What is the Impact of Consecutive versus Non-consecutive Losses?

Background: The risk of a new pregnancy loss increases with the number of previous pregnancy losses in patients with recurrent pregnancy loss (RPL). It is unknown whether the sequence of pregnancy losses plays a role for the prognosis in patients with a prior birth.

Objective: To investigate whether there a different prognostic impact of consecutive vs. non-consecutive pregnancy losses in women with secondary RPL.

Methods: Retrospective cohort study of pregnancy outcome in patients with unexplained secondary RPL included in three Danish placebo-controlled trials of intravenous immunoglobulin. No other treatments were given. Six patients with documented explained pregnancy losses (ectopic pregnancies and aneuploid miscarriages) were excluded.

Of the patients included in the trials, 127 had secondary RPL and experienced a subsequent live birth or unexplained pregnancy loss in the first pregnancy after giving informed consent to participation in the trials (the index pregnancy). Data were analyzed by multivariate analysis including the independent variables: age; number of early pregnancy losses before and after the last birth, respectively and a second trimester pregnancy loss before or after the last birth, respectively. The outcome variable was unexplained loss in the index pregnancy.

Results: In patients with secondary RPL, both a late and each early loss before the last birth did not influence the risk of pregnancy loss in the index pregnancy: Incidence rate ratio (IRR) 1.31 (95% CI 0.62-2.77) and 0.88 (95% CI 0.70-1.11), respectively. In contrast, the impact on risk of pregnancy loss conferred by a late and each early pregnancy loss occurring after the birth was significant: IRR 2.15 (95% CI 1.57-2.94, p<0.0001) and 1.14 (95% CI 1.04-1.24, p=0.002), respectively.

Conclusions: A birth in women with RPL eradicates the negative prognostic impact of previous pregnancy losses and this finding is important for our understanding of the pathogenesis. It indicates that only consecutive pregnancy losses should count in the definition of RPL.