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Recurrent Pregnancy Loss Etiology, Risk Factors, Diagnosis, and Management. Fresh Look into a Full Box

Abstract

Recurrent pregnancy loss is a complex health challenge with no universally accepted definition. Inconsistency in definitions involves not only the number of spontaneous abortions (two or three) that are accepted for recurrent pregnancy loss but the types of pregnancy and gestational age at miscarriage. Due to the heterogeneity of definitions and criteria applied by international guidelines for recurrent pregnancy loss, the true incidence of recurrent miscarriage, which is reported to range from 1% to 5%, is difficult to estimate. Moreover, the exact etiology of recurrent pregnancy loss remains questionable; thus, it is considered a polyetiological and multifactorial condition with many modifiable and non-modifiable factors involved. Even after thoroughly evaluating recurrent pregnancy loss etiology and risk factors, up to 75% of cases remain unexplained. This review aimed to summarize and critically analyze accumulated knowledge on the etiology, risk factors, relevant diagnostic options, and management approach to recurrent pregnancy loss. The relevance of various factors and their proposed roles in recurrent pregnancy loss pathogenesis remains a matter of discussion. The diagnostic approach and the management largely depend on the etiology and risk factors taken into consideration by a healthcare professional as a cause of recurrent miscarriage for a particular woman or couple. Underestimation of social and health consequences of recurrent pregnancy loss leads to compromised reproductive health and psychological well-being of women after miscarriage. Studies on etiology and risk factors for recurrent pregnancy loss, especially idiopathic, should be continued. The existing international guidelines require updates to assist clinical practice.

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References
1.
Masucci L, DIppolito S, De Maio F, Quaranta G, Mazzarella R, Bianco D . Celiac Disease Predisposition and Genital Tract Microbiota in Women Affected by Recurrent Pregnancy Loss. Nutrients. 2023; 15(1). PMC: 9823693. DOI: 10.3390/nu15010221. View

2.
Amirchaghmaghi E, Rezaei A, Moini A, Roghaei M, Hafezi M, Aflatoonian R . Gene expression analysis of VEGF and its receptors and assessment of its serum level in unexplained recurrent spontaneous abortion. Cell J. 2015; 16(4):538-45. PMC: 4297492. DOI: 10.22074/cellj.2015.498. View

3.
Magnus M, Wilcox A, Morken N, Weinberg C, Haberg S . Role of maternal age and pregnancy history in risk of miscarriage: prospective register based study. BMJ. 2019; 364:l869. PMC: 6425455. DOI: 10.1136/bmj.l869. View

4.
Devall A, Papadopoulou A, Podesek M, Haas D, Price M, Coomarasamy A . Progestogens for preventing miscarriage: a network meta-analysis. Cochrane Database Syst Rev. 2021; 4:CD013792. PMC: 8406671. DOI: 10.1002/14651858.CD013792.pub2. View

5.
Bagislar S, Ustuner I, Cengiz B, Soylemez F, Akyerli C, Ceylaner S . Extremely skewed X-chromosome inactivation patterns in women with recurrent spontaneous abortion. Aust N Z J Obstet Gynaecol. 2006; 46(5):384-7. DOI: 10.1111/j.1479-828X.2006.00622.x. View