ventriculomegaly. Transvaginal ultrasound enabled the visualization of intraventricular adhesions and small periventricular cysts. The suspected diagnosis of in utero cytomegalovirus infection was confirmed by the presence of IgM antibodies in fetal blood and subsequently by isolation of the virus from the infant's urine. The presence of mild fetal ventriculomegaly should prompt transvaginal brain imaging.

We present a rare case in which therapy of primary ovarian pregnancy, using laparoscopic laser surgery (videolaseroscopy), was successfully performed without the need of laparotomy. Because operative laparoscopy has the benefits of reduced morbidity, reduced hospitalization and rapid recovery, and because it has the advantage of reducing postoperative adhesions as compared to laparotomy, it is the preferable technique for treatment of ovarian gestation after a laparoscopic diagnosis, especially for a woman who desires to preserve her fertility potential.

A 20-year-old woman with cyanotic congenital heart disease composed of corrected transposition of the great vessels, severe pulmonic stenosis, atresia of the left pulmonary artery and a large ventricular septal defect, had a successful pregnancy following a pulmonary-systemic shunt (Blalock-Taussig). The hemoglobin decreased from 21 to 16 g/dL following the operation. The antepartum course was complicated by intrauterine growth retardation and pregnancy-induced hypertension. A normal fetal nonstress test and biophysical profile permitted continuation of the pregnancy until 38 weeks' gestation, with delivery of a healthy infant.

Objective: To describe the feasibility of diagnosing fetal congenital heart defects by transvaginal ultrasonography during the first trimester of pregnancy., Methods: Pregnant women presenting to the Ultrasonographic Unit at the Chaim Sheba Medical Center who had a diagnosis of fetal heart defects were reviewed retrospectively. Attention was paid to prenatal ultrasound studies, karyotype, and pathologic examinations., Results: Using high-resolution transvaginal ultrasonography, we were able to detect fetal tachycardia (one case), ectopia cordis with ventricular septal defect (one case), atrioventricular septal defect (two cases), ventricular septal defect with persistent truncus arteriosus (one case), tetralogy of Fallot (two cases), and large right atrium with unguarded tricuspid valve (Uhl disease) (one case). Seven of these fetuses had normal karyotypes and all showed additional sonographic abnormalities, including septated cystic hygroma (three cases), hydrops (ascites and pericardial effusions) (two cases), omphalocele (one case), and bilateral agenesis of kidneys (one case). Only one fetus with an abnormal karyotype (45,XO) showed a combination of septated cystic hygroma with hydrops., Conclusions: High-resolution duplex Doppler transvaginal ultrasonography during the first trimester of pregnancy seems to be a useful diagnostic method for detecting some congenital heart diseases.

Objective: To evaluate the clinical significance and the natural course of discordant twin growth found during the first trimester of pregnancy., Methods: This was a retrospective survey between 1992-1993 of women presenting to the ultrasonographic unit with twin pregnancies in which considerable interfetal size variation was noted in the first trimester. Discordant embryonal growth was defined as a difference in crown-rump length corresponding to 5 or more days in the estimated gestational age. Only cases that presented with continued viability of both twins were reviewed. Cases were thoroughly followed by ultrasound examinations throughout pregnancy. Neonatal records provided the outcome data., Results: Five cases with first-trimester discordant twin growth were identified. All had complications of major congenital anomalies in the smaller twin, ie, diaphragmatic hernia, ventriculomegaly, schizencephaly, critical aortic atresia, and sacral agenesis., Conclusions: The first-trimester growth-discordant twin is at increased risk for congenital anomalies. Meticulous sonographic search for congenital anomalies is indicated when inter-twin size variation is evident in the first trimester.

A high rate of ovarian multifollicular development and resulting multiple pregnancy remains the main problem of ovulation induction with human menopausal gonadotropins. The aim of this study was to examine a possible correlation between the number and size of ovarian follicles at the time of human chorionic gonadotropin (hCG) administration and to find parameters that can predict the occurrence of multiple pregnancies. Sixty-eight intrauterine pregnancies, 53 singletons and 15 multiple pregnancies in 51 patients, were included in this study. We found no significant difference in the mean estradiol levels, the total number of pre-ovulatory follicles, or the mean number of large, intermediate or small follicles at the time of hCG administration between women who had singleton pregnancies and those with multiple pregnancies. Our study demonstrates that estradiol levels and ovarian ultrasonography do not provide criteria for the prediction of the occurrence of multiple pregnancies in menotropin cycles.

First-trimester spontaneous abortions have been predicted from alterations in the gestational sac size and embryonic heart rate. To evaluate which parameter or combination of parameters has the greatest predictive value, a prospective study was carried out during the first trimester of pregnancy. Pregnancy sac size, crown-rump length and heart rate were measured in 603 embryos, of which 580 continued beyond 13 weeks' gestation and 23 ended in first-trimester spontaneous abortions. Based on the continuing pregnancies, we constructed nomograms relating the ratio of mean sac diameter to crown-rump length (S/CR) to gestational age (last menstrual period [LMP]), to crown-rump length (CRL) and to embryonic heart rate (EHR). The S/CR ratios of the 23 embryos that spontaneously aborted in the first trimester were plotted on these nomograms to determine the significance of values falling outside the 95% confidence limits. Plotting the S/CR ratios of the aborted fetuses on the S/CR versus LMP nomogram gave a sensitivity of 78.3%, a specificity of 97.8% and a false-positive rate of 2.2%. The same population was evaluated for abortion risk using EHR nomograms, giving a sensitivity of 65.2%, specificity of 98.2% and false-positive rate of 1.8%. Our findings suggest that S/CR measurement in early pregnancy may be a simple and reliable method of predicting first-trimester abortions.

Assessment of the last fetal biophysical profile score (BPS) (excluding nonstress test) prior to delivery was carried out in 35 triplet pregnancies. A normal BPS was found to be reliable in predicting nondistressed fetuses in triplets (specificity, 94.9%), while an equivocal BPS (6/8) had low sensitivity (14.3%) in predicting distressed fetuses. Two stillbirths were not detected by ultrasound prior to delivery. No correlation was found between the BPS and either neonatal morbidity or perinatal mortality. The BPS could not differentiate between distressed and nondistressed fetuses in the same pregnancy. These results suggest that an equivocal BPS has limited value in predicting fetal distress in triplet pregnancies, but a normal one could be used to predict nondistressed fetuses.