Mark Dempsey

Perinatal outcomes of women with a prior history of unexplained recurrent miscarriage

Abstract Objective: We sought to determine subsequent pregnancy outcomes in a cohort of women with a history of unexplained recurrent miscarriage (RM) who were not receiving medical treatment. Study design: This was a prospective cohort study, of women with a history of three unexplained consecutive first trimester losses, who were recruited and followed in their subsequent pregnancy. Control patients were healthy pregnant patients with no previous adverse perinatal outcome. Results: A total of 42 patients with a history of unexplained RM were recruited to the study. About nine (21.4%) experienced a further first trimester miscarriage, one case of ectopic and one case of partial molar pregnancy. About 74% (23/31) of the RM cohort had a vaginal delivery. There was one case of severe pre-eclampsia. The RM group delivered at a mean gestational age of 38 + 2 weeks and with a mean birthweight of 3.23 kg. None of the neonates were under the 10th centile for gestational age. Overall, there was no significant difference in pregnancy outcomes between the two cohorts. Conclusion: Our study confirms the reassuring prognosis for achieving a live birth in the unexplained RM population with a very low incidence of adverse events with the majority delivering appropriately grown fetuses at term.

Platelet function in patients with a history of unexplained recurrent miscarriage who subsequently miscarry again.

OBJECTIVE This study was designed to evaluate platelet aggregation in pregnant women with a history of unexplained recurrent miscarriage (RM) and to compare platelet function in such patients who go on to have either another subsequent miscarriage or a successful pregnancy. STUDY DESIGN A prospective longitudinal study was performed to evaluate platelet function in a cohort of patients with a history of unexplained RM. Platelet reactivity testing was performed at 4-7 weeks gestation, to compare platelet aggregation between those with a subsequent miscarriage and those who had successful live birth outcomes. Platelet aggregation was calculated using a modified assay of light transmission aggregometry with multiple agonists at different concentrations. RESULTS In a cohort of 39 patients with a history of RM, 30 had a successful pregnancy outcome while nine had a subsequent miscarriage again. Women with subsequent miscarriage had reduced platelet aggregation in response to adenosine diphosphate (P value 0.0012) and thrombin receptor activating peptide (P value 0.0334) when compared to those with successful pregnancies. Women with subsequent miscarriages also had a trend towards reduced platelet aggregation in response to epinephrine (P value 0.0568). CONCLUSION Patients with a background history of unexplained RM demonstrate reduced platelet function if they have a subsequent miscarriage compared to those who go on to have a successful pregnancy.

An overview of platelet function in normal and complicated pregnancies

The pregnant state must achieve a fine balance between hemorrhage and thrombosis. Platelets play a critical role in this balance yet there is a lack of clear knowledge and consensus about platelet function in pregnancy. This review will outline the mechanisms involved in platelet clot and thrombus formation, delineate the different techniques available for the assessment of platelet function and highlight the current understanding of platelet function in pregnancy. With respect to normal pregnancy, there appears to be an increase in platelet aggregation when compared with the nonpregnant state. In pregnancies complicated by pre-eclampsia and intrauterine growth restriction, platelets are further activated when compared with normal pregnancy. Platelet function testing in those with recurrent miscarriage suggests a tendency toward thrombosis. However, further studies are needed to clarify platelet function status in normal and complicated pregnancy.

Reduced spontaneous platelet aggregation: a novel risk factor for adverse pregnancy outcome

OBJECTIVE Spontaneous platelet aggregation has not been adequately assessed as a potential risk factor for adverse outcomes in pregnancy. Therefore the objective of this study was to assess spontaneous platelet aggregation (SPA), measured via a novel functional assay, as a risk factor for hypertensive disease and intra-uterine growth restriction (IUGR). STUDY DESIGN This was a prospective longitudinal study. Spontaneous platelet aggregation was assessed as a marker of platelet reactivity using a modification of light transmission aggregometry. Platelet reactivity was assessed in four groups: non-pregnant healthy female volunteers (n=30), longitudinally in normal uncomplicated pregnancy (n=50), hypertensive disorder (n=40) and IUGR (n=30). The mean percentage SPA was plotted and compared across all groups. RESULTS Spontaneous platelet aggregation was significantly reduced in the first trimester compared to the non-pregnant group (p-value=0.003). The mean aggregation for the hypertensive group was 1.9%, (95% CI -0.08 to 4.02) and for the IUGR group was 1.6%, (95% CI -0.6 to 3.72). Platelet aggregation in the hypertensive group was significantly reduced compared to the normal pregnant group (p<0.05). Spontaneous platelet aggregation was also reduced in the IUGR group compared to normal pregnancy (p<0.05). CONCLUSION This study demonstrates that a reduction of spontaneous platelet aggregation may be a novel risk factor for adverse pregnancy outcomes such as pre-eclampsia and IUGR. The most clinically significant finding is that SPA is significantly lower in pregnancies complicated by hypertension and IUGR compared to those who had a normal pregnancy outcome. Further studies should be carried out to asses if spontaneous platelet aggregation may be a clinically useful tool for the prediction of pre-eclampsia and IUGR.

PF.11 Abnormal Platelet Function is Seen in Women with Unexplained Recurrent Miscarriage During Pregnancy

Objective To evaluate platelet aggregation in patients with a history of recurrent miscarriage (RM) during a subsequent successful pregnancy and compare them to healthy pregnant controls. Study design A prospective longitudinal study was performed to compare platelet function in 30 patients with a history of three consecutive unexplained first trimester pregnancy losses and 30 healthy age-matched pregnant controls. Exclusion criteria included the use of anti-platelet medications such as aspirin and medical conditions that can affect platelet function. Light transmission aggregometry was used to assay platelet agonists at different times and concentrations to create dose-response curves. Results In contrast, to the increased platelet aggregation response seen in healthy controls, platelet reactivity in patients with RM peaked at 12–14 weeks gestation, highlighted by the increased aggregation response to epinephrine (p = 0.0008) and collagen (p < 0.0001) and then decreased in the third trimester in response to epinephrine (p < 0.0001), arachidonic acid (p < 0.0001) and Thrombin Receptor Activating Peptide (p < 0.0001). Conclusion Patients with a history of recurrent miscarriage have significantly different platelet function when compared to healthy controls, in particular during the first trimester. Knowledge of which patients have impaired platelet function may allow for more targeted therapy in the setting of recurrent miscarriage.

PP.36 The Impact of Unexplained Recurrent Miscarriage on Subsequent Pregnancy Outcomes

Aim We sought to determine subsequent pregnancy outcomes in a cohort of women with a history of unexplained recurrent miscarriage (RM) as compared to healthy pregnancy controls. Study design This was a prospective cohort study of women attending a dedicated RM clinic in the Rotunda Hospital in 2011. Inclusion criteria included women with a history of three consecutive first trimester losses that were unexplained in the past, no medical intervention and singleton pregnancies only. The inclusion criteria for the healthy controls included no history of stillbirth, intrauterine growth restriction, preeclampsia or preterm labour. Results Of the 42 women with RM recruited to the study nine (23%) experienced further first trimester miscarriages, one molar and one ectopic pregnancy. The remaining RM cohort with ongoing pregnancies (n = 31) were compared to healthy controls (n = 31) matched for age and BMI. The only statistical difference between the two groups was the earlier mean gestational delivery of the RM group (38 + 2 vs 39 + 4 weeks, p = 0.004) attributed to earlier induction due to their past history. Otherwise there was no significant difference with respect to pregnancy complications, delivery and neonatal outcomes. All of RM patients achieved successful term deliveries with a 74% vaginal delivery rate and a mean birthweight of 3.23 kg. Conclusion This study re-iterates the reassuring prognosis for women with a history of unexplained RM who undergo supportive care at a dedicated clinic. The majority delivered appropriately grown fetuses at term which was comparable to healthy controls.