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Recurrent miscarriage

Recurrent miscarriage or recurrent pregnancy loss (RPL) is the spontaneous loss of 2-3 pregnancies that is estimated to affect up to 5% of women. The exact number of pregnancy losses and gestational weeks used to define RPL differs among medical societies.[1] In the majority of cases, the exact cause of pregnancy loss is unexplained despite genetic testing and a thorough evaluation. When a cause for RPL is identified, almost half are attributed to a chromosomal abnormality (ie. aneuploidy). RPL has been associated with several risk factors including parental and genetic factors (ie. advanced maternal age, chromosomal abnormalities, sperm DNA fragmentation), congenital and acquired anatomical conditions, lifestyle factors (ie. cigarette smoking, caffeine, alcohol, stress), endocrine disorders, thrombophila (clotting disorders), immunological factors, and infections. The American Society of Reproductive Medicine recommends a thorough evaluation after 2 consecutive pregnancy losses, however, this can differ from recommendations by other medical societies.[1][2] RPL evaluation be evaluated by numerous tests and imaging studies depending on the risk factors. These range from cytogenetic studies, blood tests for clotting disorders, hormone levels, diabetes screening, thyroid function tests, sperm analysis, antibody testing, and imaging studies. Treatment is typically tailored to the relevant risk factors and test findings. RPL can have a significant impact on the psychological well-being of couples and has been associated with higher levels of depression, anxiety, and stress. Therefore, it is recommended that appropriate screening and management (ie. pharmacologic, counseling services) be considered by medical providers.   

Recurrent miscarriage

Habitual abortion, recurrent pregnancy loss (RPL)

Obstetrics

Epidemiology[edit]

Pregnancy loss, also referred to as miscarriage or spontaneous abortion, occurs in up to 25% of pregnancies. Recurrent pregnancy loss occurs less frequently and it is estimated that 5% of women experience two consecutive pregnancy losses while only 1% experience three or more.[3][4]

Advanced maternal age: is associated with increased risk of miscarriage with a rate of 50% in women over 40 years of age. This higher likelihood of pregnancy loss can be attributed to the higher incidence of trisomies, a chromosomal abnormality, seen in women over the age of 35.[3]

Maternal age

Chromosomal abnormalities: Recurrent pregnancy loss is most commonly found to be caused by in the fetus, accounting for approximately 50% of cases. These include structural aberrations (such as chromosomal inversions, insertions, deletions, and translocations) and numerical aberrations, also called aneuploidies (trisomies, monosomy X, and triploidy).[7] These can be detected by cytogenetic testing such as karyotyping (test that analyzes the structure and quantity of chromosomes), FISH, MLPA, aCGH, and SNP array.[8] Some research suggests that chromosomal abnormalities occur more frequently in sporadic pregnancy loss than in recurrent pregnancy loss, and the incidence of RPL is lower in women with 3 or more pregnancy losses.[7] Parental chromosomal abnormalities is a rare cause of RPL, found in approximately 2-4% cases. Studies comparing pregnancy outcomes in couples experiencing RPL with and without chromosomal abnormalities found that parental carriers of chromosomal abnormalities had a lower live birth rate, specifically carriers of a reciprocal/balanced Robertsonian translocation. This evidence suggests that although RPL can occur in both couples with and without chromosomal aberrations, those that do are at higher risk of pregnancy loss.[9] Previous studies produced conflicting results. Genetic evaluation of RPL is generally recommended in order to determine the need for genetic counseling and appropriate treatment.[3] This, however, can differ among medical societies where others recommend against routine cytogenetic testing for couples experiencing RPL as it is of little clinical benefit.[10] It is instead considered after individual risk assessment (ie. family history) and recommended to test parental chromosomes rather than the products of conception.[8][10]

chromosomal abnormalities

Paternal Factors: There is emerging research that suggests male factors may contribute to recurrent pregnancy loss. A systematic review found that sperm DNA fragmentation, defined as breaks in the DNA strand of sperm cells, may be associated with RPL. Their findings included higher rates of SDF and other sperm parameters (ie. lower sperm number, motility, or ejaculation volume) in men experiencing RPL. No evidence of a relationship between RPL and paternal age, BMI, smoking, or alcohol use. The European Association of Urology Guidelines on Sexual and Reproductive Health therefore recommends SDF testing in cases of infertility or recurrent pregnancy loss.[12]

[11]

Assessment[edit]

Transvaginal ultrasonography has become the primary method of assessment of the health of an early pregnancy.


In non-pregnant patients who are evaluated for recurrent pregnancy loss the following tests are usually performed. Parental chromosome testing (karyogram) is generally recommended after 2 or 3 pregnancy losses. Blood tests for thrombophilia, ovarian function, thyroid function and diabetes are performed.

Treatment[edit]

If the likely cause of recurrent pregnancy loss can be determined treatment is to be directed accordingly. In pregnant women with a history of recurrent miscarriage, anticoagulants seem to increase the live birth rate among those with antiphospholipid syndrome and perhaps those with congenital thrombophilia but not in those with unexplained recurrent miscarriage.[41] One study found that in many women with chronic endometritis, "fertility was restored after appropriate antibiotic treatment."[42]


For women with unexplained recurrent pregnancy loss, research suggests that specific antenatal counseling and psychological support may result in a higher chance of pregnancy success.[43] Some research finds that for these patients psychological support and ultrasound in early pregnancy "gives 'success rates' of between 70% and 80%".[44]


However, each additional loss worsens the prognostic for a successful pregnancy and increases the psychological and physical risks to the mother. Aspirin has no effect in preventing recurrent miscarriage in women with unexplained recurrent pregnancy loss.[45] Immunotherapy has not been found to help.[46]


In certain chromosomal situations, while treatment may not be available, in vitro fertilization with preimplantation genetic diagnosis may be able to identify embryos with a reduced risk of another pregnancy loss which then would be transferred. However, in vitro fertilization does not improve maternal-fetal tolerance imbalances.

Prognosis[edit]

Recurrent miscarriage in itself is associated with later development of coronary artery disease with an odds ratio of approximately 2,[50] increased risk of ovarian cancer,[51] increased risk of cardiovascular complications,[52] and an increased risk of all-cause mortality of 44%, 86%, and 150% for women with a history of 1, 2, or 3 miscarriages, respectively.[53]


Women with a history of recurrent miscarriage are at risk of developing preeclampsia in later pregnancies.[54]

Hoffman, Barbara (2012). Williams gynecology. New York: McGraw-Hill Medical.  9780071716727.

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