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Biomedical subjects

Yuval Yaron

Publications and source records attributed to Yuval Yaron.

33 records · Page 2Linked to original sources
PubMed2002

Decreased first trimester PAPP-A is a predictor of adverse pregnancy outcome.

OBJECTIVE: Low levels of maternal serum pregnancy associated plasma protein-A (PAPP-A) have been linked to chromosome anomalies such as trisomy 21, 13 and 18, triploidy and sex chromosome aneuploidy. Low levels of PAPP-A have also been implicated in spontaneous miscarriage. The purpose of this study was to evaluate whether low levels of first trimester PAPP-A are predictive of other adverse pregnancy outcomes. STUDY DESIGN: The study included patients with singleton pregnancies who underwent combined first trimester screening using nuchal translucency (NT) and maternal serum free beta-human chorionic gonadotrophin (free beta-hCG) and PAPP-A at 10-13 weeks' gestation. Patients with chromosome aberrations or fetal anomalies were excluded. Serum marker levels were expressed as gestational age-specific multiples of the median (MoMs). The incidences of various adverse pregnancy outcomes (spontaneous preterm labor, fetal growth restriction (FGR), proteinuric and non-proteinuric pregnancy induced hypertension (PIH), intrauterine fetal demise, oligohydramnios, spontaneous miscarriage and placental abruption) were evaluated, according to maternal PAPP-A MoM levels. RESULTS: Of the 1622 patients in the study, pregnancy complications were observed in 184 (11.3%). Patients with PAPP-A < or =0.25 MoM had significantly higher rates of FGR (RR = 3.12), proteinuric PIH (RR = 6.09), spontaneous miscarriage (RR = 8.76). No statistically significant differences were noted for other adverse outcomes evaluated Women with PAPP-A < or =0.50 MoM also had significantly higher rates of FGR (RR = 3.30) and spontaneous miscarriage (RR = 3.78). CONCLUSIONS: We conclude that decreased levels of first trimester maternal serum PAPP-A are predictive not only of chromosome anomalies but also of adverse pregnancy outcome.

Adult↗
PubMed2002

Third-trimester unexplained intrauterine fetal death is associated with inherited thrombophilia.

OBJECTIVE: To determine the risk of thrombophilias in women with unexplained intrauterine fetal deaths (IUFD). METHODS: All women with IUFD at 27 weeks' gestation or greater were initially assessed during a period of 26 months. Subjects with multiple pregnancies, congenital anomalies, intrauterine infection, chorioamnionitis, immune hydrops, diabetes mellitus, previous thromboembolism, and severe hypertensive disease were excluded. The remaining 40 women with unexplained IUFD (study group) were matched for age and ethnicity with 80 healthy women who had at least one normal pregnancy (control group). All participants were tested at least 2 months after delivery for mutations of factor V Leiden, prothrombin gene, methylenetetrahydrofolate reductase, and for deficiencies of protein S, protein C, and antithrombin III. They were also tested and found to be negative for anticardiolipin antibodies. RESULTS: The gestational age at delivery and birth weight were significantly lower in the study group. The prevalence of inherited thrombophilias was 42.5% in the study group compared with 15% in the control group (odds ratio 2.8, 95% confidence interval 1.5, 5.3, P =.001). The prothrombin mutation and protein S deficiency rates were significantly higher in the study group (odds ratio 2.3, 95% confidence interval 1.3, 4.0, and odds ratio 3.2, 95% confidence interval 2.4, 4.1, respectively). CONCLUSION: Third-trimester IUFD is significantly associated with thrombophilias. These findings suggest that thrombophilia work-ups should be part of IUFD investigations and may have therapeutic and prognostic implications in future pregnancies.

Adult↗
PubMed2002

The mitochondrial DNA mutation (deltamtDNA5286) in human oocytes: correlation with age and IVF outcome.

PURPOSE: To evaluate the correlation between the presence of a newly described mitochondrial DNA (mtDNA) mutation (deltamtDNA5286), patients' age, and in vitro fertilization (IVF) outcomes. METHODS: The presence of deltamtDNA5286 was analyzed by nested-primer PCR in 224 unfertilized oocytes of 81 women undergoing IVF for various reasons. Age, number of oocytes retrieved, fertilization and embryo cleavage, number of embryos transferred, and pregnancy rates were compared between patients with and without a mtDNA mutation in their oocytes. RESULTS: The 23 patients in which deltamtDNA5286 was detected in at least one oocyte were significantly younger than the other 58 with no mutations (30.9 years vs. 33.8 years, respectively, P = 0.03), and had a significantly lower fertilization rate (28.9% vs. 42.1%, respectively, P = 0.01). No other outcome variable was significantly different between the two groups. CONCLUSION(S): The mtDNA mutation deltamtDNA5286 may serve as a marker of decreased oocyte quality in IVF.

Adult↗
PubMed2002

Screening.

Historically, obstetrician/gynaecologists have utilized screening procedures as a major component of their routine clinical practice. The Papanicolaou (Pap) smear technique for cervical cancer is more than 50 years old and has saved countless lives by identifying who among the supposedly low-risk group of patients is in fact at high risk of cervical cancer. The introduction of alpha-fetoprotein screening for neural tube defects in the 1970s, low alpha-fetoprotein level for Down syndrome in the 80s, multiple markers in the 90s and now, after the millennium combined ultrasound and biochemistry for a more precise risk identification, has radically changed our approach towards optimizing the sensitivity, specificity and positive and negative predictive values of screening. As these techniques improve, old mainstays of attributable risks such as advanced maternal age will probably fade into oblivion as stand-alone criteria. The specifics of screening techniques will vary by disorder, but the general principles are important and can be applied to all new technologies as they come on line. In fact, the real 'take-home message' is that one must use these principles when looking at new technologies to understand their role in emerging practice.

Adult↗
PubMed2002

Maternal serum HCG is higher in the presence of a female fetus as early as week 3 post-fertilization.

BACKGROUND: Maternal serum HCG (MSHCG) is higher when the fetus is a female than when it is male. This has been demonstrated in the second and third trimesters of pregnancy, and recently at 10-14 weeks gestation. In this study we assessed whether this gender-related difference can be detected as early as week 3 post-fertilization. METHODS: The IVF setting was chosen because it provides precise dating of gestational age and early sonography for the number of gestational sacs. The study included 347 IVF cycles from 335 patients. Only pregnancies with a single implanted embryo that resulted in a single live birth of known gender were included. MSHCG was measured on days 14-20 post-fertilization, and levels were expressed as gestational age-corrected multiples of the median (MoMs). The log10 MSHCG MoMs were compared according to fetal gender. RESULTS: MSHCG levels were significantly higher (18.5%) in week 3 post-fertilization in the presence of a female fetus (P < 0.0002). CONCLUSION: Because a fetal gender-related difference in MSHCG can be demonstrated as early as week 3 post-fertilization, the difference may be attributed to placental factors and not to the effects of the fetal hypothalamic-hypophyseal-gonadal axis.

Chorionic Gonadotropin↗
PubMed2002

Rett syndrome: clinical manifestations in males with MECP2 mutations.

Rett syndrome is a neurodevelopmental disorder characterized by cognitive and adaptive regression with autistic features, loss of acquired skills, and stereotypic hand movements that almost exclusively affects females. It is an X-linked dominant disorder, with presumed lethality in males. Nonetheless, there are a few descriptions of males suspected of having Rett syndrome. With the recent discovery that the MECP2 gene is responsible for most cases of Rett syndrome, it is possible to molecularly assess cases of affected males by direct sequencing analysis. We describe an Israeli family consisting of a female having classic Rett syndrome and a male sibling with severe neonatal encephalopathy. Molecular analysis revealed that both sister and brother have the same MECP2 gene mutation; however, their mother does not. This case, as well as other published studies of males with MECP2 mutations, reveals that the clinical manifestations in viable males vary from neonates with severe encephalopathy to adults with mental retardation and demonstrate genotype-phenotype correlations.

Abnormalities, Multiple↗
PubMedDate not supplied

Spontaneous abortions in couples declining multifetal pregnancy reduction.

Multifetal pregnancy reduction (MFPR) has clearly improved the outcomes of multifetal gestations. Several recent reports have also suggested improved outcomes in nonreduced cases, but there have been methodologic concerns about the denominators, i.e. have all cases been included and is there a 'hidden mortality' of unknown lost cases. Here we assessed the outcome of patients telephoning to discuss MFPR, but who chose not to have the procedure. Over a 3-year period, 446 patients had MFPR by one operator. Nineteen patients chose not to have the procedure. There were 11 preterm births, 1 term delivery, and 5 spontaneous losses (7 of 17) prior to 24 weeks, a loss rate of 35%. Two patients delivering triplets had a loss of 1 fetus/neonate. These data suggest that the loss rates of nonreduced pregnancies may be higher than generally thought, making the improvements with MFPR even bigger than generally realized.

Abortion, Spontaneous↗
PubMedDate not supplied

First trimester maternal serum free human chorionic gonadotropin as a predictor of adverse pregnancy outcome.

OBJECTIVE: The purpose of this study was to evaluate whether abnormal levels of first trimester maternal serum free human chorionic gonadotropin (beta-hCG) are predictive of adverse pregnancy outcomes. METHODS: The study included 1,622 consecutive patients with singleton pregnancies who underwent first trimester Down syndrome screening using nuchal translucency, and maternal serum free beta-hCG and pregnancy-associated plasma protein-A. Patients with fetal anomalies or chromosome aberrations were excluded from the study. The incidences of various adverse pregnancy outcomes were evaluated according to maternal serum free beta-hCG levels. Outcome variables included spontaneous miscarriage, proteinuric and non-proteinuric pregnancy-induced hypertension, fetal growth restriction, intrauterine fetal demise, spontaneous preterm delivery, oligohydramnios and placental abruption. RESULTS: No significant differences were noted between groups for any of the demographic variables. The only statistically significant result was an increase in the relative risk for spontaneous miscarriage (RR = 6.33) at free beta-hCG <0.2 multiples of the medians. No other statistically significant result was noted for the other adverse outcomes or for the overall complication rate. CONCLUSION: Low free beta-hCG is associated with a higher incidence of spontaneous miscarriage but is a poor predictor of other pregnancy complications.

Abortion, Spontaneous↗
PubMedDate not supplied

Demographic factors for utilization of invasive genetic testing after multifetal pregnancy reduction.

OBJECTIVE: Pregnant infertility patients are commonly old enough to be offered prenatal diagnosis. However, they may be reluctant to undergo an additional invasive procedure. We, therefore, sought to determine what demographic factors, including race and ethnic group, influenced patients' decisions to undergo genetic testing in addition to multifetal pregnancy reduction (MFPR). METHODS: We retrospectively reviewed MFPR patients from July 1997 to June 1999 at our institution. Invasive genetic testing was routinely discussed. Maternal age, race, ethnicity, religion, egg source for in vitro fertilization (IVF) patients, and the remaining fetuses following MFPR were analyzed for invasive genetic testing determinants and were compared to our experiences with genetic referents to us for singleton pregnancies. 132 consecutive patients, of whom 49 were >/=35 years, including 15 having IVF with donor eggs, were included. RESULTS: Maternal age was the single most significant determinant of testing. In donor egg cases, donor age was significant. Ethnic background, previous children, and the remaining number of fetuses after MFPR were also significant determinants. CONCLUSION: MFPR patients share similar demographics to the advanced maternal age population. Despite the very stressful situations, our data suggest that maternal age, and therefore genetic risk, is the most important determinant of choosing whether or not to have testing. However, patients' decisions are, to varying degrees, modified by religious and ethnic considerations.

Adult↗
PubMedDate not supplied

A comparison between maternal serum free beta-human chorionic gonadotrophin and pregnancy-associated plasma protein A levels in first-trimester twin and singleton pregnancies.

OBJECTIVES: To determine the levels of first-trimester free beta-human chorionic gonadotrophin (free betahCG), pregnancy-associated plasma protein A (PAPP-A) and nuchal translucency (NT) in twin pregnancies. METHODS: The study included 93 patients with twin pregnancy and 4,977 with singletons who underwent first-trimester testing using free betahCG, PAPP-A and NT at 10-13 weeks of gestational age. RESULTS: In twin pregnancies, the maternal serum free betahCG level was 2.18 higher and the PAPP-A level was 2.38 higher than in singleton pregnancies. These marker levels were significantly higher than the expected 2.0 multiples of the median (MoM). In contrast, NT values did not differ between twins and singletons. CONCLUSION: These data may be used to establish first-trimester combined screening for twin pregnancies.

Adult↗
PubMedDate not supplied

Multiplex nested PCR for preimplantation genetic diagnosis of spinal muscular atrophy.

OBJECTIVE: Spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular disorder caused in most patients by homozygous deletion of the SMN1 gene. For a carrier couple at a 25% risk of affected offspring, preimplantation genetic diagnosis (PGD) offers an alternative to prenatal diagnosis and termination of affected pregnancies. Our objective was to develop an accurate and reliable single-cell multiplex nested PCR analysis for PGD of SMA. METHODS: The method was developed on single blood leukocytes, obtained from healthy controls and an adult SMA type III patient with a known homozygous deletion of SMN1 exon 7 and 8. Multiplex nested PCR on single cells was used to co-amplify exons 7 and 8 of SMN. Additional multiplexing was performed with the ZFX/ZFY gene for sexing. Following successful establishment of the multiplex nested PCR protocol in single leukocytes, the technique was employed for PGD in 4 patients for a total of 7 cycles. In 2 patients, sexing was simultaneously performed using ZFX/ZFY. RESULTS: 220 single leukocytes from a normal individual and 220 from an SMA patient were analyzed. Exon 7 of SMN1 was amplified in 99% of normal single leukocytes and in none of the SMA-affected leukocytes. Exon 7 of SMN2 was amplified in 100% of both normal and SMA-affected leukocytes. Exon 8 of SMN1 was amplified in 98% of normal cells and in none of the SMA-affected leukocytes. Exon 8 of SMN2 was amplified in 96% of both normal and SMA-affected leukocytes. Amplification efficiency was 99% for ZFX/ZFY. There were no false-negative results and no contamination was detected in all wash-drop blanks tested. Seven PGD cycles were performed in 4 SMA-carrier couples with successful molecular analysis of 34 embryos and a total of 15 normal embryos transferred in 7 cycles. One clinical pregnancy has resulted in the delivery of a healthy male. Amniocentesis performed at 17 weeks confirmed the correct diagnosis for both SMA and sexing. CONCLUSIONS: These results suggest that our multiplex nested PCR protocol offers an efficient and accurate method for PGD of SMA while enabling the simultaneous analysis of an additional loci.

Adult↗
PubMedDate not supplied

Nomograms for the sonographic measurement of the fetal philtrum and chin.

OBJECTIVE: To generate nomograms for the sonographic measurement of the fetal philtrum and chin during pregnancy. DESIGN: A prospective, cross-sectional study in normal singleton pregnancies. SUBJECTS: One hundred and fifty-three fetuses between 13 and 42 weeks of gestation were studied. METHODS: The philtrum was measured from the base of the columella to the upper lip. The chin was measured from the tip of the lower lip to the skin under the lower tip of the mandible. Predictive models were evaluated to generate graphic description of the 5th, 50th and 95th centiles for the fetal philtrum and chin. RESULTS: Fetal philtrum length increased with gestational age. The regression equation for the philtrum length (y) according to gestational age in weeks (x) is best predicted by the S-curve (Gompertz) model, as described by the following equation: y = exp(a + b/x), where a = 2.778577, and b = -23.476723 (R(2) = 85.3%, p < 0.0001). The fetal chin length increased with gestational age. The regression equation for the mean chin length (y) according to gestational age in weeks (x) is best predicted by the S-curve model as described in the following equation. y = exp(a + b/x), where a = 3.7922, b = -28.043, (R(2) = 89.0%, p < 0.0001). CONCLUSIONS: The nomograms generated in this study for the fetal philtrum and chin during pregnancy can be used in confirming subjective impression of facial dysmorphism.

Chin↗
PubMedDate not supplied

2nd-trimester maternal serum human chorionic gonadotropin and alpha-fetoprotein levels in male and female fetuses with Down syndrome.

BACKGROUND/OBJECTIVE: Several studies have shown that the 2nd-trimester maternal serum alpha-fetoprotein (AFP) level is significantly lower and that the maternal serum human chorionic gonadotropin (hCG) level is significantly higher in the presence of a female fetus. This may potentially affect Down syndrome (DS) screening such that a higher false-positive rate may occur in women carrying a female fetus, whereas a lower detection rate may result in those carrying males. The purpose of this study was to evaluate the gender impact on marker levels in DS pregnancies and its effect on DS screening. METHODS: The study included 62 DS pregnancies with a single fetus of known gender (31 male and 31 female). Only pregnancies with chromosomal analysis showing trisomy 21 were included. The maternal serum levels of hCG, AFP, and unconjugated estriol were measured at 16-20 weeks of pregnancy. These levels were expressed as gestational-age-corrected multiples of the median. RESULTS: No statistically significant differences were noted in maternal serum levels of hCG or AFP in DS pregnancies between women carrying a female and those carrying a male DS fetus. No statistically significant differences in 'screen-negative' rates were noted among male and female fetuses. CONCLUSIONS: In normal pregnancies, the maternal serum hCG level is higher, and the AFP level is lower in the presence of a female fetus. However, this gender-related difference is not apparent in DS pregnancies. Therefore, the gender-related differences in serum marker levels would not result in a lower detection rate of DS in male fetuses.

Adult↗
PubMedDate not supplied

Preimplantation genetic diagnosis of Canavan disease.

OBJECTIVE: Canavan disease is an autosomal recessive disorder which is relatively common in Ashkenazi Jews. It is characterized by developmental delay, severe hypotonia and early death, and is caused by a deficiency of aspartoacylase which is encoded by the ASPA gene. In Ashkenazi Jews, one major mutation (E285A) and one minor mutation (Y231X) account for the majority of cases. The objective of this study was to develop a preimplantation genetic diagnosis (PGD) protocol for Canavan disease. METHODS: Two carrier couples requested PGD for Canavan disease. In 1 couple each was a carrier of a different ASPA mutation (Y231X and E285A). In the other couple both were carriers of the minor mutation (Y231X). A single-cell duplex nested polymerase chain reaction (PCR) protocol was first developed on single leukocytes obtained from the known carrier parents. Following verification in single leukocytes, clinical PGD was offered to both couples. RESULTS: We evaluated 115 single leukocytes from known carriers and found an allele drop out rate of 1.7% for the fragment harboring the Y231X mutation and 0% for the fragment harboring the E285A mutation. One cycle of PGD was performed in each family. In the first, 11 embryos were successfully analyzed and 4 were found to be affected. Two unaffected embryos were transferred, but no pregnancy resulted. In the other family, 4 embryos were analyzed, 1 was affected, 2 were heterozygotes and 1 was homozygous normal. Following transfer of 2 unaffected embryos, a singleton pregnancy resulted, currently ongoing at 18 weeks gestational age. Amniocentesis performed at 16 weeks confirmed the diagnosis. CONCLUSION: Reliable PGD for Canavan disease is possible using a single-cell nested PCR approach.

Canavan Disease↗