From Exclusion to Inclusion: The Untapped Potential of 0PN and 1PN Embryos in Reproductive Medicine, finds study

Recent investigation into zygotes lacking pronuclei (0PN) and those with one pronucleus (1PN) aims to evaluate their applicability in preimplantation genetic testing for structural rearrangements (PGT-SR). While traditionally not utilized within clinical protocols due to perceived developmental deficiencies, this study seeks to determine if these embryos could enhance embryo availability amid high rates of chromosomal abnormalities encountered in PGT-SR populations.

Embryo Classification and Success Rates

Embryos were classified post-fertilization, with a cohort consisting of 610 0PN, 167 1PN, and 4091 two pronucleus (2PN) embryos derived from 4902 injected metaphase II oocytes. The study reveals that although 0PN and 1PN embryos exhibited qualities conducive to development, their rates of successful blastocyst formation were significantly lower compared to 2PN embryos (5.41% and 21.56% for 0PN and 1PN, respectively, versus 56.51% for 2PN). Thus, while capable of undergoing cleavage, both abnormal zygote types produced lower quality blastocysts.

Chromosomal Integrity Screening

Utilizing genome-wide ploidy and haplotyping, 33 0PN and 36 1PN embryos were screened for chromosomal integrity. The findings indicated a high prevalence of aneuploidy, with only 18.18% of 0PN and 11.11% of 1PN embryos being euploid. Notably, a significant proportion of the 1PN embryos underwent gynogenesis (38.89%), contrasted with a minimal occurrence in 0PN embryos (3.03%) and none in 2PN embryos. This discovery suggests that even if viable embryos are derived from 0PN and 1PN zygotes, their chromosomal integrity is frequently compromised. Statistical analysis demonstrated no significant increase in the number of transferable embryos when including both 0PN and 1PN embryos into PGT-SR cycles. Outcomes showed that while there were instances of live births achieved from the transfer of these embryos, the numbers remained statistically insignificant. Specifically, the inclusion of 0PN and 1PN did not significantly enhance the overall embryo yield needed for successful implantation, particularly when 2PN embryos were readily available. In conclusion, while 0PN and 1PN zygotes may occasionally provide opportunities for patients with limited embryo options, their routine inclusion in PGT-SR cycles is not broadly recommended. Instead, prioritization should remain on 2PN embryos, reserving the use of 0PN and 1PN as potential alternatives only when fewer than three 2PN embryos are available. The findings advocate for further validation through genome-wide haplotyping to identify viable euploid embryos among previously overlooked zygote types.

Key Points

- A study was conducted to assess the potential of zygotes lacking pronuclei (0PN) and those with one pronucleus (1PN) in preimplantation genetic testing for structural rearrangements (PGT-SR), particularly as a means to increase embryo availability amidst high chromosomal abnormality rates in PGT-SR populations.

- A total of 610 0PN, 167 1PN, and 4091 two pronucleus (2PN) embryos were classified from 4902 injected metaphase II oocytes, revealing that the rates of successful blastocyst formation were significantly lower for 0PN (5.41%) and 1PN (21.56%) compared to 2PN embryos (56.51%), indicating developmental deficits in the abnormal zygote types.

- Chromosomal integrity was assessed using genome-wide ploidy and haplotyping, revealing a high prevalence of aneuploidy among the screened embryos, with only 18.18% of 0PN and 11.11% of 1PN embryos classified as euploid; gynogenesis occurred in 38.89% of 1PN embryos but was rare in 0PN embryos (3.03%).

- Statistical analysis yielded no significant increase in transferable embryos within PGT-SR cycles when incorporating 0PN and 1PN zygotes, with live births resulting from the transfer of these zygotes remaining statistically insignificant, thus questioning their viability in enhancing implantation outcomes.

- While 0PN and 1PN zygotes may occasionally provide options for patients with limited embryo availability, their routine use in PGT-SR is not recommended. The focus should remain on prioritizing 2PN embryos, with 0PN and 1PN considered as last resorts only when fewer than three 2PN embryos are present.

- The findings underscore the need for further validation using genome-wide haplotyping to identify viable euploid embryos among the overlooked zygote types, aiming to enhance understanding of their potential role in reproductive technologies.

Reference –

Jingzhen Wang et al. (2025). The Use Of Blastocysts Developing From Nonpronuclear And Monopronuclear Zygotes Can Be Considered In PGT-SR: A Retrospective Cohort Study. *BMC Pregnancy And Childbirth*, 25. https://doi.org/10.1186/s12884-025-07621-0.