Preconceptional low-dose aspirin for the prevention of hypertensive pregnancy complications and preterm delivery after IVF: a meta-analysis with individual patient data.

STUDY QUESTION: Does preconceptionally started low-dose aspirin prevent hypertensive pregnancy complications and preterm delivery in IVF patients? SUMMARY ANSWER: The current data do not support the use of preconceptionally started low-dose aspirin treatment for the prevention of hypertensive pregnancy complications and preterm delivery in IVF women. WHAT IS KNOWN ALREADY: Studies starting low-dose aspirin treatment as prevention in the second trimester of pregnancy found no or only moderate reductions in the relative risk of developing pre-eclampsia. Low-dose aspirin was possibly started too late, that is after the first episode of trophoblast invasion. STUDY DESIGN, SIZE, DURATION: We performed a meta-analysis with individual patient data (IPD), in which four authors could provide IPD on a total of 268 pregnancies (n = 131 treated with aspirin, n = 137 placebo). Data on hypertensive pregnancy complications and preterm delivery were collected. PARTICIPANTS/MATERIALS, SETTING, METHODS: All separate databases were merged into a summary database. Treatment effect of aspirin on the incidence of hypertensive pregnancy complications (n = 187) and preterm delivery (n = 180) were estimated with odds ratios (OR) and 95% confidence intervals (95% CI) using multivariable logistic regression. MAIN RESULTS AND THE ROLE OF CHANCE: There were significantly fewer twin pregnancies in the aspirin group (OR 0.55 95% CI 0.30-0.98), but no significant differences for hypertensive pregnancy complications and preterm delivery: for singletons OR 0.62 (95% CI 0.22-1.7) and OR 0.52 (95% CI 0.16-1.7), respectively, as well as for twin pregnancies OR 1.2 (95% CI 0.35-4.4) and OR 1.6 (95% CI 0.51-5.0), respectively. LIMITATIONS, REASONS FOR CAUTION: We have to bear in mind that the included studies showed clinical heterogeneity; there was variation in the duration of low-dose aspirin therapy and degree of hypertension between the different studies. Although we combined IPD from four studies, we have to realize that the studies were not powered for the outcome of the current IPD meta-analysis. WIDER IMPLICATIONS OF THE FINDINGS: Based on the current meta-analysis with IPD we found no confirmation for the hypothesis that preconceptionally started low-dose aspirin reduces the incidence of hypertensive pregnancy complications or preterm delivery in IVF women. Larger studies are warranted.

Low-dose aspirin reduces uteroplacental vascular impedance in early and mid gestation in IVF and ICSI patients: a randomized, placebo-controlled double-blind study.

OBJECTIVE: To determine whether low-dose aspirin improves uteroplacental hemodynamics in unselected in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) subjects when medication is started concomitantly with controlled ovarian hyperstimulation. METHODS: Thirty-seven pregnant women who had undergone IVF/ICSI and had been randomized to receive 100 mg aspirin (n = 17) or placebo (n = 20) daily, started concomitantly with controlled ovarian hyperstimulation, were included in this study. Doppler ultrasound examination was performed at 6, 10, 13 and 18 weeks' gestation. Uterine artery (UtA) pulsatility index (PI) was calculated and bilateral UtA notching was noted. Subplacental arcuate artery PI was obtained at 6 and 10 weeks' gestation. Umbilical artery (UA) PI and mean velocity were calculated at 10, 13 and 18 weeks' gestation. In the aspirin group there was one early pregnancy miscarriage, and one patient discontinued the study medication owing to early pregnancy bleeding. A total of 15 women in the aspirin group and 20 women in the placebo group underwent the complete ultrasound protocol. RESULTS: At 6 weeks' gestation, arcuate artery PI and at 18 weeks' gestation, UtA PI were lower (P < 0.05) in the aspirin group than in the placebo group. At 18 weeks' gestation, bilateral UtA notching tended to be more common in the placebo group (40%) than in the aspirin group (13%) (P = 0.06). UA PI and mean velocity did not differ significantly between the groups. CONCLUSION: Low-dose aspirin reduces uteroplacental vascular impedance in early and mid pregnancy in unselected IVF/ICSI subjects when medication is started concomitantly with controlled ovarian hyperstimulation.

Significance of retrograde diastolic uterine artery blood flow during regional anesthesia in instrumented pregnant sheep.

BACKGROUND: We studied the interactions between uterine and placental hemodynamics during maternal hypotension in chronically instrumented fetal sheep. In addition, we investigated maternal hemodynamic characteristics, fetoplacental hemodynamics and fetal acid-base status when a retrograde diastolic uterine artery blood flow pattern is present during maternal hypotension. METHODS: Invasive maternal and fetal hemodynamic parameters, uterine (Q(UtA)) and placental (Q(UA)) volume blood flows and acid-base values were examined in 24 chronically instrumented sheep at baseline and during epidural-induced maternal hypotension at 117-132 (term 145) days of gestation. Uterine artery blood flow velocity waveforms were obtained by Doppler ultrasonography. RESULTS: Maternal hypotension decreased Q(UtA) without affecting Q(UA). During hypotension, eight out of 24 sheep demonstrated a retrograde diastolic blood flow velocity waveform pattern in the uterine artery. Maternal systolic, diastolic and mean arterial blood pressures were significantly lower in the retrograde group than in the antegrade group. No statistically significant differences in Q(UtA), Q(UA) and fetal blood gas values were detected between the two groups during hypotension. CONCLUSIONS: An acute decrease in uterine artery volume blood flow during maternal hypotension is not compensated by increased placental volume blood flow. A retrograde diastolic blood flow pattern in the uterine artery is related to lower maternal arterial pressures, especially during diastole. A uterine artery retrograde diastolic blood flow pattern does not have any additional detrimental short-term effects on fetal acid-base status.

Is aspirin effective in women undergoing in vitro fertilization (IVF)? Results from an individual patient data meta-analysis (IPD MA).

BACKGROUND: Aspirin is believed to improve the outcome of IVF, but previous conventional meta-analyses on the subject are conflicting. Therefore, we performed a meta-analysis with individual patient data (IPD MA) of randomized clinical trials (RCTs) on the subject. METHODS: A systematic literature search was conducted to identify RCTs assessing the effectiveness of aspirin in IVF. Authors were asked to share their original data. In a one step meta-analytic approach, the treatment effect of aspirin was estimated with odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression, based on the intention to treat principle. RESULTS: Ten studies fulfilled the inclusion criteria. Authors of six studies provided IPD, including 1119 patients (562 placebo and 557 aspirin). There were 160 clinical pregnancies in the aspirin (28.8%) and 179 (31.9%) in the placebo group [OR 0.86, 95% CI (0.69-1.1)]. There were 129 ongoing pregnancies in the aspirin (23.6%) and 147 in the placebo group (26.7%) [OR 0.85, 95% CI (0.65-1.1)]. Whereas the conventional meta-analysis limited to studies that could provide IPD showed an OR of 0.89 (95% CI 0.69-1.2), the conventional meta-analysis limited to the eight studies of which method of randomization could be confirmed showed an OR of 0.94 (95% CI 0.76-1.17) and the conventional meta-analysis including all 10 eligible RCTs identified with our search changed the OR to 1.07 (95% CI 0.81-1.41). This difference in direction of effect, derived from the studies not able to share IPD of which quality of randomization could not be confirmed. CONCLUSIONS: Aspirin does not improve pregnancy rates after IVF.