Recurrent miscarriage

“Recurrent miscarriage” is the medical term for repeated pregnancy losses. Each miscarriage is a painful experience; when it happens again, it raises the question “why”. There is no single answer. The causes are many and varied, and in each couple they are looked for one by one.

The investigation concerns both partners. It starts from the history and proceeds to specific tests for each category of cause. When the cause is found, management is tailored to it. Equally important, throughout, is psychological support and encouragement for the couple.

All couples with a history of recurrent miscarriage should have karyotype testing, that is, analysis of the chromosomes from a blood sample. In around 3–5% of couples one partner is a carrier of a balanced structural chromosomal abnormality. In that case counselling by a clinical geneticist is required about the chances of a future healthy pregnancy; one option for these couples is preimplantation genetic diagnosis as part of IVF. If there is a further loss, histological and cytogenetic analysis of the pregnancy tissue is recommended.

Congenital anomalies of the womb, such as a bicornuate or unicornuate uterus and a septum, may be responsible for miscarriages. So may large fibroids, especially those inside the cavity of the womb (submucosal). Diagnosis is by transvaginal ultrasound and hysterosalpingography. Fibroids are treated by laparoscopy or hysteroscopy, depending on their location.

Cervical insufficiency: women who have had procedures on the womb or cervix, such as curettage or cone biopsy, and also women with a constitutional make-up of the cervix, may develop shortening of the cervix in pregnancy. It is diagnosed by ultrasound measurement of the cervix. When the length falls below 2 centimetres, a cerclage, a special stitch, is placed after the 14th week and removed after the 36th week.

Hypothyroidism and diabetes are linked to recurrent miscarriage when they are not controlled. When they are controlled, they are not implicated. For that reason the check includes a glucose tolerance test, glycated haemoglobin (HbA1c) and a full thyroid panel. Obesity is associated with an increase in first-trimester miscarriages. Polycystic ovary syndrome has also been linked to miscarriage.

Antiphospholipid syndrome is an immunological condition in which antiphospholipid antibodies are found in the blood at high levels. It is associated with repeated miscarriages before the 10th week, with loss of the fetus after the 10th week, with preterm birth due to pre-eclampsia, and with venous thrombosis. It may be primary or accompany chronic autoimmune diseases such as systemic lupus erythematosus. Testing is for lupus anticoagulant (LAC) and anticardiolipin antibodies (aCL). Diagnosis requires two positive results, some weeks apart.

Thrombophilia is a predisposition to blood clots, inherited or acquired. In pregnancy the blood naturally clots more readily; in a woman with thrombophilia this tendency may affect the blood supply to the placenta and the course of the pregnancy. Thrombophilia testing is not a routine test for everyone. It is considered on the basis of history: a previous thrombosis, thrombophilia or clots in the family, or repeated pregnancy losses. If thrombophilia is found, anticoagulant treatment with low-molecular-weight heparin or aspirin may be recommended during pregnancy.

Chronic inflammation of the lining of the womb (endometritis) in the past may be implicated in recurrent miscarriage. Infections by bacteria, viruses and parasites may affect the development of the embryo in the first trimester. Today it is possible to carry out molecular testing of the endometrial microbiome, that is, the microorganisms living inside the womb, on material from the lining.

High levels of homocysteine in the blood are associated with recurrent miscarriage. One of the genetic causes is deficiency of the enzyme MTHFR. Low levels of folic acid are also related to miscarriage.