Recurrent pregnancy loss: diagnostic workup after two or three pregnancy losses? A systematic review of the literature and meta-analysis

Abstract

A search for RPL was combined with a broad search for terms indicative of number of pregnancy losses, screening/testing for pregnancy loss or the prevalence of known risk factors. Meta-analyses were performed in case of adequate clinical and statistical homogeneity. The quality of the studies was assessed using the Newcastle-Ottawa scale.OUTCOMES: From a total of 1985 identified publications, 21 were included in this systematic review and 19 were suitable for meta-analyses. For uterine abnormalities (seven studies, odds ratio (OR) 1.00, 95% CI 0.79-1.27, I 2 = 0%) and for antiphospholipid syndrome (three studies, OR 1.04, 95% CI 0.86-1.25, I 2 = 0%) we found low quality evidence for a lack of a difference in prevalence of abnormal test results between couples with two versus three or more pregnancy losses. We found insufficient evidence of a difference in prevalence of abnormal test results between couples with two versus three or more pregnancy losses for chromosomal abnormalities (10 studies, OR 0.78, 95% CI 0.55-1.10), inherited thrombophilia (five studies) and thyroid disorders (two studies, OR 0.52, 95% CI: 0.06-4.56). WIDER IMPLICATIONS:A difference in prevalence in uterine abnormalities and antiphospholipid syndrome is unlikely in women with two versus three pregnancy losses. We cannot exclude a difference in prevalence of chromosomal abnormalities, inherited thrombophilia and thyroid disorders following testing after two versus three pregnancy losses. The results of this systematic review may support investigations after two pregnancy losses in couples with RPL, but it should be stressed that additional studies of the prognostic value of test results used in the RPL population are urgently needed. An evidenced-based treatment is not currently available in the majority of cases when abnormal test results are present.Key words: recurrent pregnancy loss / investigations / screening tests / diagnostic strategy van Dijk et al.

Characterization of Copy-Number Variations and Possible Candidate Genes in Recurrent Pregnancy Losses

“…In the present study, 14 signaling pathways and 13 genes were identified by enrichment analysis, and 5 of the 13 genes overlapped with the hemoglobin assembly results. One of the consequences of meiosis failure is triploidy, which is a relatively common cause of miscarriage and RPL [40]. The identification of six genes enriched in six signaling pathways in the present may thus be associated with RPL.…”

The effects of chronic endometritis on the pregnancy outcomes

“…RPL was defined as three or more miscarriages. 21 Patients suffering from endocrine and autoimmune diseases, uterine malformation such as septate uterus, multiple myoma, endometrial polyp detected by hysteroscopy, hydrosalpinx detected by ultrasonography or adenomyosis with over a uterine wall >2.5 cm thick at the time that hysteroscopy was performed in order to diagnose CE were excluded from this study. [22][23][24][25][26][27][28][29] Patients who had received ≥7 days of antibiotics for CE treatment were also excluded.…”

Histological diagnostic criterion for chronic endometritis based on the clinical outcome.

“…RIF was defined as the failure of clinical pregnancy after 4 good quality embryo transfers, with at least three fresh or frozen IVF cycles, as per Coughlan et al [19]. RPL was defined as the patient with 3 or more miscarriage [20].…”