What Causes Multiple Miscarriages: Common Reasons

Multiple miscarriages stem from a wide range of causes, from chromosomal problems and immune disorders to uterine abnormalities and hormonal imbalances, yet in roughly half of all cases no definitive cause is found even after thorough investigation.¹ That statistic can be deeply frustrating for couples going through it, but it also reflects how many overlapping biological systems must cooperate to sustain a pregnancy. Understanding the known causes helps explain what doctors look for, what treatments exist, and why the prognosis is often better than people expect.

How Recurrent Pregnancy Loss Is Defined

Major medical societies do not completely agree on the definition. The European Society of Human Reproduction and Embryology (ESHRE) defines recurrent pregnancy loss as two or more pregnancy losses before viability, while the American Society of Reproductive Medicine (ASRM) and the Royal College of Obstetricians and Gynaecologists (RCOG) have historically used three or more.² The practical difference matters because it determines when your doctor begins a formal workup. Roughly one to two percent of couples trying to conceive experience recurrent losses.³ If you have had two consecutive miscarriages, most current guidelines support beginning at least some baseline investigations rather than waiting for a third.

Chromosomal and Genetic Causes

Chromosomal abnormalities in the embryo are the single most common reason any individual pregnancy fails, and they play a recurring role in couples who miscarry repeatedly. These abnormalities can arise in two distinct ways: sporadically in the embryo itself, or because one parent silently carries a chromosomal rearrangement that gets passed along in an unbalanced form.

Balanced translocations are the classic parental genetic cause. A person with a balanced translocation has all their genetic material intact, just rearranged between chromosomes, so they are perfectly healthy. But when their eggs or sperm form, the reshuffled chromosomes can end up in unbalanced combinations, producing embryos with too much or too little genetic material.⁴ Studies of couples with recurrent loss find parental chromosomal abnormalities in a small but meaningful fraction. One study of couples with recurrent losses detected chromosomal abnormalities in about 3% of individuals tested, with balanced translocations accounting for the majority.⁵ That percentage sounds small, but it is far higher than in the general population, and identifying it changes the path forward dramatically because preimplantation genetic testing during IVF can select embryos with the correct chromosome complement.

Maternal age independently raises the risk of embryonic chromosome errors. As women age, the molecular machinery that holds chromosomes together during egg cell division deteriorates, leading to higher rates of eggs with the wrong number of chromosomes.⁶ This is one reason miscarriage rates climb steeply after the mid-thirties, and it is also why age is factored into prognosis when counseling couples with repeated losses.

Uterine Shape and Structural Problems

The uterus needs to provide a hospitable environment for implantation and growth, so it is no surprise that structural abnormalities increase miscarriage risk. The most strongly linked anomaly is a uterine septum, a wall of tissue that partially divides the uterine cavity. In one study of women with recurrent first-trimester losses who were found to have a divided uterine cavity, virtually all turned out to have a septum rather than other types of uterine malformation.⁷ A septum is thought to cause problems because its tissue has a poor blood supply, so an embryo that implants on it cannot get the nutrients it needs. The encouraging part is that a septum can often be surgically removed with a relatively straightforward hysteroscopic procedure.

Other uterine issues that appear in workups include large fibroids that distort the cavity, uterine adhesions from prior surgery or infection, and cervical insufficiency, where the cervix opens prematurely. European guidelines recommend that all women with recurrent loss have an assessment of uterine anatomy, typically with ultrasound or a specialized imaging technique.⁸

Antiphospholipid Syndrome

Antiphospholipid syndrome (APS) is one of the most important treatable causes of recurrent miscarriage. It is an autoimmune condition in which the body produces antibodies that target certain components of cell membranes, triggering excessive blood clotting.⁹ These antibodies activate platelets, endothelial cells, and the complement system, creating a hypercoagulable state that is especially dangerous during pregnancy, when the blood is already more clot-prone than usual.¹⁰ Tiny clots in the placental blood vessels can starve the developing pregnancy of oxygen and nutrients.

Testing for APS involves checking for lupus anticoagulant and anticardiolipin antibodies, and guidelines recommend screening after as few as two pregnancy losses.⁸ When APS is confirmed, treatment with low-dose aspirin and heparin during subsequent pregnancies substantially improves outcomes. This is one of the clearest success stories in recurrent miscarriage management.

Other Blood Clotting Disorders

Beyond APS, inherited thrombophilias have long been investigated as possible contributors to recurrent loss, though the evidence is more mixed. Factor V Leiden is the best-studied inherited clotting mutation. One European study found the mutation in about 19% of women with recurrent miscarriage versus 4% of controls, suggesting a roughly fivefold increased risk.¹¹ The same study found that the prothrombin G20210A mutation also appeared more often in women with recurrent losses. However, a study from India found no significant association between Factor V Leiden and recurrent miscarriage in that population, suggesting the link may vary by ethnicity and genetic background.¹²

When both Factor V Leiden and prothrombin mutations are present together, the combination appears to have a more significant association with early fetal loss than either one alone.¹³ Despite the conflicting data, many specialists test for inherited thrombophilias if APS testing comes back negative and no other cause has been found, particularly in populations where these mutations are more common.

Thyroid Problems and Hormonal Imbalances

Thyroid dysfunction is a well-recognized risk factor for pregnancy loss. What is less widely appreciated is that even women whose thyroid hormone levels appear normal can be at elevated risk if they carry thyroid peroxidase antibodies (TPOAb). In a cohort study of over 450 women with recurrent loss, about 17% tested positive for these antibodies, and those women had a live birth rate of roughly 51% compared with 65% in antibody-negative women.¹⁴ Crucially, treatment with levothyroxine brought the live birth rate of antibody-positive women back in line with their antibody-negative peers. Another study found that thyroxine treatment led to successful births in the majority of women who had previously suffered recurrent losses linked to thyroid antibodies.¹⁵ This is why ESHRE guidelines recommend thyroid screening, including TPO antibody testing, for all women with recurrent pregnancy loss.⁸

Progesterone insufficiency is another hormonal factor. After ovulation, the corpus luteum produces progesterone to support the uterine lining. If progesterone levels drop too early or too low, the lining cannot sustain implantation. Luteal phase insufficiency is seen more often in women with polycystic ovaries and those with thyroid or prolactin disorders, and it can contribute to both implantation failure and early miscarriage.¹⁶ Treatment with progesterone supplementation or addressing the underlying hormonal disorder has been found to help, though it remains one of the more debated areas in reproductive medicine.

Chronic Endometritis and the Uterine Microbiome

A less obvious cause of recurrent miscarriage is chronic endometritis, a low-grade, persistent inflammation of the uterine lining often caused by common bacteria. Unlike acute endometritis, which produces obvious symptoms like fever and pain, chronic endometritis can be entirely silent. In a study of 360 women with unexplained recurrent loss, nearly 58% showed signs of chronic endometritis on hysteroscopy, and common bacteria were identified in the majority of those with positive cultures.¹⁷ After antibiotic treatment cleared the infection, pregnancy success rates improved.

Research into the uterine microbiome has expanded this picture. Disruption of the normal balance of bacteria in the vagina and uterus can promote inflammation and increase pro-inflammatory signaling, potentially interfering with embryo implantation.¹⁸ This is still an emerging field, but it offers a potential explanation for some cases that otherwise go unexplained and raises the possibility that relatively simple antibiotic courses could help a subset of women.

Immune System Dysregulation

Pregnancy requires the immune system to perform a delicate balancing act: it must tolerate a genetically foreign embryo while still protecting the mother from infection. When that tolerance breaks down, the immune system can attack the developing placenta. Research has highlighted abnormal activity of natural killer cells and imbalances in T and B cell populations as contributors to immune-mediated miscarriage risk.³

Uterine natural killer cells are the most studied immune cell type in this context. They are abundant in the uterine lining around the time of implantation, and their job is actually to help remodel blood vessels to feed the placenta. But when these cells are overactive or present in abnormal numbers, they appear to impair rather than support early pregnancy. The trouble is that testing uterine immune cell populations is not straightforward, and treatments aimed at suppressing immune activity remain controversial. Some clinics offer intralipid infusions, steroids, or immunoglobulin therapy, but evidence for these interventions has been inconsistent, and most major guidelines stop short of recommending them outside of clinical trials.

Transcriptomic research has revealed that women who experience four or more miscarriages show altered gene expression in their endometrial tissue, including changes related to immunity, cell adhesion, and hormone secretion. Women who eventually achieved a live birth displayed a different endometrial gene profile, with enrichment in processes related to cell structure and a reduction in immune and coagulation signals.¹⁹ This suggests that the uterine lining’s receptivity has a molecular signature that differs between women who go on to carry successfully and those who do not.

The Male Side of the Equation

Recurrent miscarriage workups have historically focused almost entirely on the woman, but evidence increasingly points to the male partner as a contributing factor. Standard semen analysis measures sperm count, motility, and shape, and it can come back entirely normal while the sperm still carries hidden damage. Sperm DNA fragmentation, which refers to breaks in the genetic material packed inside the sperm head, has been linked to recurrent pregnancy loss even when routine semen parameters look fine.²⁰

A systematic review and meta-analysis found that couples with unexplained recurrent loss had significantly higher levels of sperm DNA fragmentation compared with fertile couples, with an average difference large enough to be clinically meaningful.²¹ Despite this evidence, sperm DNA fragmentation testing is still not part of the routine evaluation at most clinics. If you have been through multiple losses and all tests on the female side have come back normal, asking about this test is reasonable.

Weight and Lifestyle Factors

Being overweight or obese raises the odds of both experiencing recurrent pregnancy loss in the first place and having yet another miscarriage once you are in that category. A meta-analysis found that women with a body mass index above 25 had about 21% higher odds of recurrent loss compared to women at a normal weight. Among women already diagnosed with recurrent loss, those with a BMI above 30 had roughly 77% higher odds of losing their next pregnancy.²² The mechanisms likely involve hormonal disruption, chronic low-grade inflammation, and impaired blood flow to the uterine lining.

Smoking, heavy alcohol use, and high caffeine consumption have also been associated with increased miscarriage risk in the broader obstetric literature, though the data specifically linking these to recurrent loss is thinner. Still, they represent modifiable factors, which makes them worth addressing regardless of whether they are the primary cause. Even modest weight loss or smoking cessation before conception can shift the odds in a favorable direction.

Psychological Stress

The relationship between stress and miscarriage is one of the most sensitive and misunderstood topics in reproductive medicine. Nobody wants to hear that they should “just relax,” and the research does not support such a simplistic message. What the evidence does suggest is that chronic, severe stress can disrupt the feedback loop between the brain and the adrenal glands, altering levels of cortisol and other stress-related hormones that influence the uterine environment.²³ Stress is unlikely to be the sole cause of recurrent loss, but it may act as a compounding factor on top of other vulnerabilities. Supportive care programs for women with recurrent losses, including dedicated early-pregnancy clinics and psychological counseling, have been associated with improved outcomes in some observational studies, though separating the psychological benefit from closer medical monitoring is difficult.

The Placental Bottleneck

Regardless of the initial trigger, most first-trimester miscarriages share a common final pathway. The developing interface between the placenta and the uterine lining becomes severely impaired, allowing maternal blood to flood into the placental space too early and in an uncontrolled way. This causes massive oxidative damage to the fragile placental tissue. Research has shown that this mechanism is common across miscarriages of different origins, with the timing within the first trimester depending on the specific underlying cause.²⁴ Understanding this shared endpoint helps explain why miscarriages from very different causes can look so similar clinically, and why protecting early placental development is a focus of several treatment approaches.

What a Typical Workup Involves

If you are going through evaluation for recurrent pregnancy loss, the testing usually follows a structured sequence. Guidelines from ESHRE recommend starting with a detailed medical and family history, since patterns in previous pregnancies and family clotting or autoimmune disorders can guide which tests are most useful.⁸ Standard investigations include:

Karyotyping: Blood tests on both partners to check for balanced translocations or other chromosomal rearrangements.
Antiphospholipid antibodies: Lupus anticoagulant and anticardiolipin antibody testing, typically repeated after 12 weeks to confirm a persistent positive.
Thyroid panel: TSH levels and thyroid peroxidase antibody status.
Uterine imaging: Ultrasound, saline infusion sonography, or hysteroscopy to look for a septum, fibroids, or adhesions.
Thrombophilia screen: Often included, especially if there is a family history of clotting events, though its value is debated.

Some clinics add tests for natural killer cell levels, sperm DNA fragmentation, hormonal profiles, and endometrial biopsy for chronic endometritis, though these are not universally recommended in all guidelines. The gap between what guidelines endorse and what specialized clinics offer is one of the more frustrating aspects of the field. A test that is “not routinely recommended” may still be the one that finds your answer if standard testing has been unrevealing.

Prognosis After Multiple Losses

Perhaps the most important thing to know about recurrent miscarriage is that the odds of a future successful pregnancy remain surprisingly good for most couples. A study tracking outcomes over two years found a cumulative pregnancy rate of about 90% and a cumulative live delivery rate of about 76% among women with recurrent first-trimester losses.²⁵ Younger women with three losses where an embryonic heartbeat had previously been detected had particularly favorable outcomes. Age over 35 and more than three prior losses were associated with a lower delivery rate, and some of these women faced a secondary difficulty in conceiving at all.

The number of previous losses and the woman’s age are the two strongest predictors of what will happen next, which means prognosis is something your doctor can estimate with reasonable accuracy even if no specific cause has been identified. For many couples, this reassurance, combined with close monitoring in an early-pregnancy unit, is itself the most effective intervention available.

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