No evidence of association between blastocyst aneuploidy and morphokinetic assessment in a selected population of poor-prognosis patients: a longitudinal cohort study (original) (raw)
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Scientific Journal of Biology, 2020
The ability to select human embryo with the highest implantation potential remains one of the greatest challenges in the management of In Vitro Fertilization patients. Here, we review current methods for embryo selection including blastocyst static morphological grading, analysis of embryo morphokinetic parameters, and preimplantation genetic testing for aneuploidy, and their impact on the success of clinical outcomes. We also discuss emerging non-invasive cell-free embryonic DNA examination of spent embryo culture media. Other experimental methods, such as metabolomics, proteomics, cumulus cells or trophectoderm biopsy sample transcriptomics remain controversial and not yet suitable for routine clinical application. These are thus beyond the scope of this review. Traditionally, embryos with superior morphology have been selected for transfer, but these static parameters have been difficult to measure objectively and to use for prediction of blastocyst implantation potential. The introduction of time-lapse imaging system and morphokinetic markers to the laboratory practice allowed to study embryo cell dynamics during early preimplantation development, enhancing the evaluation of embryo quality. Nevertheless, morphokinetic annotations and predictive algorithms might vary between clinics because of different culture environments, stimulation protocols and embryo developmental hallmarks, which overall limit their prognostic value for assessing embryo viability. Moreover, the use of an objective but invasive technique of preimplantation genetic testing for embryo aneuploidy has been shown to improve the selection of embryos with the most potential to implant and produce a healthy pregnancy. However, not all euploid embryos implant, likely owing to embryonic, endometrial factors, or both. Thus, at present, the combination of blastocyst testing for chromosomal abnormalities, analysis of embryo morphokinetics and morphological blastocyst scoring, as integrated approaches, will help to select developmentally competent embryos to maximize chances of successful reproductive outcome. Furthermore, implementing artificial intelligence to the field of Assisted Reproductive Technology may standardize the embryo selection process for a more reliable prediction of embryo quality and fate.
Day 5, 6, and 7 blastocyst ploidy status stratified by patient age
Fertility and Sterility, 2016
Interpretable results were obtained from 136 embryos. Embryos deemed unsuitable for clinical use displayed an aneuploidy rate of 95.6%, with only 6 embryos demonstrating an apparently euploid chromosomal complement. Of these 6 embryos, 3 were excluded from use due to absence of an inner cell mass and 3 due to inadequate trophectoderm formation and/or cellular degeneration. Of note, every embryo returning a euploid result underwent cavitation, leaving a 100% aneuploidy rate for embryos that failed to reach the blastocyst stage. When comparing embryos that did or did not attempt to cavitate (excluding triploid embryos), embryos failing to reach this stage contained on average twice the number of chromosomal errors (4.52 vs 2.25, p<0.0001). Unlike previously reported data utilising clinically viable blastocysts, these embryos exhibited a majority of monosomies over trisomies (65.8% vs 34.2%), likely reflecting the poorer developmental potential of monosomic embryos. Of interest, although triploid embryos are seen at the blastocyst stage, of the 7 triploid embryos identified in this cohort, 6 arrested at either one cell (3 embryos) or following their first cleavage division. The remaining triploid embryo reached cavitation but was of extremely poor quality. This suggests the rate of triploidy in early embryos may be significantly higher than that seen in clinical blastocyst samples. In addition to their standard aneuploidies, 15 embryos contained a segmental aneuploidy, however, in only one embryo was a segmental aneuploidy its only chromosomal error. Similarly, 29 embryos contained additional mosaic aneuploidies, below 50% increase or reduction but distinctly identifiable as a gain or loss. CONCLUSIONS: Embryos failing to reach the blastocyst stage in our culture system displayed universal aneuploidy, a significant finding when counseling our patients. The specific chromosomal errors in non-viable embryos do appear to impact their morphokinetic parameters, however, further work is required to elucidate these potential relationships.
2016
STUDY QUESTION: Are there correlations among human blastocyst ploidy status, standard morphology evaluation and time-lapse kinetics? SUMMARY ANSWER: Correlations were observed, in that euploid human blastocysts showed a higher percentage with top quality inner cell mass (ICM) and trophectoderm (TE), higher expansion grades and shorter time to start of blastulation, expansion and hatching, compared to aneuploid ones. WHAT IS KNOWN ALREADY: Embryo quality has always been considered an important predictor of successful implantation and pregnancy. Nevertheless, knowledge of the relative impact of each morphological parameter at the blastocyst stage needs to be increased. Recently, with the introduction of time-lapse technology, morphokinetic parameters can also be evaluated. However, a large number of studies has reported conflicting outcomes. STUDY DESIGN, SIZE, DURATION: This was a consecutive case series study. The morphology of 1730 blastocysts obtained in 530 PGS cycles performed f...
Fertility and Sterility, 2005
To verify whether advantages can derive from the implementation of preimplantation genetic diagnosis for aneuploidy in patients with a poor prognosis of full-term pregnancy, compared with conventional treatment procedures. Design: A randomized, controlled study. Setting: Reproductive Medicine Unit of the Società Italiana Studi Medicina della Riproduzione, Bologna, Italy. Patient(s): In a total of 262 stimulated cycles, women presented with the following poor-prognosis indications: maternal age of Ն36 years (n ϭ 157), Ն3 previous IVF failures (n ϭ 54), and an altered karyotype (n ϭ 51). After giving consent, 127 patients underwent preimplantation genetic diagnosis for aneuploidy, whereas 135 controls underwent assisted zona hatching. Intervention(s): Analysis of chromosomes XY, was carried out with the fluorescence in situ hybridization technique in a blastomere biopsied from day 3 embryos. Assisted zona hatching was performed on day 3 embryos from the control group. Main Outcome Measure(s): Embryo morphology and chromosomal status, number of transferred embryos, clinical pregnancies, implantation rates, and abortions.
JBRA Assisted Reproduction
Objective: The aim of the present study was to evaluate clinical and embryo parameters to predict embryo ploidy. Methods: In this retrospective analysis, we studied 838 biopsied day-5 blastocysts from 219 patients in the period from May 2021 to July 2022. All embryos were morphologically classified before biopsy and were divided into two groups according to genetic test results. Euploid embryos (299) were compared with aneuploid embryos (539) based on maternal age, anti-Mullerian hormone, antral follicle count, and embryo morphology. Results: Maternal age (36.2±3.0) of euploid embryos was lower than maternal age (37.1±2.5) of aneuploid embryos (p<0.0001). AMH levels were higher (3.9±1.2) in the group of euploid embryos than in the group of aneuploid embryos (3.6±1.3, p<0.0001). However, the AFC was not different in the group of euploid embryos (15.3±6.0) compared to the group of aneuploid embryos (14.5±5.9, p=0.07). The presence of aneuploidy was negatively correlated with top embryo quality (embryos 4AA and 4AB). All euploid embryos (299) were top quality versus 331 of 539 (61.49%) aneuploid embryos (p<0.0001). Conclusions: We found that euploid embryos were associated with lower maternal age, higher AMH levels, and higher quality embryos.
Influence of patient age on the association between euploidy and day-3 embryo morphology
Fertility and Sterility, 2010
Influence of patient age on the association between euploidy and day-3 embryo morphology A retrospective cohort study conducted in 138 patients undergoing their first preimplantation genetic screening (PGS) cycle between January 1, 2006, and December 31, 2007, demonstrated that embryos with good day-3 morphology were more likely to be euploid for X/Y, 8, 15, and 18 than those with poor morphology. The strength of association between euploidy and day-3 morphology was not influenced by maternal age. (Fertil Steril Ò 2010; 94:365-7. Ó2010 by American Society for Reproductive Medicine.) Day-3 embryo morphology is the most commonly used method to select embryos for transfer (1); however, it does not definitively correlate with euploidy (2). Many morphologically normal embryos that become day-5 blastocysts are aneuploid, particularly in women at high risk for aneuploidy (3). Because aneuploid embryos may appear morphologically normal and develop to the blastocyst stage, preimplantation genetic screening (PGS) increasingly has been used to improve embryo selection in certain patient populations. Although existing randomized, controlled trials have not demonstrated improved pregnancy rates with PGS (4-6), there are data to suggest that PGS may improve detection of specific chromosomal abnormalities that are compatible with development to the blastocyst stage, implantation, and subsequent development to term (7). The risk of aneuploidy increases with advancing maternal age (2), and the average maternal age continues to rise in the United States (8). Studies also have shown decreased cleavage rates and increased fragmentation in embryos from older patients (9). It is not known whether age impacts the usefulness of morphology as an embryo selection tool. Therefore, our study assessed the influence of maternal age on the relationship between euploidy and embryo morphology. The study was approved by the institutional review board at Beth Israel Deaconess Medical Center. We retrospectively identified all women who underwent in vitro fertilization (IVF) with their first PGS cycle for advanced maternal age, recurrent miscarriage, or recurrent IVF failure between January 1, 2006, and December 31, 2007, at Boston IVF. Women with other indications for PGS and those who had undergone prior IVF cycles at facilities other than Boston IVF were excluded.
Journal of Assisted Reproduction and Genetics, 2015
Purpose To examine the prevalence of aneuploidy in human blastocysts resulting from donated eggs and embryo implantation after transfer of normal euploid embryos. Also, to assess the necessity of preimplantation genetic screening (PGS) for embryos produced with donor eggs. Methods Blastocysts from donor-recipient cycles were biopsied for PGS (PGS group) and the samples were analyzed with DNA microarray. Euploid blastocysts were transferred to the recipients, and both clinical pregnancy and embryo implantation were examined and compared with embryos without PGS (control group). Results After PGS, 39.1 % of blastocysts were abnormal, including aneuploidy and euploid with partial chromosome deletion and/or duplication. Transfer of normal euploid blastocysts brought about 72.4 % of clinical pregnancy, 65.5 % of ongoing/delivery and 54.9 % of embryo implantation rates; these rates were slightly higher than those in the control group (66.7, 54.0 and 47.8 %, respectively), but there was no statistical difference between the two groups. By contrast, the miscarriage rate was higher in the control group (19.2 %) than in the PGS group (9.5 %), but no statistical difference was observed. Transfer of two or more embryos did not significantly increase the ongoing/delivery rates in both groups, but significantly increased the twin pregnancy rates (50.0 % in the PGS group and 43.8 % in the control group). Conclusion(s) High proportions of human blastocysts derived from donor eggs are aneuploid. Although pregnancy and embryo implantation rates were increased, and miscarriage rates were reduced by transfer of embryos selected by PGS, the efficiency was not significantly different as compared to the control, suggesting that PGS may be necessary only in some specific situations, such as single embryo transfer.
Fertility and sterility, 2014
To examine the relationship between blastocyst euploidy and implantation rates in a presumed fertile patient population. Retrospective analysis. Private IVF clinic. IVF patients undergoing comprehensive chromosome screening (CCS). Embryo biopsy at the blastocyst stage with preimplantation genetic screening using CCS. Euploidy, chemical pregnancy, and implantation rates. There was no significant difference in the number of euploid blastocysts between presumed fertile (68/118, 57.6%) and infertile (75/132, 56.8%) patients<35 years old. Likewise, there was no significant difference in the number of euploid blastocysts between presumed fertile (42/86, 48.8%) and infertile (97/206, 47.1%) patients≥35 years old. When those same patients underwent a corresponding frozen embryo transfer cycle, presumed fertile patients demonstrated a significantly higher chemical pregnancy rate when compared with infertile patients, 28/33 (84.8%) and 50/81 (61.7%), respectively. Moreover, presumed fertil...
Positive outcome after preimplantation diagnosis of aneuploidy in human embryos
Chromosomal abnormalities are responsible for a great deal of embryo wastage, which is reflected, at least partially, in decreased implantation and increased miscarriage in older women. To address this problem the transfer of only chromosomally normal embryos previously selected by preimplantation genetic diagnosis (PGD) has been proposed. We designed a multi-centre in-vitro fertilization (IVF) study to compare controls and a test group that underwent embryo biopsy and PGD for aneuploidy. Patients were matched retrospectively, but blindly, for average maternal age, number of previous IVF cycles, duration of stimulation, oestradiol concentrations on day ⍣1, and average mature follicles. All these parameters were similar in test and control groups. Only embryos classified as normal for those chromosomes were transferred after PGD. The results showed that the rates of fetal heart beat (FHB)/embryo transferred between the control and test groups were similar. However, spontaneous abortions, measured as FHB aborted/FHB detected, decreased after PGD (P < 0.05), and ongoing pregnancies and delivered babies increased (P < 0.05) in the PGD group of patients. Two conclusions were obtained: (i) PGD of aneuploidy reduced embryo loss after implantation; (ii) implantation rates were not significantly improved, but the proportion of ongoing and delivered babies was increased.