Do IVF add-ons work?

No more than vibes, apparently.

Hello everyone, happy Friday!

This week I read a line in the New York Times that was the journalistic version of a king-sized shit sandwich. The article opens with: “Every year, patients undergo millions of in vitro fertilization procedures worldwide. Only a minority result in a live birth”, followed by around 500 words of unremarkable content. And then it ends with: “Most I.V.F. cycles don’t result in a child”.

Ok, NYT 🎤 Way to ruin a lot of people’s days.

We have actually known this for years, and yet we as individuals cannot conceive of the idea that we might spend $63,000 on the most invasive treatment option out there, and not get the result we want. Against the odds, we dare to be human and hope.

But the numbers don’t lie. In 2022, the most recent year with full federal data, just over 435,000 IVF cycles were done in the US, producing 98,000 babies, which means that 22.5% of IVF cycles in the US result in a baby.

Now, the NYT is writing about fertility because The Lancet just published a very large systematic review of (friend of the show) IVF add-ons.

IVF add-ons are procedures and techniques sold on top of an IVF procedure that are designed to improve the chances of that IVF cycle succeeding. We featured IVF add-ons before, when the UK’s regulator, the HFEA, published their own review and concluded that there is very little evidence for some add-ons, and very little evidence generally that support use of IVF add-ons for improving the live birth rate.

The journal article in The Lancet looks at 10 common IVF add-ons: EmbryoGlue, endometrial scratching, PGT-A, acupuncture, immune treatments, and a few others. What surprised me most was this: 157 studies were eligible for inclusion in this meta review, but 72 were immediately excluded due to major trustworthiness issues. So, in the end, only 85 studies were included in this review. This in itself is astonishing: just over half of all research on IVF add-ons is actually credible.

The other astonishing (but not surprising) finding: almost none of these add-ons have decent evidence behind them. Endometrial scratching, scraping the uterine lining with a small instrument and hoping the resulting minor trauma helps an embryo settle in, showed a modest benefit. EmbryoGlue (a hyaluronic acid-based medium that embryos are transferred in) showed minimal improvement that vanished depending on the statistical model used. PICSI (a supposedly gentler version of ICSI) didn’t help with live birth rates but seemed to show minimal evidence of lowering miscarriage odds. And the other add-ons simply didn’t have enough quality data to draw any conclusions. And in case you’re not confused enough, the HFEA currently rates both endometrial scratching and EmbryoGlue as ‘amber’: which means there is conflicting evidence, and “on balance, it is not clear whether this add-on is effective at improving the treatment outcome”. So even amongst gold-standard research and regulatory bodies, there is divergent opinion on IVF add-ons.

Interestingly, there is a consensus statement, signed by the HFEA and other professional bodies, saying treatments without strong evidence should only be offered as part of research, and that patients should not be charged extra to take part in research.

And yet… 75% of patients will choose and pay for an IVF add-on. This means in 3 out of 4 cases, clinics are ‘selling’ patients add-ons that have no evidence. Dr. Babayev, quoted in the NYT article, says “the demand for add-ons came from desperation”. The demand might come from desperation, but let’s be very clear: our ‘desperate’ demand is gladly met by clinics, despite the lack of data.

Here’s how we think about this at Béa: in the IVF world, two things are profoundly true: 1) the science of IVF is truly magic. I recently watched fertilisation happen in an embryology lab, and it truly was one of the most profound moments of my life to watch life be created. Magical. And 2) the business practice of IVF is… not magic. The majority of IVF cycles today are delivered by clinics which are owned by private equity (PE) investors. That feeling you have when you’re thinking about IVF and feel pushed into it by a clinic, or you’re in the clinic ready for your egg collection and feel like you’re on a factory production line? That’s PE’s influence. As investors, they will push clinics to increase what they care most about: profit (the amount of money each patient pays for an IVF cycle) and growth (the no. of IVF cycles they do each year).

So what does this mean for us, the patients? How do we make sense of all of this?

If you are going for IVF, and wondering how to talk about add-ons with your clinic: be honest, don’t be afraid of asking hard questions. Hopefully, you will find yourself negotiating with your toddler, so honestly, why not get your negotiation skills honed now. Ask your doctor about this Lancet paper. Print it, write your questions on the printout, come in prepared. Ask your doctor to explain very clearly why they recommend an add-on for your case specifically, and what evidence they are relying on to make their recommendation. It may be that choosing an add-on is the right decision for you, and that’s great. But going in blind isn’t great. Knowledge is power. Use it.

For those of us not going into IVF right now, but needing a bit of a lift after a frankly depressing Béa Bulletin (sorry), I encourage you to look up Gen Z’s ‘sunny nihilism’. It’s… vibes.

Take care of yourself this weekend.

Warmly,
Tess

Co-founder & CEO