This figure, which was the starting point for a recent study American-Canadian, recalls the importance of better understanding the causes of pregnancy loss. The researchers specifically sought to determine the types and frequency of chromosomal abnormalities, explains Dr. Rina Slim, of the Child Health and Human Development Program at the Research Institute of the McGill University Health Center (IR- MUHC) and co-author of this recent study.
A wide spectrum of genomic imbalances might thus lead to recurrent pregnancy loss. The authors analyzed samples collected from 24,900 miscarriages using a new technology using chromosomal microarrays (SNP-CMA), which are chromosomal microarray analysis tests.
“We don’t know much regarding the genes that cause spontaneous abortions. This study tells us that some genetic abnormalities are not detected in the parents but occur at conception – a chromosomal defect in the fertilized egg. The fetus is not viable,” explains the researcher.
Miscarriages vary greatly, as do their causes, such as the age of the mother-to-be — the risk would be one in three from the age of 40 — maternal reproductive anatomy — abnormalities of the uterus, for example — history of miscarriage or environmental factors — tobacco, alcohol, drug addiction, but also medications, occupational hazards, infections, among other things.
Genes from mother, father or embryo
Many researchers also point out that a large proportion of recurrent miscarriages might have an underlying genetic cause – which would concern nearly 5% of couples. Such genetic abnormalities can be within the genome of the mother, the father or the embryo (the fetal genetic makeup).
This study also showed that abnormalities were observed in nearly 56% of the miscarriage samples, of which nearly 8% presented significant polyploid imbalances – these are changes in the number of chromosomes, lacking or excess. .
In humans, genes are grouped into 46 chromosomes, 23 from the father and 23 from the mother – together forming the equivalent of a book with different pages of instructions where errors can occur: missing pages, too many or duplicates, which are still hard to spot.
What is sought is above all what is called a “chromosomal translocation”: more than a loss or gain of certain genes, these are changes within the structure of one or more chromosomes – for example, abnormal breakage or sticking together — likely to affect the design.
These changes in the structure of the chromosomes pass under the radar of doctors. “In 90% of cases with such abnormalities, there will be spontaneous death,” says Dr. Slim.
The researcher also notes that “aneuploidy” – an abnormal number of chromosomes in a cell – is observed in nearly 13% of incidents.
The analysis of samples from 1103 patients with multiple miscarriages thus provides information on possible predispositions. And it turns out that each pregnancy loss would increase the risk of it happening once more – 15-20% following the first miscarriage, 25-40% following the second, up to almost 45% from the 3rd pregnancy not completed.
In study Previously, the researcher had looked into the cause of these repeated events, in a patient who had experienced 16 miscarriages. Genetic sequencing of spontaneously aborted cells had shown that a mutation in the CCNB3 gene, contributing to the cell division of the egg, would be behind these embryo losses.
About fifteen years ago, the researcher’s team had also identified the first of the genes (NLRP7) responsible for recurrent fetal loss. It is a gene transmitted by the mothers in the oocyte, which affects the viability of the embryo by the presence of chromosomal abnormalities.
How to prevent the worst?
Alerted by cramps, bleeding and pain, the woman who may be experiencing pregnancy loss will first undergo an ultrasound to detect the heartbeat of the fetus and blood tests to detect the pregnancy hormone level (beta hCG ) in the blood: a low level will indicate the death of the fetus.
An analysis of the fetal karyotype might be proposed to try to track chromosomal abnormalities. It should be noted that some do not prevent an embryo from being viable, such as trisomy 21 with the presence of a supernumerary chromosome 21 or a supernumerary fragment of chromosome 21.
When the couple encounters repeated failures in their attempts to have a child, Dr. Slim recommends genetic testing to have part of the explanation, especially for the 5% of those who fail to procreate. “This represents one more lead for these couples in distress, but it will not explain all the gray areas”, however tempers the researcher.
Not yet available in Quebec
The strength of this study is that this new American technology shows great promise for uncovering the genetic abnormalities that underlie failed pregnancies, comments Dr. Camille Sylvestre, Associate Professor in the Department of Obstetrics-Gynecology at the University of Montreal, which did not participate in this study.
This makes it possible to more accurately probe the genetic makeup of the fetus. “It’s like looking at the letters in a book, but it’s not yet available in Quebec. An intermediate technology, analysis by comparative genomic hybridization (Comparative Genomic Hybridization or CGH) instead suggests looking at the pages of the book – the amount of DNA in our chromosomes. But what is most common in Quebec as a screening is the analysis of the karyotype – which counts the chromosomes: it’s like looking at the chapters of this book, ”explains the fertility specialist, also associated with the CHU Sainte – Justine.
In Quebec, three laboratories – two in Montreal and one in Sherbrooke – offer CGH technology, but only following three pregnancy losses. “Our recommendations would be to do it from two miscarriages, because it represents a disproportionate financial and emotional cost, to wait so long to better know the reasons for the failures. Not to mention that it also takes between 3 and 4 months to have a result”, specifies the expert, member of the guideline committee of the Canadian Fertility and Andrology Society of Canada.
Ordinary screening by karyotype analysis “does not provide all the answers so you may want to push the analysis further and insist on doing these CGH tests. The companies that offer them are currently very present in fertility congresses and this would be my only criticism of the study, so there is a commercial bias, whereas as we learn from this study, this informs much more regarding the anomalies related to sporadic miscarriages (64%) than recurrent miscarriages (5%). We do not always end up with a diagnosis that explains everything and we must take into account the age of the mother, ”notes the expert once more.
Many future mothers are already old – the average is 30 in Canada for a first pregnancy – “the average age of consultation at the clinic is 38 in Quebec” – and with age, the risk of genetic abnormalities are increasing rapidly.
