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. 2019 Apr 16;4(4):CD012856.
doi: 10.1002/14651858.CD012856.pub2.

Screening hysteroscopy in subfertile women and women undergoing assisted reproduction

Mohan S Kamath  1 , Jan Bosteels, Thomas M D'Hooghe, Srividya Seshadri, Steven Weyers, Ben Willem J Mol, Frank J Broekmans, Sesh Kamal Sunkara
Affiliations

Screening hysteroscopy in subfertile women and women undergoing assisted reproduction

Mohan S Kamath et al. Cochrane Database Syst Rev. .

Abstract

Background: Screening hysteroscopy in infertile women with unexplained infertility, or prior to intrauterine insemination (IUI) or in vitro fertilisation (IVF) may reveal intrauterine pathology that may not be detected by routine transvaginal ultrasound. Hysteroscopy, whether purely diagnostic or operative may improve reproductive outcomes.

Objectives: To assess the effectiveness and safety of screening hysteroscopy in subfertile women undergoing evaluation for infertility, and subfertile women undergoing IUI or IVF.

Search methods: We searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL CRSO, MEDLINE, Embase, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform (September 2018). We searched reference lists of relevant articles and handsearched relevant conference proceedings.

Selection criteria: Randomised controlled trials comparing screening hysteroscopy versus no intervention in subfertile women wishing to conceive spontaneously, or before undergoing IUI or IVF.

Data collection and analysis: We independently screened studies, extracted data, and assessed the risk of bias. The primary outcomes were live birth rate and complications following hysteroscopy. We analysed data using risk ratio (RR) and a fixed-effect model. We assessed the quality of the evidence by using GRADE criteria.

Main results: We retrieved 11 studies. We included one trial that evaluated screening hysteroscopy versus no hysteroscopy, in women with unexplained subfertility, who were trying to conceive spontaneously. We are uncertain whether ongoing pregnancy rate improves following a screening hysteroscopy in women with at least two years of unexplained subfertility (RR 4.30, 95% CI 2.29 to 8.07; 1 RCT; participants = 200; very low-quality evidence). For a typical clinic with a 10% ongoing pregnancy rate without hysteroscopy, performing a screening hysteroscopy would be expected to result in ongoing pregnancy rates between 23% and 81%. The included study reported no adverse events in either treatment arm. We are uncertain whether clinical pregnancy rate is improved (RR 3.80, 95% CI 2.31 to 6.24; 1 RCT; participants = 200; very low-quality evidence), or miscarriage rate increases (RR 2.80, 95% CI 1.05 to 7.48; 1 RCT; participants = 200; very low-quality evidence), following screening hysteroscopy in women with at least two years of unexplained subfertility.We included ten trials that included 1836 women who had a screening hysteroscopy and 1914 women who had no hysteroscopy prior to IVF. Main limitations in the quality of evidence were inadequate reporting of study methods and higher statistical heterogeneity. Eight of the ten trials had unclear risk of bias for allocation concealment.Performing a screening hysteroscopy before IVF may increase live birth rate (RR 1.26, 95% CI 1.11 to 1.43; 6 RCTs; participants = 2745; I² = 69 %; low-quality evidence). For a typical clinic with a 22% live birth rate, performing a screening hysteroscopy would be expected to result in live birth rates between 25% and 32%. However, sensitivity analysis done by pooling results from trials at low risk of bias showed no increase in live birth rate following a screening hysteroscopy (RR 0.99, 95% CI 0.82 to 1.18; 2 RCTs; participants = 1452; I² = 0%).Only four trials reported complications following hysteroscopy; of these, three trials recorded no events in either group. We are uncertain whether a screening hysteroscopy is associated with higher adverse events (Peto odds ratio 7.47, 95% CI 0.15 to 376.42; 4 RCTs; participants = 1872; I² = not applicable; very low-quality evidence).Performing a screening hysteroscopy before IVF may increase clinical pregnancy rate (RR 1.32, 95% CI 1.20 to 1.45; 10 RCTs; participants = 3750; I² = 49%; low-quality evidence). For a typical clinic with a 28% clinical pregnancy rate, performing a screening hysteroscopy would be expected to result in clinical pregnancy rates between 33% and 40%.There may be little or no difference in miscarriage rate following screening hysteroscopy (RR 1.01, 95% CI 0.67 to 1.50; 3 RCTs; participants = 1669; I² = 0%; low-quality evidence).We found no trials that compared a screening hysteroscopy versus no hysteroscopy before IUI.

Authors' conclusions: At present, there is no high-quality evidence to support the routine use of hysteroscopy as a screening tool in the general population of subfertile women with a normal ultrasound or hysterosalpingogram in the basic fertility work-up for improving reproductive success rates.In women undergoing IVF, low-quality evidence, including all of the studies reporting these outcomes, suggests that performing a screening hysteroscopy before IVF may increase live birth and clinical pregnancy rates. However, pooled results from the only two trials with a low risk of bias did not show a benefit of screening hysteroscopy before IVF.Since the studies showing an effect are those with unclear allocation concealment, we are uncertain whether a routine screening hysteroscopy increases live birth and clinical pregnancy, be it for all women, or those with two or more failed IVF attempts. There is insufficient data to draw conclusions about the safety of screening hysteroscopy.

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Conflict of interest statement

Mohan S Kamath, Jan Bosteels, Srividya Seshadri, Steven Weyers, and Sesh Kamal Sunkara have no conflicts of interest to declare.

Thomas M D’Hooghe, MD, PhD, is a Professor in Reproductive Medicine, Department of Development and Regeneration, University of Leuven (KU Leuven), Belgium, and Professor Adjunct, Department of Obstetrics and Gynecology, Yale University, New Haven, USA. Since October 2015, he has been Vice‐President and Head of Global Medical Affairs Fertility, Merck KGaA, Darmstadt, Germany. His participation in this publication is part of his academic work. Merck KGaA is not involved in the development or marketing of products related to hysteroscopy. Professor D'Hooghe's employment by Merck is not in breach of Cochrane's Commercial Sponsorship Policy (clause 2), as he does not have a real or potential financial interest in the outcome of this review. This matter was referred to Cochrane's Funding Arbiter for advice.

Ben Willem J Mol has received consultancy fees from ObsEva Geneva, Guerbet, and Merck; payment for review preparation from European Journal of Obstetrics and Gynecology and Reproductive Biology; and travel, accommodation, and meeting expenses for various non‐commercial scientific meetings. Ben Willem J Mol was author of a trial included in the review (Smit 2016). He did not participate in selection of the studies or in extracting data from that study.

Frank J Broekmans has received monetary compensation for the following: member of the external advisory board for Merck Serono and Ferring, the Netherlands; educational activities for Ferring BV, the Netherlands; consultancy work for Gedeon Richter, Belgium; strategic co‐operation with Roche on automated anti‐Müllerian hormone (AMH) assay development; and research co‐operation with Ansh Labs. Frank K Broekmans was author of a trial included in the review (Smit 2016). He did not participate in selection of the studies or in extracting data from that study.

Figures

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1
Study flow diagram
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Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
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3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study
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4
Forest plot of comparison 1. Screening hysteroscopy versus no hysteroscopy in subfertile women. Outcome 1.1. Ongoing pregnancy was used as a surrogate outcome for live birth
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Forest plot of comparison 2. Screening hysteroscopy versus no hysteroscopy in women under IVF. Outcome 2.1. Live birth.
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Forest plot of comparison 2. Screening hysteroscopy versus no hysteroscopy in women under IVF. Outcome 2.3. Clinical pregnancy
1.1
1.1. Analysis
Comparison 1 Screening hysteroscopy versus no hysteroscopy in subfertile women wishing to conceive spontaneously, Outcome 1 Live birth.
1.2
1.2. Analysis
Comparison 1 Screening hysteroscopy versus no hysteroscopy in subfertile women wishing to conceive spontaneously, Outcome 2 Adverse outcomes.
1.3
1.3. Analysis
Comparison 1 Screening hysteroscopy versus no hysteroscopy in subfertile women wishing to conceive spontaneously, Outcome 3 Clinical pregnancy.
1.4
1.4. Analysis
Comparison 1 Screening hysteroscopy versus no hysteroscopy in subfertile women wishing to conceive spontaneously, Outcome 4 Miscarriage.
2.1
2.1. Analysis
Comparison 2 Screening hysteroscopy versus no hysteroscopy in women before IVF, Outcome 1 Live birth.
2.2
2.2. Analysis
Comparison 2 Screening hysteroscopy versus no hysteroscopy in women before IVF, Outcome 2 Adverse outcomes.
2.3
2.3. Analysis
Comparison 2 Screening hysteroscopy versus no hysteroscopy in women before IVF, Outcome 3 Clinical pregnancy.
2.4
2.4. Analysis
Comparison 2 Screening hysteroscopy versus no hysteroscopy in women before IVF, Outcome 4 Miscarriage.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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