X. Tao

Reproductive Medicine Associates of New Jersey, Somerset, New Jersey, United States

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Publications (41)98.39 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Comprehensive chromosome screening (CCS) methods are being extensively used to select chromosomally normal embryos in human assisted reproduction. Some concerns related to the stage of analysis and which aneuploidy screening method to use still remain. In this study, the reliability of blastocyst-stage aneuploidy screening and the diagnostic performance of the two mostly used CCS methods (quantitative real-time PCR (qPCR) and array comparative genome hybridization (aCGH)) has been assessed. aCGH aneuploid blastocysts were rebiopsied, blinded, and evaluated by qPCR. Discordant cases were subsequently rebiopsied, blinded, and evaluated by single-nucleotide polymorphism (SNP) array-based CCS. Although 81.7% of embryos showed the same diagnosis when comparing aCGH and qPCR-based CCS, 18.3% (22/120) of embryos gave a discordant result for at least one chromosome. SNP array reanalysis showed that a discordance was reported in ten blastocysts for aCGH, mostly due to false positives, and in four cases for qPCR. The discordant aneuploidy call rate per chromosome was significantly higher for aCGH (5.7%) compared with qPCR (0.6%; P<0.01). To corroborate these findings, 39 embryos were simultaneously biopsied for aCGH and qPCR during blastocyst-stage aneuploidy screening cycles. 35 matched including all 21 euploid embryos. Blinded SNP analysis on rebiopsies of the four embryos matched qPCR. These findings demonstrate the high reliability of diagnosis performed at the blastocyst stage with the use of different CCS methods. However, the application of aCGH can be expected to result in a higher aneuploidy rate than other contemporary methods of CCS.European Journal of Human Genetics advance online publication, 29 October 2014; doi:10.1038/ejhg.2014.222.
    European journal of human genetics: EJHG 10/2014; · 3.56 Impact Factor
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    ABSTRACT: To validate a novel and more practical system for trophectoderm DNA fingerprinting which reliably distinguishes sibling embryos from each other.
    Journal of Assisted Reproduction and Genetics 08/2014; · 1.82 Impact Factor
  • Journal of Assisted Reproduction and Genetics 08/2014; · 1.82 Impact Factor
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    ABSTRACT: OBJECTIVE: To determine whether blastocyst biopsy and rapid quantitative real-time polymerase chain reaction (qPCR)-based comprehensive chromosome screening (CCS) improves in vitro fertilization (IVF) implantation and delivery rates. DESIGN: Randomized controlled trial. SETTING: Academic reproductive medicine center. PATIENT(S): Infertile couples in whom the female partner (or oocyte donor) is between the ages of 21 and 42 years who are attempting conception through IVF. INTERVENTION(S): Embryonic aneuploidy screening. MAIN OUTCOME MEASURE(S): Sustained implantation and delivery rates. RESULT(S): We transferred 134 blastocysts to 72 patients in the study (CCS) group and 163 blastocysts to 83 patients in the routine care (control) group. Sustained implantation rates (probability that an embryo will implant and progress to delivery) were statistically significantly higher in the CCS group (89 of 134; 66.4%) compared with those from the control group (78 of 163; 47.9%). Delivery rates per cycle were also statistically significantly higher in the CCS group. Sixty one of 72 treatment cycles using CCS led to delivery (84.7%), and 56 of 83 (67.5%) control cycles ultimately delivered. Outcomes were excellent in both groups, but use of CCS clearly improved patient outcomes. CONCLUSION(S): Blastocyst biopsy with rapid qPCR-based comprehensive chromosomal screening results in statistically significantly improved IVF outcomes, as evidenced by meaningful increases in sustained implantation and delivery rates. CLINICAL TRIAL REGISTRATION NUMBER: NCT01219283.
    Fertility and sterility 05/2013; · 3.97 Impact Factor
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    ABSTRACT: OBJECTIVE: To determine whether performing comprehensive chromosome screening (CCS) and transferring a single euploid blastocyst can result in an ongoing pregnancy rate that is equivalent to transferring two untested blastocysts while reducing the risk of multiple gestation. DESIGN: Randomized, noninferiority trial. SETTING: Academic center for reproductive medicine. PATIENT(S): Infertile couples (n = 205) with a female partner less than 43 years old having a serum anti-Müllerian hormone level ≥1.2 ng/mL and day 3 FSH <12 IU/L. INTERVENTION(S): Randomization occurred when at least two blastocysts were suitable for trophectoderm biopsy. The study group (n = 89) had all viable blastocysts biopsied for real-time, polymerase chain reaction-based CCS and single euploid blastocyst transfer. The control group (n = 86) had their two best-quality, untested blastocysts transferred. MAIN OUTCOME MEASURE(S): The ongoing pregnancy rate to ≥24 weeks (primary outcome) and the multiple gestation rate. RESULT(S): The ongoing pregnancy rate per randomized patient after the first ET was similar between groups (60.7% after single euploid blastocyst transfer vs. 65.1% after untested two-blastocyst transfer; relative risk [RR], 0.9; 95% confidence interval [CI], 0.7-1.2). A difference of greater than 20% in favor of two-blastocyst transfer was excluded. The risk of multiple gestation was reduced after single euploid blastocyst transfer (53.4% to 0%), and patients were nearly twice as likely to have an ongoing singleton pregnancy (60.7% vs. 33.7%; RR, 1.8; 95% CI, 1.3-2.5). CONCLUSION(S): In women ≤42 years old, transferring a single euploid blastocyst results in ongoing pregnancy rates that are the same as transferring two untested blastocysts while dramatically reducing the risk of twins. CLINICAL TRIAL REGISTRATION NUMBER: NCT01408433.
    Fertility and sterility 03/2013; · 3.97 Impact Factor
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    ABSTRACT: OBJECTIVE: To investigate the applicability of next-generation sequencing (NGS) to preimplantation genetic diagnosis (PGD); to evaluate semiconductor-based NGS for genetic analysis of human embryos. DESIGN: Blinded. SETTING: Academic center for reproductive medicine. PATIENT(S): Six couples at risk of transmitting single gene disorders to their offspring. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Embryonic genotype consistency of NGS with two independent conventional methods of PGD. RESULT(S): NGS provided 100% equivalent PGD diagnoses of compound point mutations and small deletions and insertions compared with both reference laboratory- and internally developed quantitative polymerase chain reaction (qPCR)-based analyses. Furthermore, NGS single-gene disorder screening could be performed in parallel with qPCR-based comprehensive chromosome screening. CONCLUSION(S): NGS can provide blastocyst PGD results with a high level of consistency with established methodologies. This study and its design could serve as a model for further development of this important and emerging technology.
    Fertility and sterility 01/2013; · 3.97 Impact Factor
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    ABSTRACT: To evaluate the utility of trophectoderm biopsy for preimplantation genetic diagnosis (PGD) of mitochondrial (mt) DNA mutation load. A PGD case and analysis of blastocyst mosaicism. Academic center for reproductive medicine. A 30-year-old carrier of 35% 3243A>G mtDNA mutation load with a daughter affected by mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. Blastocyst biopsy for PGD of mutation load and gender. Variation in mutation load within and among embryos, and newborn mutation load after PGD-based selection. Oocytes and embryos were found to possess a variety of 3243A>G mutation loads from 9% to 90% in oocytes and 7% to 91% in embryos, demonstrating that PGD would be a relevant procedure. Highly consistent results were obtained within multiple biopsies of both cleavage- and blastocyst-stage embryos. Importantly, mutation loads observed in trophectoderm were predictive of the inner cell mass (r(2) = 0.97). Transfer of a male embryo, predicted to possess 12% mutation load by analysis of a trophectoderm biopsy, resulted in the delivery of a boy with tissue-specific mutation loads ranging from undetectable to 15%. This study represents the first successful clinical application of PGD to reduce the transgenerational risk of transmitting an mtDNA disorder and supports the applicability of blastocyst trophectoderm PGD for carriers of mtDNA mutations attempting reproduction.
    Fertility and sterility 08/2012; 98(5):1236-40. · 3.97 Impact Factor
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    ABSTRACT: To develop and validate a quantitative real-time polymerase chain reaction (qPCR)-based method for blastocyst trophectoderm comprehensive chromosome screening (CCS) of aneuploidy. Prospective, randomized, and blinded. Academic center for reproductive medicine. Nine cell lines were obtained from a commercial cell line repository, and 71 discarded human blastocysts were obtained from 24 IVF patients that underwent preimplantation genetic screening. None. Consistency of qPCR diagnosis of aneuploidy compared with either conventional karyotyping of cell lines or microarray-based diagnoses of human blastocysts. Samples from nine cell lines with well characterized karyotypes were diagnosed by qPCR with 97.6% (41/42) consistency. After applying a minimum threshold for concurrence, 100% consistency was achieved. Developmentally normal blastocysts designated as aneuploid or arrested blastocysts designated as euploid by single-nucleotide polymorphism microarray analyses were assigned identical 24 chromosome diagnoses by qPCR in 98.6% of cases (70/71). Overall euploidy (n = 37) and aneuploidy (n = 34) were assigned with 100% consistency. Data was obtained for both sample types in 4 hours. These data demonstrate the first qPCR technology capable of accurate aneuploidy screening of all 24 chromosomes in 4 hours. This methodology provides an opportunity to evaluate trophectoderm biopsies with subsequent fresh euploid blastocyst transfer. Randomized controlled trials to investigate the clinical efficacy of qPCR-based CCS are currently underway.
    Fertility and sterility 02/2012; 97(4):819-24. · 3.97 Impact Factor
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    ABSTRACT: Single embryo transfer (SET) provides the most certain means to reduce the risk of multiple gestation. Regrettably, prospective trials of SET have demonstrated reductions in per-cycle delivery rates. A validated method of comprehensive chromosome screening (CCS) has the potential to optimize SET by transferring only euploid embryos. This retrospective study evaluates the efficacy of SET with CCS in an infertile population. Overall and age-controlled ongoing pregnancy rates (OPR) were compared between women undergoing SET following CCS (CCS-SET, n= 140) and those undergoing SET without aneuploidy screening (control SET, n= 182). All transfers were at the blastocyst stage, with CCS performed after trophectoderm biopsy of expanded blastocysts and analysis with rapid PCR allowing for fresh transfer. In the CCS-SET and control SET groups, an OPR of 55.0 and 41.8%, respectively, was obtained. The OPR was lower for the control group (P< 0.01) despite a younger age than the CCS group (37.3 ± 3.4 versus 34.2 ± 3.9 years; P< 0.001). Birthweight and gestational age at delivery were equivalent. The proportion of clinical pregnancies resulting in miscarriage was higher in the control group (24.8 versus 10.5%, P< 0.01), with more patients requiring surgical interventions for aneuploid pregnancies. There was one monozygotic twin delivery in the CCS group and none in the control group. Compared with traditional blastocyst SET, SET after trophectoderm biopsy and rapid PCR-based CCS increases OPR and reduces the miscarriage rate. The enhanced selection empowered by CCS with SET may provide a practical way to eliminate multi-zygotic multiple gestation without compromising clinical outcomes per cycle.
    Human Reproduction 02/2012; 27(4):1217-22. · 4.67 Impact Factor
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    ABSTRACT: To determine both the negative and positive predictive values of comprehensive chromosome screening (CCS) results for clinical outcome. Data obtained from two prospective, double-blinded, nonselection studies. Academic center for reproductive medicine. One hundred forty-six couples with a mean maternal age of 34.0 ± 4.4 years and a mean paternal age of 37.3 ± 5.8 years. Embryo biopsy for DNA fingerprinting and aneuploidy assessment. Failure rate of embryos predicted aneuploid by CCS (negative predictive value) and success rate of embryos predicted euploid by CCS (positive predictive value). A total of 255 IVF-derived human embryos were cultured and selected for transfer without influence from CCS analysis. Embryos were biopsied before transfer, including 113 blastomeres at the cleavage stage and 142 trophectoderm biopsies at the blastocyst stage. Comprehensive chromosome screening was highly predictive of clinical outcome, with 96% of aneuploid predicted embryos failing to sustain implantation and 41% sustained implantation from embryos predicted to be euploid. These nonselection data provide the first prospective, blinded, clinical study directly measuring the predictive value of aneuploidy screening for clinical outcome. The clinical error rate of an aneuploidy designation is very low (4%), whereas implantation and delivery rates of euploid embryos are increased relative to the entire cohort of transferred embryos.
    Fertility and sterility 02/2012; 97(4):870-5. · 3.97 Impact Factor
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    ABSTRACT: To prove the ability to distinguish between balanced and normal chromosomes in embryos from a translocation carrier. Case report. Academic center for reproductive medicine. Woman with a balanced translocation causing Alagille syndrome seeking preimplantation genetic diagnosis (PGD). Blastocyst biopsy for PGD. Consistency of 3 methods of embryo genetic analysis (real-time polymerase chain reaction, single nucleotide polymorphism [SNP] microarray, and fluorescence in situ hybridization [FISH]) and normalcy in the newborn derived from PGD. PGD was applied to 48 embryos. Real-time polymerase chain reaction, SNP microarray, and FISH demonstrated 100% consistency, although FISH failed to detect aneuploidies observed by comprehensive SNP microarray-based analyses. Two blastocysts were identified to be normal for all 3 factors using SNP microarray technology alone. The 2 normal embryos were transferred back to the patient, resulting in the delivery of a healthy boy with a normal karyotype. This is the first report of validation and successful clinical application of microarray-based PGD to distinguish between balanced and normal chromosomes in embryos from a translocation carrier.
    Fertility and sterility 05/2011; 96(1):e58-65. · 3.97 Impact Factor
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    ABSTRACT: Embryo DNA fingerprinting represents an important tool for tracking embryo-specific outcomes after multiple embryo transfer during IVF. The situation in which two embryos are transferred and only one implants represents a unique opportunity for the most well-controlled validation of markers capable of identifying competent and incompetent embryos. Specifically, this design eliminates all patient-related variables from the comparison of embryos with or without reproductive potential. However, in order to determine which embryo implanted, the investigator must wait until newborn DNA is available upon delivery. This study validates a non-invasive cell-free fetal DNA fingerprinting method that reduces the time to identify which embryo implanted by ∼31 weeks. Thirty-four patients were studied to determine if fingerprinting of fetal DNA extracted from maternal plasma at nine gestational weeks concurred with the buccal DNA results obtained from the newborn after delivery. This validation required single nucleotide polymorphism profiles on each couples' preimplantation embryos, cell-free fetal DNA from maternal plasma at 9 weeks gestation, and newborn DNA obtained from buccal swabs after delivery. The predictions from fetal DNA-based embryo tracking and gender assignments made at 9 weeks gestation were 100% consistent with standardized methods of assessment performed after term delivery. This study demonstrates the first validated fetal DNA fingerprinting method which predicts both gender and which embryo implanted at 9 weeks gestation following multiple embryo transfer.
    Molecular Human Reproduction 02/2011; 17(7):434-8. · 4.54 Impact Factor
  • Fertility and Sterility - FERT STERIL. 01/2011; 96(3).
  • Fertility and Sterility - FERT STERIL. 01/2011; 96(3).
  • Fertility and Sterility - FERT STERIL. 01/2011; 96(3).
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    ABSTRACT: Methods of comprehensive microarray-based aneuploidy screening in single cells are rapidly emerging. Whole-genome amplification (WGA) remains a critical component for these methods to be successful. A number of commercially available WGA kits have been independently utilized in previous single-cell microarray studies. However, direct comparison of their performance on single cells has not been conducted. The present study demonstrates that among previously published methods, a single-cell GenomePlex WGA protocol provides the best combination of speed and accuracy for single nucleotide polymorphism microarray-based copy number (CN) analysis when compared with a REPLI-g- or GenomiPhi-based protocol. Alternatively, for applications that do not have constraints on turnaround time and that are directed at accurate genotyping rather than CN assignments, a REPLI-g-based protocol may provide the best solution.
    Molecular Human Reproduction 12/2010; 17(6):335-43. · 4.54 Impact Factor
  • Fertility and Sterility 09/2010; 94(4). · 4.17 Impact Factor
  • Fertility and Sterility 09/2010; 94(4). · 4.17 Impact Factor
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    ABSTRACT: Many studies estimate that chromosomal mosaicism within the cleavage-stage human embryo is high. However, comparison of two unique methods of aneuploidy screening of blastomeres within the same embryo has not been conducted and may indicate whether mosaicism has been overestimated due to technical inconsistency rather than the biological phenomena. The present study investigates the prevalence of chromosomal abnormality and mosaicism found with two different single cell aneuploidy screening techniques. Thirteen arrested cleavage-stage embryos were studied. Each was biopsied into individual cells (n = 160). The cells from each embryo were randomized into two groups. Those destined for FISH-based aneuploidy screening (n = 75) were fixed, one cell per slide. Cells for SNP microarray-based aneuploidy screening (n = 85) were put into individual tubes. Microarray was significantly more reliable (96%) than FISH (83%) for providing an interpretable result (P = 0.004). Markedly different results were obtained when comparing microarray and FISH results from individual embryos. Mosaicism was significantly less commonly observed by microarray (31%) than by FISH (100%) (P = 0.0005). Although FISH evaluated fewer chromosomes per cell and fewer cells per embryo, FISH still displayed significantly more unique genetic diagnoses per embryo (3.2 +/- 0.2) than microarray (1.3 +/- 0.2) (P < 0.0001). This is the first prospective, randomized, blinded and paired comparison between microarray and FISH-based aneuploidy screening. SNP microarray-based 24 chromosome aneuploidy screening provides more complete and consistent results than FISH. These results also suggest that FISH technology may overestimate the contribution of mitotic error to the origin of aneuploidy at the cleavage stage of human embryogenesis.
    Molecular Human Reproduction 08/2010; 16(8):583-9. · 4.54 Impact Factor
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    ABSTRACT: To develop and validate a whole genome amplification and single nucleotide polymorphism (SNP) microarray protocol for accurate single cell 24 chromosome aneuploidy screening. Prospective, randomized, and blinded study. Academic reproductive medicine center. Multiple euploid and aneuploid cell lines were obtained from a public repository and blastomeres were obtained after biopsy of cleavage stage embryos from 78 patients undergoing IVF. Accuracy of copy number assignment and consistency of individual SNPs, whole chromosomes, and single cell aneuploidy status were determined. None. Single cells extracted from karyotypically defined cell lines provided 99.2% accuracy for individual SNPs, 99.8% accuracy for whole chromosomes, and 98.6% accuracy when applying a quality control threshold for the overall assignment of aneuploidy status. The concurrence for more than 80 million SNPs in 335 single blastomeres was 96.5%. We have established and validated a SNP microarray-based single cell aneuploidy screening technology. Clinical validation studies are underway to determine the predictive value of this methodology.
    Fertility and sterility 02/2010; 94(6):2017-21. · 3.97 Impact Factor

Publication Stats

432 Citations
98.39 Total Impact Points

Institutions

  • 2008–2014
    • Reproductive Medicine Associates of New Jersey
      Somerset, New Jersey, United States
  • 2011–2013
    • Rutgers, The State University of New Jersey
      New Brunswick, New Jersey, United States
  • 2009
    • Robert Wood Johnson University Hospital
      New Brunswick, New Jersey, United States