Developing a core outcome set for future infertility research: an international consensus development study

Duffy JMN; AlAhwany H; Siladitya Bhattacharya; Collura B; Curtis C; J L H Evers; Roy G Farquharson; Franik S; Linda C Giudice; Yacoub Khalaf; Knijnenburg JML; Brigitte Leeners; Richard S Legro; Lensen S; Vazquez-Niebla JC; Mavrelos D; Ben W Mol; Niederberger C; Ng EHY; Otter AS; Puscasiu L; Rautakallio-Hokkanen S; Repping S; Sarris I; Joe Leigh Simpson; Annika Strandell; Strawbridge C; Torrance HL; A Vail; Madelon van Wely; Vercoe MA; Lan N. Vuong; Wang AY; Wang R; Wilkinson J; Youssef MA; C Farquhar

doi:10.1093/humrep/deaa241

Research Methods · Study Design

Developing a core outcome set for future infertility research: an international consensus development study

Duffy JMN, AlAhwany H, Bhattacharya S, Collura B, Curtis C, Evers JLH, Farquharson RG, Franik S, Giudice LC, Khalaf Y, Knijnenburg JML, Leeners B, Legro RS, Lensen S, Vazquez-Niebla JC, Mavrelos D, Mol BWJ, Niederberger C, Ng EHY, Otter AS, Puscasiu L, Rautakallio-Hokkanen S, Repping S, Sarris I, Simpson JL, Strandell A, Strawbridge C, Torrance HL, Vail A, van Wely M, Vercoe MA, Vuong NL, Wang AY, Wang R, Wilkinson J, Youssef MA, Farquhar CM

Published December 2020 Human Reproduction

DOI 10.1093/humrep/deaa241 PMID 33252685 PMC PMC7744160

RRM Academy Synopsis

Experts agreed on seven core outcomes for infertility treatment trials

An international Delphi survey of 372 people and a consensus meeting agreed on seven core outcomes. Randomized trials and systematic reviews of infertility treatments should report them, from early pregnancy to newborn health. Health professionals, researchers and people with fertility problems took part. A final meeting of 30 of them settled the list.

Key Findings

Round one of the Delphi survey had 372 participants from 41 countries: 261 health professionals, 57 researchers, and 54 who live with fertility problems.
The starting inventory held 101 outcomes. The steering group added 32 for round two, and 28 reached the consensus threshold. Round three found no more.
The seven core outcomes are major congenital anomaly, neonatal mortality, birthweight, gestational age at delivery, live birth, pregnancy loss and ultrasound-confirmed viable intrauterine pregnancy.
Where it applies, trials should also report time to pregnancy leading to live birth. The consensus meeting drew 30 people from 27 countries, four of them men with fertility problems.
Across the Delphi survey, 38% of participants dropped out. The authors note that only one-third of infertility trials report live birth.

Interpretation

The study reached agreement on what randomized trials and systematic reviews of infertility treatments should measure. As a consensus exercise, it reports no treatment results. Consensus meant that every stakeholder group gave the outcome a median of eight on the nine-point scale, a threshold set in advance. The authors name limits. More respondents lived in Europe (134 participants; 36%). The survey required English, a computer and internet access. People with fertility problems were more likely to withdraw. The authors call for more research on these consensus methods.

RRM Context

The paper notes that live birth rates counted per embryo transferred do not reflect the randomized comparison, which is per woman randomized. Restorative reproductive medicine cohorts can report per couple on the same terms. Live birth and time to pregnancy on the shared list let cause-based care results sit beside other trials.

Our editorial summary of this paper, not the article's abstract.

Abstract

Study Question

Can a core outcome set to standardize outcome selection, collection and reporting across future infertility research be developed?

Summary Answer

A minimum data set, known as a core outcome set, has been developed for randomized controlled trials (RCTs) and systematic reviews evaluating potential treatments for infertility.

What Is Known Already

Complex issues, including a failure to consider the perspectives of people with fertility problems when selecting outcomes, variations in outcome definitions and the selective reporting of outcomes on the basis of statistical analysis, make the results of infertility research difficult to interpret.

Study Design, Size, Duration

A three-round Delphi survey (372 participants from 41 countries) and consensus development workshop (30 participants from 27 countries).

Main Results and the Role of Chance

The core outcome set consists of: viable intrauterine pregnancy confirmed by ultrasound (accounting for singleton, twin and higher multiple pregnancy); pregnancy loss (accounting for ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy); live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital anomaly. Time to pregnancy leading to live birth should be reported when applicable.

Wider Implications of the Findings

Embedding the core outcome set within RCTs and systematic reviews should ensure the comprehensive selection, collection and reporting of core outcomes. Research funding bodies, the SPIRIT statement, and over 80 specialty journals, including Cochrane Gynaecology and Fertility Group, Fertility and Sterility and Human Reproduction, have committed to implementing this core outcome set.

Topics

Research Methods › Study Design › Randomized Controlled Trials · Assisted Reproduction › Outcomes and Effectiveness › Live Birth Rates

Siladitya Bhattacharya, Roy G Farquharson, Linda C Giudice, Yacoub Khalaf, Brigitte Leeners, Richard S Legro, Ben W Mol, Joe Leigh Simpson, Madelon van Wely

S Bhattacharya, R Farquharson, L Giudice, Y Khalaf, B Leeners, Rick Legro, Dick Legro, Rich Legro, R Legro, Benjamin Mol, B Mol, Joseph Simpson, J Simpson, M Wely

PMID 33252685 33252685 DOI 10.1093/humrep/deaa241 10.1093/humrep/deaa241 Duffy et al. 2020, Duffy 2020

Developing a core outcome set for future infertility research: an international consensus development study

Experts agreed on seven core outcomes for infertility treatment trials

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

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