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Recurrent pregnancy loss

Abstract

Recurrent pregnancy loss is a distressing pregnancy disorder experienced by ~2.5% of women trying to conceive. Recurrent pregnancy loss is defined as the failure of two or more clinically recognized pregnancies before 20–24 weeks of gestation and includes embryonic and fetal losses. The diagnosis of an early pregnancy loss is relatively straightforward, although progress in predicting and preventing recurrent pregnancy loss has been hampered by a lack of standardized definitions, the uncertainties surrounding the pathogenesis and the highly variable clinical presentation. The prognosis for couples with recurrent pregnancy loss is generally good, although the likelihood of a successful pregnancy depends on maternal age and the number of previous losses. Recurrent pregnancy loss can be caused by chromosomal errors, anatomical uterine defects, autoimmune disorders and endometrial dysfunction. Available treatments target the putative risk factors of pregnancy loss, although the effectiveness of many medical interventions is controversial. Regardless of the underlying aetiology, couples require accurate information on their chances of having a baby and appropriate support should be offered to reduce the psychological burden associated with multiple miscarriages. Future research must investigate the pathogenesis of recurrent pregnancy loss and evaluate novel diagnostic tests and treatments in adequately powered clinical trials.

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Fig. 1: Association between age and pregnancy loss.
Fig. 2: Genetic risk factors for recurrent pregnancy loss.
Fig. 3: Uterine abnormalities and recurrent pregnancy loss.
Fig. 4: Impaired endometrial function and recurrent pregnancy loss.
Fig. 5: An example of a clinical protocol for the management of recurrent pregnancy loss.

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Acknowledgements

E.D. was supported by a senior research fellowship from National Health and Medical Research of Australia (NHMRC) and E.D. and E.M. by a NHMRC research project grant. S.S. was supported by AMED under grant numbers JP18gk0110018h0003 and JP20gk0110047h0002. J.J.B. was supported by funds from the Tommy’s National Miscarriage Research Centre and a Wellcome Trust Investigator Award (212233/Z/18/Z).

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Introduction (E.D., E.M., S.S. and J.J.B.); Epidemiology (E.D. and J.J.B.); Mechanisms/pathophysiology (E.D., E.M., S.S., W.H.K. and J.J.B.); Diagnosis, screening and prevention (E.D. and W.H.K.); Management (E.D., E.M., S.S. and J.J.B.); Quality of life (E.D., E.M. and J.J.B.); Outlook (E.D., E.M., S.S. and J.J.B.); Overview of Primer (E.D.). E.D. and E.M. contributed equally to this Primer.

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Correspondence to Evdokia Dimitriadis.

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J.J.B. has filed a UKIPO patent application (no. 1911947.8) pertaining to the use of SCARA5 and DIO2 as endometrial biomarkers to assess the risk of miscarriage. All other authors declare no competing interests.

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Nature Reviews Disease Primers thanks N. Di Simone, N. Gleicher, J. Gris, D. Gupta and M. Van Wely for their contribution to the peer review of this work.

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Glossary

Clinically recognized pregnancies

Pregnancies confirmed by ultrasonography or histopathology.

Ectopic pregnancies

When embryos implant outside the uterine cavity.

Molar pregnancies

A pregnancy characterized by excessive placental growth caused by an abnormally fertilized egg.

Biochemical losses

Non-visualized pregnancy losses documented only by a positive pregnancy test (serum or urine human chorionic gonadotrophin).

Secondary recurrent pregnancy loss

At least one previous live birth or pregnancy beyond 20–24 weeks of gestation.

Primary recurrent pregnancy loss

No prior live births or pregnancies beyond 20–24 weeks.

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Dimitriadis, E., Menkhorst, E., Saito, S. et al. Recurrent pregnancy loss. Nat Rev Dis Primers 6, 98 (2020). https://doi.org/10.1038/s41572-020-00228-z

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