Experiencing a miscarriage can be emotionally difficult, especially when it happens more than once.
Recurrent miscarriage can have several possible causes, including hormonal problems, uterine conditions, immune factors, and genetic abnormalities. Among these, genetic and chromosomal problems can play an important role, particularly in early pregnancy loss.
In many cases, a miscarriage happens because the embryo has an abnormal number or structure of chromosomes and cannot develop normally. However, recurrent miscarriage is not always caused by a genetic problem. A proper evaluation is important to understand the possible cause and plan the next pregnancy.
What Are Genetic Causes of Recurrent Miscarriage?
Our body normally has 46 chromosomes arranged in 23 pairs. These chromosomes carry the genetic information needed for normal growth and development. Sometimes, an embryo may receive an extra chromosome, miss a chromosome, or have a structural change in a chromosome.
These abnormalities can happen randomly when eggs or sperm are formed or during the early development of the embryo. Most chromosomal abnormalities found in early miscarriages are not inherited from the parents.
Some genetic changes can also involve individual genes that are important for egg or sperm development, DNA repair, or early embryo development. However, research into specific gene mutations and recurrent miscarriage is still developing.
How Do Chromosomal Problems Cause Miscarriage?
Chromosomal abnormalities are commonly found in first-trimester miscarriages. An embryo with an abnormal number of chromosomes may not develop normally, which can result in pregnancy loss.
Sometimes, the problem occurs only in that particular pregnancy and does not mean that the parents have a genetic disorder. This is why one miscarriage does not necessarily indicate a genetic problem in either partner.
However, in some couples with recurrent pregnancy loss, one partner may carry a balanced chromosomal rearrangement, such as a balanced translocation. The parent may be healthy because there is no major loss or gain of genetic material, but an embryo may receive an unbalanced chromosome arrangement, increasing the risk of miscarriage. Parental chromosome rearrangements are estimated to be present in around 2%–5% of recurrent miscarriage cases.
Does Age Increase the Risk of Genetic Miscarriage?
Age is another important factor when discussing genetic causes of miscarriage. As a woman gets older, the chance of chromosomal abnormalities in eggs increases. This can increase the chance of embryos having an abnormal number of chromosomes and therefore increase the risk of miscarriage.
The effect of age is particularly important after 40, when chromosome-related problems become a more significant contributor to pregnancy loss. Paternal age may also have an effect, as increasing age can be associated with changes in sperm DNA and chromosome quality.
This does not mean that pregnancy after 35 or 40 will necessarily result in miscarriage. Many women in these age groups have healthy pregnancies. Age is simply one factor considered during a fertility and recurrent miscarriage evaluation.
Genetic Testing for Recurrent Miscarriage
Genetic testing for recurrent miscarriage may help doctors understand whether a chromosome problem contributed to a pregnancy loss. The type of test recommended depends on the couple's history and whether pregnancy tissue is available for testing.
Some commonly used genetic tests include:
Karyotyping: This test looks at the number and structure of chromosomes. It can be performed using parental blood samples or pregnancy tissue.
Chromosomal microarray: This can identify smaller gains or losses of genetic material that may not be detected by traditional karyotyping. It can provide more detailed information about chromosome abnormalities in pregnancy tissue.
Parental genetic testing: If testing suggests a chromosome rearrangement, both partners may be advised to undergo genetic evaluation. This can help identify whether one partner carries a balanced rearrangement that could affect future pregnancies.
Genetic counselling can also help couples understand their results and discuss possible options for future pregnancy.
Specific Genes Linked to Recurrent Pregnancy Loss
Along with chromosome number and structure, researchers have also looked at certain individual genes involved in blood clotting and folate metabolism that may be linked to a higher risk of recurrent pregnancy loss. These include:
- PAI1 (SERPINE1): Involved in regulating clot breakdown; certain variants have been associated with clotting-related pregnancy loss.
- PROZ: Plays a role in regulating blood clotting; some variants have been linked to clotting-related recurrent pregnancy loss.
- MTHFR: Affects folate metabolism; certain variants have been associated with a higher risk of pregnancy loss and fetal neural tube defects.
- MTR and MTRR: Also involved in folate and vitamin B12 metabolism, with certain variants linked to recurrent pregnancy loss risk.
These gene-level tests are not part of routine evaluation for everyone, but may be considered in select cases as part of a more detailed work-up, especially when other causes have been ruled out. A fertility specialist can advise whether such testing is relevant to your individual history.
Can Genetic Causes of Recurrent Miscarriage Be Treated?
Genetic abnormalities in an embryo cannot usually be corrected with medicines during pregnancy. However, when a specific genetic or chromosomal problem is identified, couples may have different options depending on their situation.
For some couples undergoing IVF, preimplantation genetic testing (PGT) may be considered. PGT-M can be used when there is a known risk of a specific single-gene disorder, while PGT-SR may be considered when one or both partners carry certain structural chromosome rearrangements.
It is important to understand that PGT is not suitable for every couple with recurrent miscarriage. For unexplained recurrent pregnancy loss, the evidence does not show a clear improvement in live birth from routinely using PGT for aneuploidy. Therefore, the decision should be made after discussing the individual medical history, test results, age, and fertility treatment options with a fertility specialist.
When Should You Consider a Genetic Evaluation?
If you have experienced repeated pregnancy losses, discussing your history with a fertility specialist can help determine whether genetic testing for recurrent miscarriage may be useful.
A doctor may consider factors such as:
- Number and timing of previous miscarriages
- Age of both partners
- Results of previous pregnancy tissue testing
- Family history of genetic conditions or repeated pregnancy loss
- Any known chromosome abnormality in either partner
- Previous IVF or fertility treatment history
It is also important to remember that recurrent miscarriage causes are not limited to genetics. Uterine problems, thyroid disorders, hormonal conditions, immune-related conditions, and other factors may also need to be evaluated.
Genetic Evaluation for Recurrent Miscarriage in Hyderabad
Genetic causes can be an important part of recurrent pregnancy loss evaluation, but every couple needs an individual assessment. Identifying a chromosome abnormality does not mean that a healthy pregnancy is impossible. Depending on the findings, appropriate testing, genetic counselling, and fertility treatment options may help in planning the next pregnancy.
Dr. Aradhya Achuri, Fertility Expert in Hyderabad, can help evaluate the possible causes of recurrent miscarriage and guide couples regarding suitable investigations and treatment options based on their individual history.
FAQs About Genetic Causes of Recurrent Miscarriage
1. Can genetic problems cause recurrent miscarriage?
Yes. Chromosomal abnormalities in the embryo or certain chromosome rearrangements in the parents can contribute to recurrent miscarriage.
2. What genetic tests are done for recurrent miscarriage?
Depending on the case, testing may include karyotyping, chromosomal microarray, or other genetic tests.
3. Can both partners have genetic testing after recurrent miscarriage?
Yes. Parental genetic testing may be recommended in certain cases, especially when a chromosome abnormality is suspected.
4. Can IVF prevent genetic miscarriage?
IVF with certain types of PGT may be considered for couples with specific genetic or chromosomal problems, but it is not suitable or necessary for everyone.
5. Does age increase the risk of genetic miscarriage?
Yes. Increasing maternal age is associated with a higher chance of chromosome abnormalities in eggs and embryos, which can increase miscarriage risk.