Monday, October 05, 2009

How many embryos should I transfer ?

This is one of the most difficult decisions which IVF patients and their doctors need to make. There are many variables which affect this, so let's look at them one by one.

If IVF had a success rate of 100%, everyone would be happy to transfer one embryo . Life would always have a happy ending and IVF doctors would no longer need to talk to their patients, since they could guarantee them a baby !

Unfortunately, the technology is not perfect, because human reproduction in not very efficient. While the world seems to be full of promiscuous teenagers who get pregnant at the drop of a hat even when they don't want to, only about 25% of normal fertile couples conceive in a month, no matter how hard they try. While IVF does improve this efficiency, it still has a cap of about 35-50% per cycle ( depending upon the clinic and the patient).

We do know that transferring more embryos does increase the success rate. Unfortunately, this increased success rate does come with a price. Transferring more embryos also increases the multiple pregnancy rate. While twins may seem to be the perfect happy ending for many infertile couples who would love to have an "instant family", when we start talking about triplets and other high order births , the risk to the babies ( as a result of prematurity) start increasing dramatically.

You also need to remember that transferring more embryos does not incrementally increase the pregnancy rate beyond a particular point. Thus, if the implantation rate with one embryo is 10%, this does not mean that the rate with 2 is 30%; the rate with 3 is 30% or the rate with 10 is 100% ! While the success rate is better with 2 than with 1; and most probably with 3 as compared to 2, after 3 you reach the point of diminishing returns. Thus transferring 4 or more embryos does not improve the chances of a pregnancy , but does end up increasing the risk of a high order multiple. If you are not going to get pregnant with the transfer of 3 embryos, you are not going to get pregnant in that cycle with 4 or 5 or 6 !

This is why , in order to reduce the risk of high order multiples, countries like the UK allow doctors to transfer only a maximum of 2 embryos; while many others are now moving towards the holy grail of SET - single embryo transfer. If you live in the UK, the decision has already been made for you, so there's little point in discussing this. It's always in the bureaucrat's best interests to minimise the multiple pregnancy rate, even if this does reduce your chances of getting pregnant.

However, what happens if you live in the US or India, where you can decide for yourself ?

Why not let your doctor make this decision for you ? While this can a good idea sometimes, the problem is that often the doctor may end up transferring too many embryos. They want to maximise their success rates, and do not worry about multiple births ( because they don't have to provide the obstetric care or take care of the premature babies) . For many IVF doctors, a triplet pregnancy is a far better outcome than not getting pregnant. While some patients may agree, not everyone will ! So how can you provide your personal input into such an important decision, which has such a huge impact on your life ?

Here's a framework which will help you make a well-informed decision. This will depend upon 3 groups of factors, so let's look at these one by one.

The first is your embryos - the number of embryos you get ; and their quality . This is a biological variable, over which you have little control. This depends upon many factors, including your age; you superovulation protocol; and the skill of the IVF laboratory.

If you only have 2 embryos, then all you can do is transfer them and hope for the best. However, what should you do if you are in the happy position that you have lots of good quality embryos on Day 2 ? In the past, all the embryologist could do was play Eenie, Meenie, Mina, Moe and select the ones he felt were the best. Since he was never sure which ones were the best ( on Day 2, they all look pretty much similar, since all they have is 4 cells), he would often be forced to transfer more, to hedge his bets, and maximise your chances of getting pregnant. This is especially true in clinics which don't have a full-time IVF embryologist !

In this case, your best option is to allow the lab to grow them to blastocyst stage and then transfer 1 or 2 . This strategy allows the embryos to compete amongst themselves , so that the doctor finds it easier to select the best embryos, and transfer only these.

What about your spare ( supernumerary) embryos ? All good IVF clinics will freeze your extra embryos for you, if you so desire. This is a very sensible option, and you should take it if available ( in fact, you should not go to a clinic which does not freeze embryos !). There are many advantages to freezing embryos ( provided your clinic is technically competent at doing so). Not only does this dramatically reduce your risk of a multiple pregnancy, it also markedly improves your success rates. In technically proficient clinics, the success rate with frozen-thaw embryos is at least as good ( and often, even better !) than with fresh embryos. This is because there is no disruption of the hormonal environment in a frozen thaw cycle ( versus a fresh cycle, where the body is filled with the superovulation hormones and has excessively high levels of estrogen and progesterone). Also, a frozen thaw cycle is much easier for you to do ( no superovulation shots !) and much less expensive as well ! The doctors who bad-mouth frozen embryos only do so because they do not have the technical expertise to freeze embryos competently.

What happens if you have many embryos on Day 2, but they are of poor quality ? This can be a problem; and in these circumstances, it may not be a good idea to try to grow the embryos to blasts, because they may arrest, and you may not have any blasts at all to freeze. While many patients are philosophical enough to accept this ( the reasoning being - if the embryo did not grow to a blast in the incubator, it most probably would not have grown in the uterus either, so at least I was spared the horrible tension-packed 2 week wait), others are very upset that the doctor could not transfer any embryos at all !

Thus, both the ability of the clinic to grow embryos to blastocyst stage; and their success rates with freezing are important variables to consider. The availability of these services allows you to optimise your choices !

This now brings us to the next improtant variable - your IVF doctor. Some clinics have a very rigid policy and will not break their protocol, no matter what your personal circumstances or desires maybe. Thus, some will transfer only one embryo, no matter. Others are willing to be more flexible and responsive; and will consider transferring more embryos if you are older or failed many earlier cycles.

Other clinics will routinely transfer 4 or 5 embryos into everyone. These are typically clinics with poor success rates, where the embryo implantation rate is not good. They try to compensate for this by transferring more embryos. However, quantity cannot compensate for quality. THese clinics do not get disturbed by triplet pregnancies because they offer selective fetal reduction to manage these. While this is an alternative approach, I do not find this reasonable, because of the high risk of second trimester miscarriages and preterm labour after selective fetal reduction.

Finally, the most important variable is your personal risk taking appetite. While some patients ( for example, those with one baby who are doing IVF for their second baby to complete their families) will be unhappy with a multiple pregnancy, others are quite happy to accept this risk and will request the doctor to transfer more embryos if this will increase their chances of conceiving. These include older women; and those who have failed multiple IVF cycles in the past.

In conclusion, there is no simple answer to this question - as is true for most simple questions. You need to find the right number for yourself, based on your personal circumstances, and discuss this with your doctor.

1 comment:

  1. Anonymous10:19 AM

    Dr Malpani: Thank you for writing this blog. I am going thru IVF right now and I find your topics very insightful. A lot of the same questions I have asked myself but found no easy answers. Thank you for taking the time to write.


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