Study examines how age affects donor egg success rates

A large study found that IVF success declines with age even when using donor eggs, suggesting the uterus may age too.

Egg quality declines with age, reducing the chances of pregnancy and increasing the risk of miscarriage. But is this still true in the case of donor eggs?

In other words, does the age of the uterus matter?

A new study by Sebastian-Leon et al. (2025) looked at how the age of the uterus affects IVF success, even when using young donor eggs. Most past studies grouped patients into broad age ranges, which makes it hard to see exactly when outcomes begin to decline. This study treated age as a continuous variable to pinpoint the specific ages when the uterus may start to lose its ability to support a pregnancy.

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Study details

• This is a retrospective cohort study that involved 19 private IVIRMA clinics across Spain, from February 2000 to September 2022.
• All women were between 35-50 years old, who transferred a single day 5 blastocyst from a donor egg (donor was <35 years old).
• No multiple embryo transfers!
• The primary outcome was live birth rate.

In terms of sample size, there were 33,141 embryo transfers from 21,029 patients: The transfers group by age:

• Age 35: 735 transfers
• Age 36: 983 transfers
• Age 37: 1,260 transfers
• Age 38: 1,584 transfers
• Age 39: 2,147 transfers
• Age 40: 2,678 transfers
• Age 41: 3,263 transfers
• Age 42: 3,700 transfers
• Age 43: 3,691 transfers
• Age 44: 3,562 transfers
• Age 45: 3,000 transfers
• Age 46: 2,322 transfers
• Age 47: 1,645 transfers
• Age 48: 1,173 transfers
• Age 49: 918 transfers
• Age 50: 480 transfers

Live birth rates declined after age 40 with donor eggs

Live birth rates began to fall after age 40, dropping steadily from 45.8% at age 40 to 32.7% by age 50. The risk of pregnancy loss started to rise from age 43, increasing from 26.5% to 37.0% across the 43–50 age range.

Note: The values shown in the graph below are approximate. They were visually estimated from a figure and may differ slightly from the original source data.

After finding that live birth rates started to decline around age 40, the researchers used that age as a cutoff to look more closely at pregnancy loss rates. Rather than comparing age groups (like under 40 vs. over 40), they analyzed age as a continuous variable, which means they looked at how each additional year of age affected pregnancy loss. They used age 40 as a reference point to see how the risk of pregnancy loss changed after that point.

What they found was that starting at age 40, the risk of pregnancy loss increased by 3.2% per year, which was statistically significant (relative risk [95% CI]: 1.032 [1.013-1.051], p= 0.0007). Before age 40, there was no significant yearly increase in risk.

This decline happened despite controlling for embryo quality and endometrial preparation protocol. The age effect, therefore, is most likely due to changes in the uterine environment, not the egg or embryo.

Conclusions

This study found that live birth rates decline after the age of 40, even when using donor eggs. The decline was gradual at first but became more pronounced starting at around age 45.

They also showed that implantation failure increases from age 39, and pregnancy loss rises from age 43 (I only shared the pregnancy loss data above). The relative risk increased each year over the age of 40: 4.2%/year for implantation failure and 3.2%/year for pregnancy loss.

The authors explain that this is likely due to age-related changes in the uterus, such as reduced blood flow, altered gene expression, immune shifts, or structural changes like fibrosis or scarring. The authors also cite prior work showing an increase in ciliated epithelial cells and molecular signs of premature endometrial aging, even in women under 35 with implantation failure.

This study challenges the assumption that age doesn’t matter once you’re using donor eggs. For patients in their 40s using donor oocytes, it may help explain why IVF still doesn’t work, and opens the door for research into anti-aging therapies targeting the uterus.

The main limitation is that this was a retrospective study, so the researchers couldn’t control for things like uterine abnormalities or other factors that might affect results. A prospective study would be more accurate, but it would be hard to do, especially in older patients, since it would require many single embryo transfers across different ages. There were also repeated transfers in some cases, and it may have been better if they only looked at first transfers.

For older patients considering IVF with donor eggs or euploid embryos, this study highlights that uterine age may still play a significant role in outcome.

The authors point out that past research on this topic has produced mixed results, likely due to differences in study design, small sample sizes, and the use of arbitrary age groupings.

Although this study was done with donor eggs, we can ask the same question with PGT-A tested euploid embryos, which also controls for embryo quality like donor eggs. I’ve covered several studies that have looked at the impact of maternal age on success rates when transferring a euploid embryo:

• Meta-analysis examines impact of age on uterus and pregnancy outcomes after IVF — this meta-analysis combined the results of 142 studies to investigate how age affects the uterus and pregnancy outcomes after IVF. They identified a number of changes, including decreased endometrial thickness and lower pregnancy rates with age.
• Euploid embryos show reduced implantation potential with advancing maternal age — this is the largest study to date on the topic, which found that women who did a euploid transfer at an older age had lower live birth rates compared to younger women.
• Study finds that female age doesn’t impact euploid embryo transfer success rates — this study compared successful and unsuccessful euploid transfers, finding that female age had no impact, while BMI, embryo quality and the type of FET used did.
• Study evaluates factors affecting pregnancy outcomes after euploid transfer — this study found no differences in pregnancy outcomes after transferring euploid embryos in women <40 and >40. They also looked at BMI, FET protocol, the day the embryo was biopsied, and AMH levels.
• Meta-analysis combines 74 studies to examine factors linked to euploid transfer success — this study found a slight influence in female age at time of retrieval and euploid success rates. They also compared a large number of other factors, like embryo quality, BMI, diagnosis, type of assisted hatching and more.

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

Sebastian-Leon P, Sanz FJ, Molinaro P, Pellicer A, Diaz-Gimeno P. Advanced maternal age was associated with an annual decline in reproductive success despite use of donor oocytes: a retrospective study. Fertil Steril. 2025 May 20:S0015-0282(25)00438-8. doi: 10.1016/j.fertnstert.2025.05.150. Epub ahead of print. PMID: 40403911.

 

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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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