O-039 Yes

Abstract The ESHRE Guidelines for Good Practice in IVF Laboratories published in 2016 (currently under revision) recommend to transfer only embryos resulting from the so-called normal oocyte fertilization pattern, defined by the presence of two pronuclei (2PN) and two polar bodies. The document clearly states that the transfer of embryos derived from 1PN or ≥ 3PN oocytes or from oocytes showing no PNs is not recommended, even if no other embryo is available for transfer. This statement was motivated by the notion that the presence of 2PN is indicative of biparental diploidy as a requirement for normal embryo development. Any other PN number was considered to reflect an abnormal ploidy condition that could possibly lead to a negative outcome including failed implantation, miscarriage, or severe pregnancy complications. With the advent of time-lapse technology (TLT), we now know that the true frequencies of 1PN and 3PN oocytes are lower than 2% and 5%, respectively. During the last years, several studies have reported pregnancies and births of healthy babies resulting from embryos derived from oocytes with PN numbers other than two, the most frequent of them being summarized below. 0PN. TLT has shown that embryo development does not occur in the absence of PN formation, but PN breakdown may happen particularly earlier than the classical 16-18 hours recommended for fertilization check. The clinical outcome related to the transfer of the so-called 0PN embryos is comparable to that of 2PN embryos suggesting that the earlier occurrence of PN breakdown has no effect on embryo development. 1PN. The presence of a single pronucleus at the fertilization check has always been associated with haploidy and for this reason, the corresponding embryos were not used clinically. However, the birth of apparently healthy infants from embryos generated by 1PN oocytes made it clear that the PN number not always reflects embryo ploidy. Accordingly, the ploidy analysis of blastocysts derived from 1PN oocytes revealed that about 50% have two sets of chromosomes. It has been postulated that the formation of a single PN may occur when the sperm entry is in close proximity of the meiotic spindle leading to the sequestering of both genomes within the same PN compartment. 2.1PN. Oocytes with a smaller PN in addition to two evenly sized PNs is not a frequent event as confirmed by TLT. They are traditionally considered unsuitable for clinical use owing to concerns of ploidy alterations. The mechanism leading to the formation of a micronucleus coupled with two normal PNs is unknown. Following ploidy analysis, the great majority of the 2.1PN embryos show a diploid configuration and the birth of apparently healthy babies has been reported. 3PN. The origin of the third PN can be maternal or paternal with different mechanisms causing the 3PN configuration. In all, ploidy analysis showed that around 45% of them have two sets of chromosomes, but there are only a very few cases reporting the transfer of embryos derived from 3PN oocytes with some babies born. In conclusion, the combination of TLT and ploidy analysis can support the clinical use of oocytes presenting with an abnormal fertilization pattern, including 1PN, 2.1PN and also 3PN zygotes. Especially in these cases, the risk exists that uniparental disomy could occur, suggesting that the conventional ploidy analysis should have karyomapping functionality. This approach opens a new era of IVF, where the assessment of fertilization becomes a molecular fertilization checking that avoids the unwarranted wastage of viable embryos.