O-040 Clinical competence of oocytes with developmental abnormalities

Abstract

Abstract For decades we have looked for marker of embryo competence. And while we have come a long way in terms of identifying markers related to embryonic competence, a lot of research is still focused on finding this simple measurable indicator predicting a positive outcome of the individual treatment. Many potential indicators have been evaluated. This includes the cumulus oocyte complex, zona pellucida, perivitelline space, polar bodies, vacuoles, refractile bodies, SER clusters, cytoplasmic granularity, and many others. For some of these there are data suggesting potential prediction of negative outcome (for review see Bartolacci et al. 2022). Embryo autonomy may result in cleavage and development despite the lack of competence to establish a pregnancy. And pregnancies may occur without the competence to go all the way to a live birth. In a study by Lundin et al. we looked into chromosomal constitution after rescuing immature (developmentally abnormal) human oocytes. And while 15% of the oocytes developed into an embryo only very few appeared chromosomally normal after cytogenetic analysis. The study concluded that the majority of hCG exposed oocytes that have not reached the MII stage at time of pick-up are defect and consequently that GV or MI oocytes should not be used in ART programs. As reproductive specialists our main task is to assist our patients in achieving their dream of having a child. We are supposed to use all our combined expertise, knowhow, craftmanship, routine and experience to optimize the chance for the patients to have a baby. However, in our ambition to help our patients we sometimes lose touch of the underlying biology of human reproduction. Oocytes from a stimulated ovary are not like those we buy in the supermarket of equal quality. The depressing fact is that only 5.0 % of the oocytes in a first cycle is biologically competent and in around 2/3 of all cycles, none of the oocytes have the potential to result in the birth of a child (Lemmen et al 2016). We also have very limited ability to determine competence of individual sperm cells – the strongest prognosticator being if they look and move like a “normal” sperm sample. Are we getting a bit desperate when we start to look for normality in the abnormal as suggested in the title of this talk? Have we reached a point were patient expectations overrides our biological training and education resulting in low willingness to accept a negative outcome dictated by our biology? And is this reinforced by patient perceptions like “we did not pay a lot of money for the oocytes not being fertilized/developed/implanted”. Embryo competence evaluation is based on markers of what have happened rather than indicators of what will happen. At the end of the day, we as health care professionals as well as our patients needs to accept the fact that there is no such thing as “CLINICAL COMPETENCE OF OOCYTES WITH DEVELOPMENTAL ABNORMALITIES”. And what will be the consequence of a marker indicating a lower implantation potential in an otherwise ok embryo? It might affect the ranking of the embryos from a particular cycle, but we would be willing transfer it anyway if needed. Embryo evaluation don’t increase pregnancy chance per se. But it may decrease time to pregnancy by improved selection between the embryos available. Maybe it is time to re-focus our efforts and move from a binary normality approach identifying “developmental abnormalities” toward a more biological oriented approach mapping “developmental variation” in embryos and their impact on pregnancy potential and thus recognizing the multi-factorial nature of embryo maturation and ongoing developing competence.