Clinical trial NCT02305420: EmbryoGen/ Blastgen for Couples With Implantation Problems or Previous Miscarriage
Official title: EmbryoGen/ Blastgen for Couples With Implantation Problems or Previous Miscarriage
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Recurrent Miscarriage
Infertility
Lead sponsor: FertilitySA
Sponsor class: INDUSTRY
Collaborators: name: University of Adelaide
First posted: 2014-12-02
Enrollment: 100
Sex: FEMALE
Minimum age (years): 25
Maximum age (years): 41
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Randomised control trial comparing EmbryoGen/ BlastGen media use with standard media in IVF
Primary purpose: TREATMENT

Brief summary: EmbryoGen and BlastGen contain the cytokine growth factor Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF), which has been documented to give significant benefit to this difficult group of patients.

Results showed a highly significant effect of 44% relative improvement in ongoing implantation rate (p=0.001) in women who have previously miscarried (Ziebe et al 2013).

We wish to undertake a randomised Controlled trial to determine if EmbryoGen/BlastGen media improves pregnancy outcomes in women with recurrent implantation failure, recurrent miscarriage and poor embryo development when compared to standard media.

Detailed description: A randomised control pilot study will be undertaken for 100 women who have implantation failure (≥ 2 embryo transfers without a pregnancy) or at least 1 previous miscarriage and are having a further IVF cycle.

At oocyte retrieval each couple will be randomised using numbered envelopes containing pre randomised group allocations by a person uninvolved in the trial to:

1. BlastGen Group (n=50): culturing their embryos in ORIGIO standard, sequential culture mediums for 3 days (EmbryoGen included) then BlastGen media (GM-CSF containing media) for remaining 2 days or
2. Standard Media Group (n=50): culturing their embryos in Cook standard sequential medium for 5 days.

The best single embryo will be transferred on day 5.

The clinical staff and participating couple will be blinded as to whether BlastGen or standard media was used in culture to day 5. Fertility SA embryologists will not be blind as to which study group a couple is in and which media is being used. The embryos will be cultured using the usual methods and lab facilities by Fertility SA's current embryology staff members who will not be blind to the media being used.

Records on the outcome of the oocyte fertilisation, blastocyst development, implantation rate and pregnancy rates will be recorded, as is standard practice. Pregnancy scans will be carried out at 7 and 12 weeks. Live birth outcomes and any congenital anomalies will be recorded.

Eligibility criteria: Inclusion Criteria:

* women undertaking an IVF or ICSI cycle

  * aged between 25 and 41 years
  * 2 or more embryos transferred without a positive pregnancy outcome OR a history of at least 1 previous pregnancy loss, OR
  * Poor embryo development (\<20% of embryo developing on time at Day 3 or no blastocyst above Grade 2 on Day 5)

Exclusion Criteria:

* male partner requiring surgical retrieval of sperm except in cases of previous vasectomy
* the use of another investigational drug within 30 days
* any severe chronic disease that would significantly influence an IVF cycle
* less than 3 follicles\>14mm on ultrasound on the day of HCG trigger

Primary outcomes:
measure: Livebirth >20 weeks
timeFrame: 9 months after closure of trial (18 +9 months)
Secondary outcomes:
measure: Congenital Anomaly Rate
timeFrame: 9 months after closure of trial (18 +9 months)
measure: Clinical pregnancy rates at 7 and 12 weeks gestation
timeFrame: 18 months
measure: Number of embryos reaching blastocyst stage
timeFrame: 18 months
measure: Day 3 and day 5 embryo scores
timeFrame: 18 months
measure: Cryopreservation outcomes
timeFrame: 18 months
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: FertilitySA
state: South Australia
Study officials:
References:
citation: Rose RD, Barry MF, Dunstan EV, Yuen SM, Cameron LP, Knight EJ, Norman RJ, Hull ML. The BlastGen study: a randomized controlled trial of blastocyst media supplemented with granulocyte-macrophage colony-stimulating factor. Reprod Biomed Online. 2020 May;40(5):645-652. doi: 10.1016/j.rbmo.2020.01.011. Epub 2020 Jan 23.