Meta-analysis shows 1PN embryos may lead to healthy births, especially if euploid

A 2025 meta-analysis found that while 1PN zygotes don’t convert to blastocyst as well and have lower success rates when untested, those confirmed as euploid can lead to healthy births, but extra care is needed to confirm they are truly normal.

Embryologists check for signs of fertilization the day after insemination. Normally, they expect to see two pronuclei (2PN) in the fertilized egg (zygote), one from the egg and one from the sperm. This is a reassuring sign that fertilization occurred correctly, with one set of chromosomes contributed by each parent.

However, sometimes zygotes show only one pronucleus (1PN), or three pronuclei (3PN). This suggests abnormal fertilization, and these embryos are often discarded or deprioritized because they may have an incorrect number of sets of chromosomes.

With PGT, some studies have shown that 1PN embryos can in fact be diploid (with 2 full sets of chromosomes, one from each parent) and euploid, suggesting that not all 1PNs are abnormal.

Despite this, guidance on how to manage 1PN embryos is inconsistent!

A new study by Lee et al. (2025) performed a meta-analysis to clarify how 1PN embryos perform, comparing their development, clinical outcomes, and neonatal health to “normal” 2PN embryos.

For more background, check my post on Abnormal fertilization.

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Study details

• This meta-analysis included 24 retrospective cohort studies (17 full studies and 7 abstracts) comparing the outcomes of 1PN and 2PN embryos.
• The analysis included data on 291,474 embryos in total.
• Studies reported on a wide range of outcomes, from embryo development to live birth and neonatal health.
• Most studies involved day 3 or day 5 transfers, and some included PGT results (euploidy/aneuploidy), while others did not.
• Studies varied in whether embryos were fresh or frozen, IVF or ICSI, and whether they were tested with PGT.
• The primary outcomes were live birth rate, clinical pregnancy rate, miscarriage rate, and blastocyst formation. Neonatal outcomes were also assessed where available.

1PN zygotes can show comparable pregnancy outcomes as 2PN

Live birth rate

• Lower live birth rate with untested 1PN vs 2PN (28.6% vs 35.5%; relative risk [95% CI]: 0.81 [0.72–0.90]; 8 studies, I2= 65%).
• No difference in live birth rates with euploid 1PN vs 2PN (relative risk [95% CI]: 0.88 [0.71–1.09]; 2 studies, I2= 0%).

This shows that untested 1PNs had lower live birth rates, although the results had substantial heterogeneity. When embryos were confirmed euploid, live birth rates were similar.

Clinical pregnancy rate

• Lower clinical pregnancy rate with untested 1PN vs 2PN embryos (35.6% vs 43.0%; relative risk [95% CI]: 0.80 [0.74–0.86]; 13 studies, I2= 49%)
• No significant difference in clinical pregnancy rate with euploid 1PN vs 2PN embryos (relative risk [95% CI]: 0.65 [0.38–1.10]; 1 study, I2= not applicable)

This shows that clinical pregnancy was less likely with untested 1PNs, though the difference was not seen with euploid embryos. Heterogeneity was borderline substantial.

Miscarriage rate

• No significant difference in miscarriage rate with untested 1PN vs 2PN (relative risk [95% CI]: 1.17 [1.00–1.36]; 13 studies, I2= 25%) — note that this result was borderline but ultimately not significant.
• Higher miscarriage rate with euploid 1PN vs 2PN (44.4% vs 15.2%; relative risk [95% CI]: 2.93 [1.37–6.23]; 1 study, I2= not applicable)

These results suggest that 1PNs have a similar miscarriage rate compared to 2PNs overall. One study did show a higher miscarriage rate for euploid 1PNs, but this was based on a very small sample size (only 9 euploid 1PNs compared to 87 euploid 2PNs), so the evidence is very limited and should be interpreted with caution.

Blastocyst conversion

• Lower blastocyst conversion rate in 1PN vs 2PN embryos (29.2% vs 46.3%; relative risk [95% CI]: 0.50 [0.48–0.51]; 15 studies, I2= 99%)
• Lower good-quality blastocyst formation rate in 1PN vs 2PN embryos (14.9% vs 32.6%; relative risk [95% CI]: 0.44 [0.41–0.46]; 9 studies, I2= 91%)

This shows that 1PNs were much less likely to reach the blastocyst stage or form good-quality embryos, but very high heterogeneity.

Euploidy rate

• No significant difference in euploidy rate between 1PN and 2PN embryos (relative risk [95% CI]: 0.91 [0.81–1.02]; 5 studies, I2= 79%)
• No significant difference in aneuploidy rate between 1PN and 2PN embryos (relative risk [95% CI]: 0.98 [0.81–1.18]; 4 studies, I2 = 0%)

This shows that the chance of being euploid was similar between 1PNs and 2PNs, though study results (heterogeneity) varied substantially. The aneuploid results were much more consistent between studies.

Neonatal outcomes

• Malformation rate: No significant difference in malformation rate between 1PNs and 2PNs (relative risk [95% CI]: 1.38 [0.52–3.68]; 8 studies, I2= 0%)
• Birthweight: No significant difference in birthweight (mean difference [95% CI]: –60.87 [–145.72, 23.98]; 5 studies, I2= 20%)
• Birth length: No significant difference in birth length (mean difference [95% CI]: 0.07 [–0.66, 0.81]; 2 studies, I2= 57%)
• Gestational age: No significant difference in gestational age (mean difference [95% CI]: –0.04 [–0.29, 0.22]; 4 studies, I2= 0%)

This shows that babies born from 1PNs had similar birth outcomes to those from 2PNs, with low heterogeneity across most studies, except for birth length, where results were more variable.

Conclusions

This meta-analysis showed that untested 1PN embryos have a lower chance of live birth and pregnancy compared to 2PNs, but have comparable success rates when the 1PN is euploid.

Miscarriage rates were similar, but not for euploids (based on a single small study).

1PN embryos have a lower chance of becoming a blastocyst, but are just as likely to be euploid as 2PNs.

There were no differences in neonatal outcomes (malformation rate, birthweight, birth length, gestational age).

This is good news for those with 1PNs, especially if they’re confirmed to be diploid/euploid. However, not all PGT-A platforms can confirm diploidy, so it’s important to check. Some versions of PGT can include SNP-based sequencing in addition to NGS, which is required to accurately determine if an abnormally fertilized zygote is truly haploid, triploid or diploid. This test will also tell you if the embryo is euploid.

The authors warn that rare cases of molar pregnancy have been reported after transferring a 1PN embryo that was euploid but androgenetic (contained only DNA from the sperm). This highlights the importance of using SNP-based PGT platforms to potentially reduce the risk of molar pregnancies, and to be cautious when transferring 1PNs that are only confirmed as euploid and not diploid.

Where PGT is limited to aneuploidy screening only (ie. only NGS and no SNP), the authors recommend that 1PN embryos should be transferred only with thorough counselling and informed consent.

For the IVF lab, time-lapse imaging is the most accurate way to assess pronuclei, but clinics using a single time point may misclassify 1PNs if the second pronucleus forms late or disappears early. The authors suggest rechecking 1PN zygotes at a second time point to reduce this risk.

Limitations of this meta-analysis include the lack of high quality RCT studies (all were retrospective) inconsistent blastocyst grading, and differences in PGT methodology (some tested only for aneuploidy, while others confirmed diploidy and parental origin).

For more information, check my post on Abnormal fertilization.

Related studies

These additional studies were referenced by the authors of the paper and haven’t been covered on Remembryo. They may be helpful if you’re exploring this topic further. This section is available for paid subscribers.

Reference

Lee T, Qi F, Peirce K, Natalwala J, Chapple V, Mark PJ, Sanders K, Liu Y. (2025). To discard or not to discard 1PNs? A systematic review and meta-analysis on 291,474 embryos. Reproductive BioMedicine Online. Advance online publication. https://doi.org/10.1016/j.rbmo.2025.105080

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About Embryoman

Embryoman (Sean Lauber) is a former embryologist and the founder of Remembryo, an IVF research and fertility education website. After working in an IVF lab in the US, he returned to Canada and now focuses on making fertility research more accessible. He holds a Master’s in Immunology and launched Remembryo in 2018 to help patients and professionals make sense of IVF research. Sean shares weekly study updates on Facebook, Instagram, and Reddit regularly. He also answers questions on Reddit or in his private Facebook group.

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