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.

Maternal HLA class II alleles and haplotypes associated with altered risk of recurrent pregnancy loss: A case‐control study

“…Although significant differences between cases of RPL and control subjects were noted in HbA1c, the values recorded for each group were within the reference range of healthy subjects. Consistent with the contribution of menarche to adverse pregnancy complications, 43,44 including RPL, 1,43 significantly lower menarche was found in women with RPL compared to control subjects but remained within the acceptable limits. As such, HbA1c, and menarche, in addition to obesity, were chosen as the covariates and controlled for in subsequent tests.…”

“…Mounting evidence connected HLA class II genes with the pathogenesis of pregnancy complications, including polycystic ovary syndrome, 21 preeclampsia, 28,29,36 and RPL 5,30,33,37 . Recent data report that HLA class II antigens are essential to the presentation of antigenic fragments and autoimmunity, and RPL is linked with an imbalance of proinflammatory and anti‐inflammatory immune mechanisms 1,38,39 . This case‐control report is the first to assess the association of specific DPB1 , DQB1 , and DRB1 alleles, and unique 3‐locus DRB1∼DQB1∼ DPB1 haplotypes with altered risk of RPL in Tunisian women of Arab descent.…”

“…Recurrent pregnancy loss (RPL) is a frequent aberration of pregnancy experienced by 1−3% of otherwise healthy women 1 . RPL is defined as two or more pregnancy losses that do not need to be consecutive according to the American Society for Reproductive Medicine (ASRM) and European Society of Human Reproduction and Embryology (ESHRE) guidelines and is verified by ultrasound or histological examination 2,3 .…”

“…The exact etiology of RPL remains unclear and acquired and constitutional risk factors were associated with its pathogenesis 4–7 . While several anatomical, acquired, genetic, immunological, and coagulation risk factors were reported, the exact cause in more than 50% of all established RPL cases remains unknown 1,8,9 …”

Molecular role of non-exonic variants in CALPAIN 10 gene in polycystic ovarian syndrome in Saudi women

“…Women diagnosed with PCOS have various reproductive, metabolic, cardiovascular, and psychological comorbidities ( 4 ). A combination of genetic and environmental factors can predict the development of PCOS in women ( 5 ), e.g., type 2 diabetes mellitus (T2DM), IR, obstructive sleep apnea, and elevated blood pressure ( 6 ).…”