Study compares outcomes after first IVF cycle, based on age

A 2024 study compared IVF outcomes and pregnancy rates for patients of different ages (<32 to >40) who had their first single embryo transfer.

How do IVF outcomes and pregnancy rates change with age?

To address this, a new study compared outcomes for patients who had their first embryo transfer — either a single cleavage stage embryo, or a blastocyst.

This post is a review of a study by Wang et al. (2024).

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Study details

• This was a retrospective study that took place at a hospital-based IVF clinic in China between 2016 and 2020.
• The inclusion criteria were: patients having their first IVF cycles with a GnRH agonist or GnRH antagonist ovarian stimulation cycle; transfer of a single embryo by fresh or frozen transfer on day 3 or day 5; no patients with chromosomal abnormalities, endocrine diseases, recurrent pregnancy losses or those requiring testicular biopsy.
• The primary outcome of this study was the clinical pregnancy rate and the ongoing pregnancy rate (defined as a pregnancy lasting more than 12 weeks).

In terms of the sample size, there were 7089 cycles included in the study:

• Age <32: 4894 cycles
• 32-34: 982 cycles
• 35-36: 539 cycles
• 37-38: 345 cycles
• 39-40: 197 cycles
• >40: 132 cycles

IVF outcomes after patients’ first transfer

The researchers reported on the number of eggs retrieved and embryos frozen for the patients’ first IVF cycle. As expected, these numbers dropped with increasing age.

One interesting finding was that patients who had more embryos frozen had a higher chance of clinical pregnancy after their first transfer (ie. without transferring any other embryos).

• Patients with 3-4 frozen embryos had a 1.50 times higher odds of pregnancy vs those with 2 or less frozen.
• For patients with 5-6 frozen embryos, the odds were 1.96 times higher.
• For patients with more than 6, it was 2.53 times higher.

This suggests that the ability to make a larger number of embryos could be tied to embryo quality. This was also found in another study that I covered: Higher number of excess blastocysts frozen after IVF linked to higher live birth rates.

Pregnancy outcomes following patients’ first transfer

Clinical pregnancy rates decreased as age increased from 64.69% for women aged <32 to 24.24% for those >40 (p< 0.001). They found a similar decrease in ongoing pregnancy rates, from 57.87% for women <32 to 12.88% for women >40 (p< 0.001).

For patients aged 34 and above, an analysis showed that there was a decrease in clinical pregnancy rates of 10%* for every 1-year increase in age (adjusted OR 0.90, 95% CI 0.84–0.96, p< 0.0001). Similarly, the ongoing pregnancy rate decreased by 16%* for every 1-year increase in age (adjusted OR 0.84, 95% CI 0.81–0.88, p< 0.0001).

*This isn’t an absolute decrease, but a percent decrease. For example, if the clinical pregnancy rate was 50% at age 34, then at 35 it would be lowered by 5% to 45% (10% of 50% is 5%), and not by 10% to 40%.

This shows that age 34 can be considered a cutoff for when the impact of infertility on age starts to take effect.

They also performed a curve fitting analysis to report a wider range of ages, which was adjusted for confounders including infertility years, types of fertilization, infertility factors, AMH, ovarian stimulation protocols, frozen embryos, transferred embryo type and endometrial thickness.

I can’t share the graph from the study because of copyright, so I did my best to estimate the values from the graph by eye to make my own graph!

They also reported on the multiple pregnancy rate after single embryo transfer:

• Age <32: 1.36%
• 32-34: 1.16%
• 35-36: 1.10%
• 37-38: 0.57%
• 39-40: 0 (small sample size)
• >40: 0 (small sample size)

The last two age groups didn’t have that many pregnancies to work with (<100), which is likely why they’re zero. They didn’t find any statistical differences in the multiple pregnancy rates between the ages.

Conclusions

This study found that the number of eggs retrieved and the number of embryos the patients froze decreased with age.

Patients with a higher number of frozen embryos had a greater chance of pregnancy after their first transfer, suggesting that these patients potentially had higher embryo quality.

As expected, clinical pregnancy rates decreased with female age. This is likely because of the increased chance of aneuploidy in the egg. I reviewed a bunch of data on this from last week that you can check out in my post Chromosomal errors in IVF: What is aneuploidy and what causes it?

They found that pregnancy rates dropped by 10%* for every year above the age of 34. *This is a percent decrease, and not an absolute decrease (ie. a 10% decrease of 50% is 45%).

They also distinguished between cleavage stage (day 3) and blastocyst (day 5) stage transfers. Pregnancy rates for a single embryo transfer were lower for cleavage stage transfers.

Reference

Wang X, Tian PZ, Zhao YJ, Lu J, Dong CY, Zhang CL. The association between female age and pregnancy outcomes in patients receiving first elective single embryo transfer cycle: a retrospective cohort study. Sci Rep. 2024 Aug 19;14(1):19216. doi: 10.1038/s41598-024-70249-1. PMID: 39160203; PMCID: PMC11333704.

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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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