Intralipid Infusions During IVF: Hype or Help?

Intralipid infusions remain controversial in the IVF world – perhaps more so than any other treatment add-on. 

Some clinics use them routinely. Others are wary. Patients, caught in the middle, just want the truth. So, let’s take a closer look at intralipids, the evidence behind them, and whether they’re right for you or not.

What an intralipid infusion actually is

Intralipids are immunosuppressants, applied intravenously via a drip. They typically contain soybean oil, egg phospholipids and glycerine. Intralipid infusions have been around since the 1960s. Preterm babies are often given infusions. Patients recovering from major surgery may have them. They’re essentially nutrition boosters.

Fast forward to the new millennium, when IVF specialists noticed something interesting. Intralipid infusions seemed to alter the behaviour of natural killer cells. A theory was formed that an elevated NK-cell count could negatively affect implantation after fertility treatment.

Natural killer cells are part of your immune system’s normal response. They’re present throughout your body, including your uterus. Some doctors thought that overactive NK cells may ‘attack’ an implanting embryo. To guard against this, they suggested that intralipid infusions might suppress that activity, protecting the embryo after its transfer.   

Others asked: really? Why would a mother’s immune system put a pregnancy in jeopardy?

Let’s start at the beginning.              

The early promise of intralipid infusions as IVF rescuer

The initial research was, it must be said, quite encouraging.

A UK study in 2011 was widely reported as bringing fresh hope to IVF patients. Intralipid infusions were given to 50 women who’d experienced multiple unsuccessful IVF cycles. Half became pregnant. The control group, which didn’t receive the infusions, had a higher miscarriage rate.

Small study, from an UK clinic chain. But compelling enough to set the fertility forums alight. And an industry, ready to capitalise in it    

Four years later, more supportive news. A slightly larger, randomised trial into intralipids and repeated implantation failure found that intralipid infusions (at 20% strength) boosted implantation, clinical pregnancy and live birth rates in ICSI patients with past failures.

Over 200 couples took part. Anyone with allergies to eggs and soybean were excluded. As were those with a history of polyps, uterine fibroids, hydrosalpinxes or endometriosis.

Four years on from that, in 2019, another study into intralipids, ICSI and past implantation failure saw similar results. The infusions led to higher implantation and live birth rates. Small study again – just over 100 women. But enough to keep fuelling interest in the infertility community.

There’s more. In a systematic review in 2021, results were pooled from five randomised trials covering 843 women. It found that intralipid infusions given at the time of embryo transfer saw higher clinical pregnancy and live birth rates for women with past implantation failures.     

Finally, a broader review of intralipid therapy from the same year saw improvements in implantation and live birth rates, plus a reduction in the miscarriage rate. This time, there were over 2,000 participants. The researchers concluded that intralipid infusions could be considered for certain patients.        

Now the reality check.

If those five studies were the whole picture, intralipid use in IVF cycles would be commonplace. That hasn’t happened, and here’s why.     

Where the evidence on IVF and intralipids falls apart

The influx of promising data on intralipids for IVF patients was from small trials. This matters. It’s all about numbers. Only large-scale, randomised trials can be trusted to make a stronger case for or against a medical intervention. Fertility treatment is full of small trials. This doesn’t negate all results, but it dilutes their credibility. A lot.   

Credibility, or lack of it, underpinned a randomised controlled trial from 2020. This looked, once again, at unexplained recurrent implantation failure and intralipids. It said the benefits for IVF patients were not significant once studies with a high risk of bias were excluded.

It also highlighted a possible increase in congenital malformations. The safety and efficacy of intralipid infusions, the researchers said, needed more investigation. So, the plethora of small trials on infusions and IVF took another hit.

And another study, from 2024, questioned the effectiveness of intralipid   infusions to improve implantation rates. It expressed an interest, as numerous trials before did, in the biochemical way infusions might help. Interest is one thing; conclusive proof is another. 

The NK cell question behind the intralipid/IVF debate

Everything about infusions and fertility treatment comes back to the same question: do elevated uterine NK cells really threaten embryos? Others may pose the question more bluntly: why on earth would they?

In the field of reproductive immunology, the answers remain elusive. IVF patients can be referred for (expensive) immunology testing. Alongside blood tests, a uterine biopsy is often taken and analysed. The biopsy looks at NK cells and inflammation markers within the endometrium.

But even if the results identity an issue, why and how would infusions help? The arguments for and against them continue. The simple truth is, intralipid infusions in the IVF context sit within a vortex of poor-quality, conflicting evidence. 

Consider the emotional response to these ‘killer’ cells. To be told your womb may be attacking your embryo is a shocking thing to hear. And gold dust for unscrupulous fertility marketeers, who thrive on hope. Anxious patients with several failed cycles behind them are, in one sense, a soft target. 

But critics of add-on treatments, like infusions, have become more vocal around the world. Most add-on treatment don’t work, they say.                 

This doesn’t mean every IVF clinic is deliberately mis-selling infusions.  Many clinics genuinely want to help patients. Most know intralipids are a niche, specific intervention that won’t benefit all patients. But everyone’s aim is to see successful outcomes. Let’s try it, clinics or patients may say. Everyone loves a breakthrough, don’t they?            

What about prednisolone instead of intralipids?

If you’re looking into the immunology side of your reproductive health, you may have heard of prednisolone. It’s a steroid that also alters immune conditions in the uterus. Taken as a daily pill, some patients consider it an easier, cheaper and safer option than a drip. 

Now the bad news. The evidence here isn’t great either. 

A 2023 clinical trial of prednisolone and live birth rates found it had little effect on live birth rates in patients with recurrent implantation failure. Another study into immunosuppressants like prednisolone found the same thing: no benefit.                 

So, prednisolone probably isn’t a better ‘alternative’ to intralipid infusions. Nor is it risk-free. The evidence for its use in IVF doesn’t stack up.

How and when do you take intralipid infusions?

If your clinic includes intralipids in your IVF protocol, you’ll need more than one.

A typical course begins with a first infusion around seven days before egg retrieval, or on it, Then, perhaps a second one close to, or on, embryo transfer day. Many clinics request  a third infusion just after a positive pregnancy test – and more infusions, every three or four weeks, until at least the end of the first trimester.

In frozen embryo cycles, the first infusion is typically applied 7 to 10 days before embryo transfer. the second a week after it, and subsequent ones to a similar schedule as above.

One scheduling tip. The first infusion in an FET cycle may fall on the same day of the first ultrasound scan. Canny patients may choose a provider that can administer both on the same visit.                   

Anecdotally, our clinic includes intralipids in frozen cycles more often than in fresh ones. This may be because frozen cycles are becoming the default approach. Or, possibly, because it doesn’t wish to disturb the careful hormonal balancing act of fresh IVF stimulation. But there’s little evidence infusions work better or worse in fresh or frozen cycles. 

As for application, an intralipid infusion takes one to two hours. It’s fed into your blood stream via a cannula in your arm.

Cost-wise, as with most fertility treatments and add-ons, prices vary. In the UK, expect to pay around £250 per infusion. You could have five or six infusions in one cycle if your get a positive HCG result. Budget carefully.

Safety and side effects of intralipid infusions

Intralipid infusions, whether used in fertility treatment or for another medical reason, are usually well tolerated. But they don’t suit everyone. 

If you have an egg or soya allergy, intralipids aren’t for you. Tell your clinic about any food allergies. Common side effects include headaches, nausea and, less frequently, vomiting. Because it’s an intravenous application, the cannula into your arm may be uncomfortable. But the infection risk is low.

Intralipid infusions and IVF – in summary

Intralipids infusions and IVF are an uneasy double act. The evidence is weak. There may be a case for their use in very specific cases where a known or suspected immunology factor exists alongside previous implantation failure. But, even then, most medics raise eyebrows.

If you have a history of recurrent implantation or miscarriage, talk to your clinic about intralipids, and immunology generally. But be realistic about whether infusions would really make a difference to your IVF treatment.   

Nobody knows if they work or not.