Why do some embryos arrest ?

It’s extremely frustrating for patients when the clinic calls them with the information that what was a beautiful 4-cell embryo on Day 2 has arrested on Day 3 and remained a 4-cell embryo, instead of dividing further to become a 8-cell embryo.

Why do some embryos arrest in vitro ? And why do so many good looking embryos fail to implant after transfer ? And why do some of the ones which do implant end up in a heart-breaking miscarriage, rather than a beautiful baby ? The amount of inefficiency which riddles human reproduction is mind-boggling. ( In fact , it seems to start right from the fact that men need to produce millions of sperm in order for one of them to be able to fertilise the egg ! )

One way of making sense of this is to hypothesize that each embryo’s life expectancy is encoded in its DNA . This is a concept we are familiar with when we consider life and death after birth. We know that there will be some people who live upto the age of 100 – but lots will die at the age of 70 – and a few unfortunate ones will die at the age of 2.  While doctors have to write down a medical cause of death on the death certificate, and we are distraught when learning of the death of a friend’s child at the age of 10 because of leukemia, the fact remains that life expectancy seems to be a random lottery , and we cannot control this.

While we use terms such as lifestyle risk factor and heredity to explain this, a far more useful concept is the term heredity, coined by Dr Manu Kothari. This means that in a “herd” ( a population , for example, a group of children), their life expectancy can be plotted on a bell-shaped curve. Where an individual will figure on this curve is still not something we can determine, but this rule of thumb is a useful way of understanding this randomness. You could try plotting the life span of your father’s classmates, for example, or that of your family members, to see how true this is.

This means that in a given group of people ( and the larger the sample size, the better this rule works),
a certain proportion will keep on dying off at a particular age , because of their genetic predisposition to do so, no matter what we do.

If this is true after birth, then isn't it logical to expect exactly the same kind of variation before birth as well, in the embryonic stage ? Just like there will be some babies who will die at the age of two hours , and some at the age of two years , similarly there will be some embryos which arrest ( die) at the age of 48 hours, while some will arrest on Day 4.

We need to think of this as a continuum , starting from the point of fertilization . This means that the embryo’s life expectancy is hardwired into its DNA , and because this is such a random process , that particular embryo could die within 24 hours ; or after 25 years ; or may live upto the age of 85. Of course, the relationship is complex, and in some cases a bad lab can kill off good embryos ( just like too much smoking can reduce life expectancy).

We still haven't been able to tease apart exactly what affects life expectancy ( though we do know that the length of the telomeres on the chromosomes correlates with aging ).  Once we understand some of this randomness , we would have a better appreciation of the fact that human reproduction is not a very efficient enterprise , and this is why IVF still does not have a success rate of 100%, even when everything seems to be perfect. Our fate seems to be hardwired in our genes , and there's precious little we can do about it at present.