Multiple miscarriages most often result from chromosomal abnormalities in the embryo, but a range of other factors can play a role, including uterine shape, immune system disorders, hormonal imbalances, clotting conditions, and age. In roughly half of couples who experience recurrent losses, no specific cause is ever identified. The clinical threshold for investigation is two or more consecutive pregnancy losses in the U.S., or three or more in the U.K.
Chromosomal Abnormalities in the Embryo
The single most common reason for any miscarriage is a chromosomal problem in the developing embryo. In a large analysis of over 2,300 recurrent pregnancy losses, nearly 57% had a detectable chromosomal abnormality. The vast majority of those (92%) were numerical errors, meaning the embryo had too many or too few chromosomes. This type of error usually happens randomly during cell division and does not reflect a genetic problem in either parent.
In a smaller number of cases, about 7.5%, the chromosomal issue is structural rather than numerical. These structural variants often point to a “balanced translocation” carried by one parent. A balanced translocation means pieces of two chromosomes have swapped places. The parent is perfectly healthy because all the genetic material is still present, just rearranged. But when that genetic material is passed to an embryo, the rearrangement can produce an unbalanced set of chromosomes, leading to miscarriage. A simple blood test called a karyotype can identify this in both partners.
Uterine Shape and Structure
The shape of the uterus matters more than many people realize. A septate uterus, where a wall of tissue partially divides the uterine cavity, is the anomaly most strongly linked to pregnancy loss. Among women with a septate uterus, 42% of pregnancies end in first-trimester miscarriage, compared to about 12% in women without a uterine anomaly. A meta-analysis found the risk of first-trimester loss was roughly 2.7 times higher, and the risk of second-trimester loss was about 3 times higher.
The septum has a poor blood supply compared to the rest of the uterine lining. When an embryo implants on the septum instead of the normal uterine wall, it may not receive enough nutrients to survive. Surgical removal of the septum through a hysteroscopy is sometimes offered to women with recurrent losses, though the decision is made on a case-by-case basis. Other uterine variations like a bicornuate uterus (heart-shaped) or uterine didelphys (double uterus) can also contribute to pregnancy complications, though their link to early miscarriage is less clear-cut.
Uterine fibroids and adhesions (scar tissue from prior surgery or infection) can also interfere with implantation or blood flow to a developing pregnancy. 3D ultrasound, sonohysterography, and MRI are the most informative tools for evaluating uterine structure. Direct visualization through hysteroscopy remains the gold standard when a problem is suspected.
Antiphospholipid Syndrome
Antiphospholipid syndrome (APS) is an autoimmune condition in which the body produces antibodies that increase blood clotting. These antibodies can damage the placenta by causing tiny clots in its blood vessels, starving the pregnancy of oxygen and nutrients. APS is one of the few treatable causes of recurrent miscarriage, making it especially important to diagnose.
Doctors test for three specific antibodies: anticardiolipin antibodies, anti-beta-2-glycoprotein-I antibodies, and lupus anticoagulant. Because antibody levels can fluctuate, a diagnosis requires positive results on at least two tests spaced 12 or more weeks apart. The clinical criteria include three or more consecutive losses before 10 weeks, or one or more losses of a normally developing fetus at or after 10 weeks. Treatment typically involves blood-thinning medication during pregnancy, which significantly improves outcomes for most women with APS.
Hormonal and Metabolic Conditions
Thyroid Problems
Both overactive and underactive thyroid function can contribute to miscarriage. Even women whose thyroid levels fall within the normal range may be at higher risk if they carry thyroid peroxidase antibodies (TPO-Ab), which signal the immune system is attacking the thyroid gland. Current guidelines suggest that women with a TSH level above 2.5 who also test positive for TPO-Ab may benefit from thyroid hormone supplementation during pregnancy. A full thyroid workup, including TSH, T3, T4, and antibody levels, is a standard part of recurrent loss evaluation.
PCOS and Insulin Resistance
Polycystic ovary syndrome (PCOS) creates a hormonal environment that can make it harder to sustain a pregnancy. Women with PCOS tend to have higher levels of testosterone, elevated luteinizing hormone (LH), and lower levels of sex-hormone binding globulin. When combined with insulin resistance, which is common in PCOS, this hormonal mix promotes chronic low-grade inflammation that can interfere with early placental development.
Research comparing women with PCOS who had recurrent losses to those who did not found that higher fasting blood sugar, higher fasting insulin, and lower insulin sensitivity were consistently linked to pregnancy loss. Treatment with a medication that improves insulin sensitivity reduced early pregnancy loss rates from about 49% to 12% in women who started it before conception and continued it through early pregnancy.
Inherited Clotting Disorders
Separate from APS, some women carry inherited genetic variants that make their blood more prone to clotting. A large meta-analysis of 89 studies involving over 30,000 individuals found that Factor V Leiden mutation increased the odds of recurrent loss by about 2.4 times, and the prothrombin gene mutation roughly doubled the odds. Protein S deficiency carried the highest risk, increasing odds by about 3.5 times.
These clotting disorders are thought to cause problems by forming small clots in the placental blood vessels, similar to the mechanism in APS. However, the evidence on whether blood-thinning treatment improves outcomes for inherited thrombophilias is less established than it is for APS, and recommendations vary between medical guidelines.
Maternal Age
Age is one of the strongest predictors of miscarriage risk, and its effect becomes dramatic after 35. A large Norwegian registry study found that miscarriage rates were lowest in women aged 25 to 29 (about 10%) and climbed steeply from there: roughly 17% for ages 35 to 39, 32% for ages 40 to 44, and over 53% for women 45 and older. The primary reason is that eggs accumulate more chromosomal errors over time, making embryos with abnormal chromosome counts increasingly common.
This means that for some women experiencing recurrent loss in their late 30s or 40s, age-related egg quality is the most likely explanation, even when all other test results come back normal. It also helps explain why “unexplained” recurrent loss becomes more common in older age groups.
Sperm DNA Damage
The male partner’s contribution is often overlooked, but sperm quality plays a measurable role. A meta-analysis of 15 studies found that male partners of women with recurrent pregnancy loss had significantly higher rates of sperm DNA fragmentation compared to partners of women without a history of loss. DNA fragmentation means the genetic material inside the sperm is broken or damaged, which can lead to abnormal embryo development even if the sperm looks normal under a microscope.
Factors that increase sperm DNA damage include smoking, high alcohol intake, obesity, heat exposure, infections, and advanced paternal age. Sperm DNA fragmentation testing is not yet part of every standard workup, but it is increasingly offered when other causes have been ruled out.
What Testing Looks Like
After two or more losses, a typical evaluation covers several categories. Blood tests check for antiphospholipid antibodies, thyroid function and antibodies, insulin resistance markers, ovarian reserve hormones, and prolactin levels. Both partners are offered a karyotype, a blood test that maps their chromosomes and can reveal balanced translocations. When tissue from the miscarriage is available, chromosomal analysis of the pregnancy itself can determine whether the loss was caused by an embryo abnormality.
Imaging of the uterus is also standard. A 2D or 3D ultrasound is typically the first step and can detect conditions like adenomyosis, fibroids, or uterine anomalies. If more detail is needed, sonohysterography (which uses saline to outline the uterine cavity) or MRI can distinguish between a septate and bicornuate uterus, a distinction that matters because the treatment options differ. Hysteroscopy, which uses a small camera inserted through the cervix, provides direct visualization and remains the definitive diagnostic tool for evaluating the uterine cavity.
Chances of a Successful Pregnancy
Even after multiple losses, the odds of a successful future pregnancy are better than many people expect. In a study of 201 women with unexplained recurrent miscarriage (median of three prior losses, all with normal test results), the overall prognosis was encouraging. Women aged 30 or younger had only a 25% chance of miscarrying their next pregnancy, meaning 75% carried to term. That rate rose to 52% in women 40 and older.
The number of prior losses also matters. After three consecutive miscarriages, the chance of the next pregnancy ending in miscarriage was 29%. After six or more, it climbed to 53%. One striking finding: women who received supportive care in a dedicated early pregnancy clinic, with regular monitoring, reassurance, and ultrasounds, had a miscarriage rate of 26%, compared to 51% among those who did not attend. No medication was involved. The emotional and psychological support itself appeared to make a meaningful difference in outcomes.