Live births resulting from 0PN-derived embryos in conventional IVF cycles

Liu, Jing; Wang, Xing Ling; Zhang, Xiao; Shen, Chun Yan; Zhang, Zhan

doi:10.1007/s10815-015-0644-6

Cited by 32 publications

(31 citation statements)

References 19 publications

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“…(2017) reported the analysis of eight fast cleaving ICSI zygotes scored as 0PNs in PGT-A cycles and found that all were diploid bi-parental in contrast to the 69.2% 1PNs. These findings suggest that ICSIed 0PNs should not be neglected from further investigations in favour of 1PNs as they are probably misclassified zygotes due to faster cell cycle progression likely leading to early pronuclear breakdown ( Manor et al , 1996 ; Feenan and Herbert, 2006 ; Liu et al , 2016 ).…”

Section: Discussionmentioning

confidence: 95%

Genome-wide haplotyping embryos developing from 0PN and 1PN zygotes increases transferrable embryos in PGT-M

et al. 2018

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STUDY QUESTIONCan genome-wide haplotyping increase success following preimplantation genetic testing for a monogenic disorder (PGT-M) by including zygotes with absence of pronuclei (0PN) or the presence of only one pronucleus (1PN)?SUMMARY ANSWERGenome-wide haplotyping 0PNs and 1PNs increases the number of PGT-M cycles reaching embryo transfer (ET) by 81% and the live-birth rate by 75%.WHAT IS KNOWN ALREADYAlthough a significant subset of 0PN and 1PN zygotes can develop into balanced, diploid and developmentally competent embryos, they are usually discarded because parental diploidy detection is not part of the routine work-up of PGT-M.STUDY DESIGN, SIZE, DURATIONThis prospective cohort study evaluated the pronuclear number in 2229 zygotes from 2337 injected metaphase II (MII) oocytes in 268 cycles. PGT-M for 0PN and 1PN embryos developing into Day 5/6 blastocysts with adequate quality for vitrification was performed in 42 of the 268 cycles (15.7%). In these 42 cycles, we genome-wide haplotyped 216 good quality embryos corresponding to 49 0PNs, 15 1PNs and 152 2PNs. The reported outcomes include parental contribution to embryonic ploidy, embryonic aneuploidy, genetic diagnosis for the monogenic disorder, cycles reaching ETs, pregnancy and live birth rates (LBR) for unaffected offspring.PARTICIPANTS/MATERIALS, SETTING, METHODSBlastomere DNA was whole-genome amplified and hybridized on the Illumina Human CytoSNP12V2.1.1 BeadChip arrays. Subsequently, genome-wide haplotyping and copy-number profiling was applied to investigate the embryonic genome architecture. Bi-parental, unaffected embryos were transferred regardless of their initial zygotic PN score.MAIN RESULTS AND THE ROLE OF CHANCEA staggering 75.51% of 0PN and 42.86% of 1PN blastocysts are diploid bi-parental allowing accurate genetic diagnosis for the monogenic disorder. In total, 31% (13/42) of the PGT-M cycles reached ET or could repeat ET with an unaffected 0PN or 1PN embryo. The LBR per initiated cycle increased from 9.52 to 16.67%.LIMITATIONS, REASONS FOR CAUTIONThe clinical efficacy of the routine inclusion of 0PN and 1PN zygotes in PGT-M cycles should be confirmed in larger cohorts from multicenter studies.WIDER IMPLICATIONS OF THE FINDINGSGenome-wide haplotyping allows the inclusion of 0PN and 1PN embryos and subsequently increases the cycles reaching ET following PGT-M and potentially PGT for aneuploidy (PGT-A) and chromosomal structural rearrangements (PGT-SR). Establishing measures of clinical efficacy could lead to an update of the ESHRE guidelines which advise against the use of these zygotes.STUDY FUNDING/COMPETING INTEREST(S)SymBioSys (PFV/10/016 and C1/018 to J.R.V. and T.V.), the Horizon 2020 WIDENLIFE: 692065 to J.R.V., T.V., E.D., A.D. and M.Z.E. M.Z.E., T.V. and J.R.V. co-invented haplarithmisis (‘Haplotyping and copy-number typing using polymorphic variant allelic frequencies’), which has been licensed to Agilent Technologies. H.M. is fully supported by the (FWO) (ZKD1543-ASP/16). The authors have no competing interests to declare.

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Section: Discussionmentioning

confidence: 95%

Genome-wide haplotyping embryos developing from 0PN and 1PN zygotes increases transferrable embryos in PGT-M

et al. 2018

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“…Births of healthy infants after transfer of 1PN‐derived embryos have been reported, but most of these were embryos obtained by IVF. The present study included only one case of a live birth from a 1PN blastocyst obtained by ICSI.…”

Section: Discussionmentioning

confidence: 99%

“…In extracorporeal fertilization methods, fertilization is confirmed by regularly observing the presence of zygotes with two pronuclei (2PN), 16‐18 hours after insemination. However, sometimes, zygotes with no pronuclei (0PN) or one pronucleus (1PN) are found, with reported frequencies of 11.3%‐20% and 1.6%‐7.7%, respectively. Such embryos are considered to be unfertilized or abnormally fertilized ova, and therefore, they are not suitable for clinical use and are discarded.…”

Section: Introductionmentioning

confidence: 99%

Clinical outcomes of transfer of frozen and thawed single blastocysts derived from nonpronuclear and monopronuclear zygotes

Hondo¹,

Arichi²,

Muramatsu³

et al. 2019

Reprod Medicine & Biology

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Purpose In assisted reproductive technology, normal zygotes are bipronuclear (2PN) during fertilization confirmation; however, sometimes, nonpronuclear zygotes (0PN) and monopronuclear zygotes (1PN) are found during routine observations. Methods To elucidate the clinical usefulness of in vitro‐fertilized embryos, we investigated the rates of clinical pregnancy, live birth, miscarriage, and congenital abnormality after transfer of frozen‐thawed 1PN‐ and 0PN‐derived single blastocysts at Denentoshi Ladies Clinic, Kanagawa, Japan. Results The rates of pregnancy and live birth for 1PN‐derived blastocysts obtained by conventional in vitro fertilization were 37.5% and 27.1%, respectively, which was not significantly different from those for 2PN‐derived blastocysts; however, the rates for 0PN‐derived blastocysts were significantly lower. The pregnancy and live birth rates for 0PN‐derived embryos obtained by intracytoplasmic sperm injection (ICSI) were 45.7% and 34.8%, respectively, which was not significantly different from those for 2PN‐derived blastocysts; however, the rates for 1PN‐derived blastocysts were significantly lower (4.0% for both) than those for 2PN‐ and 0PN‐derived blastocysts. No congenital abnormalities were found in infants resulting from transfer of 0PN‐ or 1PN‐derived blastocysts. Conclusions Both 1PN‐ and 0PN‐derived blastocysts can be used for embryo transfer; however, care should be taken in making decisions about 1PN‐derived blastocysts, especially if they are obtained by ICSI.

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“…Some studies, however, have reported 0PN-derived embryos resulted in the birth of healthy babies [3,13,14]. Liu et al also reported that 13 healthy infants resulted from 0PN-originated embryos with an implantation rate of 17.0% in conventional IVF cycles, and those authors believed that the source of embryos transferred did not have a signi cant impact on clinical pregnancies and live birth rates [4].…”

Section: Discussionmentioning

confidence: 99%

“…Destouni et al also reported genome-wide haplotyping embryos developing from 0PN zygotes increased transferrable embryos in PGT-M [16]. These results suggest that 0PN-embryos should not be eliminated from further studies since they are probably misclassi ed zygotes due to the prokaryotes form, or they may disappear too early or too late and miss the prokaryotic observation point [3,4,17].…”

Section: Discussionmentioning

confidence: 99%

Embryos from "0PN" Zygotes May Be Most Likely 2PN Embryo in L-R-ICSI

Liu

Han

Chen

et al. 2020

Preprint

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Although some zero pronuclei (0PN) zygotes cleave and develop into good embryos, they are usually discarded because they lack two distinct pronuclei (2PN). In this case report, we followed four couples to determine whether 0PN embryo could be used in late rescue intracytoplasmic sperm injection (L-R-ICSI). Here we report five healthy infants, including one set of twins, derived from "0PN" embryos from four frozen–warmed embryo transfer (FET) cycles in L-R-ICSI between 2015 and 2017. Of nine infants born from L-R-ICSI cycles in our center, five were "0PN" embryos, and all remain healthy. Embryos from "0PNs" such as 2PN can develop into healthy babies using L-R-ICSI. This finding suggests that embryos from "0PNs" in L-R-ICSI may be different from traditional 0PN gametes and more likely to originate from 2PN gametes and they may be used in those infertile couples who lack 2PN embryos, instead of discarding them. The use of "0PN" embryos increases the cycles reaching embryo transfer, allowing some infertile couples to have healthy children and to avoid mental anguish and wasted time and money.

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Live births resulting from 0PN-derived embryos in conventional IVF cycles

Cited by 32 publications

References 19 publications

Genome-wide haplotyping embryos developing from 0PN and 1PN zygotes increases transferrable embryos in PGT-M

Genome-wide haplotyping embryos developing from 0PN and 1PN zygotes increases transferrable embryos in PGT-M

Clinical outcomes of transfer of frozen and thawed single blastocysts derived from nonpronuclear and monopronuclear zygotes

Embryos from "0PN" Zygotes May Be Most Likely 2PN Embryo in L-R-ICSI

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