Science1 publisher2 min readPublished
Meta-analysis rates seven of ten popular IVF add-ons unproven for live birth
Seven of 10 popular IVF add-ons showed little to no effect, or only mixed and low-quality evidence, on live-birth odds in a recent meta-analysis. One US patient who used several of them estimates she has spent close to $200,000 on fertility treatment.
The Scientist · Science desk
What happened
- Only endometrial scratching, PICSI sperm selection and EmbryoGlue showed any evidence of a possible benefit among the ten add-ons reviewed.
- PGT-A embryo screening, endometrial receptivity testing and corticosteroids had little to no impact on the odds of a live birth.
- Surveys in the UK and Australia indicate that at least three quarters of IVF patients try add-ons at some point in their treatment.
Compiled by The ScientistSomething wrong?How this is made
Why it matters
- cost Insurance generally does not cover IVF, so the price of an add-on with no demonstrated live-birth gain falls on the patient, on top of a US base cost that often runs to tens of thousands of dollars.
- decision A clinic selling PGT-A now has to justify it against a review that found little to no live-birth effect, and patients have a specific question to ask of any extra: what did it do to live births in trials?
- constraint Candid doctors did not stop a well-informed patient from buying long-shot extras, so evidence summaries are likely to change what clinics offer more than what patients decline.
The review judged each add-on by the odds of a live birth [2]. Dowling's history shows why that endpoint matters. She was pregnant in December 2022, miscarried in January 2023, and then miscarried again [12]. "I wasn't just worried about getting pregnant anymore. I was terrified of losing another pregnancy," she said [13]. About one in five pregnancies end in miscarriage [14]. A pregnancy rate and a live-birth rate are different measures. Ozone therapy, one of her add-ons, was advertised as improving the odds of pregnancy [19].
The seven add-ons that fell short did so in different ways [1]. For the three with little to no impact on live birth, the evidence points to little or no effect [2]. Acupuncture, intralipid infusions and platelet-rich plasma injected into the uterus and ovaries had mixed or low-quality evidence [3]. For those four the effect is still unknown, and Scientific American notes that the results do not prove the treatments ineffective [6]. The three with a possible benefit cleared only a low bar [4]. Scientific American's account does not report effect sizes or name the review's authors. "Most add-ons are not proven to benefit patients going through IVF," the authors wrote [5].
The uptake figure needs a denominator. It comes from surveys in the UK and Australia and counts patients who tried an add-on at any point in their treatment [7]. So it is neither a US figure nor a rate per cycle.
Compare Dowling's purchases with the review and two of them appear by name: PGT-A in the little-to-no-effect group and acupuncture in the mixed group [2]. Growth hormone injections and ozone therapy are not among the ten add-ons the article lists [2].
Dowling did ask for proof. She is a lawyer and her husband is a physician. They searched PubMed for clinical trials, consulted fertility experts and talked to other people who had been through IVF [15]. Her doctors told her some add-ons might help some people while others would see no benefit [16], and she knew many of the ones she used were not guaranteed to improve her chances [20]. Turning down something that might help, even at low or unknowable odds, felt "impossible," she said [17]. The add-ons helped her feel she had "left no stone unturned," she said [18].
What to watch
- Effect sizes and trial counts behind the three 'possible benefit' add-ons, endometrial scratching, PICSI and EmbryoGlue, once the review's details are public.
- US survey data on add-on uptake, since the three-quarters figure comes from the UK and Australia.
- New trials measuring live birth for the four add-ons with mixed or low-quality evidence: acupuncture, intralipid infusion and uterine and ovarian PRP.