This is why you should insist that your doctor do only blastocyst transfers for you.
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.
Read more at http://www.drmalpani.com/articles/blastocyst
You can see what blastocysts look like at
http://www.drmalpani.com/blastocystimagesasttransfer
The statistical differentiation between the live birth rates from a cleaving embryo compared to a blastocyst would logically be comparable for populations with lower incidence of aneuploid embryos (e.g. women <= 35 years of age). Are any of the RCTs which were evaluated specifically targeted at older women with a higher rate of aneuploid embryos? In that scenario, I would anticipate that the live birth rate of blastocyst transfer would be much higher. This is, of course, assuming that the skill of the embryologist, the quality of the lab, or the effectiveness of the growth protocol is not in question. It is well known that all of these critical factors are not equal depending on the chosen facility.
ReplyDeleteThe conclusion that the odds of getting pregnant using a cleavage stage embryo transfer may be true in the 23 RCTs, but the true goal is a live birth. Transferring potentially incompetent embryos does not advance one toward this objective.
This excerpt of the review reveals the flaw:
"This review of 25 studies... Disappointingly, only half of the included studies reported miscarriage or live birth rates. Twelve RCTs reported live birth rates and there was evidence of a significant difference in live birth rate per couple favouring blastocyst culture (1510 women, Peto OR 1.40, 95% CI 1.13 to 1.74) (Day 2 to 3: 31%; Day 5 to 6: 38.8%, I2= 40%)."
I cannot imagine a scenario where one would not favor a statistically significant improvement to the live birth rate, and therefore do interpret the data to conclude that there is an advantage to blastocyst transfer.
You have put forth a very valid argument – I agree that the goal of any IVF cycle should be live birth ! Since blastocyst transfer has shown a small significant increase in live birth rate it should be logical to conclude that day 5 transfer is better than a day 3 transfer. The authors state that “This means that for a typical rate of 31% in clinics that use early cleavage stage cycles, the rate of live births would increase to 32% to 42% if clinics used blastocyst transfer”. The authors also state that there is no difference in clinical pregnancy rate or miscarriage rates (?) between cleavage stage embryo transfer or blastocyst transfer ! The question, ‘to blastocyst or not ’ is not even necessary in young women with lots of eggs and embryos – of course most clinics will naturally go in for a blastocyst transfer (commercially too it is a better option for them !) The argument whether day 5 ET is better than day 3 ET arises in the case of older women and women with poor ovarian reserve since these are the challenging women who have a guarded prognosis.
ReplyDeleteMy point is that I do not think blastocyst transfer can benefit older women or women with fewer embryos! The odds of achieving a successful pregnancy and live birth via IVF is compromised in older women and in women with poor ovarian reserve because the amount of eggs obtained and embryos formed is reduced ; and the presence of a high percentage of aneuploid embryos in older women further reduces their chances of success. When you have fewer embryos it is wise to be cautious and transfer the embryos as early as possible to the uterus– after all, the rule of thumb in medicine is ‘first do no harm’ ! It should be kept in mind that even in young woman with good quality embryos , the blastocyst formation rate is just 35-40 %. Will embryos which do not grow to a blastocyst in vitro achieve a viable pregnancy when transferred in vivo at an earlier stage ? When we do not have a solid answer to this question, isn’t it wise to do a day 3 transfer for women who do not have a good
prognosis ? There is a high risk that their embryos may arrest in vitro if you try to grow them to Day 5, as a result of which there maybe no embryos to transfer at all !
Another important aspect is the emotional impact on patients when they are left with no embryo to transfer ! 40 % of poor prognosis patient’s embryos will not grow to blastocysts ! Patients go through a lot of trouble when doing IVF. When they are left with no embryos to transfer , they can be devastated ! It discourages them and they are likely to give up., You may ask - ‘When there is a risk of reduced live birth rate (1-10% reduction in live birth rate !) after achieving a pregnancy with cleavage stage embryo transfer, why shouldn’t a day 5 transfer be the norm in older women too ?’ Is not getting pregnant better than not having embryos to transfer ? Is not having a live birth better than not getting pregnant at all ? Very hard questions to answer !
Another important aspect is the emotional impact on patients when they are left with no embryo to transfer ! 40 % of poor prognosis patient’s embryos will not grow to blastocysts ! Patients go through a lot of trouble when doing IVF. When they are left with no embryos to transfer , they can be devastated ! It discourages them and they are likely to give up., You may ask - ‘When there is a risk of reduced live birth rate (1-10% reduction in live birth rate !) after achieving a pregnancy with cleavage stage embryo transfer, why shouldn’t a day 5 transfer be the norm in older women too ?’ Is not getting pregnant better than not having embryos to transfer ? Is not having a live birth better than not getting pregnant at all ? Very hard questions to answer !
ReplyDeleteI believe that the cons outweigh the pros of day 5 ET in older women and women with poor ovarian reserve when compared to day 3 ET ! Studies have shown that older women have decreased chance of pregnancy with day 5 ET (I am not aware of any RCTs). When there is no valid proof in favor of day 5 ET it is good to stick to procedures which don’t cause any obvious harm : )
I believe that day 5 ET is not better than day 3 ET (I would even say day 3 ET is better for some group of women !) – and I have few embryos I will definitely avoid day 5 ET !
You have said, “I cannot imagine a scenario where one would not favor a statistically significant improvement to the live birth rate, and therefore do interpret the data to conclude that there is an advantage to blastocyst transfer” . My interpretation is that since the risk of day 5 ET outweighs its advantage, day 3 ET should be preferred until more data is available !
Thanks for initiating this valuable discussion !