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.
Myth : A day 5 embryo transfer (blastocyst transfer) is better than day 3 embryo transfer (cleavage stage embryo transfer).
Fact : When blastocyst transfer was introduced a decade back , there was a lot of hype surrounding it. It is of course amazing to watch a human embryo grow into a blastocyst in vitro ; and it is very reassuring to know that the cell culture media and laboratory culture conditions in the IVF lab have improved so much that we can routinely grow embryos to Day 5. But is it really useful from the patient’s point of view ? A few IVF centres initially claimed that pregnancy rate increased tremendously with blastocyst transfer when compared to cleavage stage embryo transfer. One such example is this paper (PMID:10856474) from the very famous CCRM in which they claimed a 70 % implantation rate (with heart tone) with the transfer of two good quality blastocysts. But as time went on and when enough clinical evidence accumulated based on several Randomised Clinical Trials (RCTs) , it became clear that as usual overenthusiastic researchers have made a mountain out of a molehill !
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 isn’t it 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 ? Also , when embryos are allowed to develop in vitro , not all of them develop into blastocysts. 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 a dramatic improvement in IVF pregnancy rates. But logical reasoning is not always enough to decipher biological secrets ! Blastocyst transfer ultimately proved to be no better than a cleavage stage embryo transfer.
A recent analysis of 23 RCTs showed that transfer of cleavage stage embryos resulted in a higher clinical pregnancy rates than blastocyst transfer (PMID:22786480). But the live birth rate is slightly higher in the blastocyst transfer group when compared to the cleavage stage embryo transfer group.
The results are surprising ! There are two reasons for the study results favouring a cleavage stage embryo transfer in terms of higher clinical pregnancy rate:
1) 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.
2) More embryos are available for freezing if the embryos are frozen at the cleavage stage, and hence there are more chances for performing subsequent frozen embryo transfer ( which improves the cumulative pregnancy rate).
This means that your odds of getting pregnant are higher if you are doing a cleavage stage embryo transfer. It is wise to opt for cleavage stage embryo transfer if you have only a few embryos for transfer ; or if you are of advanced maternal age. Further advances have to be made and more evidence is actually needed to prove that a blastocyst transfer is really better than a day 3 embryo transfer . Until then , the claim that a day 5 embryo transfer is better than cleavage stage embryo transfer is just a logical fallacy !
You can email Manju at email@example.com
Her blog is at www.myselfishgenes.blogspot.com