Saturday, October 10, 2015

Why it's always better to transfer embryos on Day 5 rather than Day 3

Lots of IVF clinics will transfer embryos on day 3 but we  prefer doing transfers on day 5.
Now, if there are lots of eggs and lots of embryos, it's quite obvious why day 5 is a better option. After all, you can allow the embryos to compete amongst themselves and then select the best embryo, so that this is the embryo which then has the best chance of becoming a baby. On day 3, on the other hand, you will have lots of embryos which look exactly the same, so then you have to play eenie-meenie-miney-mo when you decide to pick which ones to transfer. Whereas with day 5, since the embryos have competed amongst themselves, there are fewer embryos left , so it's easier to pick the best ones. The advantage is that we are not wasting any embryos because even on day 5, if there are more than the required number to transfer, we can always freeze the extra embryos, so this way, the patient has her cake and can eat it too !

    So why don't all clinics do day 5 transfers? And I think the reason is that they're concerned about their technical ability to be able to grow embryos to blastocysts . The problem is that for lots of IVF clinics, their success endpoint is an embryo transfer. This means that once they've transferred Day 3 embryos into the patient, the patient is happy , because the doctor has successfully completed the IVF treatment, irrespective of whether that embryo becomes a baby or not. On the other hand, if they continue to grow the embryos to day 5 and the embryos arrest in the lab and they don't have any blastocyst to transfer, the patient is likely to get upset and angry , and blame the doctor, and this is not something which an IVF clinic wants to risk.

    However, our perspective is very different , and even for patients with few eggs ( even 1 or 2) we still prefer a day 5 transfer, and here's the reason why. Of course with every IVF cycle, the primary goal is to have a baby, but there's also a secondary goal of acquiring useful diagnostic information which can help the patient decide what to do for the second cycle, in case the first cycle fails.

If we transfer embryos routinely on day 3, we actually lose a lot of valuable information. For example, if we transfer embryos and the patient doesn't get pregnant, this is "diagnosed" as failed implantation. We can never figure out why the patient didn't get pregnant . Was this because the embryos arrested on day 4 or 5 inside the uterus and did not develop into blastocysts, because they were not genetically competent ?  Or  were there were some other factors which affected embryo implantation ?

    Now, suppose we'd grown these embryos to day 5, and let's assume they did arrest on day 4. Of course this would cause a lot of heartache and angst for the patient who would be extremely upset that we were not able to transfer embryos for her. However, on the other hand, she would acquire extremely valuable information , which she could then use towards crafting her future treatment. The fact that she had few eggs obviously means she has poor ovarian reserve ( DOR) and her egg quality was not great. However, she may not be very keen on using donor eggs so that, even if does get a single day 3 embryo to transfer, and even if that cycle fails, she's quite happy to sign up for a second cycle and a third cycle , in the hope that maybe in the next cycle, one of her day 3 embryos will implant.

Many doctors will often recommend this kind of course of action , because not only can they do more cycles, they can also offer additional options, such as embryo pooling, where they freeze the embryos one at a time, and then transfer multiple embryos at one time. Others will recommend surrogacy , claiming that the reason the embryo failed to implant is because there's something wrong with her uterus or with her immune system or with her Natural Killer ( NK) cells.

    Actually, that's completely flawed thinking. However, because the embryos were transferred on day 3, valuable information was lost. If on the other hand, they had been kept in the lab upto day 5 to grow them to blastocysts, and if they'd arrested, then you would know for sure that the problem lay with the embryo , and not with the uterus, which means there would be no point in wasting so much money on attempting a surrogacy cycle. It would be far more sensible for them to use an alternative option to create better quality embryos ( such as donor eggs) , because the problem obviously was not with the uterus but with the embryos.

For patients with poor quality embryos, especially those as a result of poor ovarian reserve, the chances of success are much better if they use donor eggs , rather than do surrogacy. However, by prematurely transferring the embryos on day 2 or day 3, the valuable ability to extract important information by following the course of the embryo in vitro to day 5, is wasted. The patient is really no wiser as to what to do in her next cycle.

    Doctors will often do Day 3 transfer to minimize the risk, but because our embryologist is so good, and we're so confident about our lab and our ability to grow embryos to blastocysts routinely, that even if we have just one or two eggs, this is the course we would recommend to patients. If they got pregnant, that's obviously great news, but even if they didn't, they would then know what to do differently the next cycle.

    Of course, this requires a very mature patient - someone who understands the pros and cons , and is capable of understanding the rationale for this decision. Equally, it requires a very efficient laboratory and a superb embryologist who understands exactly how to grow embryos routinely to blastocysts in the IVF lab. He needs to be so confident of his ability that he can say, "If the embryo arrested in my lab, this means it would have arrested in the uterus as well, and therefore putting it back in the uterus would not have increased your chances even by 1%."

    Of course, in some labs which are bad, their ability to grow embryos to blastocysts is poor, means that the embryos which would arrest in the lab might have continued to form a baby if they were transferred back into the uterus. In these clinics, perhaps, doing a day 3 transfer makes sense, but in good clinics which have an extremely competent embryologist , growing embryos routinely to blastocysts offers invaluable information. This is information which patients and doctors would never be able to get unless they routinely follow the policy of growing all embryos to blastocysts before transferring them back to the patient.

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