From morphology to molecular validation: ethical re-evaluation of 3PN-derived embryos

In assisted reproduction, the presence of three pronuclei (3PN) in zygotes has long been considered a clear indicator of abnormal fertilization. Current international guidelines recommend the systematic discarding of 3PN-derived embryos due to presumed triploidy and the associated risk of molar pregnancy. However, some studies have demonstrated that a proportion of 3PN-derived embryos exhibit a diploid and euploid chromosomal constitution, with reports of healthy live births following the transfer of genetically confirmed diploid 3PN-derived embryos, and no documented cases of molar pregnancy. These findings challenge the theoretical risks inferred from naturally conceived triploid conceptuses and raise concerns regarding the validity of extrapolating risk estimates from spontaneous pregnancies to assisted reproduction settings. Morphology-based exclusion criteria may result in the discarding of potentially viable embryos despite molecular confirmation of chromosomal normality, thereby raising ethical issues related to beneficence and reproductive autonomy, particularly in patients with limited embryo availability. These considerations highlight the need for structured, ethically governed research pathways capable of generating the robust clinical evidence required to inform future guideline evaluation. In this paper, a cautious but proactive framework is proposed, incorporating blastocyst culture, validation by preimplantation genetic testing for aneuploidies, ethics committee oversight, extended informed consent and long-term follow-up to balance safety with innovation.