Miscarriage refers to the unexpected loss of a pregnancy before 20 weeks of gestation. These occurrences are more common than generally perceived, with estimates suggesting that between 10% and 20% of known pregnancies result in miscarriage. Many miscarriages happen very early, sometimes before a person even realizes they are pregnant. Genetic issues within the developing embryo or inherited from the parents are a significant cause of pregnancy loss.
Embryonic Genetic Abnormalities
The most frequent reason for miscarriage is genetic abnormalities within the embryo itself. These abnormalities typically arise spontaneously, meaning they are random occurrences. Such errors often occur during the formation of the egg or sperm, or during the very early stages of embryonic cell division.
A common type of embryonic genetic abnormality is aneuploidy, which involves an incorrect number of chromosomes. An aneuploid embryo might have an extra chromosome (trisomy) or a missing chromosome (monosomy). Trisomy 16 is the most common autosomal trisomy leading to miscarriage and accounts for a significant percentage of losses. Full trisomy 16 is typically incompatible with life and usually results in a first-trimester miscarriage.
Other examples include Trisomy 18 (Edwards syndrome) and Monosomy X (Turner syndrome). Trisomy 18 often leads to miscarriage. Monosomy X is also a common chromosomal cause of miscarriage. These severe genetic imbalances often prevent the embryo from developing properly, leading to miscarriage.
Another type of embryonic genetic abnormality is polyploidy, where an embryo has extra sets of chromosomes, such as triploidy. Triploidy occurs in approximately 1% of clinically recognized pregnancies and is a common cause of early miscarriage. These conditions are lethal, resulting in spontaneous pregnancy loss.
Parental Genetic Factors
While many embryonic genetic abnormalities are random, some miscarriages can be linked to genetic factors inherited from the parents. Parents can carry genetic variations or chromosomal rearrangements without experiencing any symptoms. These variations can lead to an unbalanced genetic makeup in their offspring.
A balanced chromosomal translocation is one such example, occurring when a piece of one chromosome breaks off and attaches to another chromosome, or two chromosomes exchange segments. Individuals with a balanced translocation have the correct amount of genetic material, just rearranged. When they pass these chromosomes on to their offspring, the embryo may receive an unbalanced set. This can result in miscarriage or a child born with developmental differences.
Balanced translocations are found in about 3% to 5% of couples experiencing recurrent miscarriages. Other inherited genetic conditions, such as specific gene mutations, can also increase miscarriage risk by interfering with embryonic development or implantation. These inherited factors highlight the importance of evaluating both parents in cases of recurrent pregnancy loss.
Genetic Testing for Miscarriage
Identifying the genetic causes of miscarriage often involves specific types of testing. Genetic testing can be performed on the pregnancy tissue (products of conception or POC) after a miscarriage. This analysis helps determine if a chromosomal abnormality in the embryo was the reason for the loss.
Common tests on miscarriage tissue include karyotyping, which provides a visual representation of the number and structure of all chromosomes. Chromosomal microarray analysis (CMA) offers a more detailed look, detecting smaller extra or missing pieces of chromosomes that traditional karyotyping might miss. These tests can reveal aneuploidies like trisomy or monosomy, as well as polyploidy.
In cases of recurrent miscarriage, parental genetic testing may also be recommended. This often includes karyotyping of both parents to identify balanced chromosomal translocations or other structural rearrangements. Sometimes, specific gene panels are used to screen for inherited genetic conditions known to increase miscarriage risk. Understanding these results can provide answers and inform future family planning decisions.
Managing Genetic Miscarriage Risk
Once a genetic cause for miscarriage is identified, several approaches can help manage future pregnancy risks. Genetic counseling plays a central role, providing individuals and couples with a comprehensive understanding of their test results. Counselors explain the implications of specific genetic findings, the likelihood of recurrence, and available options for future pregnancies.
For couples where one partner carries a balanced chromosomal rearrangement, preimplantation genetic testing (PGT) in conjunction with in vitro fertilization (IVF) is an option. PGT-SR (Preimplantation Genetic Testing for Structural Rearrangements) specifically screens embryos created through IVF for unbalanced chromosomal arrangements before transfer to the uterus. This allows for the selection of embryos with a balanced or normal chromosomal complement, potentially reducing the risk of miscarriage. Similarly, PGT-A (Preimplantation Genetic Testing for Aneuploidy) can be used to screen embryos for aneuploidies, even when parental chromosomes are normal. This is relevant for individuals with recurrent miscarriages due to embryonic aneuploidy, as it helps identify embryos with the correct number of chromosomes.