EmbryoGen/ Blastgen for Couples With Implantation Problems or Previous Miscarriage

Study Overview
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Brief Summary
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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
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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: 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 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.

Official Title
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EmbryoGen/ Blastgen for Couples With Implantation Problems or Previous Miscarriage

Conditions
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Recurrent Miscarriage, Infertility

Intervention / Treatment
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* Device: EmbryoGen/ BlastGen media
* Device: Standard Cook sequential media


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 41 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: Crossover Assignment
Interventional Model Description: Randomised control trial comparing EmbryoGen/ BlastGen media use with standard media in IVF
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EmbryoGen/BlastGen<br>EmbryoGen and BlasGen media containing GM-CSF 2ng/ml will be used in the experimental arm The intervention is to use EmbryoGen/BlastGen | Device: EmbryoGen/ BlastGen media<br>* Embryos will be cultured in media containing Gm-CSF (EmbryoGen/ BlastGen media)<br>* Other names: GM-CSF containing media;|
| Active Comparator: Control<br>Standard Cook sequential media | Device: Standard Cook sequential media<br>* Standard Cook IVF media will be used in the control arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Livebirth >20 weeks | Any delivery >20 resulting in a livebirth | 9 months after closure of trial (18 +9 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Congenital Anomaly Rate | number of liveborns with a congenital anomaly | 9 months after closure of trial (18 +9 months) | 
| Clinical pregnancy rates at 7 and 12 weeks gestation | Fetal Heart Beat seen on Ultrasound scan at 7 and 12 weeks | 18 months | 
| Number of embryos reaching blastocyst stage | Number of blastocysts per cycle | 18 months | 
| Day 3 and day 5 embryo scores | grade of day 3 and day 5 embryos | 18 months | 
| Cryopreservation outcomes | Number of Frozen blastocysts | 18 months |