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The genetics of miscarriage

1 in 8 pregnancies will end in miscarriage.

Growing up I always assumed that having a miscarriage was rare and getting pregnant was easy. However, as I got older and I started having conversations with other women around me, I realised that sadly neither of these are the case. Miscarriages are more common than most people realise. Among women who know that they are pregnant, estimates indicate that 1 in 8 of these pregnancies will end in miscarriage. Additionally, many more occur before a woman is even aware that she has become pregnant.

Miscarriage is defined by the World Health Organisation as the spontaneous loss of an embryo or foetus weighing <500 g, up to 20–22 weeks of gestation. There are many reasons why a miscarriage can occur, although the cause is often not identified. If a miscarriage occurs during the first trimester of pregnancy, the cause is typically due to problems with the unborn baby e.g., chromosome problems or placental problems. If it occurs after the first trimester, it may be due to underlying health conditions within the mother or infections. There are also several other factors that can increase the risk of miscarriage, particularly the age of the mother. For example, in women over 45, more than 5 in 10 pregnancies will end in miscarriage.

Regardless of the cause, pregnancy loss for any woman and her family is heart-breaking. Nonetheless, even today, women still face enormous stigma and shame when they lose a baby and are often encouraged not to talk about their experience and loss. In many cases, women can end up trapped in their own grief and feel isolated from their partners and close family.

In this blog, we will explore the genetics and stigma of miscarriage, and the technologies that are helping many women have successful pregnancies.

Genetics of miscarriage

Foetal chromosomal abnormalities

Approximately 50% of first trimester miscarriages are due to a chromosome abnormality in the foetus. Trisomies are the most frequently detected anomalies (61.2%), followed by triploidies (12.4%), monosomy X (10.5%), tetraploidies (9.2%) and structural chromosome anomalies (4.7%). Most aneuploidies are lethal, viable trisomies are restricted to only a few human chromosomes. The most common human trisomy involves chromosome 21 and is known as Down Syndrome. Humans are much more able to tolerate extra sex chromosomes than extra autosomes. After Down Syndrome the most common human aneuploidy is the condition know as Klinefelter’s syndrome (47, XXY). On the other hand, cells seem to be particularly sensitive to losing chromosomes, because the only viable human monosomy involves the X chromosome (Turner’s syndrome).

Researchers know that most aneuploidies result from the nondisjunction of chromosomes during meiosis. In recent years, results have shown that an overwhelming number of trisomies arise from errors during maternal meiosis. This observation makes sense when considering that human oocytes can be arrested in prophase I for several decades. It is well understood that the risk of trisomy increases sharply with maternal age. Hence, pregnant women over the age of 35 are routinely offered testing for foetal chromosome abnormalities. The true frequency of human aneuploidies is difficult to estimate as the most seriously affected embryos do not survive to the developmental stage.

Parental chromosomal abnormalities

The most common parent abnormalities are translocations. Although the chromosomes are rearranged, they are balanced and therefore the parent should have no health problems. However, during meiosis these chromosomes segregate and may result in the baby inheriting extra or missing pieces of a chromosome. This imbalance can cause intellectual disability and other defects, or cause a miscarriage. For couples who have experienced recurrent pregnancy loss, the chances that one of the parents has a chromosomal rearrangement is approximately 3-6%. While parents who carry these rearrangements are at increased risk of further miscarriages, they can still produce healthy children. Chromosome studies can be performed to determine which parent is a carrier of a chromosomal rearrangement.

Genetic mutations

Another cause of miscarriage is a mutation in one or more genes. This can result in specific genetic diseases or birth defects. Mutations can occur spontaneously in pregnancies or can be inherited from parents. Single gene defects have been significantly less studied than karyotypic causes of sporadic miscarriage and recurrent pregnancy loss. Major groups of single gene defects that have been associated include musculoskeletal gene mutations (including trinucleotide repeat disorders), genes involved in regulation of the immune system and implantation, thrombophilic gene mutations, and mutations in specific enzymes, including angiotensin-converting enzyme, ubiquitin-specific protease and human alkaline phosphatase.


Identifying the causes of miscarriages not only assists with genetic counselling and therapeutic management, but it also reduces the emotional distress and psychological burden on affected couples. Cytogenetic analysis of spontaneous miscarriages is essential to establish the aetiology of foetal losses and to assess patients at risk of recurrence in future pregnancies.

Recently, assisted reproductive techniques have been used to prevent further miscarriages in women with recurrent miscarriage. There are two approaches. The first involves pre‐gestational preimplantation diagnosis of known chromosomal aberrations (PGD). The other involves screening for a variety of possible chromosomal aberrations (PGS). In the case of parental chromosomal rearrangements and recurrent miscarriage, PGS seems to be a logical choice. This is also the most beneficial choice for women above the age of 40 years.

Elsewhere, developments in liquid biopsy techniques have enabled cell-free DNA (cfDNA) to be utilised for identifying chromosomal abnormalities. These advanced techniques will help reveal potential genetic reasons for miscarriage. This can help predict which couples have a higher chance of miscarriage.  


Miscarriages, both sporadic and recurrent, have a genetic component. Understanding these complexities can not only provide some clarity for parents but can also help with therapeutic management. Unfortunately, miscarriage can result in mental health problems, such as depression, anxiety and post-traumatic stress disorder. As shown with model and talk show host Chrissy Teigen’s recent public announcement about her miscarriage at 20-24 weeks, publicly talking about experiences of miscarriage is still a taboo subject. The coronavirus pandemic, in particular, has had a major impact for women who have had a miscarriage. Harnessing advanced technologies to further understand miscarriage and to guide couples through assisted reproductive techniques is vital. But above all, raising awareness of miscarriage and creating an environment where women feel safe enough to share their stories is imperative to end the stigma and prevent downstream mental health problems.

Image credit:  By Andrii Yalanskyi –

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