Podcast: Growth factor-supplemented culture media for women undergoing assisted reproduction

The Cochrane Gynaecology and Fertility Group has produced more than 80 reviews on assisted reproduction and continues to add to these. In July 2020, they added a new review on the use of growth-factor supplemented culture media and we asked the lead author, Sarah Armstrong from the University of Sheffield in the UK to tell us what they found.

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Monaz: Hello, I'm Monaz Mehta, editor in the Cochrane Editorial and Methods department. The Cochrane Gynaecology and Fertility Group has produced more than 80 reviews on assisted reproduction and continues to add to these. In July 2020, they added a new review on the use of growth-factor supplemented culture media and we asked the lead author, Sarah Armstrong from the University of Sheffield in the UK to tell us what they found.

Sarah: Assisted reproduction, be it IVF or ICSI, provides infertile couples with the chance to become parents, but despite it being over 40 years since the first baby was born from IVF, the chance of taking home a baby has plateaued at approximately 30% per cycle. A number of 'add-on’ treatments have been developed to try to improve livebirth rate from assisted reproduction, of which growth-factor supplemented culture media is one.
IVF or ICSI involves a series of steps that culminates in the transfer of an embryo into a woman. One important step in this process is embryo culture, where a fertilised egg is first placed into a solution called culture media, to incubate for 2 to 5 days. In recent years, culture media supplemented with a growth factor commonly called GM-CSF, have been developed. This is based on findings from initial animal and human embryo studies that GM-CSF improved the growth of embryos and reduced apoptosis, which is also known as programmed cell death. GM-CSF supplemented culture media has entered fertility clinics across the globe and is often recommended for women with recurrent biochemical pregnancy loss or miscarriage, recurrent implantation failure, unexplained infertility or advanced maternal age. 
We did this review, therefore, to explore the effectiveness and safety of GM-CSF supplemented culture media compared to culture media that has been not supplemented with GM-CSF. 
We found five randomised trials but could only include three of these in our meta-analysis, which allowed us to use data from approximately 1500 women.
This very low to low quality evidence shows that GM-CSF supplemented culture media might be no more or less effective than culture media not supplemented with GM-CSF for important outcomes, including live birth, miscarriage, clinical pregnancy, multiple gestation, preterm birth, birth defects and aneuploidy, which is where the baby has an abnormal number of chromosomes. 
We also looked specifically at the two randomised trials that included 200 women who had suffered recurrent miscarriage or implantation failure. This allowed us to explore whether our conclusions were different in these women, but we found that these subgroup analyses do not change our conclusions or support the claim that GM-CSF supplemented culture media improves the outcomes of IVF in these women.
In conclusion, it’s important that clinicians, embryologists and women considering using GM-CSF supplemented culture media are aware that the available evidence neither supports nor opposes its use. Also, given the uncertainty around the effects of this type of culture media, independent information on the available evidence needs to be made easily accessible to those considering using it and we need more well designed, large studies to increase the certainty of our conclusions.

Monaz: If you would like to read more about the existing evidence and to watch for an update to this review if these new studies become available, you can find the review online. It’s at Cochrane Library dot com and can be retrieved with a simple search for 'GM-CSF for assisted reproduction'.

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