Could there be genetic causes behind pregnancy loss? When and what tests should be done after a miscarriage to clarify it? We are talking about it with prof. Anna Latos-Bieleńska, head of the Chair and Department of Medical Genetics at the Medical University of Poznań, a specialist in clinical genetics from the GENESIS Medical Genetics Center.

  • Are couples after pregnancy loss a large group of genetic clinic patients?

Big and important, after all, 10-15% of diagnosed pregnancies end in early death and spontaneous miscarriage. In Poland, with 400,000 births a year, as many as 40-60,000 couples experience the loss of a child in the first weeks after conception. Even if only about half of pregnancies are planned and awaited, in the first few weeks, also in the case of an unplanned pregnancy, there is a strong emotional connection with the developing child, the couple already see themselves as happy parents. Losing a pregnancy is always a trauma, we hear about it from couples who come to the genetic clinic, and the comments on the Internet are also an expression of suffering.

  • What are the genetic causes of pregnancy loss - incorrect genetic material of a woman or a man?

Not a woman or a man, but just a developing baby. The child has his own genetic material, he receives half from his mother in the egg and half from his father in the sperm. For a baby's karyotype to be normal, the reproductive germ cells must have the correct number of chromosomes of 23 (they have one of each pair's chromosomes), but about 20-30% of the eggs and about 10% of the sperm have the wrong number of chromosomes. If a reproductive cell with abnormal chromosomes is involved in fertilization, a child will conceive who has the abnormal chromosomes in every cell in the body and almost always has to die, most often by the 10th week of pregnancy. It should be added that not infrequently there is no pregnancy at all, because the embryo dies before implanting in the uterine mucosa. Abnormal karyotype is found in as many as 60% of embryos and fetuses aborted in the first trimester.

  • Where do genetic errors in reproductive cells come from and can they be prevented?

Genetic errors in reproductive cells are most often caused by abnormalitieschromosome division during meiosis, i.e. cell division during which a reproductive cell with 23 chromosomes is created from a cell containing 46 chromosomes. Geneticists study the causes of chromosome breakdowns, there are several theories. The age of the woman is a known factor, 38-40-year-old women, although they have a preserved ovation cycle, produce most of the reproductive cells with abnormal genetic material. Therefore, geneticists in Europe are observing with great concern the increasing age of pregnant women, especially the postponement of the decision about the first pregnancy. Many couples postpone the decision about a child until they achieve a professional position and material stability, when they enjoy freedom and explore the world. But sometimes it turns out that the road to parenthood is long and difficult, and the decision about a child is late. In Poland, the situation is not as bad as in Western European countries, but we also have a clear tendency to postpone parenting.

  • Is it possible to detect an increased risk of genetic defects in a child by doing genetic testing in a couple after a pregnancy loss?

Genetic errors in reproductive cells are usually random and occur with the perfectly normal karyotype (karyotype - a person's set of chromosomes) of both partners. However, there are couples who have a higher risk of a genetic defect in a baby and an associated risk of pregnancy loss. I would distinguish three groups of such couples. The first group are pairs in which one of the partners has a balanced chromosomal aberration. It can be called a translocation or inversion in which the carrier of such a lesion is a completely he althy person and until reproductive failure occurs or a sick child is born, completely unaware of the carrier of the aberration. The second group is carriers of very small chromosome changes that are difficult to detect, fortunately such a situation is rare. The third group consists of pairs in which one of the partners is prone to errors in the division of chromosomes during the production of reproductive cells, while having a completely normal own karyotype.

  • So what genetic tests should be done after the loss of pregnancy and when?

In the case of reproductive failure (no pregnancy, spontaneous miscarriage), it is recommended to consult a genetic clinic. A geneticist will collect an interview regarding a medical problem, family history, and select genetic tests.

Important

Genetic tests after miscarriage

  • Karyotype testing in both partners

Should be done if there were 2 early pregnancies, but if in the family - especially in the mother, sister or sister-in-law -were lost pregnancies, or a child was born with congenital abnormalities, a karyotype test should be performed after one loss of pregnancy and even before the first planned pregnancy. The same should be done with the karyotype of both partners if there was one pregnancy loss after 13 weeks. The test is to exclude the carrier of the aberration in one of the partners. It should be noted that carrying a chromosomal aberration almost never eliminates the chance of he althy children.
For the karyotype test you need 1-3 ml of venous blood collected for heparin (preferably in a special test tube).

  • Genetic testing of miscarriage material

Genetic examination of the chorion from a miscarriage allows to determine whether the cause of the pregnancy loss was an abnormal karyotype of the fetus. This situation affects as much as 60% of early pregnancy losses. The finding of a chromosomal aberration in a dead / aborted embryo / fetus shows the cause of pregnancy loss, the prognosis for the maintenance of subsequent pregnancies, and sometimes reveals a hidden chromosomal aberration in one of the partners. Genetic examination of the material helps to guide further diagnosis of the causes of miscarriages and is of great psychological importance for a couple who lost pregnancy.
The test can be performed using the QF-PCR method (shows the most frequent changes in the number of chromosomes) or the microarray method (shows aberrations of the number and structure of chromosomes, even very small ones, unavailable for testing by other methods).
For the genetic material testing from a miscarriage, a fragment of the chorion should be secured (during the cleaning of the uterine cavity after death of pregnancy), or the excreted fragment of the chorion may be secured in the course of spontaneous abortion. You can use a sterile vessel (e.g. a plastic urine test container available at a pharmacy), and cover fragments of biological material with sterile physiological saline (available at a pharmacy).

  • Genetic testing of a woman for congenital thrombophilia

In women with miscarriages, especially if chromosomal aberrations have been excluded when examining the material from the miscarriage, testing for congenital thrombophilia should be considered. Congenital thrombophilia is a genetically determined coagulation disorder, a tendency to blood clots and vascular embolism. This examination is recommended especially in cases where there was a family history of blockages and blood clots, but many gynecologists also recommend it without a burdened family history. Genetic testing for congenital thrombophilia in women with miscarriage is not on the list of international recommendations, but due to the serious effects of congenital thrombophilia (risk of serious complications during pregnancy, there are also reports ofincreased risk of certain birth defects in a child) and treatment options, I could not ignore this information.
For genetic testing for congenital thrombophilia, 1-3 ml of EDTA blood is needed (special test tubes are used), or tests can also be done on the basis of a swab from the oral mucosa (special kits are used).