SubfertilityPhase 4NCT01501214
Use of Atosiban in in Vitro Fertilization (IVF) Treatment
A Phase 4 study testing Atosiban and Normal saline in people with Subfertility, run by The University of Hong Kong at 2 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 43 years, women only
- Conditions the study is for
- Subfertility
- What is being tested?
- Atosiban and Normal saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 800 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Dec 2011to Dec 2013
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 43 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Age < 43 years
- Normal uterine cavity shown on ultrasound scanning
Who cannot join
- 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
Show all 9Show fewer
- Blastocyst transfer
- Undergoing preimplantation genetic diagnosis
- Recruited in the same study before
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
China1 site
Reproductive Medical Center of Nanfang Hospital
Guangzhou, Guangdong, 510515
About this study
Official title: A Randomized Double Blind Comparison of Atosiban in Patients Undergoing in Vitro Fertilization Treatment
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.
Read the 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.
- Conditions
- Subfertility
- Being tested
- Atosiban, Normal saline
- Keywords
- atosiban, in vitro fertilization, subfertility
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtosibanDrug
Also called Tractocile
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 salineDrug
Normal saline given
| Study group | Role | What they receive |
|---|---|---|
| Atosiban | Active comparator | Not described Receives: Drug: Atosiban |
| Placebo | Placebo comparator | Normal saline Receives: Drug: Normal saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
live birth rate
Measured: 9 months
Secondary outcomes (1)
Ongoing pregnancy rate
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2011 (estimated)
- Study startDec 2011
- Primary completionDec 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for SubfertilityStudies of the same condition, open and under way.
- More trials run by The University of Hong KongThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 800 participants (actual)
Sponsor and investigators
- Lead sponsor
- The University of Hong Kong
- Sponsor type
- University, hospital or other
- Collaborators
- Vietnam National University, Nanfang Hospital, Southern Medical University
- Responsible party
- Sponsor
- Investigators
- Ernest HY Ng, MD, Principal investigator, The University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01501214
- Sponsor's protocol ID
- HKUQMHCARE001
- Status last verified
- Jan 2014
- First submitted
- 20 Dec 2011
- Last updated
- 7 Jan 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Ayoubi JM, Epiney M, Brioschi PA, Fanchin R, Chardonnens D, de Ziegler D. Comparison of changes in uterine contraction frequency after ovulation in the menstrual cycle and in in vitro fertilization cycles. Fertil Steril. 2003 May;79(5):1101-5. doi: 10.1016/s0015-0282(03)00179-1.
PubMed 12738502Bernabeu R, Roca M, Torres A, Ten J. Indomethacin effect on implantation rates in oocyte recipients. Hum Reprod. 2006 Feb;21(2):364-9. doi: 10.1093/humrep/dei343. Epub 2005 Nov 10.
PubMed 16284067Blockeel C, Pierson R, Popovic-Todorovic B, Visnova HA, Garcı´a-Velasco HA, Mra´zek M, Barri PN, Pierzynski P, Kuczynski W, Devroey P, Breinholt V, Erichsen L, Klein BM, Arce JC. Effects of barusiban and atosiban on frequency of uterine contractions in the luteal phase after stimulation: a randomized placebo controlled trial. Hum. Reprod. 24 (Suppl. 1), i26, 2009.
Fanchin R, Ayoubi JM. Uterine dynamics: impact on the human reproduction process. Reprod Biomed Online. 2009;18 Suppl 2:57-62. doi: 10.1016/s1472-6483(10)60450-6.
PubMed 19406033Fanchin R, Righini C, Olivennes F, Taylor S, de Ziegler D, Frydman R. Uterine contractions at the time of embryo transfer alter pregnancy rates after in-vitro fertilization. Hum Reprod. 1998 Jul;13(7):1968-74. doi: 10.1093/humrep/13.7.1968.
PubMed 9740459Liedman R, Hansson SR, Howe D, Igidbashian S, McLeod A, Russell RJ, Akerlund M. Reproductive hormones in plasma over the menstrual cycle in primary dysmenorrhea compared with healthy subjects. Gynecol Endocrinol. 2008 Sep;24(9):508-13. doi: 10.1080/09513590802306218.
PubMed 18958771Moon HS, Park SH, Lee JO, Kim KS, Joo BS. Treatment with piroxicam before embryo transfer increases the pregnancy rate after in vitro fertilization and embryo transfer. Fertil Steril. 2004 Oct;82(4):816-20. doi: 10.1016/j.fertnstert.2004.02.140.
PubMed 15482753Pierson R, Deptuch JJ, Invik J, Klein BM, Breinholt V, Arce JC. Reproducibility of uterine contractility assessments based on transvaginal ultrasound cine-loop recordings. Hum. Reprod. 24 (Suppl. 1), i103, 2009.
Pierzynski P, Gajda B, Smorag Z, Rasmussen AD, Kuczynski W. Effect of atosiban on rabbit embryo development and human sperm motility. Fertil Steril. 2007 May;87(5):1147-52. doi: 10.1016/j.fertnstert.2006.08.089. Epub 2007 Jan 16.
PubMed 17224148Richter ON, Kubler K, Schmolling J, Kupka M, Reinsberg J, Ulrich U, van der Ven H, Wardelmann E, van der Ven K. Oxytocin receptor gene expression of estrogen-stimulated human myometrium in extracorporeally perfused non-pregnant uteri. Mol Hum Reprod. 2004 May;10(5):339-46. doi: 10.1093/molehr/gah039. Epub 2004 Mar 25.
PubMed 15044599Tsirigotis M, Pelekanos M, Gilhespie S, Gregorakis S, Pistofidis G. Ritodrine use during the peri-implantation period reduces uterine contractility and improves implantation and pregnancy rates post-ivf. Hum. Reprod. 15, (Abs. Bk 1), O-024, 10, 2000.
Vedernikov Y, Betancourt A, Shi S, Shi L, Reinheimer T, Garfield R. (2006) Oxytocin antagonistic effect of barusiban and atosiban in isolated uterine artery from late pregnant rats. In: Annual scientific meeting of the Society for Gynecologic Investigation. Toronto, Canada.
Visnova H, Coroleu B, Piro M, Blockeel C, Mrazek M, Arce JC. Barusiban and atosiban for reduction of uterine contractions on day of embryo transfer do not alter the endocrine profile at time of implantation. Hum. Reprod. 24 (Suppl. 1), i178, 2009.
Ng EH, Li RH, Chen L, Lan VT, Tuong HM, Quan S. A randomized double blind comparison of atosiban in patients undergoing IVF treatment. Hum Reprod. 2014 Dec;29(12):2687-94. doi: 10.1093/humrep/deu263. Epub 2014 Oct 21.
PubMed 25336707
Study at a glance
From the registry record, last updated by the sponsor on 7 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Double Blind Comparison of Atosiban in Patients Undergoing in Vitro Fertilization Treatment
- ClinicalTrials.gov ID
- NCT01501214
- Acronym / sponsor ID
- HKUQMHCARE001
- Conditions
- Subfertility
- Keywords
- atosiban, in vitro fertilization, subfertility
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 800 participants (actual)
- Lead sponsor
- The University of Hong KongUniversity, hospital or other
- Collaborators
- Vietnam National University, Nanfang Hospital, Southern Medical University
- Study start
- Dec 2011
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 29 Dec 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Atosiban | Active comparator | Drug: Atosiban |
| Placebo | Placebo comparator | Drug: Normal salineNormal saline |
Who may qualify
- Ages
- 18 to 43 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Age < 43 years
- Normal uterine cavity shown on ultrasound scanning
Key exclusion criteria (9 listed)
- Age >=43
- Three previous IVF cycles
- Use of donor oocytes
- Natural IVF or IVM cycles
- Abnormal uterine cavity on ultrasound scanning
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AtosibanAlso: TractocilePatients 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. | Drug | Atosiban |
| Normal salineNormal saline given | Drug | Placebo |
Primary outcome
live birth rate
Time frame: 9 months
1 secondary outcome
Ongoing pregnancy rate
Time frame: 3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jan 2014.
- Background: PubMed 12738502Ayoubi JM, Epiney M, Brioschi PA, Fanchin R, Chardonnens D, de Ziegler D. Comparison of changes in uterine contraction frequency after ovulation in the menstrual cycle and in in vitro fertilization cycles. Fertil Steril. 2003 May;79(5):1101-5. doi: 10.1016/s0015-0282(03)00179-1.
- Background: PubMed 16284067Bernabeu R, Roca M, Torres A, Ten J. Indomethacin effect on implantation rates in oocyte recipients. Hum Reprod. 2006 Feb;21(2):364-9. doi: 10.1093/humrep/dei343. Epub 2005 Nov 10.
- BackgroundBlockeel C, Pierson R, Popovic-Todorovic B, Visnova HA, Garcı´a-Velasco HA, Mra´zek M, Barri PN, Pierzynski P, Kuczynski W, Devroey P, Breinholt V, Erichsen L, Klein BM, Arce JC. Effects of barusiban and atosiban on frequency of uterine contractions in the luteal phase after stimulation: a randomized placebo controlled trial. Hum. Reprod. 24 (Suppl. 1), i26, 2009.
- Background: PubMed 19406033Fanchin R, Ayoubi JM. Uterine dynamics: impact on the human reproduction process. Reprod Biomed Online. 2009;18 Suppl 2:57-62. doi: 10.1016/s1472-6483(10)60450-6.
- Background: PubMed 9740459Fanchin R, Righini C, Olivennes F, Taylor S, de Ziegler D, Frydman R. Uterine contractions at the time of embryo transfer alter pregnancy rates after in-vitro fertilization. Hum Reprod. 1998 Jul;13(7):1968-74. doi: 10.1093/humrep/13.7.1968.
- Background: PubMed 18958771Liedman R, Hansson SR, Howe D, Igidbashian S, McLeod A, Russell RJ, Akerlund M. Reproductive hormones in plasma over the menstrual cycle in primary dysmenorrhea compared with healthy subjects. Gynecol Endocrinol. 2008 Sep;24(9):508-13. doi: 10.1080/09513590802306218.
- Background: PubMed 15482753Moon HS, Park SH, Lee JO, Kim KS, Joo BS. Treatment with piroxicam before embryo transfer increases the pregnancy rate after in vitro fertilization and embryo transfer. Fertil Steril. 2004 Oct;82(4):816-20. doi: 10.1016/j.fertnstert.2004.02.140.
- BackgroundPierson R, Deptuch JJ, Invik J, Klein BM, Breinholt V, Arce JC. Reproducibility of uterine contractility assessments based on transvaginal ultrasound cine-loop recordings. Hum. Reprod. 24 (Suppl. 1), i103, 2009.
- Background: PubMed 17224148Pierzynski P, Gajda B, Smorag Z, Rasmussen AD, Kuczynski W. Effect of atosiban on rabbit embryo development and human sperm motility. Fertil Steril. 2007 May;87(5):1147-52. doi: 10.1016/j.fertnstert.2006.08.089. Epub 2007 Jan 16.
- Background: PubMed 15044599Richter ON, Kubler K, Schmolling J, Kupka M, Reinsberg J, Ulrich U, van der Ven H, Wardelmann E, van der Ven K. Oxytocin receptor gene expression of estrogen-stimulated human myometrium in extracorporeally perfused non-pregnant uteri. Mol Hum Reprod. 2004 May;10(5):339-46. doi: 10.1093/molehr/gah039. Epub 2004 Mar 25.
- BackgroundTsirigotis M, Pelekanos M, Gilhespie S, Gregorakis S, Pistofidis G. Ritodrine use during the peri-implantation period reduces uterine contractility and improves implantation and pregnancy rates post-ivf. Hum. Reprod. 15, (Abs. Bk 1), O-024, 10, 2000.
- BackgroundVedernikov Y, Betancourt A, Shi S, Shi L, Reinheimer T, Garfield R. (2006) Oxytocin antagonistic effect of barusiban and atosiban in isolated uterine artery from late pregnant rats. In: Annual scientific meeting of the Society for Gynecologic Investigation. Toronto, Canada.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ernest HY Ng, MD principal investigator
The University of Hong Kong
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Atosiban and Normal saline in people with Subfertility, run by The University of Hong Kong at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China, Vietnam. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
live birth rate (time frame: 9 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01501214, which also lists 14 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jan 2014.