How common is natural conception in women who have had a livebirth via assisted reproductive technology? Systematic review and meta-analysis

Abstract

Study question: What is the proportion of women who experience natural conception after a livebirth via assisted reproductive technology (ART)?

Summary answer: Current evidence suggests that natural conception pregnancy may occur in at least one in five women after having a baby via IVF or ICSI.

What is known already: It is widely known that some women having babies via ART go on to conceive naturally. This reproductive history is of media interest and often described as 'miracle' pregnancies.

Study design, size, duration: A systematic review with meta-analysis was carried out. Ovid Medline, Embase, and PsycINFO were searched until 24 September 2021 for English language, human studies from 1980. Search terms were used for the concepts of natural conception pregnancy, assisted reproduction, and livebirth.

Participants/materials, setting, methods: The inclusion criterion was studies with an outcome measure of the proportion of women experiencing natural conception pregnancy after an ART livebirth. Quality of studies was assessed using the Critical Appraisal Skills Programme cohort study checklist or AXIS Appraisal tool for cross-sectional studies, and a risk of bias assessment was carried out. No studies were excluded based on quality. Random-effects meta-analyses were adopted to produce a pooled effect estimate of the proportion of natural conception pregnancy after ART livebirth.

Main results and the role of chance: A total of 1108 distinct studies were identified, resulting in 54 studies after screening by title and abstract. Eleven studies including 5180 women were selected for this review. The included studies were mostly of moderate quality with a maximum follow-up period ranging from 2 to 15 years. Four studies reported natural conception livebirths which were used as known underestimates of natural conception pregnancies. The pooled estimate for the proportion of women having natural conception pregnancies after ART livebirth was 0.20 (95% CI, 0.17-0.22).

Limitations, reasons for caution: The studies varied widely according to methodology, population, cause of subfertility, type and outcome of fertility treatment, and length of follow-up, leading to potential bias relating to confounding, selection bias, and missing data.

Wider implications of the findings: Current evidence suggests that contrary to widely held views, natural conception pregnancy after ART livebirth is far from rare. National, data-linked studies are needed to provide more accurate estimates of this incidence and analysis of associated factors and trends over time to facilitate tailored counselling of couples considering further ART.

Study funding/competing interest(s): This work was conducted as part of an academic clinical fellowship awarded to AT by the National Institute for Health Research (NIHR). NIHR has had no input into the study design, data collection, and analysis, nor the writing of this study. No authors have any conflicts of interest.

Registration number: PROSPERO (CRD42022322627).

Keywords: ARTs; ICSI; IVF; infertility; live birth; meta-analysis; systematic review.

Figure 1.

PRISMA flowchart of a systematic review. *Full text unavailable despite interlibrary loan request made to The British Library. The abstract described a review study with no report of the outcome of interest.

Figure 2.

Risk of bias traffic light plot.

Figure 3.

Forest plot of studies of the proportions of spontaneous pregnancies after livebirth via ART. Abbreviations: ES, effect size; event number, number of women having subsequent spontaneous pregnancy/livebirth.