Day 3 or Day 5 embryo transfer?

Is it better to transfer on day 3 or risk losing embryos by going to day 5? Is the uterus a better environment or the lab?

This is an older post (from 2019) that may contain out-of-date information. Please bear with me as I update some of my older posts. For the latest information on a topic presented here, search for that topic and check out more recent posts. Thank you!

Is the uterus better for a day 3 or day 5 embryo?

People ask this question all the time. And many people think that the uterus is a better home for the embryo.

It might surprise you that the uterine environment may not be a better environment for a day 3 embryo.

That’s because it takes about 4 days for the embryo to make it to the uterus. On day 3, the embryo is still making its way through the Fallopian tube so this environment may be better suited.

By day 5, the embryo is in the uterus. And this synchronization between embryo and the uterus may be an important factor for success. Some believe that day 3 embryos may experience stress in this environment (Glujovsky et al. 2016).

Why do we think day 5 is better than day 3?

Basically, a couple of reasons (Glujovsky et al. 2016):

• The uterine environment is more synchronized with a day 5 embryo vs a day 3 embryo (see previous section)
• Day 3 embryos have a higher aneuploidy rate so some may drop out, or arrest, by going to day 5.

Let’s look at another example to understand what I mean by “dropping out” or arresting.

In the example below there are 5 day 3 embryos labeled A to E:

• 3 of them arrest (A, B and D)
• 2 go on to make blasts (C and E) and 1 of these blasts (E) produces a pregnancy.

So out of these 5 day 3 embryos, only 2 “had the right stuff” to go on to make a blast on day 5. The ones that failed were probably aneuploid and wouldn’t result in a pregnancy (though we’d never know!).

For those fortunate enough to have a bunch of day 3 embryos, it’s easier to pick the best ones by “weeding out” the poorer ones by going to day 5.

But what if you don’t have a lot of embryos? Or what if your embryos consistently fail to make it to blast? Then you may be encouraged to transfer on day 3 – because maybe they’ll perform better (but again – we’ll never know!).

In other words, using the example above, if we transferred all those day 3 embryos, would we get the same result?

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Or would we get a different result? Where maybe embryo B and E make a pregnancy?

Does this kind of thing happen? Maybe. But we can’t test this because we can’t both simultaneously transfer an embryo on day 3 and culture it to day 5.

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Do day 5 embryo transfers have higher success rates than day 3?

A Cochrane review compared day 3 and day 5 transfers (Glujovsky et al. 2016):

• Higher live births with day 5 transfers (low quality evidence)
• Higher pregnancy with day 5 transfers (moderate quality)
• No difference in miscarriage rates (low quality)
• No difference in cumulative pregnancy rates (very low quality)

De Vos et al. (2016) compared single embryo day 3 and day 5 transfers in their retrospective study:

• Higher birth rate with a fresh ET on day 5 vs day 3 (36.8% vs 30.5%)
• No difference in birth rate per frozen ET (20.7% vs 21.5%)
• No difference in cumulative births (48.5% vs 48.0%)
• Fewer cycles needed to achieve live birth with day 5 transfers:

The ASRM reviewed the data in their committee opinion (ASRM 2018):

• In good prognosis patients – day 5 transfers have higher success
• In poor prognosis patients this is less clear
• There are fewer available embryos for freeze/transfer on day 5

SART summarized the national outcomes from 2004 to 2013, based on 236,000 frozen embryo transfers (Holden et al. 2018):

• Day 5 transfers had a higher live birth rate vs day 3 (37.9% vs 28.8%)
• Day 5 had a higher cumulative pregnancy (60.6% vs 47.7%)
• Slightly lower odds of miscarriage with day 5 transfers
• Slightly increased odds of delivery before 37 weeks with day 5 transfers
• No differences in ectopic pregnancies or in birth weight

Yang et al. (2018) compared the transfer of a time-lapse selected day 3 embryo to a morphologically graded day 5 embryo in their RCT (single embryo transfers):

• Day 5 had a higher ongoing pregnancy rate compared to day 3 (68.4% vs 59.4%)
• No difference in miscarriage rates

A big problem with all this is the variability between studies: different culture media, different freezing methods, different number of embryos transferred, some only looked at fresh transfers, etc. This makes it hard to make conclusions, but overall it seems that day 5 is superior to day 3.

Are Day 3 transfers better for poor prognosis women compared to day 5 transfers?

Fernández-Shaw et al. 2015 did a small RCT that looked at advanced age and day 3 vs day 5 transfers. For women <35 they found no differences, but for >35:

• Higher pregnancy rate with day 5 vs day 3 (54.8% vs 29%)
• Higher ongoing pregnancy with day 5 (48.4% vs 19.3%)
• Higher cumulative pregnancy with day 5 (58% vs 25.8%)

Although these women were older (average age of around 38), they were otherwise good prognosis (first cycle, lots of eggs collected, 3-4 embryos frozen).

Haas et al. (2019) looked at poor prognosis women who had only 1-2 good quality embryos available on day 3 and compared success rates (average age ~37):

• No difference in cumulative pregnancy rates with day 5 vs day 3 (24.6% vs 22%)
• No difference in cumulative ongoing pregnancy (20.2% vs 20%)

Some of the day 5 transfers included morulas and early blasts, and when they removed these from the statistics:

• Higher cumulative pregnancy rates with day 5 vs day 3 (34% vs 22%)
• Higher cumulative ongoing pregnancy (30% vs 20%)

So Day 5 transfers performed better provided the patients had expanded blasts (anything above expansion of “3” – like a 3BB or 4AA, etc). This group represented 59.2% of the Day 5 women. 27.5% of women only had morulas/early blasts on Day 5, while 13.2% of women had their embryos arrest and no transfer was done.

So the data (as far as I’ve found) seems to suggest that day 5 is better for poor prognosis women.

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Pros and cons of day 3 and day 5 embryo transfers

This list is compiled mainly from ASRM (2018)

For day 3 transfers:

• Higher number of embryos available for transfer/freezing
• Potentially higher cumulative rates (controversial)
• Less cost to transfer than to start a new cycle
• Lower implantation/pregnancy rates

For Day 5 transfers:

• Higher implantation/pregnancy rates
• Potentially higher cumulative rates (controversial)
• Potential for choosing best quality embryo for single embryo transfer
• Better synchronization with uterus
• Higher chance of cancelled transfer
• Fewer embryos available for transfer/freezing

Haas et al. (2019) feel that the main advantage for day 3 transfers is a psychological one. For some women, to go through the IVF procedure and to come out without anything to transfer is devastating. Some would prefer that their body is the deciding factor and not the lab for this. The truth is we don’t know what will happen in your specific situation, and the science is far from conclusive.

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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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