Screening hysteroscopy in subfertile women and women undergoing assisted reproduction

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

doi:10.1002/14651858.CD012856.pub2

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Figure 1

Study flow diagram

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Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies

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Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study

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Figure 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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Figure 5

Forest plot of comparison 2. Screening hysteroscopy versus no hysteroscopy in women under IVF. Outcome 2.1. Live birth.

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Figure 6

Forest plot of comparison 2. Screening hysteroscopy versus no hysteroscopy in women under IVF. Outcome 2.3. Clinical pregnancy

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Analysis 1.1

Comparison 1 Screening hysteroscopy versus no hysteroscopy in subfertile women wishing to conceive spontaneously, Outcome 1 Live birth.

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Analysis 1.2

Comparison 1 Screening hysteroscopy versus no hysteroscopy in subfertile women wishing to conceive spontaneously, Outcome 2 Adverse outcomes.

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Analysis 1.3

Comparison 1 Screening hysteroscopy versus no hysteroscopy in subfertile women wishing to conceive spontaneously, Outcome 3 Clinical pregnancy.

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Analysis 1.4

Comparison 1 Screening hysteroscopy versus no hysteroscopy in subfertile women wishing to conceive spontaneously, Outcome 4 Miscarriage.

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Analysis 2.1

Comparison 2 Screening hysteroscopy versus no hysteroscopy in women before IVF, Outcome 1 Live birth.

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Analysis 2.2

Comparison 2 Screening hysteroscopy versus no hysteroscopy in women before IVF, Outcome 2 Adverse outcomes.

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Analysis 2.3

Comparison 2 Screening hysteroscopy versus no hysteroscopy in women before IVF, Outcome 3 Clinical pregnancy.

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Analysis 2.4

Comparison 2 Screening hysteroscopy versus no hysteroscopy in women before IVF, Outcome 4 Miscarriage.

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Summary of findings for the main comparison. Screening hysteroscopy versus no hysteroscopy in women wishing to conceive spontaneously

Hysteroscopy compared with no hysteroscopy in women wishing to conceive spontaneously
Patient or population: women with unexplained subfertility wishing to conceive spontaneously Settings: Arafa Hospital, Fayoum, Egypt Intervention: screening hysteroscopy Comparison: no hysteroscopy
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
Outcomes	Risk with no hysteroscopy	Risk with hysteroscopy	Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
Live birth	100 per 1000	430 per 1000 (229 to 807)	RR 4.30 (2.29 to 8.07)	200 (1 RCT)	⊕⊕⊝⊝ very low^a,b
Adverse events	0 per 1000	0 per 1000 (0 to 0)	not estimable	(1 RCT)	⊕⊝⊝⊝ very low^a,b.c
Clinical pregnancy	150 per 1000	570 per 1000 (347 to 936)	RR 3.80 (2.31 to 6.24)	200 (1 RCT)	⊕⊕⊝⊝ very low^a,b
Miscarriage	50 per 1000	140 per 1000 (52 to 374)	RR 2.80 (1.05 to 7.48)	200 (1 RCT)	⊕⊝⊝⊝ very low^a,b,c
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk Ratio
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
^aVery serious risk of bias, downgraded by two levels: unclear random sequence generation and allocation concealment ‐ high risk of selective outcome reporting ^bSerious risk of indirectness, downgraded by one level; only one single‐centre study ^cSerious risk of imprecision, downgraded by one level; no or low number of events

Summary of findings for the main comparison. Screening hysteroscopy versus no hysteroscopy in women wishing to conceive spontaneously

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Summary of findings 2. Screening hysteroscopy versus no hysteroscopy in women before IVF

Screening hysteroscopy versus no hysteroscopy in women before IVF
Patient or population: women before IVF treatment Setting: academic and private clinics Intervention: screening hysteroscopy Comparison: no hysteroscopy
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Outcomes	Risk with no hysteroscopy	Risk with hysteroscopy	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Live birth	221 per 1000	279 per 1000 (245 to 316)	RR 1.26 (1.11 to 1.43)	2745 (6 RCTs)	⊕⊕⊝⊝ low^a,b
Adverse events	0 per 1000	0 per 1000 (0 to 0)	Peto OR 7.47 (0.15 to 376.42)	1872 (4 RCTs)	⊕⊕⊝⊝ very low^a,c
Clinical pregnancy	278 per 1000	368 per 1000 (334 to 404)	RR 1.32 (1.20 to 1.45)	3750 (10 RCTs)	⊕⊕⊝⊝ low^a,d
Miscarriage	53 per 1000	53 per 1000 (35 to 79)	RR 1.01 (0.67 to 1.50)	1669 (3 RCTs)	⊕⊕⊝⊝ low^a,e
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio; OR: Odds ratio;
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
^aSerious risk of bias, downgraded by one level: only two studies had low risk of bias for all the domains. The rest of the studies had unclear risk for allocation concealment. One study was categorised at high risk for 'other' domain. There is a likely chance of overestimating the treatment. ^bSerious inconsistency, downgraded by one level: there is a statistical heterogeneity of 69%, which is substantial. ^cVery serious risk of imprecision, downgraded by two levels: due to wide confidence interval; number of events is too low. ^dSerious inconsistency, downgraded by one level: there is a statistical heterogeneity of 49%, which is moderate. ^eSerious risk of imprecision, downgraded by one level: due to wide confidence interval.

Summary of findings 2. Screening hysteroscopy versus no hysteroscopy in women before IVF

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Table 1. Cycle characteristics of included trials

Study ID	Population	Previous HSG or hysteroscopy	Intervention	Additional endometrial biopsy	Detected abnormalities treated	Timing of hysteroscopy
Seyam 2015	Unexplained infertility of 2 years duration	Normal HSG	Hysteroscopy	No	Yes	Follicular phase
Aghahosseini 2012	Two or more IVF failures	Normal HSG; no hysteroscopy in previous 2 months	Hysteroscopy	No	No details	No details available
Alleyassin 2017	First IVF	Normal HSG; women with history of hysteroscopy excluded.	Hysteroscopy	No	Yes	Preceding cycle; luteal phase
Demirol 2004	Two or more IVF failures	Normal HSG; no details of history of hysteroscopy	Hysteroscopy	No	Yes	Preceding cycle; follicular phase
El‐Nashar 2011	Unselected IVF population	No details of HSG; no details of history of hysteroscopy	Hysteroscopy	Yes	Yes	No details
Elsetohy 2015	First IVF	Normal HSG; no details of history of hysteroscopy	Hysteroscopy	No	Yes	Within 3 months of IVF; follicular phase
El‐Toukhy 2016	Two or more IVF failures	Hysteroscopy done within two months were excluded; Included women with previous history of hysteroscopy (45% in hysteroscopy group vs 44% in control)	Hysteroscopy	No	Yes; (only one partial septum not treated).	Preceding cycle; follicular phase
Juul Hare 2018	One IVF failure	No details available	Hysteroscopy	Yes	No details available	No details available
Rama Raju 2006	Two or more IVF failures	Normal HSG; no details of history of hysteroscopy	Hysteroscopy	Yes	Yes	Preceding cycle; follicular phase
Shawki 2012	Unselected IVF population	Normal HSG; no details of history of hysteroscopy	Hysteroscopy	Those with suspicious lesion after injecting methylene blue were biopsied.	Yes	No details available
Smit 2016	First IVF	Excluded those with previous hysteroscopy	Hysteroscopy	No	Yes; (31/43 abnormalities treated; 5 septum and 2 submucous fibroids not treated)	1 to 3 months before IVF; follicular phase
IVF: in vitro fertilisation HSG: hysterosalpingography

Table 1. Cycle characteristics of included trials

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Comparison 1. Screening hysteroscopy versus no hysteroscopy in subfertile women wishing to conceive spontaneously

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Live birth Show forest plot	1	200	Risk Ratio (M‐H, Fixed, 95% CI)	4.3 [2.29, 8.07]

2 Adverse outcomes Show forest plot	1	200	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

3 Clinical pregnancy Show forest plot	1	200	Risk Ratio (M‐H, Fixed, 95% CI)	3.8 [2.31, 6.24]

4 Miscarriage Show forest plot	1	200	Risk Ratio (M‐H, Fixed, 95% CI)	2.8 [1.05, 7.48]

Comparison 1. Screening hysteroscopy versus no hysteroscopy in subfertile women wishing to conceive spontaneously

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Comparison 2. Screening hysteroscopy versus no hysteroscopy in women before IVF

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Live birth Show forest plot	6	2745	Risk Ratio (M‐H, Fixed, 95% CI)	1.26 [1.11, 1.43]

1.1 Unselected	1	217	Risk Ratio (M‐H, Fixed, 95% CI)	1.23 [0.63, 2.40]
1.2 First IVF	2	953	Risk Ratio (M‐H, Fixed, 95% CI)	1.20 [0.96, 1.49]
1.3 Two or more IVF failures	3	1575	Risk Ratio (M‐H, Fixed, 95% CI)	1.30 [1.10, 1.53]
2 Adverse outcomes Show forest plot	4	1872	Peto Odds Ratio (Peto, Fixed, 95% CI)	7.47 [0.15, 376.42]

2.1 Unselected	1	217	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.2 First IVF	2	953	Peto Odds Ratio (Peto, Fixed, 95% CI)	7.47 [0.15, 376.42]
2.3 Two or more IVF failures	1	702	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 Clinical pregnancy Show forest plot	10	3750	Risk Ratio (M‐H, Fixed, 95% CI)	1.32 [1.20, 1.45]

3.1 Unselected	3	581	Risk Ratio (M‐H, Fixed, 95% CI)	1.40 [1.07, 1.84]
3.2 First IVF	3	1173	Risk Ratio (M‐H, Fixed, 95% CI)	1.20 [1.02, 1.41]
3.3 Two or more IVF failures	4	1996	Risk Ratio (M‐H, Fixed, 95% CI)	1.37 [1.21, 1.56]
4 Miscarriage Show forest plot	3	1669	Risk Ratio (M‐H, Fixed, 95% CI)	1.01 [0.67, 1.50]

4.1 Unselected	1	217	Risk Ratio (M‐H, Fixed, 95% CI)	2.81 [0.12, 68.33]
4.2 First IVF	1	750	Risk Ratio (M‐H, Fixed, 95% CI)	1.29 [0.59, 2.80]
4.3 Two or more IVF failures	1	702	Risk Ratio (M‐H, Fixed, 95% CI)	0.88 [0.55, 1.42]

Comparison 2. Screening hysteroscopy versus no hysteroscopy in women before IVF

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