It’s far to soon to tell patients platelet-rich plasma injections can treat infertility

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Alice Howarthhttps://dralice.blog/
Dr Alice Howarth is a research academic working in pharmacology and therapeutics at the University of Liverpool. She is vice president of the Merseyside Skeptics Society, has written for The Guardian, Breast Cancer Now and is co-host of the skeptical podcast Skeptics with a K. In August 2020 Alice took on the role of deputy editor for The Skeptic.

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Platelet-rich plasma (PRP) injections are all the rage these days, for a lot of things. They’re responsible for the “vampire facial”. They’re the key ingredient of the “O” – an injection into the vagina and clitoris to apparently improve orgasm. They’re also key to the penile equivalent, the “P” shot, where PRP is injected directly into the head of the penis.

PRP is produced by taking a patient’s blood into a test tube and spinning it in a centrifuge. The heavy red blood cells are pulled to the bottom of the test tube and the lighter plasma – made of platelets and white blood cells – is separated up at the top of the tube. This plasma can be removed to a fresh tube and further concentrated by spinning it once more in a centrifuge, so that the heavier platelets coalesce at the very end of the tube as a pellet. Then, the top two thirds of the plasma is removed before recombining the platelet pellet into the remaining plasma.

There are other methods of doing this, one involving spinning the blood at a higher speed so it separates into three fractions – the red blood cell layer, the plasma layer and, between the two, the “buffy coat”, where the white blood cells and the platelets sit together. Then you can remove the plasma from the top layer and very carefully take the buffy coat out separately. I’ve actually done this before in the lab, but it’s tricky because the buffy coat is very sticky and likes to take some red blood cell off with it, if you’re not careful or skilled.

What’s so great about platelet-rich plasma?

Platelets are one of the many different things floating around in our blood. We have red blood cells – the ones that carry oxygen and carbon dioxide around our body. And then we have white blood cells – there’s many different types of those: granulocytes include basophils, eosinophils, neutrophils, and mast cells and agranulocytes which include lymphocytes (those are your T and B cells and your natural killer cells) and monocytes, which can become macrophages. The white blood cells are part of our immune system.

But we also have platelets. Platelets aren’t really cells; they’re more like fragments of cells. They’re made by really big cells that hang out in the bone marrow called megakaryocytes, which grow really fat and then package up some of their insides into pre-platelet structures and then release them. Once they’ve done their job, they get shifted out into the blood and head to the lungs for the lung immune cells (alveolar macrophages) to eat them.

Platelets are important because they help us plug wounds. When you get a wound, any platelets that are already in the area first grab on to the edges of the wound. Pretty much immediately after this happens, a signalling pathway that activates platelets is triggered. At this point, the platelets start to change shape – they send out protrusions, which are like fibres, to allow all the platelets in the area to grab onto each other and aggregate, forming a plug that fills up the wound and prevents bleeding.

Platelets are also full of growth factors, which help stimulate the pathways needed to heal the wound once it’s been temporarily plugged. The theory is that we can use PRP in any situation where we want to promote healing – it’s been trialled for arthritis, rotor cuff damage, and elbow tendinitis for example.

However, those aren’t the applications I want to discuss. I want to talk about the application I found while scrolling the webpages of Goop, when I came across the headline “Is Ovarian Rejuvenation an Effective Fertility Treatment?”. Of course my interest was piqued.

The article, published in May this year, says:

“Platelet-rich plasma (PRP) therapy, which uses your own plasma to try to restore the cells and tissues in your body, is widely used for orthopedics, dentistry, hair growth, and skin care. But its use for ovarian rejuvenation—a procedure where a doctor injects PRP directly into the ovary—is a new frontier in the fertility world.”

I am always hesitant with “new frontiers” when it comes to any medical treatment. I think science is incredible, and has made remarkable strides when it comes to improving healthcare. But it is not magic. It can be a slow process, filled with lots of false starts. There are many exciting treatments that have lots of scientific plausibility that just never pan out. And there are many others that do eventually pan out, but take decades or more to develop. It’s not that I’m cynical about “new frontiers”, it’s just that I’m pragmatic. We need to wait it out until we have more information. And while we are waiting, we need to be careful when it comes to giving patients false hope around these novel treatments.

The Goop article continues:

Pink baby shoes on a bench

Photo by 🇸🇮 Janko Ferlič on Unsplash

“It is both promising and potentially too good to be true: Studied effects include increased chances of conception, improved hormone regulation, and no response at all. It is too early to know definitively whether it’s worth your time and your money. But the early research is certainly intriguing.”

This is precisely where I think we need to be careful. Patients exploring fertility treatments are often particularly vulnerable to the risk of false hope or the weight or expectation and pressure. I don’t think you can add a couple of caveats and think you are absolved of any responsibility. 

That being said – the Goop article is surprisingly balanced. In an article with fewer than 800 words, it mentions the possibility or likelihood of this treatment not working no less than seven times. It’s just hard to know how much their readers will take those caveats into consideration.

Platelet-rich plasma and infertility

A systematic review was published earlier this year in BMC Pregnancy Childbirth, looking at 14 studies to find out more about the potential application of platelet-rich plasma for infertility.  

It concluded:

“Although there was an improvement of baseline hormones (AMH, FSH and E2) after intraovarian injection of PRP, this improvement failed to reach statistical significance (except the improvement of serum AMH analyzed in quasi-experimental studies).”

In other words, there was no improvement in baseline hormones identified, because failing to reach statistical significance means those differences could just be normal variation.

The strongest positive effect the meta-analysis found was an increase in antral follicle count – this is a measure taken by counting the number of follicles visible on the ovaries using ultrasound and is a reasonable measure of fertility, as fertility measures go – we don’t really have any good measures of fertility. But there are a number of limitations to the data in this study.

Firstly, none of the studies were randomised control trials, studies where patients are randomly assigned to either a test group or a control group. There is a high possibility of bias when patient groups aren’t randomised in this way.

Most of the studies didn’t look at “clinically significant outcomes such as pregnancy and live birth rates” – and as I said before, we don’t have great fertility measures. The best way to measure someone’s fertility is to look at the pregnancies or births.

Where studies did report pregnancy and births, they didn’t compare the results to pre-treatment measures, or controls. So, we can’t actually know if there’s been an increase or not.

All 14 studies were very variable in their study design, baseline hormonal levels, timing of PRP injection, the time for the outcomes assessment and reporting of outcomes. This makes it very hard to compare the results across these studies.

For me, the take-home message from this review is that it’s far, far too early to say anything about PRP intra-ovarian PRP injections. What we have is almost as good as no data. It might be enough to encourage further studies, but we shouldn’t be offering false hope to patients that this is a potential treatment, or one they might have access to any time soon.

Too often, we’re too quick to share the next big possibility when it comes to helping patients and we don’t question whether doing so is ethical or reasonable. I work in open research – I believe in making research accessible, but that also means we have to work hard to contextualise it, and avoid sensationalising it.

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