Every year, patients undergo millions of in vitro fertilization procedures worldwide. Only a minority result in a live birth.
In an effort to improve the odds, scientists have developed an array of “add-ons” that could in theory identify the most robust eggs, sperm and embryos or make the uterine lining more hospitable. Some patients pay thousands of dollars for these procedures, on top of the high costs of I.V.F.
But a study published Tuesday found no indication that most of these add-ons work.
“There isn’t great evidence that most I.V.F. add-ons help patients to get pregnant and have a baby,” said Sarah Lensen, a senior research fellow at the University of Melbourne and lead author of the study, which was published in The Lancet Obstetrics, Gynecology and Women’s Health.
Only three of the 10 add-ons the researchers examined were supported by high-quality studies.
One of these was endometrial scratching, in which the uterine lining is scratched to try to make it more receptive to an embryo. The authors concluded it “might be associated with a small increase in the chance of live birth.”
A technique called physiological intracytoplasmic sperm injection, or PICSI, which purports to identify the best sperm, appeared to lower the chance of miscarriage — but its effect on live births was not clear.
Some of the analyses the researchers ran suggested that EmbryoGlue, a product advertised as helping embryos to implant, might increase the probability of pregnancy and live birth. But another did not suggest any benefit.
Corticosteroid drugs, biopsies to determine the best time for embryo implantation and chromosomal screening of embryos showed no apparent impact on live births. And for the remaining add-ons included in the study — acupuncture, an infusion of a fatty substance called intralipid, injection of platelet-rich plasma into the ovaries and infusion of it into the uterus — there wasn’t enough reliable data to draw conclusions.
It’s possible that some add-ons do have benefits, but no one has done the necessary research to know, said Pedro Melo, a co-author of the study and a senior fellow in women’s and reproductive health at the University of Oxford. What is needed, he said, is more funding for high-quality studies that include large numbers of patients; otherwise, “we may find ourselves without evidence that would shift the needle.”
Without solid evidence that they improve the odds of a live birth, it is harder to justify some of these methods, since they are expensive and can come with risks, Dr. Melo said.
Corticosteroids, for example, suppress the immune system, and procedures that involve injecting or infusing a medication into an organ can, in rare cases, lead to abscesses or other complications.
The researchers created a website that lays out the evidence related to each add-on. Dr. Lensen said they planned to search for new studies every six months and update the site accordingly.
Diana Laird, a professor of obstetrics, gynecology and reproductive sciences at the University of California, San Francisco, who was not involved in the study, described it as rigorous and thorough. She said she was “unpleasantly surprised” by the findings, which she called “hugely disappointing for patients.”
Because many insurance plans don’t cover I.V.F. add-ons, many people are paying out of pocket and “having to make decisions which have, until now, been not well-informed,” Dr. Laird said — not because fertility clinics intentionally mislead patients, she added, but because individual providers don’t have the time or resources to systematically analyze studies.
The researchers screened thousands of studies but identified only 85 strong enough to rely on for their analysis. Many others weren’t randomized controlled trials, or looked at only a small number of patients. In other cases, some studies had serious methodological flaws, the statistical analysis contained errors or contradictions or their authors did not register them in advance.
Registration establishes the methods researchers will use, the outcomes they will measure and how they will define success. Without it, Dr. Melo said, there is no way to know whether the authors changed course midway through and, for example, decided to measure a different outcome.
Elnur Babayev, an assistant professor of obstetrics and gynecology at Northwestern University who was not involved in the study, said the demand for add-ons came from desperation. Most I.V.F. cycles don’t result in a child. Doing multiple cycles increases the odds, but also the costs, and many women still won’t get pregnant. Patients are eager for something to improve their chances, and clinicians want to offer it.
But while there may be specific groups of people for whom a particular add-on could be appropriate, Dr. Babayev said, “this should not be routinely offered to every I.V.F. patient.”
