Don’t fear the C-grade: Study finds no higher risk of birth defects with poor-quality embryos

A 2025 study of single-blastocyst transfers found no increase in birth defects or adverse pregnancy outcomes when transferring poor quality embryos compared to good quality ones.

Transferring C-graded embryos can be a difficult choice, especially when higher-grade ones aren’t available.

While embryo grading helps predict pregnancy rates, it’s not clear if there’s any relationship with birth defects (congenital malformations). Previous studies have shown mixed results, but these can be limited by small sample sizes or inconsistent grading criteria.

To clarify whether embryo quality is linked to birth defect risk, Du et al. (2025) examined outcomes of singleton births following frozen embryo transfer.

⚠️ Remembryo summarizes and interprets IVF research for educational purposes. Posts highlight selected findings and may simplify or omit study details, including methods, analyses, author interpretations, limitations, and protocol specifics (such as timing, dosing, or eligibility criteria). These summaries are not a substitute for the original study. Always review the full publication before treatment decisions.

🔗 Original studies are referenced in this post or within the linked Remembryo posts.

💡 Reminder: Terms underlined with a dotted black line are linked to glossary entries. Clicking these does not count toward your paywall limit.

Study details

  • Study type: Retrospective cohort study that took place between 2014 and 2023 at a single IVF center in China.
  • Participants: 3,986 first, single-blastocyst FET cycles leading to singleton live births, including 3,023 good quality embryos and 963 poor quality embryos. After propensity score matching, these groups were reduced to 1,162 and 581. After matching, the average maternal age was about 32.
  • Exclusions: No donor gametes, PGT-A cycles or patients with chromosomal abnormalities, endometriosis, Müllerian anomalies, diabetes, or thyroid disorders.
  • Embryo grading: Gardner system; “good quality” = ≥3BB on day 5 or ≥4BB on day 6 (about 90% were day 5). All others were considered “poor quality,” mostly those with a C grade for the ICM or trophectoderm.
  • Primary outcome: Congenital malformations.
  • Statistical adjustment: Propensity score matching and multivariate logistic regression were used to minimize confounding, adjusting for maternal age, BMI, infertility type, fertilization method (IVF or ICSI), endometrial preparation protocol, embryo development day (Day 5 or 6), and parity.

No increased risk of birth defects with poor quality embryos

They found no differences in the rate of birth defects for good quality vs poor quality embryos (1.72% vs 2.07%, adjusted odds ratio [95% CI]: 1.14 [0.54–2.41], p= 0.73).

This was based on 15 ICD-10 codes (Q00–Q99), representing a range of congenital malformations such as heart defects (Q21), spina bifida (Q05), cleft palate (Q37), digestive system anomalies (Q42–Q43), limb or musculoskeletal defects (Q79), and chromosomal abnormalities (Q90, Q99).

They found no differences in any of these categories, and birth defects in each category were rare (<1%).

No differences in adverse pregnancy outcomes with poor quality embryos

They found no differences in:

  • Neonatal outcomes: including gestational age at birth, preterm birth, birthweight and length, sex, congenital malformations, birthweight categories (very low, low, and high), size-for-gestational-age classifications (very small, small, large, and very large), NICU admission, and stillbirth.
  • Obstetric complications: including gestational hypertension, gestational diabetes, fetal distress, amniotic fluid abnormalities, premature rupture of membranes, placenta previa, placental implantation disease, placental abruption, and cervical insufficiency.
  • Cesarean delivery.

Conclusions

In this large study, researchers showed that there’s no increased risk of birth defects with poor vs good quality blastocysts.

They also found no differences in a number of adverse pregnancy and birth outcomes, like preterm birth, birthweight, gestational hypertension and gestational diabetes.

There are very limited data on this topic, and large numbers of births are needed to detect rare birth defects, making it hard to draw conclusions.

A larger 2019 study reported a modest increase in congenital malformations from poor-quality day 5 embryos, particularly musculoskeletal and chromosomal anomalies. The authors of the current study noted limitations in that earlier work, including a less standardized grading system and the inclusion of twin births, which may have introduced bias. Other smaller studies have found no link between embryo grade and birth defects, so results remain mixed. It’s possible that the increased risk of aneuploidy in poor quality embryos is related to this, but it’s not clear.

High-quality, large-scale studies are still needed to better understand how embryo grading relates to birth outcomes.

Limitations: Single-center design, possible unmeasured confounders not accounted for in propensity score matching, lack of long-term follow-up beyond infancy, and a larger sample size may be needed to account for rarer birth defects.

Want to read more about poor quality embryos?

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

Du, L., Ye, T., Fan, W. et al. Blastocyst quality and congenital malformation risk in singleton births after frozen embryo transfer. Sci Rep 15, 36326 (2025). https://doi.org/10.1038/s41598-025-20150-2

If you liked this post and want to support what I do, please consider a paid subscription, Patreon or donate through PayPal!

 


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.