Prolonged embryo storage >6 years may reduce pregnancy, live birth rates

Researchers in a 2022 study found that blastocysts stored for longer than 6 years showed reductions in clinical pregnancy and live birth rates.

The impact of long-term cryostorage of embryos is not clear and it’s possible that this can have an effect on success rates.

Yan et al. (2022), in their retrospective study, compared pregnancy outcomes after transferring 6,829 blastocysts cryopreserved for different lengths of time. The study took place at a single center in China between 2011 and 2021, and involved women who all had a previous live birth with IVF and stored excess embryos from the same cycle.

Key points:

Only blastocysts were transferred
No PGT-A
Vitrification was used to freeze embryos (not slow-freeze)
Natural frozen embryo transfers (FETs) and medicated FETs were used

In terms of the baseline characteristics, there were a number of differences. These confounders were statistically adjusted in their analysis:

Maternal age (at time of transfer)
Infertility diagnosis
Number of basal follicles
Number of eggs retrieved
Number of blastocysts frozen
Number of blastocysts transferred
Blastocyst quality before freezing and after thawing
Endometrial preparation (natural, medicated FETs)
Endometrial thickness

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Embryo survival after thaw decreased with prolonged storage

Embryos that were stored for a longer period of time had a significantly lower survival rate that ranged from 93.51% for <3 years to 75.27% for 6-10.5 years. Each step showed statistical significance compared to the <3 year group (p<0.0001).

embryo survival rate after prolonged storage — *“n” refers to the sample size (number of patients thawing embryos)*

Decrease in clinical pregnancy, live birth rates when embryos stored for 6 or more years

There were no differences in clinical pregnancy or live birth rates up to 6 years of embryo storage, however from 6-10.5 years there was a statistically significant decrease compared to <3 years for clinical pregnancy (62.75% vs 50.13%, p<0.05) and live birth rates (52.77% vs 40.78%, p<0.05).

After statistical adjustment for clinical pregnancy rates, there was still a decrease (odds ratio [95% CI]: 0.69 [0.54-0.87]). This means that after adjustment for confounders (shown above: maternal age at transfer, diagnosis, etc.), the odds of having a clinical pregnancy after transferring an embryo stored for 6-10.5 years was 0.69 times that of having a clinical pregnancy after using an embryo stored for <3 years.

After statistical adjustment for live birth rates, there was still a decrease (odds ratio [95% CI]: 0.73 [0.58-0.93]). This means that after adjustment for confounders (shown above: maternal age at transfer, diagnosis, etc.), the odds of having a live birth after transferring an embryo stored for 6-10.5 years was 0.73 times that of having a clinical pregnancy after using an embryo stored for <3 years.

There were no differences in miscarriage rates.

No differences in ectopic pregnancies, neonatal outcomes with prolonged embryo storage

The researchers found no differences in ectopic pregnancy rates, and the babies born showed no differences in preterm birth rates, normal birth weights and low birth weights.

Conclusions

This study found decreases in the survival of thawed embryos starting after 3 years of storage and reductions in clinical pregnancy and live birth rates after 6 years. There were no differences in miscarriage, ectopic pregnancies or neonatal outcomes.

According to the authors, these decreases may be due to a number of factors, including the high levels of cryoprotectants used during storage or inadequate maintenance of cryostorage containers, for example. George and Keefe 2023 suggest that these differences might be due to embryologist technique, since 2011 (when this study started) is when vitrification started to become available in the lab and mistakes may have been made initially.

Limitations of this study include its retrospective design, and smaller sample size for the 6-10.5 year group.

Reference

Yan Y, Zhang Q, Yang L, Zhou W, Ni T, Yan J. Pregnancy and neonatal outcomes after long-term vitrification of blastocysts among 6,900 patients after their last live birth. Fertil Steril. 2023 Jan;119(1):36-44. doi: 10.1016/j.fertnstert.2022.10.016. Epub 2022 Nov 29. PMID: 36456212.

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.