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Biomedical subjects

Y Yaron

Publications and source records attributed to Y Yaron.

At least 55 records · Page 3Linked to original sources

Alternatively spliced mRNA transcripts encoding the extracellular domain of the FSH receptor gene. Expression in the mouse ovary during the ovulatory cycle.

OBJECTIVE: To evaluate regulation of follicle-stimulating hormone (FSH) receptor expression in the mouse ovary during different stages of an artificially induced ovulatory cycle. STUDY DESIGN: Follicular maturation was achieved in pubertal female mice by pregnant mares' serum gonadotropin (PMSG). Ovulation was induced 48 hours later by human chorionic gonadotropin (hCG). Ovaries were harvested before treatment, at 24 and 48 hours after PMSG and at 3, 9 and 12 hours after hCG. RNA was extracted using a single-step isolation method and used for reverse transcription. The cDNA was amplified by polymerase chain reaction (PCR) using primers designed to amplify a 512-basepair product corresponding to the extracellular fragment of the FSH receptor. RESULTS: PCR products, resolved by electrophoresis on agarose gels, showed four bands corresponding to four discrete, alternatively spliced forms of the FSH receptor. Expression of the various transcripts varied at different stages of the ovulatory cycle such that the larger transcripts increased up to 48 hours following PMSG and began to decrease thereafter, reaching a trough 12 hours following hCG administration. Conversely, a smaller transcript reached a peak 9 hours following hCG administration and decreased thereafter. CONCLUSION: The various transcripts represent different FSH receptor mRNA splicing and may mediate changes in receptor function. Since these alternative spliced forms encode different portions of the extracellular domain, it is possible that they have altered hormone-binding affinity serving a regulatory purpose, such as decreasing hormone binding affinity.

Alternative Splicing↗

Differential increases in AFP, hCG, and uE3 in twin pregnancies: impact on attempts to quantify Down syndrome screening calculations.

Since the advent of multiple marker screening (MMS) for Down syndrome (DS) risk calculations, limitations for twins have been apparent. Recent attempts have been made to extrapolate mathematically singleton risks to twins. Here we investigate the pattern of levels among AFP, hCG, and uE3 in twins. MMS screening data from 4,443 twin pregnancies were compared to those from 258,885 singletons from 14-21 weeks of gestational age during a 3-year period (1992-1994) in our laboratory. Medians were determined for singletons and twins, and the ratios of twins to singletons were derived. Median AFP levels for twins are approximately double those of singletons, but median increases for hCG and uE3 are less than double. The data were divided further by ethnic groups (white, African American, Asian, and Hispanic), among which there were significant variations in medians, but not in the ratios of twins to singletons. The increased serum levels of different markers in twins are not consistent across analytes, possibly reflecting independent development of different compartments. Such differences mean that a mere mathematical conversion of singleton DS risks would be imbalanced among the analytes and cannot be applied reasonably to twins. Ethnic-specific databases are as important in twins as they are in singletons.

Biomarkers↗

The geriatric gravida: multifetal pregnancy reduction, donor eggs, and aggressive infertility treatments.

OBJECTIVE: Recent technologic advances and societal acceptance have dramatically increased the use of donor eggs for infertile couples who require assisted reproductive technologies. Now many "older" couples can access assisted reproductive technologies to achieve pregnancies. We sought to evaluate the changing pattern of patients referred for multifetal pregnancy reduction as a result of donor eggs and age factors in aggressive infertility treatment. STUDY DESIGN: Patients undergoing multifetal pregnancy reduction from 1986 to 1996 were included and categorized by year groupings, age, and the use of donor eggs. RESULTS: A total of 523 patients were referred for and underwent multifetal pregnancy reduction. Before 1994, only 4 of 226 (1.8%) had received donor eggs, whereas in 1994 to 1996, 29 of 297 (9.8%) had received donor eggs (chi 2 = 12.6, p < 0.001). Eight of 9 patients aged > or = 45 years undergoing multifetal pregnancy reduction received donor eggs. There were no patients aged > or = 45 years before 1994 but 9 in 1994 to 1996. Four of 9 patients aged > or = 45 years with multifetal pregnancies chose reduction to singleton gestation. The proportions of patients aged > or = 40 years have increased from 0% to 11% in the last 8 years. CONCLUSIONS: The availability of donor eggs has dramatically increased the use of assisted reproductive technologies and subsequent use of multifetal pregnancy reduction in older patients. Older patients are more inclined to want reduction to singleton gestation; they cite parental demands, financial issues, and their ability to parent in their 60s and 70s as reasons for reduction to singleton gestation.

Adult↗

Race-ethnicity-specific variation in multiple-marker biochemical screening: alpha-fetoprotein, hCG, and estriol.

OBJECTIVE: To identify any race-ethnicity-specific differences in serum alpha-fetoprotein (AFP), hCG, and unconjugated estriol (E3) levels in women between 14 and 21 weeks' gestation. METHODS: Data from the 3-year period 1992-1994 were analyzed from 208,257 women who had AFP screening, of whom 155,142 also had hCG and 62,121 also had E3 screened, between 14 and 21 weeks' gestation. Subjects were categorized into four groups: white, black, Asian, and Hispanic. RESULTS: There was a consistent pattern of analyte differences across gestational ages. Levels for AFP were generally higher in Asian and black women than in Hispanic and white women (median AFP at 16 weeks-31.2, 30.9, 27.4, 27.3, respectively), and levels of hCG and E3 were highest in Asians (hCG at 16 weeks-34.7, 30.3, 28.2, 26.8, respectively). Weight correction for AFP, hCG, and E3 levels did not compensate for the ethnic differences. CONCLUSIONS: Because hCG and E3 demonstrate the same general pattern of differences as AFP among ethnic groups, averaging values for all ethnic groups tends inappropriately to lower calculated Down syndrome risks for black and Asian women. Additionally, the slopes of the curves are not parallel, such that separate data bases are preferable to multiplicative correction factors. Separate data bases should be used in laboratories with volume sufficient to permit the establishment of race-ethnicity-specific regressions. Use of separate data bases should result in more accurate screening.

Chorionic Gonadotropin↗

Gene therapy. Is the future here yet?

Despite the overwhelming number of articles on gene therapy that have been published in the last few years, there is a paucity of trials that have successfully demonstrated the clinical usefulness of this modality. The enthusiasm characterizing some of the earlier studies has given way to a more realistic approach. The next step is to develop more efficient vectors for effective targeting and persistent gene expression.

Forecasting↗

Genetic testing for male infertility: a postulated role for mutations in sperm nuclear matrix attachment regions.

Numerous reports have suggested that disturbances in nuclear condensation may result in male infertility. This notion has been supported by the observation of infertile individuals with a decrease or absence of the male sperm-specific chromatin packaging protamine proteins. To date, no correlation between the absence of protamine proteins and a mutation within the coding regions of the protamine genes has been documented. To address this issue, PCR-based mutation scanning analysis has been performed across the human male haploid expressed PRM1-->PRM2-->TNP2 domain in several oligozoospermic infertile individuals. This analysis identified a candidate mutation in a region of contact with the sperm nuclear matrix from 2 of 5 affected individuals. This is the first report of a mutation scan covering the entire PRM1-->PRM2-->TNP2 locus in affected individuals.

Chromosomal Proteins, Non-Histone↗

The optimal number of embryos to be transferred in shared oocyte donation: walking the thin line between low pregnancy rates and multiple pregnancies.

There has been growing concern about the number of multiple gestations resulting from assisted reproductive technologies. For in-vitro fertilization (IVF), there are guidelines concerning the number of embryos to be transferred. In oocyte donation, however, there is a paucity of studies addressing this issue and common practice is extrapolated from standard IVF procedures. This may not be correct since endometrial receptivity has been shown to be altered in oocyte donation. Thus the purpose of this study was to assess the optimal number of embryos to be transferred in oocyte donation. The study population included 254 patients with ovarian failure who underwent a total of 601 embryo transfers in a single shared oocyte donation programme. Pregnancy rates (PRs), multiple pregnancies, triplet pregnancy rates, and implantation rates were evaluated according to the number of embryos transferred. A significant linear increase in PRs was noted with the increasing number of embryos transferred up to five (11.1% for one embryo, 36.7% for five embryos). Multiple pregnancies increased significantly from 15.8% for two embryos transferred, to 44.4% for five embryos. The rate of triplet pregnancies also increased from 2.7% for three embryos transferred, to 8.3% for five embryos. Optimization of the number of embryos to be transferred is discussed.

Adult↗

Second-trimester maternal serum alpha-fetoprotein, human chorionic gonadotropin, and unconjugated oestriol after early transvaginal multifetal pregnancy reduction.

Maternal serum alpha-fetoprotein (MSAFP), human chorionic gonadotropin (hCG), and unconjugated oestriol (UE3) are used as second-trimester screening markers for the detection of various fetal abnormalities. Previous studies have suggested that second-trimester MSAFP is consistently elevated after late first-trimester transabdominal multifetal pregnancy reduction (MFPR). The present study was undertaken to evaluate the levels of all three markers after early transvaginal MFPR. Maternal serum was examined for MSAFP, hCG, and UE3 at 16-18 weeks' gestation in 28 patients who underwent transvaginal MFPR at approximately 10 weeks' gestation. The mean interval between the reduction procedure and the screening test was 7.2 +/- 0.9 weeks. The mean MSAFP value in 24 patients carrying viable twins was 2.49 +/- 0.99 multiples of the median (MOM). Two patients had elevated MSAFP values: one in association with omphalocoele and the other in relation to an adverse pregnancy outcome. All but two patients had normal hCG values (mean 1.98 +/- 1.26 MOM). Two cases with elevated hCG were associated with an adverse pregnancy outcome. Unconjugated oestriol values were within the normal range in all patients (mean 1.69 +/- 0.61 MOM). These results suggest that early transvaginal MFPR, at approximately 10 weeks' gestation, does not appear to influence second-trimester MSAFP, hCG, and UE3 levels. The values of these markers may therefore be interpreted by using the same criteria as those for the general obstetric population.

Adult↗

Abnormal nuchal findings on screening ultrasonography: aneuploidy stratification on the basis of ultrasonographic anomaly and gestational age at detection.

OBJECTIVE: Our purpose was to determine the specific likelihood of different aneuploidies by gestational age in patients with nuchal folds and simple and septated nuchal membranes. STUDY DESIGN: Retrospective database analysis was performed of 158 consecutive patients with a nuchal fold or simple or septated nuchal membrane on either abdominal or vaginal ultrasonography. RESULTS: Thirty-eight patients with nuchal folds, 65 with simple nuchal membranes, and 55 with septated nuchal membranes were evaluated. Septated nuchal membranes were associated with the highest incidence of karyotypic abnormalities (> 50%). A peak incidence of trisomy 21 (27%) was found in the early midtrimester, leveling off to 11% by the late midtrimester. The late first trimester had a high incidence of trisomy 18 (22%), occurring more frequently than 45,X. CONCLUSION: Ultrasonographic anomalies in the posterior neck are associated with aneuploidy from 21% to 58% of the patients in this selected population. Each anomaly has different risks for aneuploidy type, varying with gestational age at diagnosis.

Aneuploidy↗

Pregnancy outcome after multifetal pregnancy reduction to twins compared with spontaneously conceived twins.

Multifetal pregnancy reduction (MFPR) appears to be an efficacious method for improving the perinatal outcome of 'high order' multifetal gestations. The present study was undertaken to evaluate pregnancy outcomes after MFPR to twins in comparison with spontaneously conceived twins. In all, 10 patients with quadruplet gestation (group 1) and 30 patients with triplet gestation (group 2), who underwent MFPR to twins, were prospectively enrolled. Pregnancy complications, gestational age at delivery, mode of delivery and birthweights were compared with 30 consecutive spontaneous twin gestations (group 3) matched by maternal age and parity. Mean gestational age at delivery and mean birthweights were significantly lower in group 1, compared with groups 2 and 3 (33.2, 35.9, 36.9 weeks, and 1843, 2209, 2361 g respectively). The incidence of pregnancy complications was significantly higher in group 1 compared with group 3. There was also a clear trend of increased incidence of specific pregnancy complications in group 1 compared with groups 2 and 3, especially premature contractions (PMC; 50, 27 and 13% respectively), and pregnancy-induced hypertension (PIH; 40, 23 and 7% respectively). In conclusion, the initial number of fetuses before reduction was inversely correlated with gestational age at delivery and birthweight, and positively correlated with pregnancy complications. Contrary to previous studies, we found a higher incidence of pregnancy complications after MFPR compared with spontaneous twins, especially PMC and PIH.

Adult↗

Prospective study of incidence and predisposing factors for clavicular fracture in the newborn.

OBJECTIVE: To determine the incidence of clavicular fracture, associated fetal and maternal risk factors and its connection with quality care control. SUBJECTS AND METHODS: A total of 3030 newborns delivered vaginally were evaluated for clavicular fractures by three separate physicians. The study group included all newborns with fractured clavicle. A control group consisted of 52 newborns delivered vaginally with no history of fractures. Maternal records were evaluated for possible predisposing factors. RESULTS: Forty-six (l.5%) newborns were found to have clavicular fractures. When compared to the control group, they were found to have a higher birthweight (3710+/-352gm vs 3235+/-405gm) an older maternal age (30.5+/-5 bs 27.7+/-6), a longer second stage of labor (34 min vs 23 min), higher rate of instrumental deliveries (13/46 vs 6/52) and shoulder dystocia (6/46 vs 1/52). Nearly 80% of newborns with clavicular fractures weighed less than 4000 gm. Multivariate analysis demonstrated two independent variables; birthweight over 3500 gm and maternal age >29. CONCLUSION: Clavicular fractures are associated with higher birthweight, older maternal age, longer second stage of labor, instrumental deliveries and shoulder dystocia. However, in most cases this injury cannot be predicted prior to delivery and thus cannot be an indicator of quality control.

Apgar Score↗

Patients with Turner's syndrome may have an inherent endometrial abnormality affecting receptivity in oocyte donation.

OBJECTIVE: To evaluate whether endometrial receptivity is compromised in patients with premature ovarian failure (POF) due to Turner's syndrome who undergo oocyte donation. DESIGN: Retrospective analysis. SETTING: In vitro fertilization-ET units, anonymous oocyte donation program. PATIENTS: The study included 53 patients with POF who underwent oocyte donation. These included 7 patients with Turner's syndrome (45,X) who underwent 22 ET cycles, 15 women with Turner variants (mosaics, deletions, or isochromosomes) who underwent 36 ET cycles, and 31 other patients with POF and a normal karyotype who underwent 69 oocyte donation cycles. INTERVENTION: All patients on standby for donation were treated with E2 valerate 6 mg/d until oocytes became available; then P 100 mg/d was added. Oocyte donors were healthy women < 34 years who underwent IVF themselves. MAIN OUTCOME MEASURES: Clinical pregnancy rates (PRs), biochemical pregnancies, early abortions, and delivery rates were evaluated. RESULTS: Turner's syndrome patients had a significantly higher rate of biochemical pregnancies (22.7% versus 4.3%), a lower clinical PR (22.7% versus 33.3%), a significantly higher rate of early abortions (60% versus 8.7%), and a significantly lower rate of deliveries per pregnancy (20.0% versus 73.1%) compared with non-Turner patients. CONCLUSIONS: Patients with a complete or partial deficiency of an X chromosome have reduced PRs and an increase in early implantation failure after oocyte donation. This may indicate an inherent endometrial abnormality, possibly associated with a deficiency of X-linked genes regulating endometrial receptivity.

Adult↗

The development of the fetal eye: in utero ultrasonographic measurements of the vitreous and lens.

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.

Cross-Sectional Studies↗

In vitro fertilization and oocyte donation in women 45 years of age and older.

OBJECTIVE: To assess the reproductive potential in women > or = 45 years of age. DESIGN: Retrospective analysis. SETTING: In vitro fertilization-embryo transfer unit, standard IVF and oocyte donation programs. PATIENTS: One hundred twenty-seven patients > or = 45 years old who applied for treatment of infertility. INTERVENTION: Thirty-one patients underwent 52 treatment cycles in standard IVF. Ninety-six patients underwent 220 oocyte donation cycles. RESULTS: Of the 52 standard IVF cycles, oocytes were retrieved successfully in only 32. Of these, fertilization and ET were performed in 21 cycles. None of these treatment cycles resulted in a clinical pregnancy. Of the 220 oocyte donation cycles, fertilization and ET were accomplished in 189 cycles. These resulted in 33 (17.5% per transfer) clinical pregnancies. CONCLUSIONS: These results suggest that oocyte donation may extend the reproductive potential in women > or = 45 years old when little hope is offered by standard IVF.

Embryo Transfer↗

Transfer of six or more embryos improves success rates in patients with repeated in vitro fertilization failures.

OBJECTIVE: To examine the results of six or more embryos transferred to patients whose IVF-ET cycles repeatedly met with failure. DESIGN: Prospective clinical evaluation of pregnancy rates and pregnancy outcome. SETTING: IVF-ET Unit. PATIENTS: Seventy-two IVF patients who had failed at least four previous IVF cycles. INTERVENTIONS: Forty-one patients (group A) received six or more embryos, and 31 patients (group B) chose to receive five embryos. MAIN OUTCOME MEASURES: Per embryo implantation rate, pregnancy rate, multiple pregnancies, and outcome were evaluated. RESULTS: With the transfer of six or more embryos, the pregnancy rate was significantly higher than with the transfer of five embryos (56% versus 29%, respectively). This was associated with a slight, but insignificant, increase in multiple gestations. No difference in pregnancy outcome was noted among the groups. CONCLUSIONS: Patients who have had repeated IVF failures may have higher pregnancy rates if six or more embryos are transferred in subsequent cycles.

Adult↗

Uterine preparation with estrogen for oocyte donation: assessing the effect of treatment duration on pregnancy rates.

OBJECTIVE: To assess the effect of the duration of uterine preparation with E2 on pregnancy rates (PRs) in oocyte donation. DESIGN: A retrospective study. SETTING: IVF-ET Unit, oocyte donation program. PATIENTS: Four hundred eleven patients undergoing 865 ET cycles after oocyte donation. Uterine preparation consisted of 6 mg/d E2 valerate. The duration of treatment varied according to the availability of the oocytes for donation. Progesterone, 100 mg/d, was added upon oocyte retrieval. Patients were divided into seven groups according to the duration of uterine preparation with E2, in 5-day ranks. MAIN OUTCOME MEASURES: Pregnancy rates per ET according to the duration of uterine preparation. RESULTS: No differences were noted in the mean age, number of oocytes received, fertilization rates, or number of embryos transferred when comparing all groups. Pregnancy rates ranged from 19% to 27% for E2 treatment of 5 to 35 days. CONCLUSION: Endometrial preparation in anonymous oocyte donation programs is achieved with continuous administration of E2 until oocytes become available. Our results show that this treatment may be extended for as long as 5 weeks with no significant decrease in PRs.

Adult↗

The effect of an in-vitro fertilization pregnancy on a woman with genital tuberculosis.

The coexistence of an in-vitro fertilization (IVF) pregnancy and genital tuberculosis may pose life-threatening consequences. This case report describes catastrophic dissemination of latent genital tuberculosis, followed by IVF and pregnancy. The role of both IVF manipulation and the pregnancy itself in the exacerbation of latent tuberculosis is discussed. In addition, some measures for the detection, follow-up and treatment of latent genital tuberculosis in patients who undergo IVF are proposed.

Adult↗