A hormone procedure commonly offered to IVF patients globally as an ’add-on’ does not improve chances of falling pregnant, according to an international analysis led by the University of Sydney.
The study, published in Human Reproduction Update, found that intrauterine administration of the hormone human chorionic gonadotropin (hCG) before embryo transfer does not increase pregnancy or live birth rates.
The hormone procedure is used internationally, including in Australia, the United States, Europe and parts of Asia, and has been promoted since the early to mid-2010s to improve implantation during IVF, largely based on earlier studies that reported positive effects.
However, when the researchers looked in detail at the raw data behind these studies, rather than on published results, they found that claims about the positive effects of the hormone procedure do not stack up.
“For patients and clinicians, the message is clear: this add-on does not improve fertility outcomes,” said Dr Rui Wang, lead author and Academic Lead of Evidence Integration Group at the NHMRC Clinical Trials Centre.
“This hormone shouldn’t be routinely offered as part of IVF treatment.”
Unpicking the data
Instead of relying on published results from clinical trials, the researchers conducted an individual participant data meta-analysis, which involved collecting and re-analysing raw, de-identified data from each patient involved in all clinical trials on this topic.
Out of 28 randomised trials conducted across multiple countries — including the United States, Austria, Thailand and Japan — that tested intrauterine hCG before embryo transfer, seven high-quality trials involving 2,244 IVF patients met the criteria for analysis.
The researchers found that the procedure did not improve live birth rates or clinical pregnancy rates, and that this was that case across all subgroups of patients studied.
“There was no evidence of benefit in any group we analysed, including fresh or frozen transfers, different embryo stages, or different doses,” Dr Wang said.
Earlier reviews had suggested intrauterine hCG was one of the most promising IVF add-ons, reporting significant improvements in pregnancy rates. These findings were widely cited and influenced clinical practice.
According to Dr Wang, most trials reporting positive effects failed basic trustworthiness checks.
“When we restricted the analysis to studies where the raw data could be reviewed and verified, the effect disappeared completely,” he said.
The findings highlight growing concerns about unreliable or untrustworthy trial data in women’s health research, particularly in areas where evidence is rapidly translated into clinical care.
For patients and clinicians, the message is clear: this add-on does not improve fertility outcomes.
Dr Rui Wang
NHMRC Clinical Trials Centre, Faculty of Medicine and Health
What this means for patients
In Australia, intrauterine hCG typically costs around $50 to $100 per procedure. While relatively inexpensive compared to the overall cost of IVF, it is not always clearly listed or itemised by clinics, and patients may combine it with multiple other add-ons across repeated treatment cycles.
“Every procedure offered to patients should be backed by reliable evidence,” said Dr Wang. “When patients are already going through multiple IVF cycles, adding procedures with no proven benefit is an unnecessary burden on people navigating an already difficult journey.”
Experts say many IVF patients choose add-ons in the hope of even a small improvement in their chances, often under significant emotional pressure and uncertainty about what treatments are supported by robust evidence.
“Patients deserve access to accurate, reliable evidence,” Dr Wang said. “This study is about supporting informed decision-making, not blaming clinics or patients.”
A call for better evidence in IVF
The researchers say the findings may be the tip of the iceberg, pointing to a wider problem within reproductive medicine where some treatments and add-ons are adopted into practice based on unreliable evidence.
“Many IVF add-ons look promising on paper because early studies report benefits,” Dr Wang said. “But if those studies are flawed or the data can’t be verified, patients may be making decisions based on evidence that doesn’t hold up.”
The study highlights how conclusions drawn from traditional systematic reviews can be distorted when they rely on untrustworthy trials, and why analysing raw participant-level data is critical.
“Systematic reviews are only as good as the studies they include,” Dr Wang said. “When we analyse the original data from real patients, we get a much clearer picture of what actually works, what doesn’t, and where uncertainty remains.”
The researchers say applying this approach more widely could help identify which IVF interventions work for whom, and those that offer little or no benefit, protecting patients from unnecessary procedures and ensuring treatment decisions are based on the strongest possible evidence.
Research
Wang, Rui et al., ‘Intrauterine human chorionic gonadotropin administration before embryo transfer (IHABT): an individual participant data meta-analysis of randomised controlled trials’, Human Reproduction Update (2026)
DOI: 10.1093/humupd/dmag009
Declaration
Dr Rui Wang is supported by a National Health and Medical Research Council Emerging Leadership Investigator Grant.
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