The predictive value of static morphologic and cinematographic analysis for genetic normalcy in human embryos
The human embryo is unique in its imperfection regarding genetic euploidy.
This fact is thought to be one of the main reasons for implantation failure and spontaneous abortion. To date, several techniques have been developed to screen preimplantation embryos for chromosomal anomalies. However, these techniques are invasive for the embryo, labor-intensive and expensive, and currently do not result in significantly improving IVF-results when applied to comprehensive chromosome screening. Therefore, a search is ongoing for alternative, less invasive and less cost-intensive assessments. It is commonly accepted that embryo morphology, which is easy to assess, correlates with implantation rates; thus, implying that embryo morphology may partly be a predictor of chromosomal health. Formerly, embryologists were restricted to distinct time-points for morphology assessment; nowadays, modern time-lapse systems are available. Recent publications indicate that already the first cleavages of the fertilized oocyte are predictive of euploidy, while others report that the chromosomal status is only visible in the kinetics of the later stages.
We analyzed 235 embryos from 37 patients and 44 cycles allocated for PGD/PGS, either due to diagnosed parental translocations (82), or due to advanced maternal age (AMA; 153); all embryos were cultured in a time-lapse incubator. They underwent a trophectoderm biopsy, and genetic analysis was performed by aCGH or FISH, depending on medical indications. Retrospectively, maternal age, cleavage kinetics, and morphologic evaluation of blastocysts - both static and cinematographic were correlated with PGD results.
In accordance with other studies, we found that independent of maternal age, the early cleavages as well as the later events, including blastocyst formation, were slightly delayed in aneuploid embryos, compared to euploid ones. Furthermore, the time-point of blastulation occurred slightly later in aneuploid embryos. However, no statistically significant predictive value for aneuploidy was found when applying published cutoff limits for t5, cc3, and t5-t2. The same was true for static morphological evaluation of day 2 or day 3 embryos. A statistical significance was found when the onset of blastulation exceeded 96.2 hours; in this case, embryos were 21.5% more likely to be aneuploid, compared to faster-developing embryos (P < 0.001). However, the static morphological evaluation of blastocysts on day 5 prior to embryo transfer was found to have a comparable and also statistically significant predictive value for aneuploidy. We found that suboptimal quality blastocysts were 19.9% more likely to be genetically abnormal when compared to the high quality blastocysts (P < 0.01). For the detection of unbalanced translocations, neither kinetics nor morphological observations were found to be statistically significant factors. However, a trend towards a lower rate of embryos with unbalanced translocations was found when they were classified as high quality blastocysts.
In summary, for the selection of chromosomal normal embryos with euploidy, our data show no superiority of cinematographic evaluations of embryos in comparison to static morphological observations. Blastocyst culture with static morphological observation currently appears to be one of the best and most cost effective methods for the selection of embryos for ET.