Most IVF 'add-ons' show little evidence of boosting births, researchers find

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There is a lack of evidence to suggest the majority of in vitro fertilization (IVF) add-ons improve fertility in patients undergoing IVF, according to a systematic review and meta-analysis published in The Lancet Obstetrics, Gynaecology, & Women's Health. There is weak evidence for some possible benefit from three IVF add-ons: EmbryoGlue, endometrial scratching and physiological intracytoplasmic sperm injection.

Many people with infertility use IVF; however, the probability of having a baby following IVF is only approximately 30%–40% per cycle and decreases significantly with age.

Over the past decade, many "add-on" therapies—extra procedures, medicines or techniques used in addition to standard IVF with the aim of increasing the chance of success—have become available. The use of IVF add-ons is widespread; more than 70% of IVF patients in Australia, New Zealand and the U.K. report using one or more add-ons during IVF treatment.

Author Dr. Sarah Lensen, University of Melbourne (Australia), says, "In many countries, infertility care is largely provided by private clinics where IVF is highly commercialized, and some add-ons are extremely expensive. Our review finds a lack of evidence that most of the IVF add-ons we assessed provide any benefit to patients.

"Unproven add-ons can lead to false hope, greater financial strain and unnecessary medical procedures at what can already be a very difficult time for patients. IVF clinics and clinicians should carefully consider whether it is appropriate to offer unproven add-ons, as their availability is often perceived by patients as an implicit endorsement of benefit."

Trustworthy trials narrowed the field

There has been growing concern about the prevalence of problematic or untrustworthy randomized controlled trials within reproductive medicine, including those looking at IVF add-ons. The aim of this meta-analysis was to provide a comprehensive overview of the effectiveness and safety of 10 common IVF add-ons, limited to high-quality studies with no trustworthiness concerns.

Of 157 potentially eligible trials, 72 were excluded on trustworthiness grounds. Authors pooled data from the remaining 85 trials assessed to be trustworthy and looked at the effectiveness of 10 widely used IVF add-ons for which patients have expressed a strong demand for evidence-based information.

Most add-ons lacked solid support

The study found either no effect on fertility or inconclusive results due to limited or low-quality data for the following seven IVF add-ons:

  • Acupuncture—inserting thin needles into points on the body
  • Corticosteroids—medication to reduce inflammation and suppress immune system activity
  • Endometrial receptivity testing—a biopsy of the uterine lining to assess gene expression patterns
  • Intralipid infusion—a liquid containing fats (soybean oil and egg yolk) that is administered into the blood
  • Intraovarian injection of platelet-rich plasma—injecting platelet-rich plasma, made from a patient's own blood and containing a higher concentration of blood platelets than normal blood, into the ovaries
  • Intrauterine infusion of platelet-rich plasma—insertion of platelet-rich plasma into the uterus
  • Pre-implantation genetic testing for aneuploidy—a screening test to check whether embryos have the expected number of chromosomes

The review found weak evidence of some possible benefit from three IVF add-ons:

  • EmbryoGlue—an embryo transfer medium containing hyaluronic acid, a natural substance found in the reproductive tract that is considered important for embryo implantation. The evidence review found it may increase the probability of pregnancy and live birth; however, the effect on live birth rates was not robust.
  • Endometrial scratching—a minor procedure undertaken to scratch or disturb the lining of the uterus. The review finds this procedure may increase the probability of pregnancy and live birth.
  • Physiological intracytoplasmic sperm injection (PICSI)—a technique used to select sperm based on their ability to bind to hyaluronic acid, which may be a sign that the sperm is mature and capable of fertilizing an egg. There is weak evidence this may lower the risk of miscarriage.

A clearer source for patients

To address the widespread availability of poor-quality information about IVF add-ons, Lensen and her team developed the Evidence-based IVF website, providing patients with impartial, evidence-based information to help them make decisions about using IVF add-ons.

In a second study, also published in The Lancet Obstetrics, Gynaecology, & Women's Health, a randomized controlled trial found the impartial website improved patients' understanding of the benefits, risks and evidence quality of IVF add-ons, compared with typical online information about these add-ons.

The study also found 92% of the IVF patients surveyed in Australia relied heavily on IVF clinic websites for information, and more than 60% of patients reported using social media platforms such as Facebook and Reddit for information to guide their IVF decision-making.

Lensen says, "There is widespread misinformation about IVF add-ons, with private clinic websites and patient forums on social media—major information sources for patients—often overstating the benefits and omitting the costs and risks of add-ons.

"Our trial shows an evidence-based website, free from commercial interests, increased understanding and information satisfaction among IVF patients, addressing a clear unmet need. Although developed in Australia, the evidence is applicable to IVF patients globally, and we hope to see this new resource endorsed and used by fertility specialists, clinics and patients around the world."

Previous IVF patient and author on the website trial Deanna De Cicco says, "When you are going through IVF you can be so overloaded with conflicting information, add in some intense emotions and it can be almost impossible to make a properly informed decision. This website really helps by giving patients an easy way to access the facts in a digestible way, helping to guide them to make a well-informed personal choice."

Limits and a broader standard

The researchers note some limitations of their studies, including recognizing that the TRACT checklist used to measure trustworthiness in the meta-analysis has not been validated and it is possible that some of the excluded trials provide reliable data.

For the trial looking at the website, authors note that all participants were living in Australia, meaning there may be differences from other regions in characteristics such as education and health literacy, which may limit generalizability to other settings.

Writing in a linked Comment, Dr. David Barad from the Center for Human Reproduction, New York, who was not involved in the study, says, "These ... papers are a case study in what evidence-based fertility care ought to look like. Claims should be judged against trustworthy trials; uncertainty should be communicated clearly, not concealed beneath optimistic language; and patient information should be treated as part of the clinical intervention, not as a marketing accessory."

More information

Safety and effectiveness of ten common in-vitro fertilisation add-ons: a systematic review and meta-analysis, The Lancet Obstetrics, Gynaecology, & Women's Health (2026). DOI: 10.1016/S3050-5038(26)00054-3 www.thelancet.com/journals/lan … (26)00054-3/fulltext

The Lancet Obstetrics, Gynaecology, & Women's Health (2026). www.thelancet.com/journals/lan … (26)00114-7/fulltext

Clinical categories

Obstetrics & gynecologyReproductive healthWomen's health Provided by Lancet Who's behind this story?

Sadie Harley

BSc Life Sciences & Ecology. Microbiology lab background with pharmaceutical news experience in oil, gas, and renewable industries. Full profile →

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