A groundbreaking meta-analysis published in The Lancet Obstetrics, Gynaecology & Women’s Health offers a comprehensive evaluation of the efficacy and safety of commonly used in vitro fertilisation (IVF) add-ons, revealing that the majority lack conclusive evidence of benefit. This investigation synthesises data from 85 high-quality randomised controlled trials (RCTs) after rigorous vetting for methodological trustworthiness, foregrounding an urgent call for enhanced transparency and scientific rigour in the field of reproductive medicine.
IVF is a vital reproductive technology for individuals experiencing infertility, yet its success rates hover around 30-40% per treatment cycle and decline sharply with advancing maternal age. Over recent years, numerous adjunctive treatments or ‘add-ons’—ranging from pharmaceutical agents to physical procedures—have been incorporated alongside standard IVF protocols, aiming to augment the likelihood of conception and live birth. These add-ons, however, vary widely in their scientific validation and clinical application.
The meta-analysis by Dr. Sarah Lensen and colleagues from the University of Melbourne meticulously filtered out nearly half of potentially eligible RCTs due to significant concerns regarding trial transparency, data integrity, or lack of prospective registration. This stringent exclusion reflects a growing apprehension within reproductive medicine surrounding the overabundance of underpowered, poorly reported, or otherwise untrustworthy studies that may mislead clinical decisions.
Among the ten prevalent IVF add-ons scrutinised, seven showed no demonstrable effect or yielded inconclusive findings attributable to limited or low-quality data. These include acupuncture, corticosteroids for immunomodulation, endometrial receptivity testing—which biopsies the uterine lining to evaluate gene expression patterns thought to affect implantation—, intralipid infusion, platelet-rich plasma injections directly into the ovaries or uterus, and pre-implantation genetic testing for aneuploidies, despite their widespread clinical adoption.
Intriguingly, the meta-analysis identified only three add-ons with weak evidence suggesting potential benefits. EmbryoGlue, an embryonic transfer medium enriched with hyaluronic acid, appeared to marginally increase pregnancy and live birth probabilities, although robustness regarding live birth outcomes remains uncertain. Endometrial scratching, a minor uterine lining procedure postulated to enhance implantation, showed some promise in increasing pregnancy and live birth rates. Physiological intracytoplasmic sperm injection (PICSI), a sperm selection technique based on binding to hyaluronic acid, demonstrated weak evidence for possibly reducing miscarriage risks.
These findings challenge the prevalent use of expensive and invasive adjunct therapies in IVF settings, particularly in the context of private clinics where commercial pressures may influence treatment offerings. Dr. Lensen highlights the ethical and practical implications of administering unproven add-ons, warning of the resultant false hope, financial burdens, and unnecessary medical interventions that can exacerbate the distress of individuals and couples undergoing fertility treatments.
In response to pervasive misinformation surrounding IVF add-ons, exacerbated by commercially driven clinic websites and patient forums on social media, the research team developed the Evidence-based IVF website. This resource delivers impartial, science-backed information designed to empower patients with a clear understanding of the potential benefits, risks, costs, and quality of evidence linked to various add-ons. It represents a novel approach to patient education, seeking to transform informed consent into a truly evidence-informed decision-making process.
A concurrent randomised clinical trial assessed the impact of this new evidence-based platform on patient comprehension. Results demonstrated significant improvements in understanding the nuanced benefits, harms, and evidentiary quality of IVF add-ons relative to conventional online information sources. The majority of surveyed patients relied heavily on IVF clinic websites and social media—platforms known to frequently overstate benefits and downplay risks—highlighting the critical gap this tool addresses.
The study underscores that accurately communicating scientific uncertainty and promoting transparent, trustworthy evidence are paramount in fertility care. The researchers advocate for fertility specialists and clinics worldwide to adopt and endorse such impartial educational resources, aiming for a global uplift in the standard of IVF patient counselling and the minimisation of unwarranted interventions.
Nonetheless, the investigators acknowledge certain study limitations, including the non-validated nature of the TRACT checklist employed to evaluate trial trustworthiness. While designed to exclude unreliable data, this method might inadvertently omit some useful trials. Further, the patient trial was conducted exclusively in Australia, and regional variations in health literacy and educational backgrounds may influence generalisability across different health systems and cultural contexts.
Commenting on this work, Dr. David Barad of the Center for Human Reproduction in New York praises these studies as exemplary of evidence-based fertility care. He emphasizes that claims regarding IVF add-ons must be grounded in trustworthy RCTs, with transparent communication of uncertainty. Moreover, he stresses that patient information should be integral to clinical care rather than an adjunct promotional tool, thereby fostering genuine patient autonomy and informed choice.
This comprehensive examination of IVF add-ons arrives at a pivotal moment when the proliferation of unproven fertility interventions risks undermining patient welfare and public trust. The findings serve as a clarion call for the reproductive medicine community to commit to rigorous, transparent research practices and to prioritize patient-centred communication grounded in the best available scientific evidence.
Subject of Research: People
Article Title: Safety and effectiveness of ten common in-vitro fertilisation add-ons: a systematic review and meta-analysis
News Publication Date: 23-Jun-2026
Web References:
- Evidence-based IVF website: www.unimelb.edu.au/ivf
- Meta-analysis: https://www.thelancet.com/journals/lanogw/article/PIIS3050-5038(26)00054-3/fulltext
- Website impact trial: https://www.thelancet.com/journals/lanogw/article/PIIS3050-5038(26)00114-7/fulltext
References:
- Trustworthiness in Randomised Controlled Trials (TRACT) checklist
- Australian National Health and Medical Research Council funding information
Keywords: In vitro fertilization, IVF add-ons, reproductive medicine, systematic review, meta-analysis, patient information, fertility treatment, evidence-based medicine, clinical trials, EmbryoGlue, endometrial scratching, physiological intracytoplasmic sperm injection, patient education
