Infertility
Recurrent pregnancy loss
Two or more miscarriages: assessment and treatment according to the ESHRE and ASRM guidelines
Miscarriage is the most common complication of pregnancy. Depending on the study, about 15-20% of clinically confirmed pregnancies end in miscarriage. Most miscarriages in the first trimester, about 50-60%, are caused by a random chromosomal abnormality of the embryo. A second or third miscarriage, however, is not always a matter of chance.
In its 2022 guideline, the European Society of Human Reproduction and Embryology (ESHRE) defines recurrent pregnancy loss as the loss of two or more pregnancies before 24 weeks. This includes pregnancies that were only detectable in a pregnancy test or in the blood, and pregnancies after fertility treatment. Ectopic pregnancies, molar pregnancies and implantation failure are not included. In its 2026 committee opinion, the American Society for Reproductive Medicine (ASRM) uses a similar definition: two or more pregnancy losses before 22 weeks, including biochemical pregnancies, because their risk of recurrence is similar to that of clinical losses. The losses do not have to be consecutive.
According to ESHRE, about 1-2% of women are affected when three losses are used as the definition, and about 2-3% when biochemical pregnancies are also counted. ASRM considers recurrent pregnancy loss a condition of its own, separate from infertility, with its own assessment and treatment.
What is the outlook?
Losing a pregnancy is an experience of grief, and a repeat loss brings fear of the next time. One clear statement is important, however: according to ASRM, 50-80% of women with recurrent pregnancy loss have a baby in a later pregnancy, even without specific treatment. One of the doctor’s most important tasks is to explain this natural course.
ESHRE recommends basing the outlook on the woman's age and her complete pregnancy history: the number of losses, the number of births and their order. The risk of miscarriage is lowest between the ages of 20 and 35 and rises rapidly after 40. In women with recurrent pregnancy loss, an age of 35 or more roughly doubles the risk of a further loss. The man's age also seems to play an important role. Several studies show a link between more miscarriages and possible sperm dysfunction in men over 50. More in the article “Pregnancy at an older age”.
What do the numbers say about the outlook?
Birth of a child in a later pregnancy
Miscarriage risk by age
Why is it a question of long-term health?
ASRM points out that women with recurrent pregnancy loss have a higher risk later in life of cardiovascular disease, stroke, diabetes, autoimmune diseases and mental health disorders. This applies especially when the losses involved embryos with normal chromosomes. It therefore recommends a broader health assessment of both partners, and not only a search for the cause of the losses.
Which lifestyle and risk factors matter?
Smoking. Both guidelines recommend stopping smoking. Passive smoking is also linked to a higher risk.
Weight. According to ESHRE, both obesity and marked underweight affect the outcome. In women with obesity and recurrent pregnancy loss, the risk of a further miscarriage was about 70% higher, and a larger share of the losses involved embryos with normal chromosomes. The aim is a healthy weight.
Alcohol and caffeine. Excessive alcohol is a possible risk factor for miscarriage and a proven risk factor for harm to the baby. ESHRE recommends limiting alcohol. ASRM describes a link with more than three alcoholic drinks per week and with more than about 100 milligrams of caffeine per day, but the data are not consistent.
Stress and exercise. Stress is more common in women with recurrent pregnancy loss. According to ESHRE, however, there is no proof that stress itself causes a miscarriage. Light and moderate exercise is not linked to miscarriage.
Which tests make sense?
In more than 50% of couples, even a complete assessment finds no clear cause. In the others, it finds one or more factors, often acting together. The guidelines distinguish carefully between tests that are useful and tests that are not.
Genetic testing of the pregnancy tissue. According to ESHRE, it is not routinely needed, but it can be done to explain the loss. The laboratory should use a modern method (array-CGH). In its 2026 committee opinion, ASRM goes further and recommends testing the tissue, ideally from the second miscarriage. When the embryo had a chromosomal abnormality, the loss is explained and the outlook for the future is better. The more losses a woman has had, however, the more often they involve embryos with normal chromosomes.
The parents' chromosomes. According to ESHRE, testing the chromosomes of both partners is an option after an individual risk assessment. ASRM recommends it when an unbalanced translocation was found in the pregnancy tissue or when the tissue could not be tested. In observational studies, couples with a balanced translocation had a chance of a live birth of about 70%, even without assisted reproduction. When a result is abnormal, genetic counseling is needed.
Antiphospholipid syndrome. This is an autoimmune disease that increases blood clotting, and it is the most important treatable cause. ESHRE recommends testing for lupus anticoagulant and anticardiolipin antibodies (IgG and IgM) after two losses. Testing for antibodies against beta-2 glycoprotein I can be considered. A positive result needs a repeat test after 12 weeks for confirmation. ASRM recommends testing after three or more consecutive losses or with a history of thrombosis, but not when all losses had a chromosomal abnormality of the embryo.
The thyroid. ESHRE recommends measuring TSH and TPO antibodies in all women, and T4 when the TSH is abnormal. ASRM recommends TSH testing when there are risk factors or symptoms, when the lost embryos had normal chromosomes, or when the tissue was not tested. It does not recommend routine testing for thyroid antibodies.
The uterus. Both guidelines recommend assessing the uterus in all women. According to ESHRE, 3D ultrasound is the preferred method. Ultrasound with fluid in the uterus (sonohysterography) is more accurate than an X-ray of the uterus and is an option when 3D ultrasound is not available or when the fallopian tubes also need to be checked. MRI is an alternative, but not the first choice. Adenomyosis can be assessed with ultrasound. When a congenital anomaly of the uterus is found, an assessment of the kidneys and urinary tract makes sense.
The man. ESHRE recommends assessing the man's lifestyle: age, smoking, alcohol, exercise and weight. Testing for sperm DNA fragmentation can be considered. ASRM recommends it in unexplained recurrent pregnancy loss or when infertility is also present.
Prolactin, blood sugar and metabolism. Both guidelines recommend measuring prolactin only when there are symptoms, such as absent ovulation or milk discharge from the breast. ESHRE does not recommend testing for PCOS, fasting insulin or fasting blood sugar to improve the outlook. ASRM, on the other hand, recommends measuring HbA1c when there are risk factors: PCOS/PMOS, obesity, age over 40, diabetes in the family or a history of gestational diabetes.
Chronic endometritis. Chronic inflammation of the lining of the uterus is described in 7-58% of women with recurrent pregnancy loss, depending on the method. ESHRE makes no recommendation on testing and calls for more research. ASRM sees a biopsy as an option in unexplained recurrent pregnancy loss or when infertility is also present, but points out that a high-quality randomized trial showed no benefit from antibiotic treatment.
What is not recommended?
In recurrent pregnancy loss, tests and treatments without proven benefit are often offered. They cost money and give false hope. ESHRE does not recommend routine testing for inherited thrombophilia, unless there are additional risk factors. It does not recommend testing HLA, NK cells in the blood or in the lining of the uterus, cytokines, anti-HLA antibodies, ovarian reserve, the luteal phase, androgens, LH or homocysteine. ASRM likewise does not recommend thrombophilia panels, screening for thyroid antibodies, tests of NK cells or endometrial receptivity, microbiome testing or routine immune testing.
Specialization also means knowing what is not needed, so that attention stays on the things that really matter.
Which tests help and which do not?
Proven benefit
No proven benefit
What treatment helps when there is a known cause?
Antiphospholipid syndrome. In women with three or more losses and a confirmed result, ESHRE recommends low-dose aspirin (75 to 100 milligrams per day) from before conception, plus heparin at a preventive dose from the first positive pregnancy test. With two losses, ESHRE recommends this treatment only within research studies. For ASRM, heparin and low-dose aspirin are the standard treatment of antiphospholipid syndrome.
The thyroid. Overt hypothyroidism always needs treatment with levothyroxine. In mild hypothyroidism, the data are conflicting according to ESHRE, and the doctor weighs benefits and risks. ASRM recommends levothyroxine when the TSH is above 4 mIU/l or above the laboratory's upper limit of normal. In women with positive antibodies only and normal thyroid function, the large TABLET trial showed that treatment does not increase live births. Neither guideline therefore recommends treatment in this case. In a new pregnancy, these women should have their TSH checked at 7 to 9 weeks.
The uterus. Removing a septum by hysteroscopy did not improve the outcome in the only randomized trial. ASRM sees it as an option after a shared decision. For polyps, fibroids in the uterine cavity and adhesions, the data are not sufficient according to ESHRE. ASRM considers removing polyps and fibroids that distort the cavity reasonable because of the low rate of complications. Fibroids in the muscle wall that do not distort the cavity do not need removal. Surgical correction of a bicornuate uterus with a normal cervix or of a unicornuate uterus is not recommended.
Losses in the second trimester. After a loss in the second trimester, ESHRE recommends regular ultrasound checks of the cervix in the next pregnancy. With a weak cervix, a cervical stitch (cerclage) can be considered in singleton pregnancies.
Metabolism. According to ESHRE, the data are not sufficient to recommend metformin to prevent miscarriage. ASRM considers metformin a reasonable option in women with PCOS/PMOS and insulin resistance and otherwise unexplained losses. Uncontrolled diabetes needs good control before pregnancy, and raised prolactin needs treatment. More in the article “PCOS and infertility”.
Genetic causes. When the parents' chromosomes or the pregnancy tissue show an abnormality, ESHRE recommends genetic counseling and information about all options with their advantages and disadvantages. According to both guidelines, preimplantation genetic testing for chromosomal abnormalities (PGT-A) has not improved the number of miscarriages or live births. ASRM considers a discussion about it useful only in women over 40 whose previous loss had a proven chromosomal abnormality.
What helps in unexplained recurrent pregnancy loss?
Progesterone. The large PRISM trial showed that vaginal progesterone can improve the chance of a live birth in women with previous miscarriages and bleeding at the start of the new pregnancy, especially after three or more losses. ESHRE recommends it in this situation. ASRM considers vaginal progesterone an option in early pregnancy, with bleeding or with recurrent unexplained miscarriage, after a shared decision with the woman. Dydrogesterone tablets may also help, but the data are still limited. Giving progesterone without bleeding, only because of previous losses, showed no clear benefit in the PROMISE trial. The data are not sufficient for treatment with hCG.
What does not help. Heparin or aspirin without antiphospholipid syndrome do not increase the chance of a live birth, as the ALIFE trial showed. Neither guideline therefore recommends them. Steroids, lymphocyte immunization, intralipid infusions, G-CSF and endometrial scratching are also not recommended. ESHRE sees a possible benefit of high-dose immunoglobulins in women with four or more unexplained losses, whereas ASRM does not consider them effective. In men, antioxidants and special methods of sperm selection showed no benefit.
Vitamins. Folic acid is recommended for all women before pregnancy. It does not, however, prevent miscarriage, and a high dose is not needed without a specific reason. Vitamin D can be taken before conception. With multivitamins, only products that are safe in pregnancy make sense. High doses of vitamins A and E can cause harm.
What about the emotional burden?
Recurrent pregnancy loss is a heavy emotional burden. Grief and a sense of failure grow with each further loss. According to ASRM, women with recurrent pregnancy loss have depression about five times more often, and their partners also have a clearly higher risk of depression and anxiety. Many couples receive little support from the people around them.
Both guidelines therefore recommend psychological support for all couples planning a new pregnancy. ASRM recommends acknowledging the couple's experience, asking about mood disorders, referring to a psychotherapist when needed and avoiding any blame. ESHRE describes a specialized clinic with experienced staff, enough time for questions, good ultrasound and honest information about what the tests can and cannot find. Data on the effect of close care on the number of live births are limited. According to ESHRE, however, nothing speaks against it.
How should the next pregnancy be prepared?
Preparing for the next pregnancy starts before conception: controlling the thyroid and metabolism, treating known conditions of the mother such as high blood pressure or lupus, taking folic acid, stopping smoking, limiting alcohol and reaching a healthy weight. When there are known findings, the plan is ready in advance: aspirin and heparin in antiphospholipid syndrome, a TSH check at 7 to 9 weeks for women with thyroid changes, and progesterone if there is bleeding at the start of the pregnancy. Close care in the first weeks with early ultrasound scans gives reassurance when fear is greatest.
The practice's approach
The assessment follows the ESHRE and ASRM guidelines, with a particular focus on hormonal and metabolic factors, the thyroid, the luteal phase and antiphospholipid syndrome. ESHRE does not recommend testing the luteal phase. Clinical practice and experience, however, call for testing and correcting a possible luteal phase deficiency. The doctor chooses the tests in a targeted way and assesses all results together. The practice does not recommend tests and treatments without proven benefit.
The goal of the practice is a clear plan for the next pregnancy and close care in the first weeks, in cooperation with the gynecologist who looks after the pregnancy.
Sources: ESHRE – Guideline Recurrent Pregnancy Loss, update 2022 (ESHRE Guideline Group on RPL, Human Reproduction Open 2023). American Society for Reproductive Medicine Practice Committee – Recurrent pregnancy loss: a committee opinion, Fertility and Sterility 2026. Dhillon-Smith RK et al., New England Journal of Medicine 2019 (TABLET). Coomarasamy A et al., New England Journal of Medicine 2019 (PRISM). Coomarasamy A et al., New England Journal of Medicine 2015 (PROMISE). Kaandorp SP et al., New England Journal of Medicine 2010 (ALIFE).