Over the past decade, a growing number of in-vitro fertilisation (IVF) add-on therapies have become available. These IVF therapies are additional procedures, medications, or techniques intended to improve IVF success rates. Existing systematic reviews are outdated, and many include studies with trustworthiness concerns. This meta-review provides comprehensive systematic reviews of ten common IVF add-ons, including a trustworthiness assessment to identify and exclude untrustworthy trials.
In this systematic review and meta-analysis, we searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception up to Jan 13, 2026 for prospectively registered randomised trials that had no serious trustworthiness concerns per the Trustworthiness in Randomised Controlled Trials (TRACT) checklist and compared one or more of the following IVF add-ons with no treatment or placebo in people using IVF: preimplantation genetic testing for aneuploidy (PGT-A); endometrial receptivity testing; corticosteroids; EmbryoGlue; endometrial scratching; physiological intracytoplasmic sperm injection; platelet-rich-plasma injection into the ovary; platelet-rich-plasma infusion into the uterus; acupuncture; and intralipid infusion. The primary outcome was live birth. Studies were evaluated using the Cochrane Risk of Bias 1 tool, and we used the TRACT checklist to identify trustworthiness concerns. The quality of evidence was assessed using the GRADE approach. Two reviewers independently screened and extracted data; disagreements were resolved by discussion. We did meta-analyses with the random-effects method and summarised the effects of the intervention as odds ratios (ORs) and 95% CIs. The protocol of each systematic review was prospectively registered (CD009517, CD007421, CD005996, CD009602, CD005291, CD005291, CD013875, CD006920, CD016209, and CD010461).
Of 12 398 search results, 85 trials were included across the ten systematic reviews and meta-analyses; 72 other potentially eligible studies were excluded for possible trustworthiness concerns, such as the absence of prospective trial registration. For the primary outcome of live birth, endometrial scratching might be associated with a small increase in the chance of live birth (OR 1·20, 95% CI 1·02–1·41; p=0·02; I2=39%; 19 randomised controlled trials [RCTs]; moderate certainty). Four add-ons appeared to have no effect: EmbryoGlue (OR 1·12, 0·91–1·37; p=0·29; I2=47%; seven RCTs; low-certainty evidence); PGT-A (OR 1·16, 0·91–1·47; p=0·23; I2=42%; five trials; moderate certainty); endometrial receptivity testing (three trials; meta-analysis not undertaken; moderate certainty); and corticosteroids (OR 0·95, 0·70–1·27; p=0·71; I2=0%; two trials; moderate certainty). For five add-ons the evidence was unclear because of the poor quality or scarcity of the data: physiological intracytoplasmic sperm injection (OR 1·12, 0·98–1·29; p=0·16; one trial; low certainty); acupuncture (ten trials; very-low certainty); and intralipid (one trial; very-low certainty); platelet-rich plasma injection into the ovary (one trial; very-low certainty); and platelet-rich plasma infusion into the uterus (two trials; very-low certainty).
In this systematic review and meta-analysis we found that most add-ons are not proven to benefit patients going through IVF. In many cases, the quality of evidence was poor, contributing to uncertainty regarding effectiveness, and many studies were excluded for trustworthiness concerns. Well designed, large-scale RCTs are needed to generate reliable evidence on the effect of these interventions.
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