We report differences in segregation modes in embryos obtained from PGD cycles according to the gender of reciprocal translocation carrier. However, these differences did not affect the proportion of balanced embryos and the take home baby rate. The analysis of the meiotic behaviour of chromosomes and the differences between the meiotic products of female and male for a chromosomal rearrangement could help predict the outcome of PGD for translocation carriers.

Purpose Investigate whether R72P on p53 gene polymorphism has a higher prevalence among women with a history of recurrent implantation failure (RIF) and pregnancy loss (RPL) and its influence in their IVF cycle outcome. Material and methods p53 polymorphism R72P has been studied in 181 women. The control group included 83 oocyte donors. In the study group 98 women were included: 44 with RIF and 54 with RPL. From the study group, 76 patients underwent IVF-cycles (55 RPL and 21 RIF). Results The frequency of PP genotypes on p53 among RIF was 11.4 % compared with 18.5 % for RPL and 6 % in controls (p <0.01). There were no significant differences with respect to patient characteristics. Significant differences were reported in pregnancy rate (69.4 % for RR/RP and 33.3 % for PP; p < 0.05), embryo implantation rate (33.3 % for RR/RP and 7.3 % for PP; p <0.05) and ongoing pregnancy rate (53.1 % for RR/ RP and 14.3 % for PP; p <0.05) among RIF and RPL. Conclusions This investigation reveals that in RIF and RPL patients R72P on p53 gene is more prevalent than fertile population. Moreover, patients carrying a PP genotype on p53 codon 72 will have less chance to achieve an ongoing pregnancy. This information together with some additional markers will allow development of diagnostic tests for detects risk for RIF and RPL before infertility treatment is initiated.

STUDY QUESTION Do mitochondrial DNA (mtDNA) copy number and heteroplasmy in human embryos affect the ongoing pregnancy rate? SUMMARY ANSWER Our study suggests that mtDNA copy number above a specific threshold is associated with the ongoing pregnancy rate. WHAT IS KNOWN ALREADY Mitochondria play a vital role in cell function. Recently, there has been increasing research on mtDNA as a biomarker of embryo implantation. Although reports showed that high levels of mtDNA in the blastocyst are associated with low implantation potential, other publications were unable to confirm this. Confounding factors may influence the mtDNA copy number in euploid embryos. On the other hand it has been speculated that both mtDNA heteroplasmy and copy number contribute to mitochondrial function. Next generation sequencing (NGS) allows us to study in depth mtDNA heteroplasmy and copy number simultaneously. STUDY DESIGN, SIZE, DURATION A prospective non-selection study was performed. We included 159 blastocyst biopsies from 142 couples who attended our clinic for preimplantation genetic testing for aneuploidies (PGT-A), from January 2017 to December 2017. All embryos were biopsied on Day 5 or Day 6. The aneuploid testing was performed by NGS. All blastocysts were diagnosed as euploid non-mosaic and were transferred. The mtDNA analysis was performed once the embryo diagnosis was known. PARTICIPANTS/MATERIALS, SETTING, METHODS Sequencing reads mapping to the mtDNA genome were extracted from indexed bam files to identify copy number and heteroplasmy. The relative measure of mtDNA copy number was calculated by dividing the mtDNA reads by the nuclear DNA value to normalize for technical variants and the number of cells collected at the biopsy. All the results were subjected to a mathematical correction factor according to the embryo genome. Heteroplasmy was assigned by MitoSeek. MAIN RESULTS AND THE ROLE OF CHANCE The mean average copy number and SD of mtDNA per genome was 0.0016 ± 0.0012. Regarding heteroplasmy, 40 embryos were heteroplasmy carriers (26.32%). MtDNA variants were detected in coding and non-coding regions and the highest number of variants in an embryo was eight. With respect to IVF outcome for mtDNA copy number analysis, we set a threshold of 0.003 for the following analysis. The vast majority of the embryos were below the threshold (142/159, 89.31%) and 17 embryos were classified as having higher mtDNA levels. We showed a reduction in ongoing pregnancy rate associated with elevated mtDNA copy number (42.96% versus 17.65%, P < 0.05). This result was independent of maternal age and day of the biopsy: these factors were included as confounding factors because mtDNA copy number was negatively correlated with female age (25 –30 y: 0.0017 ± 0.0011, 30 –35 y: 0.0012 ± 0.0007, 35 –40 y: 0.0016 ± 0.0009, over 40 y: 0.0024 + 0.001...

FISH: fluorescent in situ hybridization; CGH: comparative genomic hybridization; ESHRE: European Society of Human Reproduction and Embryology; ASRM: American Society for Reproductive Medicine; RPL: recurrent pregnancy loss; WHO: World Health Organization; ISCN: International System for Human Cytogenetic Nomenclature guidelines; WGA: whole genome amplification; SPSS: Statistical Package for Social Sciences.

No negative effect was observed for intermediate-sized CGG repeats on ovarian stimulation and clinical outcome using a non-confounding model of oocyte donation. These results disagree with previous studies performed on infertility patients. Owing to the present study, fragile X genetic screening should not be considered for prediction of response to ovarian stimulation.