Dual tocolysis with fenoterol and atosiban in human myometrium demonstrates additive effect in vitro

Introduction: A combination of tocolytic agents may be reasonable in order to expand therapeutic options. In vitro studies in rats have demonstrated that the combination of ritodrine with atosiban led to a synergistic inhibition of myometrial contractility. Currently there are no studies in human myometrium.

Materials and methods: Human myometrial biopsies were obtained during elective caesarean sections of singleton pregnancies at term. Stripes were clamped in a myograph and regular spontaneous contractions were set as reference level. Samples were exposed to atosiban, fenoterol, atosiban plus fenoterol or Krebs solution. Inhibition of contractility was expressed as area under the curve (AUC). Contractility was compared using a paired Student's t test. An additive effect of dual tocolysis was assumed when no significant difference occurred between observed and expected inhibition. When inhibition was greater or lower than expected, the dual combination was characterized as synergistic or antagonistic.

Results: Spontaneous contractions (AUC) were reduced by atosiban, fenoterol and the combination atosiban plus fenoterol by 37% (+/-40), 36% (+/-39) and 58% (+/-41), respectively (n = 21). The expected combined tocolytic effect was 50 (+/-47)%. The combined tocolysis was significantly more effective than single treatment with atosiban (p = 0.024) or fenoterol (p = 0.025). The difference between observed and expected inhibition was not statistically significant (p = 0.413).

Conclusion: The combination of a beta-mimetic agent with atosiban seems to have an additive tocolytic effect in spontaneous contractions and has a significantly better effect than fenoterol or atosiban alone.