Approximately 4% of couples with recurrent miscarriages have a chromosomal abnormality in the karyotype of one of the parents. The karyotype is analysed by a blood test. It is the representation of a person’s chromosomes arranged according to their morphology and size. Each cell has 46 chromosomes, 23 pairs inherited from the mother and 23 from the father.

Chromosomal abnormalities often affect the karyotype structure: missing a piece or having an extra piece. In the carrier parent the alteration is in balance, but it can be transmitted in an unbalanced way.

The vast majority of miscarriages are due to alterations in the number of chromosomes in the embryo because the sperm and/or the egg do not have the appropriate chromosomal endowment. According to studies carried out at Institut Marquès, in the best of situations, i.e. embryos from donor sperm and eggs, almost half of them have chromosomal abnormalities. It seems a lot, but human reproduction is not very efficient.

The percentage of abnormal embryos increases with the age of the woman, with 78% of the embryos of patients in their 40s being altered.

In the egg cell nucleus, after ovulation, the 46 chromosomes are placed face to face to separate. The filaments that bind them together are released, leaving 23 chromosomes. As a woman gets older, the passage of time causes alterations in this process (in young women the rods that separate them effectively are resistant. With age they become weaker and can break like the filaments of a light bulb). Therefore, there may be extra chromosomes left over (if it is 21 it will give rise to Down’s Syndrome) or less, causing fertilisation failures or embryos with genetic alterations which will mostly be early miscarriages

The risk of miscarriage for a 35-year-old woman is 20%, at 40 years of age 40%, and at 45 years of age 80%. However, ovarian age is not always the same as chronological age.

In order to know the risk of another miscarriage, we must study the patient’s ovarian reserve by analysing the anti-mullerian hormone (calculate your ovarian age by clicking on this link). To rule out that it is due to abnormalities in the chromosomal endowment of the sperm, a study in semen called FISH is recommended. Meiosis and double-stranded DNA fragmentation studies may also be adviced.

The indicated treatment for recurrent miscarriages caused by genetic alterations is In Vitro Fertilisation with Genetic Analysis of the Embryos (PGT). In this way, only chromosomally healthy embryos are transferred into the mother’s uterus.

In the case of a miscarriage, we can already determine a possible genetic cause with just a blood test.

The most common cause of miscarriage is chromosomal abnormalities in the embryo. A blood test of the patient now allows us to determine the karyotype of the non-evolving embryo within 4 days.

As soon as the embryo is implanted, embryonic DNA is found in the mother, so the analysis can be carried out following any miscarriage, even with only a week’s delay. 

This is a great advance because when this study is carried out on the abortion remains, by means of curettage or chorion biopsy, there are many failures when it comes to obtaining the result and, in addition, the sample may have been contaminated with DNA from the mother.

At Institut Marquès we obtain the blood sample in our own clinic to carry out the “PregnancyLoss” analysis. The total cost is 480 euros.

• Antiphospholipid syndrome is diagnosed by testing for anticardiolipin antibodies (ACA), lupus anticoagulant antibodies (LA) and anti-beta2-glycoprotein antibodies.
• Autoimmune Hypothyroidism presents with low T4 hormone and elevated HRT. The antibodies tested are thyroglobulin antibodies (TgAb) and thyroid peroxidase antibodies (TPO).
• Classic Coeliac Disease presents with diarrhoea, vomiting, heavy digestion and, in children, short stature and underweight. In adults, the symptoms of coeliac disease are usually different, with extra-digestive symptoms being more common. Diagnosis is completed by testing for coeliac disease antibodies.

• Antiphospholipid Syndrome requires a personalised assessment in terms of doses of acetylsalicylic acid and anticoagulants such as low molecular weight heparin. Eighty percent of patients respond to this treatment, but 20% develop Refractory Antiphospholipid Syndrome. This has a worse prognosis but, in these cases, treatment with corticosteroids is associated.
• Autoimmune hypothyroidism is treated with thyroid hormone tablets. Levels should be monitored during pregnancy as they tend to fluctuate. In patients with elevated anti-TPO and anti-TGL levels, we also recommend adding Aspirin to the thyroid hormone treatment.
• Coeliac disease is controlled by eliminating gluten-containing foods.

The standard test for diagnosing genetic thrombophilia is a blood test for Protein C, Protein S, Antithrombin III and Leyden’s Factor V. But this test can only identify 20% of cases. The study of the genetic profile of thrombophilias allows 85% of patients with this disease to be detected.

Treatment for patients with genetic thrombophilia is carried out on an individualised basis with Low Molecular Weight Heparin.

Alterations of the uterus are diagnosed by means of:

• Classical ultrasound, three-dimensional (3D) ultrasound allows us to see more detail.
• Hysterosalpingography HSG. It is a radiological test. It consists of injecting a contrast medium through the cervix that fills the uterine cavity and shows the shape of its internal cavity.
• Hysteroscopy. This consists of the introduction of a very fine optic through the vagina and cervix. It is connected to a video camera and allows the uterine cavity to be viewed on a screen.

• Malformations. Surgical correction of uterine malformation has not been shown to decrease the rate of miscarriage. In addition, these operations may leave scarring tissue and worsen the situation. It is only recommended in cases of a very marked septate uterus in patients with a poor obstetric history. It is not indicated to operate on T-shaped uteri.
• Fibroids. To improve the evolution of the pregnancy, it is indicated to remove “submucous” fibroids inside the uterus and large “intramural” fibroids that deform the uterine cavity. In these cases, when the woman desires a new pregnancy, embolisation of the fibroids is contraindicated.
•  Synechiae. If they are mild, they are easily removed by surgical hysteroscopy. If they are important, as in Asherman’s Syndrome, the prognosis is worse, it is usually necessary to perform several surgical hysteroscopies and there is a risk of complications, of re-formation, or of not being able to free the entire uterine cavity.