Recurrent miscarriages are defined as the loss of three or more consecutive pregnancies. Recurrent miscarriages are a heterogeneous condition that has many possible causes, and many factors at the same time may contribute to their appearance. Recurrent miscarriage is an unpleasant problem that affects 1% of all women. The frequency is greater than that expected by chance alone, as 10-15% of all clinically recognized pregnancies end up in miscarriage and the theoretical risk for three consecutive pregnancy losses is 0.34%. Therefore, only a proportion of women who experience recurrent miscarriages have a specific cause that justifies them.
All couples with a history of recurrent miscarriages should be screened for peripheral blood karyotype. The finding of abnormal karyotype raises the need to refer the couple to a clinical geneticist. Approximately in 3-5% of couples with a history of recurrent miscarriages, one of the partners is the carrier of a balanced structural chromosomal abnormality. The most common types are Robertson’s balanced mutations or shifts. For the possibility of a future healthy pregnancy, counseling by a clinical geneticist is considered necessary. Recently, preimplantation diagnosis with IVF is used as the therapeutic option for these couples.
In couples with a history of recurrent miscarriages, histopathological and cytogenetic analysis of pregnancy products should be performed in the event of a new miscarriage. Recurrent miscarriages may be due to an embryo with an “incompatible with life” disorder (chromosomal abnormalities or congenital malformation). Cytogenetic analysis, although it is a therapeutic option, is costly and must have specific indications.
It is difficult to know the exact contribution of congenital uterine abnormalities to the onset of recurrent miscarriages. The prevalence and reproductive extensions of uterine abnormalities in the general population have not been adequately documented. The reported frequency of these abnormalities ranges from 1.8 to 37.6%, and this variability is due to the lack of consistent criteria and techniques for diagnosing them.
The use of hysterosalpingography as a method of clinical population test in women with recurrent miscarriages is in question. New promising methods for diagnosis are hydro-ultrasound and three-dimensional ultrasound. Their use can sometimes offer diagnosis and make other tests unnecessary, such as hysteroscopy and laparoscopy. All women with recurrent miscarriages should undergo a pelvic ultrasound examination to assess the anatomy and morphology of the uterus.
Cervical ligament is associated with potential dangers from surgery and with a risk of stimulating myometrial activity and should therefore be recommended to women who may benefit from it. So far, there is no objective and satisfactory test that can identify women with cervical insufficiency apart from pregnancy. The diagnosis is based on the history of late fetal loss, with automatic follicle rupture and painless cervical dilation. Measuring cervical length with transvaginal ultrasound during pregnancy may predict premature delivery in some cases of cervical insufficiency.
Epidemiological data have shown a correlation between recurrent miscarriages and hypothyroidism and diabetes mellitus. However, well-regulated DM or healed hypothyroidism do not pose a risk for miscarriage.
So check for:
- Glucose tolerance test
- Glycosylated hemoglobin (HbA1C)
- Thyroid function tests
Obesity is associated with a statistically significant increase in the risk of first-trimester miscarriages and recurrent miscarriages (Odds ratio: 1,2 and 3,5 respectively). Weight loss is the first therapeutic option for obese and sub-fertile women.
Polycystic ovary syndrome has been associated with miscarriages. LH hypersecretion, a frequent phenomenon in the syndrome, has been reported as a risk factor for early fetal loss. However, reducing pre-pregnancy LH levels in women with recurrent miscarriages and polycystic ovaries that overexpress LH does not improve the rate of successful pregnancies.
Detection of thyroid antibodies at the level of clinical population control in women with recurrent miscarriages is not advisable.
Primary APS refers to the association between antiphospholipid antibodies (aPL) and the adverse outcome of pregnancy or vascular thrombosis. The adverse outcome includes:
- Three or more miscarriages before the 10th week,
- One or more morphologically normal embryonic deaths after the 10th week and
- One or more preterm births before the 34th week due to severe pre-eclampsia, eclampsia or placental insufficiency.
Where APS is present in a territory of chronic inflammatory disorders, such as SLE, it is referred to as secondary.These women should be tested for aPL:
- Lupus anticoagulant (LAC)
- Anti-cardiolipin antibodies (aCL)
For APS diagnosis, it is necessary for the patient to have two positive tests at least 6 weeks apart, either for LAC or for aCL, with IgG and / or IgM antibodies having a moderate or high titer.
In women with suspected hereditary thrombophilia, the following should be checked:
- Factor V Leiden
- Resistance to activated protein C
- S-protein deficiency
- Prothrombin G20210A
High levels of homocysteine are associated with recurrent miscarriages. One of the genetic causes of homocysteinaemia is the deficiency of the enzyme methyl-tetrahydrofolate reductase (MTHFR). Also, low folate levels have been associated with first-trimester miscarriages.
Bacterial, viral or parasite infections may affect fetal development in the first trimester, but none of these are documented to be an important cause of recurrent miscarriages. Clinical population control for TORCH infections appears to be of limited value for the prevention and prognosis of recurrent miscarriages.
There is much information about the role of environmental toxins. First trimester miscarriage correlation with factors such as ionizing radiation, organic solvents, alcohol, mercury and lead is documented. On the contrary, the role of caffeine, hyperthermia and smoking is under discussion.
- Medical history (Obstetric, personal commemorative, family)
- General blood test
- Glucose tolerance test, HbA1C
- Thyroid tests
- Transvaginal ultrasound / hysterosalpingography
- Hysteroscopy / Laparoscopy
- Antiphospholipid Ab (LAC, aCL)
- Homocysteine, MTHFR, folate
- Thrombophilia test
- Parental karyotype peripheral blood test
- Cytogenetic / Histopathological study of elimination products
- Treatments with well-established benefit:
- Particular attention to pregnancy
- Health tips (diet, coffee, smoking, alcohol)
Treatments that benefits but requires more studies:
- Aspirin and / or Low Molecular Weight Heparines in women with APS or thrombophilia
Progesterone in women with unexplained early and late miscarriages.
Folic acid in women with homocysteinaemia.
Treatments without an established benefit:
- Immunotherapy with parental leukocytes or trophoblastic membranes.
- Administering multivitamin tablets.
Treatments that may harm but rather benefit:
- Corticosteroids in the first half of pregnancy.