P-773 The absence and heterogeneity of pregnancy outcome definitions in randomized controlled trials of infertility: an overview of the literature
Authors: Feng Q , Li W , Li W , Longobardi S , D’Hooghe T , Mol B 
Published: July 2024

Study question

What proportion of infertility trials reported pregnancy and live birth, how often were these outcomes defined, and what is the consistency in their definitions?

Summary answer

Almost 2/3 of infertility trials did not report live birth. One in four did not define clinical pregnancy. There was considerable heterogeneity in outcome definitions.

What is known already

The absent or inconsistent outcome definitions in randomized controlled trials (RCTs) complicate the interpretation of the trial results and undermine evidence synthesis. While reporting live births in infertility trials has been a long-running recommendation, the extent to which this is adhered to is unclear. Furthermore, it is unknown if the use of core outcome sets in infertility has improved the standardization of outcome reporting and what is the uptake of its recommendation on reporting live birth.

Study design, size, duration

We studied all RCTs in reproductive medicine published between 2012 and 2023. We aim to ascertain i) whether clinical pregnancy, ongoing pregnancy and live birth were reported; and ii) whether and how these pregnancy outcomes were defined.

Participants/materials, setting, methods

We systematically searched Embase, Medline and CENTRAL for RCTs in reproductive medicine from 2012 to 2023. RCTs involving infertile women that reported either biochemical pregnancy, clinical pregnancy, ongoing pregnancy, or live birth were eligible, while conference abstracts, secondary analyses or non-English written RCTs were not. Two authors independently screened articles. We used text-mining to extract pregnancy definitions in R. The accuracy of automatic data extraction was verified with a random sample of 20 articles.

Main results and the role of chance

After screening 5708 articles, 1,311 were included, of which 21 have been retracted. Manual checks of 20 papers confirmed the accuracy of text-mining.

Among 1311 RCTs, 61% of articles reported pregnancy without data on live birth, while only 14% of all RCTs reported on clinical pregnancy, ongoing pregnancy and live birth; 13% of RCTs reported pregnancy without specifying a definition (biochemical, clinical or ongoing). Definitions for clinical pregnancy, ongoing pregnancy and live birth were not provided in 27% (270/1010), 39% (153/389) and 68% (373/549) of articles reporting data on respectively clinical pregnancy, ongoing pregnancy and live birth.

Among 740 clinical pregnancy definitions, 46% included gestational age (weeks), ranging from 3 to 16 weeks, typically at 6 to 7 weeks in 40% of definitions. Gestational sac and fetal heartbeat appeared respectively in 64% and 55% of the definitions. Of 236 ongoing pregnancy definitions, 94% included gestational age (weeks), stretching from 6 to 28 weeks, typically at 12 weeks in 52% of definitions. Gestational sac and fetal heartbeat appeared in 9% and 63% of the definitions, respectively. Among 176 live birth definitions, 64% used a gestational age (weeks) threshold, varying from 20 to 34 weeks, typically at week 24 in 30% of definitions.

Limitations, reasons for caution

While we optimized the text-mining algorithm attempting to identify all types of outcome definitions and manually curated all extracted definitions, there were definitions that we incorrectly omitted.

Wider implications of the findings

Despite recommendations to report live births in core outcome sets, only a third of RCTs did so, highlighting a disconnection between the advocated outcome and what researchers are reporting. The significant lack and variability of pregnancy definitions underscore the imperative to increase the dissemination and uptake of standardized pregnancy outcomes.

Trial registration number

Not applicable