Image result for blastocyst transfer

This is an excerpt from our forthcoming, book, The Expert Patient's Guide to IVF. This being authored by our expert patient, Manju and me.

Is a day 5 embryo transfer (blastocyst transfer) better than a day 3 embryo transfer (cleavage stage embryo transfer).

Fact : Yes, this is true, if you have lots of embryos and you are taking treatment in a good IVF lab. This is because growing embryos to Day 5 allows us to select the best embryos. By allowing the embryos to compete amongst themselves, we can choose the ones which have the highest potential to implant. However, if you have only a few embryos, then matters become more complex.

The Process

Before going into the details, here is a brief summary about human embryo development:

  • A human embryo starts its development as a zygote. A zygote is the initial cell which is formed when an egg and a sperm fuse with each other
  • It carries the genetic material from both the parents
  • Approximately at around 30 hours after fertilization a zygote divides into two cells and the cells are called blastomeres
  • On the third day of fertilization a zygote usually contains 8 blastomeres
  • A cleavage stage embryo transfer is usually performed at this stage
  • The zygote further divides and at around day 5 of fertilization it contains around 70-100 cells
  • From this time onwards a zygote is called a blastocyst. The blastocyst contains an inner cell mass (ICM) which subsequently forms the embryo and an outer layer of cells called trophoblast which develops into the placenta.
  • The meeting of egg and the sperm takes place in the fallopian tube and the embryo thus formed resides in the fallopian tube for upto 4 days
  • The gentle contractions of the fallopian tube pushes the embryo towards the uterus and the embryo reaches the uterus usually at around day 4-5 of fertilization; that is in the blastocyst stage.

If an embryo reaches the uterus when it is a blastocyst , then it is logical to transfer the embryo produced in vitro back to the uterus during the same time period , so that the synchrony between the endometrium and the embryo is not lost. 

Some Questions 

Many embryos arrest during the initial developmental stages:

  • If this is the case , then doesn't doing a blastocyst transfer ensures that you transfer only embryos which are viable enough to develop into a baby when compared to cleavage stage embryo transfer?
  • Won't better embryo selection improve pregnancy rates? All these logical questions led to the development and propagation of blastocyst transfer with great expectations.
It was assumed ( quite logically !) that a blastocyst transfer will lead to an improvement in IVF pregnancy rates.  And it will, provided there are enough embryos, and the lab is good at growing blastocysts !

Read more- IVF success rates , blastocyst transfer , and simplifying IVF

  • The risk is that a blastocyst transfer can lead to higher embryo transfer cancellation rate. Not all the embryos develop into a blastocyst and the blastocyst formation rate are less for women of advanced maternal age ; women with poor ovarian reserve ; and women with poor embryo quality. Such women are at higher risk of cycle cancellation if none of their embryos reach the blastocyst stage. This is a major issue when the IVF lab is of poor quality, and they don't have the experience and skill to grow embryos to the blastocyst stage.

This means that your odds of getting pregnant are higher if you are doing a blastocyst transfer , provided your IVF clinic is good, and if you have enough embryos .

In our clinic, we do blastocyst transfers routinely for all patients.

Why you should insist that your doctor do only blastocyst transfers

In the past, most embryo transfers were done on day two or day three. However, most good clinics have moved on to doing day five (blastocyst ) transfers routinely. Sadly, in India this is still not the standard option , and lots of IVF clinic continue to transfer embryos on day two or three. This is primarily because they're not very confident about the quality of their laboratory ; and the ability of their embryologist to culture embryos to day five.  This is why they prefer putting back the embryos into the uterus, and justify this by telling the patient that the uterus provides a better environment as compared to an incubator.  However, this has a lot  of disadvantages, and you should insist that your doctor do a blastocyst transfer for you .

For one thing, blastocysts have a better chance of implantation, which means the success rate with blastocyst transfers is higher as compared with Day 2 or 3 transfers. Because they're more highly developed and have more cells, they have a higher chance of  implanting. This also allows the doctor to reduce the number of embryos he transfers, so he can actually transfer just one or two blastocysts, and still have as good a pregnancy rate as compared to transferring three or four Day 3 embryos.

Also, since the doctor is transferring only 1 - 2 blastocysts, you can freeze the extra blastocysts , which means you get a chance to do more cycles . This makes it more cost-effective , because the cumulative pregnancy rate goes up.

Finally, the most important reason you should insist on a Day 5 transfer is because you don't need to put yourself through that horrible 2  week wait (  2ww) of not being sure whether you're going to get pregnant or not if you have poor quality embryos .  Thus, if the IVF cycle fails after transferring Day 3 embryos, you never know whether the problem was because the embryo did not develop any further in vivo , or if there was some other reason for the failed implantation.  Putting the embryo back too early reduces the pressure for the doctor, because he can claim that at least he did the embryo transfer for you; but you pay the price for this,  because you remain in  the dark about whether your embryos were able to grow to Day 5. In case the cycle fails, this means you have wasted a chance to get priceless information which could help you to plan your future cycles.

This is specially true for the older woman who has few eggs. This is the group who's at much higher risk for IVF failure because they are more likely to have embryos which arrest and do not reach the blastocyst stage. Lots of their embryos will have genetic problems, because their eggs  are older , which is why they are less likely to implant successfully.

These are the patients for whom a blastocyst transfer is extremely useful. However, they are often poor ovarian responders, and when the doctor collects only 3-4 eggs and therefore gets very few embryos, he is very reluctant to grow them to the blastocyst stage, because he is scared that if the embryos arrest in vitro in the lab, the patient will blame him for the IVF failure. This is why they'd much rather transfer the embryos back in the uterus, and if the cycle fails, they can blame this on " implantation failure" .

However, after the embryo transfer , the patient is deluded into feeling, "Well, maybe this embryo may implant and become a baby" which is why they are very hopeful during the 2ww.

This false hope is harmful.  When the cycle fails, they feel that it was their uterus which rejected the embryo , and then they are advised to go down the surrogacy route. This is bad advice which is completely flawed, because the problem is with the egg and not with the uterus.

Yes, it can be heartbreaking to see your embryos arrest in the laboratory because the doctor tried to grow them to the blastocyst stage. You then have no embryos to transfer at all, and this can be painful. However, the short-term pain is worth it, because of the long-term gain. This gives you a lot of clarity as to what the reason for the failure was, so you can come to terms with it . It's then much easier to explore find alternative treatment options, rather than muddling around in the dark because you're completely confused.

Of course, this option requires a very determined patient and a courageous doctor, both of whom understand the risks and benefits of the path they have chosen to explore.

You can see what blastocysts look like at https://www.drmalpani.com/blastocystimages


Read more- Why even perfect blastocysts do not result in a baby


Authored by : Dr Aniruddha Malpani, MD and reviewed by Dr Anjali Malpani.

Open Video