Balanced translocation & recurrent miscarriage
Dear Professor Winston
I have had 5 Pregnancies. 1 Miscarriage, Stillbirth full term healthy girl 6lb 3 (2012) followed by 3 recurrent miscarriages. No exact reasons were found although after the stillbirth we were told I have balanced translocation and put stillbirth down to the placenta. I am now trying aspirin and high dose folic acid although no tests have shown need for this or any reason to take the aspirin. I have no problems actually getting pregnant but seem unable to get further than 8 weeks and with the added upset of losing our little girl to stillbirth just wondered what your thoughts were to this situation and any pointers for a positive outcome. We are still awaiting an appointment with a Consultant at the recurrent miscarriage clinic (at a university hospital) after the last miscarriage in May, but our consultant at our local hospital has said not to worry if I get pregnant before this appointment- just take the high dose folic acid and aspirin. At my age (36) they don’t really want to have too many delays for us trying. But as said no tests after the stillbirth etc are showing anything to stop us trying or a reason which is good and bad. The last test from the miscarriage was also normal. Thanks and I look forward to any advice. A
Dear A,

Yours is a very sad story – especially the history of a stillbirth. Were you ever given an explanation for this?

But first, for those reading this page, let me explain a bit. All our genetic material is carried on 23 pairs of chromosomes. One half set of chromosomes comes from our mother (in the egg) and one from our father (in the sperm). During reproduction, bits of these chromosomes split up randomly so that we inherit genetic material from both parents. A translocation is where a bit of one chromosome (let’s call it chromosome A) becomes attached to another chromosome from a different pair (call it B) usually at the time of conception. When there is no loss of genetic material as in the case of a so-called balanced translocation – the dislodged bit of chromosome from B simply moving over to the chromosome A – the health of person is generally entirely unaffected.

Because reallocation of genetic material occurs during fertilisation, any oddity including prior rearrangements of chromosomes in this way sometimes cause problems including infertility. Such rearrangements are, for example, one of the commoner causes of recurrent miscarriage. For reasons which are not entirely clear, a mother with a balanced translocation seems slightly more likely to have a miscarriage than when her male partner has this chromosomal rearrangement.

In your case, A, as I am sure you know your translocation (which presumably occurred at your conception or when one of your ancestors was conceived) you are entirely normal. It also figures that people like you with a balanced translocation will often finally have a successful conception but having repeated miscarriages takes a severe toll and few people want to contemplate this. It is also true that because it may make it more difficult to conceive in the first place, this agonising wait for a child becomes unbearable. Incidentally it is said that translocations between certain chromosomes make a miscarriage more likely. But I do not know the precise nature if your translocation so I cannot advise you on this. In my view a consultation with a genetic counsellor could be very helpful, and I would strongly advise this.

Until the Genesis Research Trust uniquely funded work in this field, the only ‘treatment’ for people like you was to keep trying to get pregnant and face the deeply unpleasant prospect of complete sterility or the regular misery of miscarriages. In the late 1980s, the Trust funded research into preimplantation genetic diagnosis and the first babies, free of a gene defect, were born in 1990. Then we expanded this research to help people specifically with translocations and the first babies were born a year or so later. So it is now possible to screen the chromosomes of embryos shortly after fertilisation. The doctors can avoid transferring those with a clear chromosome abnormality as a result of one other parent having a balanced translocation, and the success rate is really quite good. The problem is the screening is quite specialised and the clinics that do it charge quite a lot of money.

The alternatives which may be offered include blastocyst transfer, rather than transfer of an embryo at an earlier stage, as there are unconfirmed reports that this itself makes the likelihood of transferring a less viable embryo likely. When the male parent has the chromosome translocation, some clinics have tried filtering the sperm, but it isn’t clear to me how successful this is, and in any case this would not be applicable in your case.

There is certainly no reason not to take folic acid (though I doubt this will make much difference) and I don’t follow why you were advised to take aspirin. But my feeling is that the IVF route may well be worth considering in your case – it may depend on the precise position of the translocation and also whether the clinic has the advanced technology available to screen for the translocation present in your case. The technology is getting more and more advanced and bit is now possible to map virtually the entire genetic background of an embryo so there is hope in your case.

I am sorry that this letter is so long but I hope it is helpful to you and indeed, anybody else reading it.
Best wishes
Robert Winston

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