Designed to minimize chances of genetically abnormal embryos, preimplantation genetic diagnosis (PGD) involves fertilization (IVF), embryo biopsy, diagnosis and selective embryo transfer. Preimplantation genetic testing for aneuploidy (PGT-A) aims to avoid miscarriage and live born trisomic offspring and to improve IVF success. Diagnostic approaches include fluorescence hybridization (FISH) and more contemporary comprehensive chromosome screening (CCS) including array comparative genomic hybridization (aCGH), quantitative polymerase chain reaction (PCR), next-generation sequencing (NGS) and karyomapping. NGS has an improved dynamic range, and karyomapping can detect chromosomal and monogenic disorders simultaneously. Mosaicism (commonplace in human embryos) can arise by several mechanisms; those arising initially meiotically (but with a subsequent post-zygotic 'trisomy rescue' event) usually lead to adverse outcomes, whereas the extent to which mosaics that are initially chromosomally normal (but then arise purely post-zygotically) can lead to unaffected live births is uncertain. Polar body (PB) biopsy is the least common sampling method, having drawbacks including cost and inability to detect any paternal contribution. Historically, cleavage-stage (blastomere) biopsy has been the most popular; however, higher abnormality levels, mosaicism and potential for embryo damage have led to it being superseded by blastocyst (trophectoderm - TE) biopsy, which provides more cells for analysis. Improved biopsy, diagnosis and freeze-all strategies collectively have the potential to revolutionize PGT-A, and there is increasing evidence of their combined efficacy. Nonetheless, PGT-A continues to attract criticism, prompting questions of when we consider the evidence base sufficient to justify routine PGT-A? Basic biological research is essential to address unanswered questions concerning the chromosome complement of human embryos, and we thus entreat companies, governments and charities to fund more. This will benefit both IVF patients and prospective parents at risk of aneuploid offspring following natural conception. The aim of this review is to appraise the 'state of the art' in terms of PGT-A, including the controversial areas, and to suggest a practical 'way forward' in terms of future diagnosis and applied research.

The aim of this study was to analyse to what extent sperm aneuploidy is associated with sperm morphology and subsequently with embryo aneuploidy. Fifty-nine men with variable degrees of teratozoospermia and previously poor assisted reproduction prognosis were included in the study. Samples from 10 normozoospermic men with proven fertility were used as controls. Individual spermatozoa were scored for chromosomes 13, 21 and for 18, X, Y separately. Compared with controls, 23 out of 59 cases (39.0%) were found to have increased sperm aneuploidy for at least one of the chromosomes analysed in a treatment cycle. Fifty-two patients underwent a treatment cycle and were documented according to the pregnancy and spermatozoa fluorescence in-situ hybridization results. A total of 121 previous unsuccessful assisted reproduction cycles of the cases were then retrospectively reviewed. In 23 of the latest cycles, preimplantation genetic diagnosis was applied to 106 cleavage stage embryos and 47 of 94 embryos analysed (50.0%) were found to be chromosomally abnormal. Furthermore, 16 of 47 (34.0%) embryos with chromosomal abnormality were carrying complex chromosomal defects. The results imply that increased aneuploidy is present in both spermatozoa and embryos in couples with severe male infertility with a history of repeated unsuccessful attempts. Therefore, proper genetic counselling should be considered in these cases.

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Objective: To assess the probability of finding at least one euploid embryo (POE) and euploidy rate in preimplantation genetic screening (PGS) cycles for aneuploidy testing with fluorescent in situ hybridization (FISH) and array comparative genomic hybridization (aCGH) based on the number of retrieved oocytes after adjustment for age. Design: Retrospective data analysis. Setting: Private in vitro fertilization center in a general hospital, Istanbul, Turkey. Patient(s): In this study, 1412 couples with 1739 cycles were included. Intervention(s): Embryo biopsy at cleavage stage or trophectoderm biopsy analyzed by FISH or aCGH techniques. Main outcome measure(s): Probability of finding at least one euploid embryo for transfer and euploidy rate according to retrieved oocytes after adjustment for age. Result(s): Estimated probabilities of finding at least one euploid embryo were plotted based on age and number of retrieved oocytes. When controlled for age, the POE increased with each additional oocyte retrieved (OR 1.11, 95% CI 1.08-1.14), but the euploidy rate did not. When retrieved oocytes were subgrouped, we found that the odds of finding at least one euploidy embryo were highest when 16-20 oocytes were retrieved compared to 1-5 oocytes with both FISH (OR 8.62, 95% CI 4.67-15.93) and aCGH (OR 2.78, 95% CI 1.07-7.21). However, the chances did not increase with the retrieval of more than 20 oocytes. Conclusion(s): The estimated probabilities of finding at least one transferrable embryo would enable more accurate counselling of patients based on age and the number of retrieved oocytes. As the highest estimates for finding one euploidy embryo were achieved with 15-20 oocytes, deciding the best protocol for ovarian stimulation to achieve the maximum number of oocytes for retrieval based on the patients age and ovarian reserve would be of crucial importance.