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Focus on Recurrent Miscarriage Phenotypes

Multiple, later-stage miscarriages may be a sign of treatable medical problems, such as diabetes or autoimmunity. Dr. David Barad discusses efforts to understand and treat recurrent miscarriages, for the medical journal fertility & sterility.

Hi, I’m Dr. Barad from the Center of Human Reproduction here in New York and I want to thank the editors of “Fertility and Sterility” for inviting me to comment on the paper by Michael Feichtinger and his colleagues.

Dr. Feichtinger paper was titled “Transcervical embryoscopy and primary and secondary reproductive pregnancy loss”. We thought this was a particularly interesting paper because we generally think of pregnancy losses, mostly being related to aneuploidy.

Interesting things it showed was that women with primary recurrent pregnancy loss, there’s actually a lower risk of aneuploidy than in those with secondary recurrent pregnancy loss or those who just had simple pregnancy loss. This suggests that there’s something else going on in those women with the primary recurrent pregnancy loss and in the commentary, we expanded on that a little bit, so what could it be?

ARM generally recommends that women with recurrent pregnancy loss be evaluated with maternal and paternal karyotype, with thrombophilia workup, with an endocrine workup and with a workup for possible autoimmunity.

I think we have to focus a little bit more on this autoimmune issue, which has really been discounted greatly in the past, but likely because we didn’t focus enough on who the people with recurrent pregnancy loss that we are trying to evaluate or treat were.

If we throw everybody with pregnancy loss into the same bin and then try to treat them with the same interventions we don’t really have a chance of trying to see an effect, so one of the contributions that Feichtinger and his colleagues have made is to help us focus on what the different types of pregnancy loss, recurrent pregnancy loss, might be and the more we can focus the more we can target both our diagnostic efforts and our therapeutic effort in the future.

For instance, it’s not surprising if we are turning to address immune problems or diagnosing problems and people who by and large have had aneuploidy losses that we may not see an effect. On the other hand, if we can identify a group that’s more likely to had euploid pregnancy losses we have a better chance of trying both diagnose and treat.

Past efforts of looking for autoimmune effects have focused on trying to find specific sets of autoimmunity like natural killer cells or antiphospholipids. I think we have to remember that the entire pregnancy is dependent on development of immune tolerance, so that the surprising thing is that all of us have survived our pregnancies in which our mothers had to tolerate the paternal antigens that are present in all fetuses. So one of the things we have to look for are ways of measuring the extent to which immune tolerance has been achieved and what we can do to try to modulate that.

As we mentioned, our commentary, we’re at CHR currently working on some projects to try to better identify these factors, and possible treat. One of the surprising observations at Feichtinger paper was that there were morphological abnormalities even among the euploid pregnancies, and one wonders, where is that coming from? We know that certain maternal exposures, diet and alcohol, and perhaps others, can affect the developing fetus. Possibly these are epigenetics effects acting on the developing fetus. It’s clear that the better understanding of recurrent pregnancy loss is needed, and that there’s still much more work to do in this area, far from being closed to a subject, there’s much opportunity for further investigation.