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Biomedical subjects

J Itskovitz-Eldor

Publications and source records attributed to J Itskovitz-Eldor.

At least 55 records · Page 3Linked to original sources

Growth of the fetal nose width and nostril distance in normal pregnancies.

The study was planned to obtain the dimensions of the fetal nose width and nostril distance during normal pregnancy as a basis for further studies and for identification of deviations in growth. The study group included 302 healthy pregnant women at 14-40 weeks' gestation. Routine biometric measurements were obtained from all the participants, including biparietal diameter, head and abdominal circumferences, measurements of the long bones and dimensions of the fetal nose width and nostril distance. The nose width and nostril distance were also calculated for each gestational age. A linear growth relationship was observed between nose width and gestational age (r = 0.88; p < 0.0001; y = 0.27 + 0.57 x gestational age), biparietal diameter (r = 0.92; p < 0.0001; y = 0.41 + 0.23 x biparietal diameter), head circumference (r = 0.91; p < 0.00001; y = 0.85 + 0.63 x head circumference), femoral length (r = 0.91; p < 0.0001; y = 3.18 + 0.26 x femoral length) and humeral length (r = 0.73; p < 0.0001; y = 1.94 + 0.11 humeral length). A linear growth function was also observed between nostril distance and gestational age (r = 0.54; p < 0.00001; y = 2.77 + 0.15 x gestational age), biparietal diameter (r = 0.71; p < 0.00001; y = 1.83 + 0.08 x biparietal diameter), head circumference (r = 0.70; p < 0.00001; y = 1.99 + 0.2 x head circumference), femoral length (r = 0.75; p < 0.00001; y = 2.49 + 0.09 x femoral length) and humeral length (r = 0.91; p < 0.00001; y = 1.89 + 0.32 x humeral length). A linear growth relationship was found between nose width and nostril distance (r = 0.71; p < 0.00001; y = 1.81 + 0.31 x nose width). These results provide normative data of the fetal nose width and nostril distance in various dimensions and across gestational age. In addition, the data offer the potential for prenatal diagnosis of nose and nostril abnormalities.

Female↗

Assisted implantation: direct intraendometrial embryo transfer.

We report herein a technique for direct intraendometrial transfer (DIET) of human embryos. In this study we evaluated whether 2-day embryos injected into the endometrial stroma can develop normally into viable pregnancies. After in vitro fertilization the embryos were injected into the endometrium of 14 women under direct visualization using a CO2-pulsed flexible hysteroscope. A total of 44 embryos were transferred, resulting in 2 clinical (14.3% per cycle) and 2 chemical pregnancies. In 1 patient, amniocentesis revealed monosomy X and the pregnancy was terminated at 18 weeks. The 2nd patient had an uneventful pregnancy and delivered a healthy baby. The results from the present study, demonstrating a low implantation rate after DIET of 2-day embryos, suggest that the endometrial stroma does not provide an optimal environment for early embryonic development. The acidifying effect of CO2 used for insufflation may also explain the low pregnancy rate after DIET. We conclude that it is possible to achieve pregnancy by DIET in humans, but presently this procedure can be considered only in cases where the implantation site needs to be precisely determined.

Adult↗

Ovarian origin of plasma and peritoneal fluid prorenin in early pregnancy and in patients with ovarian hyperstimulation syndrome.

Prorenin is the major product of renin gene expression in the ovary. Plasma levels of prorenin are elevated in ovarian-stimulated patients and during early pregnancy. To further elucidate the source of the elevated plasma levels of prorenin, we measured prorenin, renin activity, angiotensinogen, and steroid hormone levels in the plasma, luteal fluids (luteal cysts), ascitic fluid, and in ovarian venous samples collected from a patient with severe ovarian hyperstimulation syndrome (OHSS) and ectopic pregnancy. Prorenin/renin was also measured in plasma and in peritoneal fluid obtained during, therapeutic paracentesis from four patients with OHSS. Several corpora luteal fluids were obtained that were rich in estradiol (E2) and progesterone (P). Ovarian venous E2 and P were 20-fold higher than in arterial blood and as high or higher than the levels detected in the luteal fluids. The ratios of the hormonal levels in ascitic fluid and plasma were 1.9 for P and 1.4 for E2. A wide range of prorenin concentrations [1279 +/- 918 SD ng/mL/hr, n = 6] were found in corpora luteal fluids, but in each the prorenin concentration was higher than in plasma (494 ng/mL/hr). Prorenin but not renin was higher (+23%) in ovarian venous than arterial blood. Prorenin in the 7 liters of ascitic fluid aspirated (2686 ng/mL/hr) was 5-fold higher than in plasma and similar to the levels measured in the corpora lutea with the highest prorenin concentrations. Renin in luteal cysts and ascitic fluid constituted 3% and 6% of the total renin (renin+prorenin), respectively. Total renin was also higher in peritoneal fluid (1538 +/- 925 ng/mL/hr) than in plasma (375 +/- 237 ng/mL/hr) of the 4 additional patients with severe OHSS. These findings indicate that the ovary secretes prorenin during early pregnancy and that its secretion is directed preferentially from the luteal cysts into the peritoneal cavity. In light of recent evidence of an effect of prorenin on the vascular system, the presence of a huge reservoir of prorenin in the peritoneal cavity of patients with OHSS suggests a potential role for prorenin in the pathogenesis of this syndrome.

Adult↗

The effect of isosorbide dinitrate on uterine artery and umbilical artery flow velocity waveforms at mid-pregnancy.

OBJECTIVE: To study the effect of isosorbide dinitrate, a nitric oxide donor, on the maternal cardiovascular system and on uterine and umbilical artery blood flow velocities in mid-pregnancy. METHODS: Eighteen women with low-risk pregnancy at 17-24 weeks' gestation were given a single 5-mg dose of sublingual isosorbide dinitrate, a nitrovasodilator. Blood flow velocity waveforms in the ascending uterine artery and in the umbilical artery were measured by an image-directed, pulsed color Doppler ultrasound scan before and after the medication was administered. Maternal blood pressure (BP) and heart rate were also obtained. RESULTS: The mean arterial BP decreased from 86 mmHg (95% confidence interval [CI] 72-99) to a nadir of 73 mmHg at 6 minutes (95% CI 61-85, P < .04). Mean maternal heart rate increased from 85 beats per minute (95% CI 80-90) to 96 beats per minute at 6 minutes (95% CI 87-105, P < .01). Mean systolic-diastolic flow velocity ratio (S/D) in the umbilical artery rapidly declined from 4.18 (95% CI 3.80-4.56), reaching a nadir of 3.12 at 6 minutes (95% CI 2.65-3.84, P < .001). The S/D in the uterine artery decreased from 4.83 (95% CI 3.99-5.56) to a nadir of 4.02 at 10 minutes (95% CI 3.41-4.63, P < .001). CONCLUSION: Isosorbide dinitrate, a donor of nitric acid, lowers mean maternal BP and reduces the Doppler impedance in the umbilical and uterine arteries. This drug could prove to be beneficial when endothelial cell dysfunction leads to insufficient synthesis and release of endothelium-derived relaxing factor, resulting in generalized vasoconstriction and increased resistance to flow in the uteroplacental circulation.

Adolescent↗

Intracranial fetus-in-fetu.

Fetus-in-fetu is an extremely rare tumor diagnosed in utero. We present a case report of prenatal diagnosis of intracranial fetus-in-fetu.

Adult↗

does intravenous administration of human albumin prevent severe ovarian hyperstimulation syndrome?

OBJECTIVE: To report our experience with i.v. albumin as a means to prevent ovarian hyperstimulation syndrome (OHSS) in high-risk patients. DESIGN: Retrospective case-series. SETTING: University hospital-based IVF program. PATIENTS: Five women undergoing controlled ovarian stimulation for IVF-Based on previous history and/or E2 measurements and number of ovarian follicles, these patients were considered to be at high risk for developing OHSS. INTERVENTIONS: Intravenous albumin was given at the time of oocyte retrieval. Additional doses were given 12 and 24 hours later. MAIN OUTCOME MEASURE: Development of OHSS. RESULTS: Four patients developed OHSS; two of them had the severe form of the syndrome. CONCLUSIONS: Severe OHSS may develop in high-risk patients despite the prophylactic administration of i.v. albumin.

Female↗

The incidence and possible relevance of Y-linked microdeletions in babies born after intracytoplasmic sperm injection and their infertile fathers.

Microdeletions linked to deletion intervals 5 and 6 of the Y chromosome have been associated with male factor infertility. Members from at least two gene families lie in the region containing azoospermia factor (AZF), namely YRRM and DAZ. With the advent of intracytoplasmic sperm injection (ICSI), it is possible for men with severe male factor infertility to produce a child. The genetic consequences of such a procedure have been questioned. This report describes the first study of a population (32 couples) of infertile fathers and their sons born after ICSI. The objectives were firstly to determine the incidence and map location of Y chromosome microdeletions and to compare the frequencies with other population studies involving severe male factor infertility, and secondly to formulate a working hypothesis concerning developmental aetiology of Y chromosome microdeletions. The incidence of microdeletions in the ICSI population was shown to be 9.4% (within the range 9-18% reported for populations of severe male factor infertility patients). Microdeletions in two out of three affected father/son pairs mapped in the region between AZFb and AZFc and the third involved a large microdeletion in AZFb and AZFc. Of three affected father/son pairs, microdeletions were detected in the blood of one infertile propositus father and three babies. Assuming that the gonomes of the ICSI-derived babies are direct reflections of those of their fathers germ lines, it is possible that two of three infertile fathers were mosaic for intact Y and microdeleted Y chromosomes. In such cases, the developmental aetiology of the microdeletion may be due to a de-novo microdeletion arising as a post-zygotic mitotic error in the infertile propositus father, thus producing a mosaic individual who may or may not transmit the deletion to his ICSI-derived sons depending on the extent of primordial germ cell mosaicism. In one of three affected fathers, the microdeletion detected in his blood was also detected in his ICSI-derived son. In this case the de-novo event giving rise to the microdeletion may have occurred due to a post- (or pre-) meiotic error in the germ line of this father's normally fertile father (i.e. the ICSI-derived baby's grandfather).

Adult↗

Undocumented embryos: do not trash them, FISH them.

Pronuclei formation is routinely assessed 16-20 h after oocyte insemination in in-vitro fertilization (IVF). Occasionally, the pronuclei disappear before this time, rendering them as 'undocumented'. Since the number of pronuclei detected is used to distinguish normal from abnormal embryos in the context of ploidy, the diploidy of undocumented embryos is questionable, and therefore they are routinely discarded. The introduction of fluorescent in-situ hybridization (FISH) technology allows the assessment of ploidy status in undocumented embryos that continue to cleave to form blostomeres. In this study, we used FISH to analyse the chromosomal status of 23 undocumented embryos obtained from 10 patients. Biopsied blastomeres were fixed and probed for five chromosomes (X, Y, 13, 18, 21). Diploidy was confirmed in 13 (57%) embryos while the remaining 10 embryos displayed various chromosomal anomalies. Six of the diploid embryos were transferred subsequently to the patients. One ongoing pregnancy was achieved following transfer of an undocumented, analysed embryo, which was already cleaved when assessed 20 h after insemination. We suggest that accelerated dismantling of the pronuclear membrane and subsequent cleavage do not necessarily indicate abnormal chromosomal content and may result in normal pregnancy. In a patient with a small number of embryos, FISH may be used to ascertain diploidy of undocumented embryos, thereby increasing the number of available embryos for transfer.

Blastomeres↗

Comparison of gonadotrophin-releasing hormone analogues and human chorionic gonadotrophin for the induction of ovulation and prevention of ovarian hyperstimulation syndrome: a case-control study.

Gonadotrophin-releasing hormone analogue (GnRHa) has been suggested as an alternative to human chorionic gonadotrophin (HCG) for triggering ovulation, while preventing ovarian hyperstimulation syndrome (OHSS). Since a prospective, controlled study would be unethical at this point, we used a retrospective, case-self control approach to compare GnRHa with HCG in that context. A group of 16 in-vitro fertilization (IVF) patients who had severe OHSS in previous cycles, in which HCG was given to trigger ovulation, were studied in subsequent cycles in which GnRHa was used. Each GnRHa cycle (case) was compared to a previous HCG cycle that resulted in OHSS (self control). None of these subsequent cycles resulted in severe OHSS. The use of GnRHa did not affect the number of oocytes retrieved or their quality. Serum oestradiol concentrations on the day of ovulation triggering were significantly (P < 0.01) higher in the GnRHa cycles compared to HCG cycles. Exogenous progesterone and oestradiol were effective in maintaining relatively constant serum oestradiol and progesterone serum concentrations during the luteal phase. Pregnancy rate per cycle was similar in the two groups. In conclusion, the use of GnRHa to induce ovulation in IVF patients, who are at high risk for developing OHSS, effectively eliminates this risk without affecting other parameters of the stimulation cycle.

Case-Control Studies↗

Central and peripheral haemodynamic changes in post-term fetuses: correlation with oligohydramnios and abnormal fetal heart rate pattern.

OBJECTIVE: To assess the hypothesis that the occurrence of oligohydramnios and abnormal fetal heart rate (FHR) pattern in post-term fetuses is associated with impaired fetal cardiac function. DESIGN: A cross sectional study was performed on post-term and term fetuses. Fetal tests included a computerised analysis of the FHR, a biophysical profile and Doppler studies of the abdominal aorta, umbilical artery, middle cerebral artery and the fetal heart. Pulsatility index (PI) was calculated from the abdominal aorta, umbilical and middle cerebral artery flow velocity waveforms. Peak velocity, velocity time integral (VTI), E:A ratio, and heart rate (HR) were calculated from the flow velocity waveforms obtained from the aortic and pulmonic outflow, and from the mitral and tricuspid valves. SETTING: Maternal fetal laboratory, Department of Obstetrics. SAMPLE: One hundred and twenty post-term and 42 term fetuses. RESULTS: Only the tricuspid E:A ratio was significantly higher (P < 0.05) in post-term fetuses with a normal amniotic fluid index compared with term fetuses. Post-term fetuses with an abnormal amniotic fluid index had a significantly lower aortic peak velocity (P < 0.01), aortic VTI x HR (P < 0.01), and mitral VTI x HR (P < 0.05) compared with post-term fetuses with a normal amniotic fluid index or compared with term fetuses. Post-term fetuses with reduced FHR variation had a significantly lower aortic peak velocity (P < 0.01), pulmonic peak velocity (P < 0.05), aortic VTI x HR (P < 0.01), pulmonic VTI x HR (P < 0.05) and a significantly lower mitral VTI x HR (P < 0.05) when compared with post-term fetuses with normal FHR variation. Similar results were obtained in comparing fetuses with normal and adverse perinatal outcome. CONCLUSION: The occurrence of oligohydramnios and abnormal FHR pattern in post-term fetuses appears to be associated with impaired fetal cardiac function. This finding should allow further investigations of post-term fetuses.

Adult↗

Thyroid function in early normal pregnancy: transient suppression of thyroid-stimulating hormone and stimulation of triiodothyronine.

In order to determine the effect of gestation on thyroid function in healthy subjects, we have prospectively evaluated thyroid function in pregnant individuals undergoing termination of pregnancy, and repeated the tests 2-3 months later. Venous blood was tested for human chorionic gonadotropin (hCG), thyroid-stimulating hormone (TSH), free thyroxine (FT4) and total triiodothyronine (TT3). Early pregnancy thyroid function tests showed a significant decrease (p < 0.001) in TSH and a significant increase (p < 0.001) in TT3 as compared to the nonpregnant state; FT4, however, did not change significantly. In 8 (11.2%) pregnant subjects, TT3 levels were above the normal range for nonpregnant controls. Elevated thyroid function in early pregnancy is transient, and does not usually warrant antithyroid treatment. Thus, any conclusion regarding thyroid function in early pregnancy should be based on pregnant controls rather than general population controls.

Abortion, Induced↗

Sonographic measurement of amniotic fluid volume in the first trimester of pregnancy.

The sonographic estimate of amniotic fluid volume from 7 to 13 weeks of gestation in 95 pregnancies was calculated. Amniotic fluid volume increased from 1.5 ml at 7 weeks to 25 ml at 10 weeks and 100 ml at 13 weeks. The nomograms constructed may be used in the objective evaluation of the fetal condition in the first trimester.

Amniotic Fluid↗

Massive vulvar edema in pregnancy. A case report.

Massive vulvar edema in pregnancy is a rarely reported condition. We treated a case of severe labial edema complicating pregnancy. Massive edema of the vulva appears to usually be a sequela of an underlying, systemic disease in pregnant women.

Adult↗

Failure of meiotic competence in human oocytes.

The administration of hCG to women undergoing in vitro fertilization and embryo transfer (IVF/ET) results in the meiotic maturation of cumulus-oocyte complexes (COC). Sometimes oocytes being aspirated for IVF/ET fail to resume meiosis in vivo and even after a subsequent 20-h incubation in vitro and are thus defined as meiotic competence failure (MCF) oocytes. The relationship between the proportion of MCF oocytes and other IVF/ET outcomes was studied over 3 years in 703 tested cycles of 487 women. Women yielding one or more MCF oocytes in at least one menstrual cycle represented 8.6% of this population and were defined as MCF women. Cumulus state in the MCF oocyte population was characterized as mature in 57.4 +/- 6.7%, intermediate in 13.9 +/- 4.0%, immature in 24.1 +/- 8.7%, and atretic in 4.6 +/- 2.7%. These values differed significantly, by 0.6-, 2.9-, 7.1-, and 4.6-fold, respectively, as compared to the corresponding COC aspirated from women yielding only meiotically competent (MC) oocytes. In a menstrual cycle yielding both MC and MCF oocytes, the IVF/ET variables were evaluated in the MC oocytes. Thus, in such cases the incidence of fertilization or cleavage and the number of blastomeres per embryo were significantly reduced concomitant with the increase in percentage of MCF oocytes. When the percentage of MCF oocytes was 25% or more, no pregnancy was achieved. Various follicular parameters and serum 17 beta-estradiol (E2) and progesterone (P4) levels were compared in MC and MCF women over the four days preceding day of aspiration.(ABSTRACT TRUNCATED AT 250 WORDS)

Chorionic Gonadotropin↗

Estradiol- and progesterone-related increases in the renin-aldosterone system: studies during ovarian stimulation and early pregnancy.

To investigate the degree to which endogenous increases in estradiol (E2) and progesterone (P4) are associated with changes in the renin system, we studied eight patients undergoing ovarian stimulation for in vitro fertilization (FSH/human menopausal gonadotropin or clomiphene citrate for 5-11 days, followed by hCG). Three conceived and were followed for up to 62 days after hCG treatment. The others were followed until the end of the luteal phase. During the follicular phase, E2 increased 10-fold, PRA increased 2-fold, and absolute levels of E2 and P4 were positively correlated (r = 0.63; P < 0.05). After ovulation, which was induced by hCG, E2 fell by 50% (day 7), but there was a 50-fold increase in P4 and a further 5-fold increase in PRA. By day 14, E2 increased again in the women who conceived, to levels even higher than those in the follicular phase, and both P4 and PRA increased 2- to 3-fold between days 7 and 14. In contrast, E2, P4, and PRA returned toward baseline levels in the nonpregnant women. On day 21, E2, P4, and PRA remained very high in the pregnant women [E2, 2297 +/- 255 pg/mL (8430 pmol/L); P4, 103 +/- 22 pg/mL (328 pmol/L); PRA, 33 +/- 8 ng/mL.h (9.17 ng/L.s)]. During the luteal phase and early pregnancy, there was a positive relationship between PRA and P4 (r = 0.68; P < 0.05). There was also a positive relationship between PRA and E2 (r = 0.54; P < 0.05); compared to the follicular phase level, PRA was 4-fold higher in the luteal phase at any E2 level. Like renin, urinary aldosterone excretion (UA) increased 5-fold during the luteal phase (day 7) and by a further 3-fold between days 7 and 21 in the pregnant women, reaching very high levels [135 +/- 28 micrograms/day (375 nmol/day); n = 3]. PRA and UA positively correlated (r = 0.59; P < 0.08). Plasma angiotensinogen increased from 2146 +/- 283 ng angiotensin-I/mL (n = 8) to 3682 +/- 607 (n = 8) on day 7 and to 5353 +/- 799 (n = 3) on day 21. Urinary sodium excretion did not fall, and urinary potassium did not increase in coordination with the changes in renin and aldosterone. There was no hypokalemia. These results demonstrate marked increases in plasma renin and UA in coordination with increases in plasma E2 and P4 during ovarian stimulation and early pregnancy, and coordinated falls during luteolysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗