Use of Atosiban in in Vitro Fertilization (IVF) Treatment
Condition: Subfertility
MeSH terms: Infertility
Study type: Interventional
Phase: Phase 4

Summary: 
      The hypothesis of this randomized double blind study is that the live birth rates are
      significantly higher after the use of atosiban prior to the embryo transfer in patients
      undergoing in vitro fertilization (IVF) treatment. This study aims to compare the live birth
      rates of IVF treatment between patients receiving atosiban and placebo prior to the transfer.
    

Detailed description: 
      In-vitro fertilization-embryo transfer (IVF-ET) treatment involves multiple follicular
      development following ovarian stimulation, oocyte retrieval and ET after fertilization.
      Despite recent advances in ovarian stimulation, the method of assisted fertilization and
      improved culture conditions, the implantation potential of embryos remains around 20-25% for
      a long time.

      ET is the final step of an IVF cycle and its success depends on the embryo quality, the
      endometrial receptivity and uterine contractions. Uterine contractions play an important role
      in embryo implantation (Fanchin, 2009) as excessive uterine contractions may expel embryos
      from the uterus and decrease the implantation potential of embryos (Fanchin et al., 1998).

      Ovarian stimulation is used in the great majority of IVF programs so that multiple embryos
      are available for selection and transfer. However, supraphysiological concentrations of
      oestradiol following ovarian stimulation may induce endometrial production of oxytocin,
      formation of oxytocin receptors, and indirectly formation/release of PGF2a (Richter et al.,
      2004; Liedman et al., 2008). It has been shown that uterine contractile activity in IVF
      cycles is increased by approximately 6-fold when measured before ET as compared with the
      situation before ovulation in the natural cycle (Ayoubi et al., 2003). Fanchin et al. (1998)
      have estimated that about 30% of patients undergoing ET have pronounced uterine contractions.
      Uterine contractions can also be triggered after excessive cervical manipulation in difficult
      transfer procedure (Fanchin et al., 1998).

      Drugs to inhibit increased uterine contractions at the time of ET are an attractive approach
      to improve the IVF success. However, the use of beta agonists or non-steroid
      anti-inflammatory drugs has not been shown to provide sufficient benefit (Bernabeu et al.,
      2006; Moon et al., 2004; Tsirigotis et al., 2000). Uterine contractions involve oxytocin and
      therefore inhibition of oxytocin receptors may improve the IVF success by decreasing uterine
      contractions, interfering with PGF2a/oxytocin systems and possibly improving endometrial
      perfusion (Vedernikov et al., 2006).

      Atosiban, a combined oxytocin/vasopressin V1A antagonist, is currently registered for
      clinical use in women suffering from preterm labour. In a multicentre, randomized,
      placebo-controlled trial, it has been shown to reduce the frequency and amplitude of uterine
      contractions in egg donors when compared with placebo (Blockeel et al., 2009; Pierson et al.,
      2009; Visnova et al., 2009). There was a lack of an embryotoxic effect of atosiban in
      concentrations up to 50-fold therapeutic blood concentrations (Pierzynski et al., 2007).
      Atosiban did not affect the survival of 1-cell rabbit embryos, nor decrease the percentage of
      hatched rabbit blastocysts. The human sperm motility bioassay also showed no adverse
      influence.
    

Intervention name(s): Atosiban; Normal saline
Intervention type(s): Drug; Drug
Intervention description(s): Patients in the atosiban group will receive intravenous atosiban 30 min before the transfer with a bolus dose of 6.75 mg, and the infusion will be continued with an infusion rate of 18 mg/h. After performing ET, the dose of atosiban will be reduced to 6 mg/h and the infusion will be continued for 2 hours (total administered dose: 37.5 mg). Those in the placebo group will receive normal saline only.; Normal saline given
Other intervention name(s): Tractocile
Intervention MeSH terms: Atosiban
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: atosiban; in vitro fertilization; subfertility