Summary
Recurrent miscarriage is defined by the European Society for Human Reproduction and Embryology and the American Society for Reproductive Medicine as 2 or more failed clinical pregnancies (i.e., documented by ultrasound or histopathology).[1][2] It affects about 1% of all fertile couples trying to conceive, in comparison with sporadic nonconsecutive miscarriages, which occur in about 15% to 20% of all pregnancies.[3] A miscarriage includes any pregnancy that ends before the age of viability, which currently stands at 24 weeks' gestation. A miscarriage that occurs before 12 weeks' gestation is commonly termed an early or first-trimester miscarriage, and one that occurs between 13 and 24 weeks' gestation is known as a late or second-trimester miscarriage.
Evaluation can start after 2 or 3 consecutive miscarriages, as prevalence of causes is similar in those with 2, 3, or more miscarriages.[4] Despite a wide range of investigations, no apparent cause is found in >50% of cases of recurrent miscarriage.[5] About 70% of patients with no cause found will achieve a live birth in the subsequent pregnancy depending on the age of the woman and the number of previous miscarriages.[4][5][Figure caption and citation for the preceding image starts]: Predicted percentage success rate of subsequent pregnancy according to age and previous miscarriage historyCreated by the BMJ Group; data from Brigham SA, et al. Hum Reprod. 1999;14:2868-2871 [Citation ends].
Definite associations of recurrent miscarriage include chromosomal abnormalities, antiphospholipid syndrome, certain structural uterine abnormalities such as septate uterus, and certain thrombophilias. However, a reduction in risk of miscarriage in a subsequent pregnancy following treatment has not been proven unequivocally for most of these conditions. Controversy surrounds the possible association of other conditions with recurrent miscarriage, including immunologic factors, other uterine abnormalities (e.g., cervical incompetence), infection, and male and endocrinologic factors. There is a need for high-quality and methodologically sound research to guide management of these patients.[6]
Risk factors
Increasing maternal age reduces the chance of a successful live birth. Women ages 20 years with 2 previous miscarriages have a 92% chance of success in the next pregnancy compared with only a 60% chance of success in women ages 45 years with 2 previous miscarriages.[7]
Advanced paternal age also appears to be associated with greater risk for spontaneous miscarriage.[8][9][10] Increased frequency of chromosomal anomalies in sperm has been implicated.[11] In one systematic review and meta-analysis, risk for pregnancy loss <20 weeks was increased by 23% and 43% among men ages 40-44 and ≥45 years, respectively (compared with men ages 25-29 years).[10]
Primigravidas and patients who consistently have successful pregnancies have only about 5% risk of miscarriage, compared with 24% in patients who have previously miscarried.[12] Other studies similarly show a trend of miscarriage rate increasing with the number of previous miscarriages.[7][13] Therefore, the risk of miscarriage is directly related to the outcome of previous pregnancies.
Recurrent miscarriage is a stressful condition, so alongside medical investigations and appropriate treatment, patient education, counseling, and support should be provided.
Differentials
Common
- Idiopathic recurrent miscarriage
- Fetal chromosomal abnormality
- Chronic endometritis
Uncommon
- Parental chromosomal abnormality
- Antiphospholipid syndrome
- Cervical incompetence
- Uncontrolled diabetes mellitus
- Uncontrolled thyroid dysfunction
- Thrombophilias
- Uterine abnormalities (e.g., bicornuate, septate, or arcuate uterus)
- Bacterial vaginosis
- Polycystic ovarian syndrome (PCOS)
- Smoking, caffeine intake
Contributors
Authors
Winifred Mak, MD, PhD
Associate Professor
Women's health
Dell Medical School
University of Texas
Austin
TX
Disclosures
WM declares that she has been a paid speaker at an epigenetic conference for Ohana Biosciences.
Acknowledgements
Dr Winifred Mak would like to gratefully acknowledge Dr Ai-Wei Tang and Dr Siobhan Quenby, the previous contributors to this topic. AT declares that she has no competing intrests. SQ is an author of a reference cited in this topic. SQ declares that she has no competing interests.
Disclosures
AT declared that she had no competing interests. SQ is an author of a reference cited in this topic. SQ declared that she had no competing interests.
Peer reviewers
Justin C. Konje, MBBS, FMCOG, MRCOG, FWACS, MD, MBA
Professor of Obstetrics and Gynaecology
Leicester Royal Infirmary
Leicester
UK
Disclosures
JCK is an author of a reference cited in this topic.
Frederique van Dunné, MD, PHD, FRANZCOG
Obstetrician
Erasmus Medical Center
Rotterdam
The Netherlands
Disclosures
FVD declares that he has no competing interests.
Veronica Gomez-Lobo, MD
Associate Professor of Obstetrics and Gynecology
Georgetown University
Washington Hospital Center
Washington
DC
Disclosures
VGL declares that she has no competing interests.
Patient information
Bacterial vaginosis
Polycystic ovary syndrome
More Patient information
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