Although the role of embryo cryopreservation will doubtless hold its essential niche in the modern IVF unit, it is not yet known exactly how newer molecular testing techniques will affect this aspect of assisted fertility treatment. As more practice jurisdictions move toward a mandatory single embryo transfer policy, it may be that pre-transfer assessment of embryos by aCGH (or some other screening method) will become a regular procedure in IVF. Should fresh transfers be limited only to single embryos which undergo routine chromosomal screening, then the number of surplus cryopreserved embryos may be expected to rise. But thus far, clinical research has focused on application of comprehensive chromosomal screening specifically for patients with known translocation, multiple implantation failure or recurrent pregnancy loss [7
]. To our knowledge, a prospective study of cryopreservation yield following aCGH screening of embryos from IVF patients without such history (i.e., first cycle IVF, age <35 and good prognosis) has not yet been conducted. The present investigation was undertaken to address this gap in the literature by providing measurements on rate of blastocyst cryopreservation as a function of aCGH inputs in this setting.
Among young patients with normal karyotype undertaking their first IVF cycle, with no miscarriage history or other predictors of poor prognosis, the present study found euploidy in only 226 of 425 blastocysts (53.1%) as determined by aCGH testing. Although most (92.7%) patients in this group had at least one euploid blastocyst for cryopreservation after fresh transfers, just 67 blastocysts remained for cryopreservation in this group (29.6%). When embryo cryopreservation was performed on the basis of standard morphology assessment alone, all study 48 patients had at least one blastocyst available for cryopreservation. For this group, a total of 154 (39.6%) blastocysts were frozen. Since all study patients were <35 years of age, a very good chance to achieve surplus blastocysts for cryopreservation was expected regardless of randomization group (100% vs. 92.7%). However, a significantly lower (p
=0.017) proportion of surplus blastocysts were available for cryopreservation when aCGH testing was performed (39.6% vs. 29.6%). Interestingly, when cryopreservation yield is calculated on the basis of blastocysts remaining after fresh transfers rather than absolute (total) number of blastocysts, this difference between study groups persists. Such findings underscore the need for careful counseling for IVF patients throughout the treatment sequence, particularly as the critical time for embryo cryopreservation nears [36
Our work extends prior observations to younger, lower-risk IVF population and finds conventional morphological criteria alone to be insufficiently accurate to select blastocysts for cryopreservation. Focusing on a good-prognosis IVF patient population, the current study provides further evidence of substantial genetic abnormality (including monosomy and complex aneuploidy [7
]) in apparently normal blastocysts which otherwise would have been destined for cryostorage. We believe IVF patients should be counseled that the benefits of aCGH screening are likely to come at the cost of sharply limiting the number of surplus embryos available for cryopreservation. While we favor use of comprehensive chromosomal screening during IVF, these data place the shortcomings of standard embryo morphology -even for good prognosis IVF patients- in sharp relief. From this background an important clinical question emerges: If aCGH were to be become routinely integrated into the IVF treatment sequence, then what is the expected impact on the number of embryos available for cryopreservation?
Several limitations of our investigation should be acknowledged. Because blastocysts in our control group were selected by morphology alone, they were cryopreserved without any genetic testing and therefore have an uncertain reproductive potential. This study was not designed to measure reproductive outcomes after thaw and transfer. Additionally, we were not confident to include a power analysis prior to this investigation because the actual incidence of embryo aneuploidy in first-time IVF patients with no risk factors is unknown (i.e., if no significant difference had been identified, type II error could not have been excluded).
A changing public perception of better prognosis from IVF specifically when frozen embryos are thawed and transferred [39
] has further increased general awareness of cryopreservation's central role in the advanced reproductive technologies [38
]. Moreover, recent advancements in whole genome amplification and comprehensive chromosomal screening have permitted levels of human embryo surveillance that were not possible only a few years ago. These developments offer opportunities to verify an embryo's genetic composition before cryopreservation. The present study suggests that designating an embryo for freezing without the benefit of information gained from aCGH would entail the preservation and storage of a reproductively incompetent -albeit morphologically normal- embryo. A multi-center randomized clinical trial with a larger sample will be helpful to validate these preliminary findings.