IVF add-ons are common in Australia, but there's no proof most work

Deanna Carr's early 20s looked very different to most people's.

"While everyone was travelling Europe and doing all those great things, I was hanging out in IVF clinics," she said.

"It felt very isolating, none of my friends were going through the same thing."

Mrs Carr always wanted to be a young mum, but struggled to fall pregnant naturally.

She was 22 when she started in vitro fertilisation (IVF).

Over the next four years, Mrs Carr had four egg collections, seven embryo transfers and saw multiple specialists, desperate to start the family she and her husband longed for.

Mrs Carr said they were "willing to try anything" to improve their chance of having a healthy baby, including using what's known as IVF add-ons.

These optional add-on therapies — which include steroids, EmbryoGlue, and acupuncture — are offered by clinics to increase someone's chance of IVF success.

Some cost thousands of dollars and significantly increase the out-of-pocket cost for patients.

But a new systematic review and meta-analysis, published today in The Lancet Obstetrics, Gynaecology, & Women's Health, found there's a lack of evidence that most IVF add-ons actually improve the chance of a live birth.

Study author Sarah Lensen, senior research fellow at the University of Melbourne, said IVF add-ons were used by at least 75 per cent of IVF patients in Australia, many of whom echoed similar views as Mrs Carr.

"I remember this patient vividly saying she was so desperate she would have chopped her arm off if it increased her chance of pregnancy,"

she said.

"These patients are desperate, and I guess that's part of why these add-ons are so available and so widely used."

'Weak evidence' for only three add-on therapies

Australia has one of the highest rates of IVF use in the world per capita, with more than 100,000 assisted reproductive technology cycles performed every year.

But Dr Lensen said Australia's IVF success rate remained a "modest" 30–40 per cent, and over the past 10 years a growing number of IVF add-on therapies had become available to patients.

In their review, researchers used data from 85 medical trials to evaluate the safety and effectiveness of 10 common IVF add-ons.

"Ultimately, we found out of the 10 add-ons, for seven there was no evidence that they helped patients having IVF," Dr Lensen said.

"And for three of them, there was some evidence of possible benefit, but there's caveats in each of those cases."

The seven add-ons researchers found had either no effect on fertility or inconclusive results were:

Acupuncture: inserting thin needles into specific points on the body

Corticosteroids: medications to reduce inflammation and suppress the immune system

Endometrial receptivity testing: a biopsy of the uterine lining to assess gene expression patterns

Intralipid infusion: a liquid containing fats administered into the blood

Intraovarian injection of platelet-rich plasma: injecting platelet-rich plasma, made from a patient’s blood, into the ovaries

Intrauterine infusion of platelet-rich plasma: insertion of platelet-rich plasma, made from a patient's blood, into the uterus

Pre-implantation genetic testing for aneuploidy: screening test to check the number of chromosomes in embryos

The study found weak evidence or some possible benefit from three add-ons:

EmbryoGlue: an embryo transfer medium containing hyaluronic acid, a natural substance found in the reproductive tract

Endometrial scratching: a minor procedure undertaken to scratch or disturb the lining of the uterus

Physiological intracytoplasmic sperm injection (PICSI): a technique used to select sperm based on their ability to bind to hyaluronic acid

Australian IVF clinics already aware of limitations

Australian fertility experts say the review's findings come as no surprise, highlighting the need for conversations about the risks and benefits of add-ons before patients use them.

Devini Ameratunga, a Brisbane-based reproductive endocrinologist not involved in the study, said although there was "low evidence" for some add-on procedures, there could be some small benefit for individual clients with specific needs.

For example, she said physiological intracytoplasmic sperm injection (PICSI) — which the review found weak evidence for — could offer some benefit for patients with male fertility issues, but was unlikely to help clients with basic infertility problems.

"I don't think that this [study] means [add-ons] can't be offered, it just allows patients to have open eyes and informed consent," she said.

"The bottom line is that the majority of add-ons don't have good evidence, so you need to be careful if using them."

Dr Ameratunga said IVF add-ons were offered in about three-out-of-four Australian IVF clinics, including hers.

"We do routinely offer some of them, like EmbryoGlue, we think there's enough evidence for that and we take on the cost of that," she said.

Sydney-based fertility specialist and gynaecologist Kath Whitton, who did not contribute to the review, said IVF add-ons had been a hot topic for many years at fertility conferences in Australia and overseas.

Dr Whitton said, based on existing evidence, there wasn't enough data to prove most IVF add-ons were effective, but there were studies currently underway investigating their efficacy.

This research, she added, took time and money.

"IVF and reproductive medicine is quite a young specialty of medicine, we're learning more and more all the time." she said.

"The evidence is getting more robust, but it's not there yet in terms of these add-ons."

Doctors cite commercial, patient pressure

Dr Lensen said there were multiple reasons why add-ons with very little strong evidence behind them were being routinely offered in Australia.

She said some doctors cited "commercial pressure" as a reason for offering add-ons. Most clinics are operated by private providers, with Australia's assisted reproductive technology industry worth about $810 million a year.

But Dr Ameratunga, who works directly with patients, doesn't believe that many — if any — Australian IVF clinics were offering add-ons to make a profit.

One key reason, she said, was pressure from patients themselves who had seen the therapies on social media or via search engines and wanted to try them.

Dr Ameratunga said she often experienced this pressure first-hand, adding that it was typically her patients who approached her asking for a service, not the other way around.

"It's more to do with the fact that everyone wants to get the patient pregnant,"

she said.

Dr Lenson said some fertility specialists continued to offer add-ons as they were available in other clinics, or because they wanted to be the first to offer an experimental treatment of give themselves a "unique selling point".

But even offering add-ons as an optional extra can be seen as "implicit endorsement" of the potential benefit, she said.

And using them could "lead to false hope, greater financial strain and unnecessary medical procedures at what already can be a very difficult time for patients", Dr Lenson added.

New evidence-based IVF website launched

As people undergoing or considering IVF were often desperate and could be vulnerable, Dr Lensen said it was crucial they had access to accurate medical information.

But, she said, two major sources of information for patients undergoing IVF are clinic websites and patient forums on social media, which often contained "misleading" information about add-ons, overstated potential benefits and omitted information about risks and cost.

In a bid to combat misinformation, last year Dr Lensen and her team launched an evidence-based IVF website, hosted by the University of Melbourne, which aims to provide people with impartial information.

A recent evaluation of this website, also published in The Lancet Obstetrics, Gynaecology, & Women's Health, found that Australian IVF patients "felt worse" after reading the information on the site, but had a better understanding of the benefits, risks, and evidence quality of IVF add-ons, compared to the control group that received content generated from high-ranking Google search results.

Mrs Carr was one of the people who helped test and build the website, and is listed as a co-author on the second study.

She said patients undergoing IVF were often "overloaded with conflicting information" and emotionally vulnerable, which made it hard to make an informed choice.

Looking back at her IVF journey, Mrs Carr said it was "deflating" to know she'd paid large amounts of money for therapies not backed by strong evidence, including acupuncture and an intralipid infusion that gave her an allergic reaction.

Co-author of the second study, Genia Rozen, a gynaecologist and fertility specialist at Royal Women's Hospital and Genea Fertility, said IVF patients were making "emotional, expensive and time-sensitive decisions".

"If an add-on does not clearly improve the chance of having a baby, patients deserve to know that," Dr Rozen, who is also a lecturer at the University of Melbourne, said.

"It is about protecting patients from false hope, unnecessary costs and extra interventions that may not help and actually cause harm in some instances.

"Good fertility care should support hope, but it should also be honest."

While not everyone who undergoes IVF has success, 10 months ago, Mrs Carr and her husband welcomed their much-loved and longed-for daughter Amélie.

"She's very busy, she says lots of words now, was crawling at five months and has no time for sleep," Mrs Carr said.

"She took a long time to get here, and now she has to try and do everything all at once."

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