Use of Atosiban in in Vitro Fertilization (IVF) Treatment

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Randomized Double Blind Comparison of Atosiban in Patients Undergoing in Vitro Fertilization Treatment

Conditions
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Subfertility

Intervention / Treatment
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* Drug: Atosiban
* Drug: Normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age < 43 years Normal uterine cavity shown on ultrasound scanning Exclusion Criteria: Age >=43 Three previous IVF cycles Use of donor oocytes Natural IVF or IVM cycles Abnormal uterine cavity on ultrasound scanning ET canceled because of absent fertilization or risk of ovarian hyperstimulation syndrome Blastocyst transfer Undergoing preimplantation genetic diagnosis Recruited in the same study before

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 43 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Atosiban<br> | Drug: Atosiban<br>* 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.<br>* Other names: Tractocile;|
| Placebo Comparator: Placebo<br>Normal saline | Drug: Normal saline<br>* Normal saline given<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| live birth rate |  | 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ongoing pregnancy rate |  | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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atosiban, in vitro fertilization, subfertility