No Benefit From Endometrial Scratching Before IVF: Global Trial

Marlene Busko

January 23, 2019

It is time to stop scratching the endothelium with a pipelle prior to in vitro fertilization (IVF) in an attempt to improve the odds of a live birth, new results from a large pragmatic randomized controlled trial, Pipelle for Pregnancy (PIP), indicate.

The rate of live births was 26.1% among women, regardless of whether or not they had undergone this common add-on treatment to IVF.

In fact, "subgroup analyses did not identify any populations of women who might benefit," lead author Sarah Lensen, PhD, from the University of Auckland, New Zealand, and colleagues report in the study, published online January 24 in the New England Journal of Medicine.

Moreover, this common IVF add-on "was also associated with a mild amount of pain and a small number of adverse events," they note.

"This is far from the first example of a well-intended intervention that in truth has no benefit," Ben W. Mol, MD, PhD, from Monash University, Clayton, Australia, and Kurt T. Barnhart, MD, MSCE, from the University of Pennsylvania, Philadelphia, write in an accompanying editorial.

In contrast to prior studies, the results of the current trial "should be trusted," according to the editorialists, because it was a large, pragmatic trial, conducted in five countries, that examined current procedures in women with either first-time IVF or previous failed IVF.

The "well-conducted" PIP study "underscores that all adjuvants to IVF, and fertility treatments in general, should be evaluated carefully before being offered to infertile couples who may be receptive to anything that might hypothetically increase their chances of having a baby," Mol and Barnhart summarize.

"Endometrial Injury: Widely Adopted, Simple, Cheap Procedure"

An IVF cycle results in a live birth only about 25% to 30% of the time, Lensen and colleagues explain.

To improve this rate, various add-on treatments have been suggested, including purposefully scratching the endometrium to cause an immunologic and inflammatory response that alters the uterine microenvironment. It had been hoped that this would enhance the viability of the transferred embryo.

A Cochrane review of 14 pooled randomized trials of endometrial injury in 2015 appeared to support this practice (odds ratio of a live birth or ongoing pregnancy of 1.42, compared with a sham procedure or no procedure), Mol and Barnhart write. However, the original studies were small, and evidence from other studies was conflicting.

Nevertheless, "this simple and cheap procedure has been widely adopted by infertility specialists and used in tens of thousands of women around the world, for a usual fee between $200 and $500," they note.

And 83% of fertility experts in the United Kingdom, Australia, and New Zealand offer or recommend endometrial scratching, according to Lensen and colleagues.

To investigate this, the PIP trial randomly assigned 1364 women who were undergoing IVF in 13 clinics in Australia, New Zealand, Sweden, Belgium, and the United Kingdom from 2014 through 2017 to the endometrial-scratch group (690) or to the control group (674), which consisted of no intervention.

Women in both groups had similar characteristics; the median age was 35 years, and the median body mass index was 24.

Just fewer than half (46%) were undergoing embryo transfer for the first time, and 30% had undergone two or more previous embryo transfers.

Approximately two thirds of women in both the scratch and the control groups received a fresh embryo. The remainder were implanted with frozen embryos.

The live-birth rate was exactly the same in the endometrial scratch and the control groups (adjusted odds ratio, 1.00).

Moreover, the editorialists note, "there was no suggestion of benefit in any secondary outcome, including clinical pregnancy or miscarriage, nor in subgroups defined by the number of previous IVF cycles or the duration or cause of infertility."

Furthermore, for women in the endometrial-scratch group, the median pain score was 3.5 (on a scale of 1 to 10 in which 10 indicated the worst pain). Fourteen patients experienced adverse reactions: five experienced excessive pain (one presented to the emergency department), seven fainted or felt very dizzy or nauseous, and two experienced excessive bleeding.

So the IVF community "can take solace" in this incidence of harm, say Mol and Barnhart in their editorial.

Selling Snake Oil to Vulnerable Couples?

IVF was 40 years old in 2018, and Mol and Barnhart say that "an unanswered public health question is whether IVF clinics and doctors around the world should continue to offer unevaluated adjuvants, recognizing the likelihood that they will be proven ineffective once properly evaluated and that some might cause harm."

Couples affected by infertility have a strong desire to succeed and have been described as "vulnerable"; in one highly publicized case, a couple became the first in the United Kingdom to sue over misleading information on the effectiveness of adjuvants in IVF.

"The goals of reproductive medicine are the same as those of other fields of medicine," Mol and Barnhart conclude: "provide compassionate and effective care, do no harm, and do not offer false hope or sell snake oil."

The Pipelle for Pregnancy study was funded by the University of Auckland, the A+ Trust, the Auckland District Health Board, the Nurture Foundation, and the Maurice and Phyllis Paykel Trust, all of which are in New Zealand. The financial disclosures of the authors are listed in the original article.

N Engl J Med. Published online January 24, 2019. Abstract, Editorial

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