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Advanced paternal age does not affect embryo aneuploidy following blastocyst biopsy in egg donor cycles.

ABSTRACT: PURPOSE:To study the impact of advanced paternal age on embryo aneuploidy. METHODS:This is a multicenter international retrospective case series of couples undergoing assisted reproduction via in vitro fertilization using donor eggs to control for maternal factors and preimplantation genetic testing for aneuploidy via next-generation sequencing at Igenomix reproductive testing centers. The main outcome measure was the prevalence of embryo aneuploidy in egg donor cycles. Semen analysis data was retrieved for a small subset of the male patients. RESULTS:Data from 1202 IVF/ICSI egg donor cycles using ejaculated sperm (total 6934 embryos) evaluated using PGT-A between January 2016 and April 2018 in a global population across all Igenomix centers were included. No significant association was identified between advancing paternal age and the prevalence of embryo aneuploidy overall and when analyzing for each chromosome. There was also no significant association between advancing paternal age and specific aneuploid conditions (monosomy, trisomy, partial deletion/duplication) for all chromosomes in the genome. CONCLUSIONS:This is the largest study of its kind in an international patient population to evaluate the impact of advancing paternal age on embryo aneuploidy. We conclude there is no specific effect of paternal age on the prevalence of embryo aneuploidy in the context of embryo biopsies from egg donor cycles.

SUBMITTER: Carrasquillo RJ

PROVIDER: S-EPMC6823410 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Advanced paternal age does not affect embryo aneuploidy following blastocyst biopsy in egg donor cycles.

Carrasquillo Robert J RJ Kohn Taylor P TP Cinnioglu Cengiz C Rubio Carmen C Simon Carlos C Ramasamy Ranjith R Al-Asmar Nasser N

Journal of assisted reproduction and genetics 20190805 10

<h4>Purpose</h4>To study the impact of advanced paternal age on embryo aneuploidy.<h4>Methods</h4>This is a multicenter international retrospective case series of couples undergoing assisted reproduction via in vitro fertilization using donor eggs to control for maternal factors and preimplantation genetic testing for aneuploidy via next-generation sequencing at Igenomix reproductive testing centers. The main outcome measure was the prevalence of embryo aneuploidy in egg donor cycles. Semen anal ...[more]

PMID: 31385121

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Project description:PurposeThis study aims to test the hypothesis, in a single-center retrospective analysis, that live birth rates are significantly different when utilizing preimplantation genetic screening (PGS) compared to not utilizing PGS in frozen-thawed embryo transfers in our patients that use eggs from young, anonymous donors. The question therefore arises of whether PGS is an appropriate intervention for donor egg cycles.MethodsLive birth rates per cycle and live birth rates per embryo transferred after 398 frozen embryo transfer (FET) cycles were examined from patients who elected to have PGS compared to those who did not. Blastocysts derived from donor eggs underwent trophectoderm biopsy and were tested for aneuploidy using array comparative genomic hybridization (aCGH) or next-generation sequencing (NGS), then vitrified for future use (test) or were vitrified untested (control). Embryos were subsequently warmed and transferred into a recipient or gestational carrier uterus. Data was analyzed separately for single embryo transfer (SET), double embryo transfer (DET), and for own recipient uterus and gestational carrier (GC) uterus recipients.ResultsRates of implantation of embryos leading to a live birth were significantly higher in the PGS groups transferring two embryos (DET) compared to the no PGS group (GC, 72 vs. 56 %; own uterus, 60 vs. 36 %). The live birth implantation rate in the own uterus group for SET was higher in the PGS group compared to the control (58 vs. 36 %), and this almost reached significance but the live birth implantation rate for the SET GC group remained the same for both tested and untested embryos. Live births per cycle were nominally higher in the PGS GC DET and own uterus SET and DET groups compared to the non-PGS embryo transfers. These differences almost reached significance. The live birth rate per cycle in the SET GC group was almost identical.ConclusionsSignificant differences were noted only for DET; however, benefits need to be balanced against risks associated with multiple pregnancies. Results observed for SET need to be confirmed on larger series and with randomized cohorts.

Project description:Preimplantation Genetic Testing (PGT), which encompasses both Preimplantation Genetic Diagnosis (PGD) and Preimplantation Genetic Screening (PGS), is a form of prenatal screening done on embryos conceived through assisted reproduction techniques (ART) prior to the initiation of pregnancy to ensure that only select embryos are used for transfer. PGT is typically performed on 8-cell embryos derived from either in vitro fertilization or intracytoplasmic sperm injection (ICSI) followed by extended culture. PGT requires a highly invasive embryo biopsy procedure that involves 1) incubating embryos in divalent-cation-deficient medium to disrupt cell adhesion, 2) breaching the protective zona pellucida with acid Tyrodeâs, laser drilling, or mechanical force and 3) aspirating one or two blastomeres. In this study we developed a mouse model of the embryo biopsy procedure inherent to PGT to determine the effect of various aspects of the procedure (incubation in Ca2+/Mg2+-free medium (CMF), acid Tyrodeâs treatment, blastomere aspiration), performed individually or in combination, on global patterns of gene expression in the resulting blastocysts. Experiment Overall Design: The comprehensive embryo biopsy procedure was done as outlined below and was modified according to the specific experimental treatment being performed. Experiment Overall Design: Eight-cell embryos with rounded blastomeres and no fragmentation were initially incubated in CMF-Chatot-Ziomek-Brinster medium for 5 min at 37oC in a humidified atmosphere of 5% CO2 in air to loosen cell-cell contacts and then transferred to CMF-Dulbeccoâs Phosphate-Buffered Saline. The biopsies were done on the stage of a Nikon Eclipse TE2000 microscope equipped with Hoffman optics and motorized Eppendorf micromanipulators. No more than three embryos were manipulated outside of the incubator at any time. Embryos were held in place by gentle suction on an Eppendorf Sterile VacuTip holding pipette (15 Î¼m diameter), and a dual-holder system was used to control the pipette containing acid Tyrodeâs (6 Î¼m diameter) and the biopsy pipette (15 Î¼m diameter). The zona pellucida was breached by gentle expulsion of a steady stream of acid Tyrodeâs solution (pH 1.6), and a single blastomere with a clear nucleus was removed by aspiration. Following each respective treatment, embryos were cultured individually in 10 Î¼l drops of Potassium Simplex Optimization Medium supplemented with amino acids at 37oC in a humidified atmosphere of 5% CO2 in air until 96 h post-hCG injection. Four replicates of these five experimental groups, each containing 20 embryos, were generated for a total of 20 samples and 400 embryos. Experiment Overall Design: To determine the effect of the various aspects of the embryo biopsy procedure on global patterns of gene expression, total RNA was extracted from each set of 20 embryos in each treatment group at 96 h post-hCG injection. This total RNA was then used to prepare target cRNA by linear two-round amplification as described previously. The final yield of biotinylated cRNA/20 embryos ranged from 34 Î¼g -78 Î¼g, of which 20 Î¼g was fragmented and submitted to the University of Pennsylvania Microarray Facility where the samples were serially hybridized to the MOE430v2 GeneChip. Quality control parameters for all samples were within the following ranges: scale factor: 0.27-0.47, percent of genes detected: 44-51%, actin 3â/5â signal ratio: 1.5-4.2, and GAPDH 3â/5â signal ratio: 3.1-4.3. The GC-RMA algorithm was used to quantify and normalize microarray signals using Stratagene Array Assist Lite, Version 3.4. The resulting .chp files were imported to GeneSpring (v7.31, Agilent Technologies) where probe sets were filtered to retain those that were flagged as P (present) in at least 3 of the 20 samples. The data was log2-transformed and subjected to analysis using Partek Genomics Suite (v6.3, Partek, Inc).

Project description:Time-lapse imaging combined with embryo morphokinetics may offer a non-invasive means for improving embryo selection. Data from clinics worldwide are necessary to compare and ultimately develop embryo classifications models using kinetic data. The primary objective of this study was to determine if there were kinetic differences between embryos with limited potential and those more often associated with in vitro blastocyst formation and/or implantation. We also wanted to compare putative kinetic markers for embryo selection as proposed by other laboratories to what we were observing in our own laboratory setting.Kinetic data and cycle outcomes were retrospectively analyzed in patients age 39 and younger with 7 or more zygotes cultured in the Embryoscope. Timing of specific events from the point of insemination were determined using time-lapse (TL) imaging. The following kinetic markers were assessed: time to syngamy (tPNf), t2, time to two cells (c), 3c (t3), 4c ( t4), 5c (t5), 8c (t8), morula (tMor), start of blastulation (tSB); tBL, blastocyst (tBL); expanded blastocyst (tEBL). Durations of the second (cc2) and third (cc3) cell cycles, the t5-t2 interval as well as time to complete synchronous divisions s1, s2 and s3 were calculated. Incidence and impact on development of nuclear and cleavage anomalies were also assessed.A total of 648 embryos transferred on day 5 were analyzed. The clinical pregnancy and implantation rate were 72% and 50%, respectively. Morphokinetic data showed that tPNf, t2,t4, t8, s1, s2,s3 and cc2 were significantly different in embryos forming blastocysts (ET or frozen) versus those with limited potential either failing to blastulate or else forming poor quality blastocysts ,ultimately discarded. Comparison of embryo kinetics in cycles with all embryos implanting (KID+) versus no implantation (KID-) suggested that markers of embryo competence to implant may be different from ability to form a blastocyst. The incidence of multinucleation and reverse cleavage amongst the embryos observed was 25% and 7%, respectively. Over 40% of embryos exhibiting these characteristics did however form blastocysts meeting our criteria for freezing.These data provide us with a platform with which to potentially enhance embryo selection for transfer.

Project description:INTRODUCTION:Preimplantation genetic diagnosis and/or screening (PGD/PGS) allow the assessment of the genetic health of an embryo before transferring it into the uterus. These techniques require the removal of cellular material (polar bodies, blastomere(s) or trophectoderm cells) in order to perform the proper genetic analysis. We report the implantation and live birth outcome of a vitrified-warmed blastocyst developed after triple biopsy and double vitrification procedures at oocyte, cleavage embryo and blastocyst stage. CASE DESCRIPTION:An infertile couple, with family history of ?-thalassemia, searched for IVF procedure and PGD. First polar bodies biopsy with subsequent vitrification was uninformative due to meiotic crossing-over, so oocytes were inseminated after warming. Two embryos were obtained and blastomere biopsy was performed on day 3 with inconclusive results on their genetic status. Their culture resulted in one expanded blastocyst stage on day 7 that underwent trophectoderm biopsy and vitrification. This embryo showed to be normal. It was then warmed and transferred in an artificial cycle. DISCUSSION AND EVALUATION:Preconception genetic analysis by removal and analysis of the first polar body is technically possible, but the genetic information that we can obtain at this stage may be limited and the oocytes to be inseminated is not predictable. Compared to blastomere biopsy, trophectoderm biopsy has more diagnostic efficiency with respect to both chromosomal mosaicism and PCR accuracy, reducing the problems of amplification failure and allele drop out. Moreover, embryos biopsied at the cleavage stage seem to have lower implantation rate than biopsied blastocyst. CONCLUSIONS:This is the first case report of a live birth obtained from a three step biopsy and double vitrification procedures of a blastocyst. This case report seems also to suggest the harmlessness of all these procedures if carefully performed by a skilled biologist in an IVF lab with quality management system. Finally, our study highlight that blastocyst cryopreserved on day 7 have clinically important potential and embryos that not reach blastocyst stage on day 6 should not to be discharged because they may result in an ongoing pregnancy.

Dataset Information

Advanced paternal age does not affect embryo aneuploidy following blastocyst biopsy in egg donor cycles.

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Advanced paternal age does not affect embryo aneuploidy following blastocyst biopsy in egg donor cycles.

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