A failed IVF cycle can be quite a traumatic experience, and the one question which every patient wants an answer to is - Why did the embryo not implant ? Was there a problem with the embryos ? or is there a problem with the uterus ? This is the million dollar question, which we still cannot answer, so that when patients don't get clear answers, they will often change the doctor, to do a new IVF cycle.

Often this cycle will fail as well as, and the patient then hunts for another doctor ! This is common pattern of behavior, but there are lots of problems with switching from doctor to doctor. The biggest problem is that patients usually do IVF treatment on an ad hoc basis - they fail to plan for failure. This is why, when the cycle fails, patients feel disheartened and disappointed, and are not sure what to do next. When the cycle fails, a lot of doctors also become very inaccessible, and the patient feels abandoned, which is why they hunt for a new doctor. The tragedy is that the new doctor now wants to repeat all the investigations the old one did - and often in this game of one-upmanship, patients end up spending a lot of money on expensive ( and useless ) tests. Most of these investigations don't provide any useful information for the poor patient !

For example, I saw a patient today who had done an IVF cycle elsewhere. The doctor had transferred three embryos on Day 2, but she didn't get pregnant. Because her doctor could not provide an adequate explanation as to why the cycle failed, she switched clinics. However , the new clinic repeated exactly the same process. I think patients need think a little more logically. What's the point of changing the doctor if the new doctor does exactly what the old one did ? Ideally, the doctor should have tried to grow the embryos to Day 5, so they could have obtained more information as to the cause of the failed implantation. If the embryos did not develop into blastocysts on Day 5, then this would suggest that the reason for the failed implantation was an embryo problem, rather than a uterine problem ( assuming the lab was good and was confident of growing blastocysts routinely in their lab).

The patient would then understand that if the problem was with her embryos, it would mean that her eggs were not of good quality ( because we know the major determinant of embryo quality is the energy provided for cell division from the mitochondria in the oocyte). She would understand that poor egg quality was causing her embryos to arrest in vitro - and if they were doing so in a good IVF lab, the chances were high that they would do this in utero as well. She could then start thinking in terms of alternative options, such as using donor eggs.

However, if the embryo continues to develop to Day 5, this provides a little more reassurance that there is nothing major wrong with her embryos. If she then fails three blastocyst transfer cycles, considering surrogacy would be a reasonable option. In the future, once the technology is mature, it will be possible to routinely select the best blastocysts using comprehensive chromosomal screening ( CCS), as this would ensure that the blastocysts which are transferred are chromosomally normal.

Unfortunately, because patients don't think through their options systematically, or because all IVF clinics don't offer all these facilities and services, patients end up just repeating the same thing in different clinics. They get stuck, and are unable to make sense of their problem, inspite of many IVF cycles.

If you have failed an IVF cycle after a Day 2 or Day 3 transfer, one way of logically determining whether the problem is with the embryo or with the uterus is to grow the embryos to blastocyst stage in the lab. This will provide objective evidence that the embryo is competent enough to reach the blastocyst stage. Of course, this does not mean that it is genetically normal; or that it will continue to grow on Day 6; or that it is competent enough to implant or become a baby, but at least this approach removes some of the uncertainties associated with analyzing a failed IVF cycle after a Day 2 or Day 3 transfer.

Most patients who reach the stage of transferring genetically normal blastocysts naively assume that this means their cycle is going to succeed ! Unfortunately, this is not true ! What happens if you have failed after transferring Day 5 embryos which were proven to be genetically normal by CCS ? Doesn't this establish that the problem is with uterine receptivity rather than with the embryos ? Won't surrogacy be your best option ? No ! Remember that CCS also has limitations - all it does is allow us to count the number of chromosomes and check for large deletions ! Even CCSs normal embryos may have lethal genetic defects, which are incompatible with life. Our technology still has a long way to go !

So what is the poor patient to do ? She cannot wait forever for the technology to improve. Under these circumstances, here's a logical course of action.

  1. You hypothesise that even though the uterus looks perfect, there is a defect within it, which we cannot test for. You can then transfer your genetically normal embryos into a surrogate, with the hope that they will implant. However, do remember that the success rate with surrogacy is not 100% either !
  2. You accept the fact that most embryos do not implant because of genetic problems within the egg, and consider using donor eggs ( even though we have not been able to identify a genetic defect or problem with your eggs or embryos). Remember that when embryos fail to implant, 9 times out of 10, the problem is with the embryo, rather than with the uterus. This is true, even if the embryos are of Grade A quality, and it's a rule in medicine that if you hear hooves, you should think of horses - not zebras !

Since our tools are so limited ( both for testing endometrial receptivity and embryo quality), it can be very difficult to make a decision when there is so much uncertainty. Sometimes, you need to follow your heart - and make decisions based on your personal preference, understanding that doctors do not have all the answers !

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

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