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Does the fertility industry peddle costly add-on treatments without evidence that they work?
Red light, green light
Many bells and whistles sold by fertility clinics to patients remain unproven. Britain's fertility regulator says that has to change.
The Human Fertilisation and Embryology Authority (HFEA), the body that regulates assisted human reproduction in the UK, published an astonishing document last week. It lists a dozen or so "add-on" treatments offered by fertility clinics, often at high cost, and it grades them, using a traffic light system, according to how useful and safe they are.
Spoiler alert: not one of them got a green.
It’s somehow breathtaking to see a regulator do its job. Equally impressive, eleven key players in the UK fertility sector, including societies of andrologists, embryologists, counsellors, nurses and obstetrician-gynecologists, have signed on to a consensus statement calling for change in the way these extras are offered to patients.
They say they want clinics to be honest with patients when what's being offered is little more than an experimental treatment — and they want clinics to stop charging patients for essentially taking part in clinical trials. Where evidence is still scant, they encourage clinics to share their data in order to add to the evidence base. As well, they remind doctors to always be transparent with patients about the financial and other interests they might have in any technique they are offering.
The HFEA says it looks forward to a future where new treatments will only be available to patients — outside a research setting — after we know that they work and are safe. And it wants to have a serious conversation about who is going to pay for all this.
Kudos to the HFEA. Patients around the world will benefit from this work.
Fries with that?
According to the HFEA's most recent national fertility patient survey, 74 per cent of people who had fertility treatment in the last two years also had at least one kind of treatment add-on. But are they worthwhile or just upsells?
"The only way to be confident that a treatment is effective enough to be used routinely is to carry out a randomized controlled trial (RCT)," explains the HFEA. "In an RCT, patients are assigned randomly to two groups: a treatment group, given the new treatment, and a control group, given either a well-tried treatment or a placebo. The number of patients included is very important, with more patients giving more accurate results. Ideally, several different groups of researchers or scientists should have performed high-quality RCTs and follow-up studies to be sure a new procedure is effective and safe."
The HFEA developed a traffic light system to grade different treatment add-ons:
GREEN means that more than one high quality RCT has shown that the procedure is effective and safe.
AMBER/YELLOW means there is only a small body of evidence, or that the evidence is conflicting. More research is needed.
RED means there is no evidence to show the procedure is effective and safe.
Below, I list ten of the add-ons studied by the HFEA and briefly note the conclusion on each. I highly recommend reading the full descriptions, risk assessments and conclusions published by the HFEA on its website.
Assisted Hatching - RED
"Assisted hatching is not recommended because it has not been shown to improve pregnancy rates."
Artificial egg activation calcium ionophore - AMBER/YELLOW
"There are no RCTs to show that it is effective and there are no follow up studies on the safety of this technique."
Elective freeze all cycles - AMBER/YELLOW
"Research into freeze all cycles is progressing quickly. Some research suggests that pregnancy rates are increased by using frozen embryo transfers rather than fresh transfers, and that the risks to mother and baby are lower. These include the risk of OHSS and of low birthweight. However, at the moment, doctors don't know with enough confidence whether freeze all cycles are safer and more effective... There is currently a large clinical trial of freeze all cycles call E-Freeze" taking place in the UK.
Embryo glue - AMBER/YELLOW
"There is one high quality study... which shows that the use of embryo glue improves pregnancy and live birth rates...Further high quality studies are needed before doctors can be confident."
Endometrial scratching - AMBER/YELLOW
"The current... rating for endometrial scratching is based on a small number of moderate quality studies. There are currently three large clinical trials looking into endometrial scratching and the early findings suggest that the benefits... may be less certain than initially thought."
Pre-implantation genetic screening (PGS) - RED for day three embryos - AMBER/YELLOW for day five embryos
"There is no evidence to show that this type of PGS is beneficial for [women over 37, couples who have had several miscarriages or failed IVF cycles, people with a family history of chromosome problems, or men whose sperm may carry abnormal chromosomes.] In fact, studies have shown that this type of PGS can actually reduce success rates, probably because of damage to the embryo."
"Some small studies have shown that PGS carried out at a later stage... on day five or six, might be helpful in selecting a viable embryo to transfer in younger patients who are typically under 37 with no history of miscarriage or failed IVF cycles... PGS will not increase your overall chances of having a baby. It may help to reduce the likelihood of having a miscarriage..."
Reproductive immunology tests and treatment - RED
[This includes steroids like prednisolone, intravenous immunoglobulin (IVIg), TNF-a blocking agents like adalimumab and infliximab, and intralipid infusions.]
"Not only will reproductive immunology treatments not improve your chances of getting pregnant, there are risks attached to these treatments, some of which are very serious."
Time-lapse imaging - AMBER/YELLOW
"Initial research has shown some promise, but it's still very early days. Indeed, being undisturbed while they grow may improve the quality of the embryos but there's certainly not enough evidence to show that time-lapse imaging improves birth rates..."
Intracytoplasmic morphologic sperm injection (IMSI) - RED
"Systematic reviews suggest that IMSI could be beneficial in specific situations... [but] does not support the use of IMSI over standard ICSI for infertile men."
Physiological intracytoplasmic sperm injection (PICSI) - RED
"There have been a number of studies comparing PICSI with standard ICSI, however there is very little evidence to suggest any benefit of using it. A large randomized study was recently carried out which showed that using PICSI did not increase the chances of having a baby."
"Currently, none of the treatment add-ons we have assessed have been rated green," the HFEA writes. "This means that we don't think any of these techniques should be used routinely."
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