No Evidence for Increased Prevalence of JAK2 V617F in Women with a History of Recurrent Miscarriage

Abstract Myeloproliferative neoplasms (MPN) have been associated with increased rates of pregnancy complications. Women with essential thrombocythemia (ET), and, much less frequently, polycythemia vera (PV) present at a childbearing age and it has been reported that up to a third of MPN pregnancies may fail as first trimester miscarriages. A recent study has demonstrated that the JAK2 V617F mutation, seen in nearly all PV cases and half of those with ET, was significantly more common in women with a first unexplained pregnancy loss compared to controls, although the overall incidence was low (1.06% of women with a first unexplained pregnancy loss versus 0.2% in controls, p<0.001). We hypothesized that JAK2 V617F may be further enriched in women who had multiple miscarriages. We studied peripheral blood leukocyte DNA from 389 women who had suffered at least three consecutive spontaneous early miscarriages (<10 weeks gestation) or at least one late pregnancy loss (>10 weeks) by a tetra-primer amplification refractory mutation system (ARMS) polymerase chain reaction (PCR) assay with a sensitivity of detection of 1% JAK2 V617F. 92% of women had a history of early miscarriage and 14.1% of late miscarriage. Detailed clinical information was available for 230 (59%) cases: the mean age was 35.9 years (standard deviation=5.4; range: 20–50) and the median number of miscarriages was 3 (range: 3–7). Factors known to be associated with recurrent miscarriages were excluded. The JAK2 V617F mutation was not detected in any case, yielding a 95% confidence interval for the prevalence of the mutation ranging from 0 to 0.009 and excluding a 1% prevalence of JAK2 V617F in this population (p=0.038 for the overall population; p=0.057 for early miscarriages only; 2-tailed Clopper-Pearson exact test). Our study therefore demonstrates no enrichment of JAK2 V617F among unselected women with a history of recurrent miscarriages. Although we cannot exclude the possibility of a small, significant excess of V617F over background levels, our findings indicate that a latent maternal JAK2 V617F-positive MPN is an unlikely cause of miscarriage.