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J Itskovitz-Eldor

Publications and source records attributed to J Itskovitz-Eldor.

At least 37 records · Page 2Linked to original sources
PubMed2000

Severe OHSS: yes, there is a strategy to prevent it!

Effective measures to prevent ovarian hyperstimulation syndrome (OHSS) remain controversial. It became almost 'common knowledge' that there is no strategy that may completely prevent OHSS. Extensive clinical experience (albeit not derived from prospective randomized studies) clearly documents the ability of a single administration of gonadotrophin-releasing hormone (GnRH) agonist to effectively trigger ovulation, while completely eliminating any threat of clinically significant OHSS. This strategy cannot be used if the pituitary is down-regulated (as is the case in most assisted reproductive cycles today), however, the newly-introduced GnRH antagonists open new opportunities for implementing this strategy, since the pituitary preserves its responsiveness to GnRH agonists. Combining GnRH antagonist-based ovarian stimulation (particularly in 'high responders'), with GnRH agonist-driven ovulation triggering will make severe OHSS a disease of the past in assisted reproduction.

Female↗
PubMed2000

Use of a single bolus of GnRH agonist triptorelin to trigger ovulation after GnRH antagonist ganirelix treatment in women undergoing ovarian stimulation for assisted reproduction, with special reference to the prevention of ovarian hyperstimulation syndrome: preliminary report: short communication.

A new treatment option for patients undergoing ovarian stimulation is the gonadotrophin-releasing hormone (GnRH) antagonist protocol, with the possibility to trigger a mid-cycle LH surge using a single bolus of GnRH agonist, reducing the risk of developing ovarian hyperstimulation syndrome (OHSS) in high responders and the chance of cycle cancellation. This report describes the use of 0.2 mg triptorelin (Decapeptyl) to trigger ovulation in eight patients who underwent controlled ovarian hyperstimulation with recombinant FSH (rFSH, Puregon) and concomitant treatment with the GnRH antagonist ganirelix (Orgalutran) for the prevention of premature LH surges. All patients were considered to have an increased risk for developing OHSS (at least 20 follicles > or =11 mm and/or serum oestradiol at least 3000 pg/ml). On the day of triggering the LH surge, the mean number of follicles > or =11 mm was 25.1 +/- 4.5 and the median serum oestradiol concentration was 3675 (range 2980-7670) pg/ml. After GnRH agonist injection, endogenous serum LH and FSH surges were observed with median peak values of 219 and 19 IU/l respectively, measured 4 h after injection. The mean number of oocytes obtained was 23.4 +/- 15.4, of which 83% were mature (metaphase II). None of the patients developed any signs or symptoms of OHSS. So far, four clinical pregnancies have been achieved from the embryos obtained during these cycles, including the first birth following this approach. It is concluded that GnRH agonist effectively triggers an endogenous LH surge for final oocyte maturation after ganirelix treatment in stimulated cycles. Our preliminary results suggest that this regimen may prove effective in triggering ovulation and could be said to prevent OHSS in high responders. The efficacy and safety of such new treatment regimen needs to be established in comparative randomized studies.

Adult↗
PubMed2000

The DAZL1 gene is expressed in human male and female embryonic gonads before meiosis.

The human DAZL1 gene (known also as DAZH or DAZLA) is the autosomal homologue of the Y-chromosomal DAZ gene which has been found to be deleted in azoospermic males. Evidence suggests that the role of DAZL1 may not be restricted to spermatogenesis, but may include oogenesis as well. In order to study the function of human DAZL1 gene in the ovary, we observed its expression pattern during embryonic development. RNA in-situ hybridization showed that DAZL1 transcripts were localized to a subset of cells (somatic versus germ cells) in human embryonic ovary (23 weeks of gestation) and testis (21 weeks gestation). In the ovary, DAZL1 transcripts were found in oogonia and in oocytes and granulosa cells of primordial follicles. In the testis, DAZL1 transcripts were identified exclusively in the germ cells. Our results demonstrate high similarity between the human DAZL1 and the mouse Dazl1 gene expression patterns during embryonic development, suggesting that the human gene functions at the first phase of gametogenesis, just as in the mouse, where Dazl1 mutations cause male and female sterility.

Animals↗
PubMed2000

Differentiation of human embryonic stem cells into embryoid bodies compromising the three embryonic germ layers.

BACKGROUND: Embryonic stem (ES) cells are lines of cells that are isolated from blastocysts. The murine ES cells were demonstrated to be true pluripotent cells as they differentiate into all embryonic lineages. Yet, in vitro differentiation of rhesus ES cells was somewhat inconsistent and disorganized. The recent isolation of human ES cells calls for exploring their pluripotential nature. MATERIALS AND METHODS: Human ES cells were grown in suspension to induce their differentiation into embryoid bodies (EBs). The differentiation status of the human ES cells and EBs was analyzed by following the expression pattern of several lineage-specific molecular markers using reverse transcription polymerase chain reaction (RT-PCR) and in situ hybridization. RESULTS: Here we report the induction in vitro of cystic embryoid bodies from human ES cells. Our findings demonstrate induction of expression of cell-specific genes during differentiation of the human ES cells into EBs. In the human EBs, we could show a characteristic regional expression of embryonic markers specific to different cellular lineages, namely, zeta-globin (mesoderm), neurofilament 68Kd (ectoderm), and alpha-fetoprotein (endoderm). Moreover, we present a synchronously pulsing embryoid body that expresses the myocardium marker alpha-cardiac actin. In addition, dissociating the embryoid bodies and plating the cells as monolayers results in multiple morphologies, among them cells with neuronal appearance that express neurofilament 68Kd chain. CONCLUSION: Human ES cells can reproducibly differentiate in vitro into EBs comprising the three embryonic germ layers. The ability to induce formation of human embryoid bodies that contain cells of neuronal, hematopoietic and cardiac origins will be useful in studying early human embryonic development as well as in transplantation medicine.

Animals↗
PubMed1999

Cardiac compliance in fetuses of diabetic women.

OBJECTIVE: To examine possible changes in cardiac function in fetuses of pregestational diabetic mothers. METHODS: We conducted a prospective longitudinal study of 31 women whose pregnancies were between 22 weeks' gestation and term, and who had pregestational diabetes. All diabetic women included in the study had glycosylated hemoglobin lower than 6.5%. All patients included in the study had an early ultrasound confirming gestational age. Doppler studies of the blood flow through the mitral and tricuspid valves were done every 4 weeks using a pulsed-wave Doppler ultrasound device with a 3.5- or 5-MHz transducer. The following indices were calculated from the flow velocity waveforms: the peak velocity during the rapid ventricular filling (E wave) and during the atrial systole (A wave), and the ratio between these velocities (E/A ratio); and the velocity time integral of the atrioventricular blood flow (this integral correlates with volume flow). A comparison between the Doppler indices obtained in fetuses of diabetic women and of normal women was made by using the Mann-Whitney test. RESULTS: Each patient had four to five fetal echocardiographic examinations at 22, 26, 30, 34, and 38 weeks' gestation. The E/A ratio of the mitral and tricuspid valves did not increase in fetuses of diabetic women during the third trimester and was significantly higher in fetuses of nondiabetic women compared with fetuses of diabetic women at 34 and 38 weeks' gestation. The velocity time integral of the mitral and tricuspid valves multiplied by heart rate was higher, but not significantly, in fetuses of nondiabetic women compared with fetuses of diabetic women at 34 and 38 weeks' gestation. The E-wave of the mitral and tricuspid valves increased in both groups throughout gestation. The A-wave of the mitral and tricuspid valves increased only in fetuses of diabetic women throughout the third trimester and was significantly higher at 34 and 38 weeks' gestation compared with fetuses of nondiabetic women. CONCLUSION: Differences in atrioventricular blood flow patterns between fetuses of diabetic women and normal fetuses do not necessarily result from differences in cardiac compliance.

Diabetes, Gestational↗
PubMed1999

The effect of isosorbide dinitrate on placental blood flow and maternal blood pressure in women with pregnancy induced hypertension.

The effect of isosorbide dinitrate (ISDN) on maternal and fetal circulation was assessed in 23 women with pregnancy induced hypertension (PIH). A double-blind randomized design was employed. Each woman was given a sublingual tablet of ISDN (5 mg) or placebo. Maternal blood pressure (BP) and heart rate (HR) were measured before and every 2 min after the medication or placebo, for a total of 20 min. Flow velocity waveforms in the uterine and umbilical arteries were recorded at the same time periods, using pulsed Doppler ultrasound. The ratio of peak systolic to end-diastolic flow velocity (S/D) in those vessels was calculated. After ISDN mean maternal BP fell from 103 +/- 1.8 mm Hg to 90.5 +/- 2.9 mm Hg at 14 min (P < .0001) and mean maternal HR increased from 97.3 +/- 3.8 beats/min to 115.7 +/- 3.5 beats/min at 12 min (P < .0001). The mean S/D in the umbilical artery fell from 3.07 +/- 0.33 to 2.58 +/- 0.23 at 8 min (P < .0007). The mean S/D in the uterine artery fell from 3.27 +/- 0.6 to 2.38 +/- 0.28 at 10 min (P < .0001). In seven of 12 women with an early diastolic notch in the uterine artery flow velocity waveform the notch diminished or disappeared within the first 6 min after the medication. No significant change in any of the measured parameters was observed in the placebo group. Our finding that ISDN altered maternal and fetal hemodynamics in PIH lends support to the further exploration of nitric oxide donors in the treatment and prevention of pregnancy induced hypertension.

Adult↗
PubMed1999

Unequal pronuclear size--a powerful predictor of embryonic chromosome anomalies.

PURPOSE: Our purpose was to evaluate whether pronuclei of unequal size, observed in 13.7% of zygotes evaluated after in vitro fertilization (IVF), are predictive of chromosome anomalies in the developing embryo. METHODS: Five ploidy of 38 embryos grown from zygotes with unequal-sized pronuclei was assessed by fluorescent in situ hybridization (FISH). Twenty-six embryos developed after intracytoplasmic injection of sperm (ICSI) and 12 embryos were derived from conventional IVF. RESULTS: Chromosome anomalies were documented in the ICSI and IVF groups in 88.5 and 50% of cases, respectively. CONCLUSIONS: We suggest that FISH should be employed to examine the ploidy of zygotes with unequal pronuclei, prior to embryo transfer.

Adult↗
PubMed1999

A prospective randomized study comparing intramuscular with intravaginal natural progesterone in programmed thaw cycles.

A simple programmed thaw cycle is described, during which the endometrium is prepared with oral oestradiol, followed by a natural progesterone source. This method involves minimal blood tests and uses inexpensive medications. Originally, an i.m. progesterone-in-oil preparation was used. Although highly successful in achieving high serum progesterone concentrations, the daily injections of the oily compound were found to be problematic from the patients' perspective. To examine the possibility of replacing the injectable progesterone with a vaginal preparation we conducted a prospective randomized study of 1 year's duration, during which time 170 and 184 thawing cycles were done with injectable and vaginal progesterone respectively. Although the progesterone blood concentrations obtained with the injectable preparation were more than twice those obtained with the vaginal progesterone, the clinical pregnancy rates (defined as percentage thawing cycles with gestational sac(s)/embryo transfer as demonstrated on ultrasound, 4 weeks after embryo transfer) were similar for both groups (15.9 and 16.8% respectively). Implantation and abortion rates were also comparable. These results agree with previous reports of higher uterine progesterone concentrations after the vaginal application. We conclude that the combination of oral oestradiol and vaginal progesterone is an effective, simple and inexpensive approach for programmed thaw cycles.

Administration, Intravaginal↗
PubMed1999

Early transvaginal embryo aspiration: a safer method for selective reduction in high order multiple gestations.

Assisted reproduction technologies and ovulation induction for treatment of infertility continue to cause high order multiple gestations. Increased perinatal morbidity and mortality, as well as maternal morbidity, may complicate these pregnancies. Selective fetal reduction, an acceptable therapeutic approach in these cases, is usually performed at or after the ninth week of gestation, with KCl injected in the vicinity of the fetal heart, and is associated with a total pregnancy loss rate of 11.7%. We report our experience with 90 women who underwent early (mean 7.5 weeks gestation, range 7. 0-8.0 weeks) transvaginal selective embryo aspiration. The mean number of viable embryos before and after reduction was 3.5 and 2.1 respectively. Six (6.7%) pregnancies were lost before 24 gestational weeks. One miscarriage occurred at the tenth gestational week. The other five pregnancies were aborted at 17.3-21.6 weeks gestation. Additional interventions were performed in three of these pregnancies: genetic amniocentesis in two cases and cervical suture in one case. In the subset of 39 patients with>/=4 embryos, only one (2.6%) pregnancy loss was recorded. This loss rate is significantly lower (P < 0.05) than the 15.3% loss rate in patients with >/=4 fetuses calculated from other work. Four (4.4%) other pregnancies were complicated by premature delivery (25-28 weeks gestation). Mean gestational age of delivered pregnancies in our series was 35.7 weeks. In conclusion, early transvaginal embryo aspiration is a simple and relatively safe method for multiple pregnancy reduction. The overall pregnancy loss rate associated with early embryo aspiration is similar to that of procedures performed at later gestational age, but is significantly lower when the initial number of embryos is four or greater.

Evaluation Studies as Topic↗
PubMed1999

High doses of gonadotrophin-releasing hormone antagonist in in-vitro fertilization cycles do not adversely affect the outcome of subsequent freeze-thaw cycles.

The clinical application of gonadotrophin-releasing hormone (GnRH) antagonists instead of GnRH agonists, to prevent spontaneous premature luteinizing hormone surge during ovarian stimulation for assisted reproduction treatment has been advocated. A recent, double-blind, dose-finding study, including six dosages of the GnRH antagonist ganirelix, in women undergoing ovarian stimulation with recombinant follicle stimulating hormone (FSH), has indicated that high doses of GnRH antagonist (1 or 2 mg once daily) are associated with a low implantation rate. This follow-up study reports on the pregnancy rate after replacement of cryopreserved embryos obtained in stimulation cycles of the above-mentioned trial. Ovarian stimulation was initiated on day 2 of the cycle, with daily injections of 150 IU recombinant FSH. Ganirelix (0.0625, 0.125, 0.25, 0.5, 1.0 or 2.0 mg) was administered once daily from stimulation day 6 onwards, up to and including the day of human chorionic gonadotrophin. Retrieved oocytes were fertilized by in-vitro fertilization (IVF) or intracytoplasmic sperm injection and a maximum of three fresh embryos was transferred. Excess embryos were frozen, and subsequently used in either natural or programmed cycles. Until June 1998, 11 ongoing pregnancies (12-16 weeks after embryo transfer) were achieved from 46 cycles in which embryos had been first frozen (23.9% per transfer). Six of these 11 patients had been treated with a high dose of ganirelix (1.0 or 2.0 mg) during the IVF cycles in which the embryos were obtained. In conclusion, our data suggest that high dosages of ganirelix do not adversely affect the potential of embryos to establish clinical pregnancy in freeze-thaw cycles.

Adult↗
PubMed1998

Embryonic stem cell lines derived from human blastocysts.

Human blastocyst-derived, pluripotent cell lines are described that have normal karyotypes, express high levels of telomerase activity, and express cell surface markers that characterize primate embryonic stem cells but do not characterize other early lineages. After undifferentiated proliferation in vitro for 4 to 5 months, these cells still maintained the developmental potential to form trophoblast and derivatives of all three embryonic germ layers, including gut epithelium (endoderm); cartilage, bone, smooth muscle, and striated muscle (mesoderm); and neural epithelium, embryonic ganglia, and stratified squamous epithelium (ectoderm). These cell lines should be useful in human developmental biology, drug discovery, and transplantation medicine.

Animals↗
PubMed1998

Preimplantation diagnosis by FISH: the Rambam experience.

PURPOSE: Our purpose was to summarize our experience gained using fluorescence in situ hybridization for preimplantation diagnosis at the Rambam Medical Center. METHODS: Seventy-three embryos (29 cycles) were analyzed for preimplantation diagnosis for the following indications: advanced maternal age (> 39 years), X-linked diseases, poor-quality embryos, repeated failure in vitro fertilization cycles and fast-dividing embryos. An additional 38 embryos with unequal pronuclei size were examined for ploidy. Biopsy of embryonic blastomeres was performed at the six- to eight-cell stage. Five fluorescence probes, for chromosomes X, Y, 13, 18, and 21, were applied for ploidy detection. RESULTS: Eighty-four (87%) blastomeres of the 73 embryos analyzed showed clear signals. Six of the blastomeres were lost during spreading. Two of the embryos were destroyed following biopsy. No nucleus was found in five of the blastomeres, while in nine, more than one nucleus was verified. Transfer was performed in 10 patients (32 embryos). Two pregnancies were achieved. Two healthy babies were born. Fifty-seven percent of the fast-dividing embryos demonstrated normal signals. In two groups of embryos of unequal pronuclei size following conventional insemination and intracytoplasmic sperm injection, 50 and 11.4% demonstrated normal signals. CONCLUSIONS: The efficiency of fluorescence in situ hybridization for aneuploidy detection is 87 and 97% for autosomes and gonosomes, respectively. The preimplantation genetic diagnosis is suitable for selected in vitro fertilization cases including fast-dividing embryos and embryos with unequal pronuclei size following regular in vitro fertilization.

Adult↗
PubMed1998

The effect of a nitric oxide donor on Doppler flow velocity waveforms in the uterine artery during the first trimester of pregnancy.

Our objectives were to study the effect of a nitric oxide donor on uterine blood flow velocity waveforms and maternal heart rate and blood pressure during the first trimester of pregnancy. Eleven women were examined at 8-12 weeks' gestation, prior to elective termination of pregnancy. Each woman was randomly given a sublingual tablet containing 5 mg of isosorbide dinitrate or placebo, on two consecutive days. Measurements of maternal blood pressure, heart rate and Doppler flow velocity waveforms of the ascending branch of the main uterine artery were obtained before, and every 2 min (for 20 min) after taking the drug or placebo. Following administration of isosorbide dinitrate, the mean arterial blood pressure fell from a control value of 82.5 +/- 5.6 mmHg to a nadir of 73 +/- 4.1 mmHg at 16 min (p < 0.0001). The mean maternal heart rate increased from a control value of 80.9 +/- 2.8 beats/min to a peak of 90.4 +/- 4.6 beats/min at 10 min (p < 0.001). The mean resistance index in the uterine artery fell from a control value of 0.80 +/- 0.02 to a nadir of 0.73 +/- 0.03 at 10 min (p < 0.0001). Analysis of covariance was employed to compensate for the effect of heart rate on the resistance index. The drug had a significant effect on the resistance index in the uterine artery, independent of maternal heart rate. These results suggest that drugs such as isosorbide dinitrate may have a potential benefit under such conditions where the production of nitric oxide (i.e. endothelium-derived relaxing factor) is decreased.

Adult↗
PubMed1998

Growth of the fetal orbit and lens in normal pregnancies.

OBJECTIVE: To construct nomograms of the size of the fetal orbit and lens during gestation. SUBJECTS: The study group included 349 normal pregnant women at 14-36 weeks' gestation. METHODS: Routine biometric measurements were obtained in all the participants; these included biparietal diameter, head and abdominal circumferences, measurements of the long bones and the diameters of the fetal orbit and lens. The orbital and lens circumference measurements were also related to gestational ages. RESULTS: A linear growth function was observed between gestational age (GA) and orbital diameter (r = 0.94; p < 0.00001; y = -0.66 + 0.5 x GA), orbital circumference (r = 0.94; p < 0.00001; y = -2.1 + 1.5 x GA) and orbital area (r = 0.94; p < 0.00001; y = -98.1 + 8.3 x GA). Significant correlation was also found between femoral length (FL) and orbital diameter (r = 0.95; p < 0.00001; y = 3.3 + 1.9 x FL), orbital circumference (r = 0.95; p < 0.00001; y = 10.3 + 5.9 x FL) and orbital area (r = 0.93; p < 0.00001; y = -28.2 + 32.2 x FL). A linear growth function was observed between orbital circumference and biparietal diameter (r = 0.94; p < 0.00001) and head circumference (r = 0.95; p < 0.00001). A linear growth function was also observed between gestational age and the diameter of the lens (r = 0.89; p < 0.00001; y = 0.88 + 1.4 x GA) the circumference of the lens (r = 0.89; p < 0.00001; y = 2.78 + 0.4 x GA) and the area of the lens (r = 0.89; p < 0.00001; y = -7.95 + 1.0 x GA). The correlation was found between the ratios of the diameters, circumferences and areas of the lens and the orbit. CONCLUSIONS: These results provide normative data of the growth of the fetal orbit and lens and may aid future studies relating to fetal eye anomalies.

Adult↗
PubMed1998

First established pregnancy after controlled ovarian hyperstimulation with recombinant follicle stimulating hormone and the gonadotrophin-releasing hormone antagonist ganirelix (Org 37462).

This case report describes the first established pregnancy after the use of gonadotrophin-releasing hormone (GnRH) antagonist, ganirelix (Org 37462; Organon), to prevent a premature luteinizing hormone surge during ovarian hyperstimulation with recombinant human follicle stimulating hormone (rhFSH). The pregnancy progressed normally and ended with the birth of a healthy boy and a girl after an elective Caesarean section at gestational age of 37 weeks. This case illustrates, for the first time, the use of a GnRH antagonist in combination with a pure FSH preparation for ovarian stimulation.

Adult↗
PubMed1997

Fetal atrioventricular blood flow throughout gestation.

The relative contribution of rapid ventricular filling to total ventricular filling increases as gestational age advances. A possible explanation for this observation is that the fetal cardiac compliance improves throughout gestation.

Adult↗
PubMed1997

The presence of a sponsoring embryo in a batch of poor quality thawed embryos significantly increases pregnancy and implantation rate.

OBJECTIVE: To evaluate quantitatively the effect of one good-quality (sponsoring) embryo in a batch of low-quality thawed embryos on the implantation and pregnancy rates (PR). DESIGN: Retrospective analysis of data. SETTING: Tertiary care center IVF clinic affiliated with a university medical school. PATIENT(S): Between March 1988 and April 1995, 392 IVF patients underwent a total of 440 thawing and ET cycles of 1,436 multicellular embryos. MAIN OUTCOME MEASURE(S): Implantation, clinical pregnancy, and multiple pregnancy rates. RESULT(S): In the absence of sponsoring embryos in the thawed batch of embryos, a PR of 9.8% with an implantation rate of 3.1% was achieved. In the presence of a single sponsoring embryo, the PR nearly doubled (18.2%), with a significantly higher implantation rate of 7.0%. Only singleton pregnancies were achieved in the absence of sponsoring embryos compared with 21.7% multiple pregnancies in the single sponsoring embryo group. CONCLUSION(S): The presence of a sponsoring embryo in a batch of poor quality thawed embryos is an important factor that significantly increased pregnancy and implantation rates. The optimal strategy for planning batches of multicellular frozen embryos is to include at least one sponsoring embryo in each batch when possible. We speculate that the sponsoring embryo may favorably influence the chances of low-quality embryos to undergo successful implantation.

Adult↗