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Disclaimer: This article is for informational purposes only and is not intended to diagnose any conditions. LifeDNA does not provide diagnostic services for any conditions mentioned in this or any other article.
Human reproduction is incredible, but it doesn’t always go as planned. Nearly 70% of successful conceptions end before reaching full term pregnancy (recurrent miscarriages). One major reason for an early pregnancy loss is genetic abnormalities, particularly issues with chromosomes, the structures that carry our DNA. For example, when an embryo has too many or too few chromosomes, it most often cannot develop properly, leading to miscarriage.
While these genetic errors often happen by chance, some couples experience multiple pregnancy losses due to inherited genetic factors. This condition is known as recurrent miscarriage or recurrent pregnancy loss;RPL.
15% to 25% of known pregnancies end in miscarriage. In nearly half of early miscarriages, the cause is a problem with the baby’s chromosomes. When a woman experiences two or more miscarriages in a row before 20 weeks of pregnancy, it is called recurrent miscarriage (RPL). This condition affects about 1 in every 300 women trying to conceive. This usually happens by chance, but in some cases, it may be inherited.
Other factors, such as hormone imbalances, uterine abnormalities, or immune system disorders, may also lead to pregnancy loss. Doctors can run various tests to determine the cause and help improve the chances of a healthy pregnancy. Identifying the underlying cause may be key to finding solutions and increasing the chances of carrying a pregnancy to term.
Our genes carry instructions that control how our bodies grow and function. During pregnancy, these genetic instructions need to work correctly to support the baby’s development and the mother’s health. Sometimes, problems in these genes may lead to miscarriage. Some of the common genetic problems that may increase the risk of miscarriage include:
By understanding these genetic factors, doctors may help aspiring parents figure out why miscarriages are happening and what steps might improve the chances of a healthy pregnancy in the future.
Aneuploidy occurs when an embryo has an abnormal number of chromosomes, either missing one, which is called monosomy, or having an extra copy, termed trisomy. It is one of the leading causes of pregnancy loss. Studies show that most of these happen by chance when the egg or sperm is forming, which means that they can affect anyone. Interestingly, women with recurrent pregnancy loss (RPL) are less likely to have miscarriages due to chromosomal abnormalities than those with one-time miscarriages, meaning other factors may be more significant.
In cases where both parents have a balanced chromosomal translocation, pregnancy loss is more likely to occur due to the inheritance of an unbalanced translocation by the embryo. Translocations involve a rearrangement of chromosome segments, which may not affect the carrier parent but can lead to severe genetic imbalances in the offspring.Â
Mosaicism happens when some cells in an embryo have different chromosomes from others. This can cause problems, depending on which cells are affected. If too many cells have the wrong chromosomes, it can lead to miscarriage.
When doctors test small cells from an embryo ( blastomeres) to check for problems, they might get wrong results. This is because the cells in the embryo could have different chromosomes, a condition called mosaicism. Testing just one cell may give false results—either showing a problem that’s not there (false positive) or missing a real problem (false negative). Testing a second cell might help, but it could reduce the chances of the embryo surviving. Since only a tiny amount of material is available to test, doctors need to use special methods, which can make the process more challenging.
Single-gene alterations are changes in a single gene that can affect important body functions during pregnancy. These mutations can cause problems with things like blood clotting, the immune system, or how the placenta works. Some of the most studied single-gene alterations linked to recurrent miscarriage include:
The so-called Factor V Leiden mutation in the prothrombin (F2) gene increases the tendency of blood to clot, leading to thrombophilia (an abnormal blood-clotting condition). In pregnant women, excessive clotting can reduce blood flow to the placenta, increasing the risk of miscarriage, stillbirth, and other complications.
The methylenetetrahydrofolate reductase (MTHFR) gene plays a crucial role in folic acid metabolism. Certain inherited variants in this gene can lead to elevated homocysteine levels, which damage blood vessels and impair placental function. High homocysteine levels have been associated with an increased risk of pregnancy loss, particularly in women with two copies of certain MTHFR variants.
Research has also identified polygenic risk factors that contribute to the likelihood of recurrent miscarriage. These involve multiple gene mutations that, when combined, increase the overall risk of miscarriage. While no single gene mutation is solely responsible, the interaction of multiple genetic variants can create a higher predisposition to pregnancy loss.
Genetic testing is important in diagnosing and managing recurrent miscarriage. Specific tests can help identify specific genetic causes, allowing for personalized medical interventions. Some of these tests include:
This test examines the chromosomes of both parents to look for abnormalities, such as balanced translocations (where pieces of chromosomes are swapped). These abnormalities can increase the risk of miscarriage. Doctors can also test fetal tissue from a miscarriage to see if chromosomal issues contributed to the loss.
Genetic tests can also look for mutations in specific genes like MTHFR and ACE. These mutations may affect processes like blood clotting, immune function, and metabolism, which can contribute to pregnancy loss. By identifying these mutations, doctors can offer advice on lifestyle changes or medications to reduce risks in future pregnancies.
While not all miscarriages due to genetic causescan be prevented, early detection through genetic testing and appropriate medical interventions may significantly improve the chances of a successful pregnancy.Â
Couples experiencing recurrent miscarriage should seek medical advice to explore potential genetic factors and available treatment options. Advances in genetic research and reproductive medicine continue to offer hope for those experiencing recurrent pregnancy losses.
Once a genetic cause for recurrent miscarriages is identified, a couple of treatment options are available that may help improve the chances of a successful pregnancy. Here are some of the main approaches:
Genetic Counseling: This is an essential step for couples dealing with recurrent miscarriages. It provides them with a clear understanding of the genetic risks they may face, as well as available reproductive options. One option discussed during counseling is preimplantation genetic testing (PGT) combined with in vitro fertilization (IVF). This process allows doctors to test embryos for genetic abnormalities before implantation, reducing the likelihood of miscarriage caused by serious issues. Genetic counseling empowers couples to make informed decisions about their reproductive future.
Folic Acid and Vitamin Supplements: Women with MTHFR gene mutations may benefit from taking high-dose folic acid and other vitamin B supplements. These supplements help lower homocysteine levels in the blood, which can otherwise interfere with healthy pregnancy outcomes. High homocysteine levels are associated with an increased risk of miscarriage, so by managing these levels, the chances of carrying a pregnancy to term can improve. Supplementing with folic acid is a simple yet important step for some women facing recurrent miscarriages.
Immunotherapy for Autoimmune-Related Pregnancy Loss: For women whose recurrent miscarriages are linked to autoimmune issues, treatments like intravenous immunoglobulin (IVIG) therapy or corticosteroids can be used to help manage immune system responses. Autoimmune disorders, such as antiphospholipid syndrome may cause the immune system to attack the body’s own cells, leading to complications during pregnancy. IVIG therapy and corticosteroids may help suppress the immune system’s overactive response, lowering the risk of miscarriage in future pregnancies.
Lifestyle Modifications: Certain lifestyle changes may also support a healthy pregnancy. Maintaining a healthy weight, avoiding smoking, and managing stress are all crucial in improving fertility and pregnancy outcomes. Additionally, controlling chronic conditions like diabetes and thyroid disorders can help prevent complications that might lead to miscarriage. By taking a proactive approach to their health, women can increase their chances of having a successful pregnancy, even when facing genetic challenges.
