Natural cycle in vitro fertilisation (IVF) for subfertile couples

Thomas Allersma; Cindy Farquhar; Astrid EP Cantineau

doi:10.1002/14651858.CD010550.pub2

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Figure 1

Study flow diagram.

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Figure 2

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

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Figure 3

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 4

Forest plot of comparison: 1 Natural cycle IVF versus standard IVF, outcome: 1.1 Live births.

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Figure 5

Forest plot of comparison: 1 Natural cycle IVF versus standard IVF, outcome: 1.2 OHSS.

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Figure 6

Forest plot of comparison: 1 Natural cycle IVF versus standard IVF, outcome: 1.3 Clinical pregnancy.

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Figure 7

Forest plot of comparison: 1 Natural cycle IVF versus standard IVF, outcome: 1.4 Ongoing pregnancy.

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Figure 8

Forest plot of comparison: 1 Natural cycle IVF versus standard IVF, outcome: 1.11 Cycle cancellations.

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Analysis 1.1

Comparison 1 Natural cycle IVF versus standard IVF, Outcome 1 Live births.

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Analysis 1.2

Comparison 1 Natural cycle IVF versus standard IVF, Outcome 2 OHSS.

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Analysis 1.3

Comparison 1 Natural cycle IVF versus standard IVF, Outcome 3 Clinical pregnancy.

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Analysis 1.4

Comparison 1 Natural cycle IVF versus standard IVF, Outcome 4 Ongoing pregnancy.

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Analysis 1.5

Comparison 1 Natural cycle IVF versus standard IVF, Outcome 5 Oocytes retrieved.

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Analysis 1.8

Comparison 1 Natural cycle IVF versus standard IVF, Outcome 8 Multiple pregnancies.

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Analysis 1.9

Comparison 1 Natural cycle IVF versus standard IVF, Outcome 9 Gestational abnormalities.

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Analysis 1.11

Comparison 1 Natural cycle IVF versus standard IVF, Outcome 11 Cycle cancellations.

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Analysis 1.12

Comparison 1 Natural cycle IVF versus standard IVF, Outcome 12 Costs.

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Analysis 1.13

Comparison 1 Natural cycle IVF versus standard IVF, Outcome 13 Subgroup analysis: Clinical pregnancy rate by intervention.

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Summary of findings for the main comparison. Natural cycle IVF versus standard IVF for subfertile couples

DRAFT Natural cycle IVF versus standard IVF for subfertile couples
Patient or population: Subfertile couples Settings: Assisted reproductive technology Intervention: Natural cycle IVF versus standard IVF
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Standard IVF	Natural cycle IVF
Live birth per woman	530 per 1000	434 per 1000 (342 to 532)	OR 0.68 (0.46 to 1.01)	425 (2 studies)	⊕⊕⊕⊝ Moderate¹
OHSS per woman	67 per 1000	13 per 1000 (1 to 225)	OR 0.19 (0.01 to 4.06)	60 (1)	⊕⊝⊝⊝ Very low²
Clinical pregnancy per woman	207 per 1000	119 per 1000 (42 to 295)	OR 0.52 (0.17 to 1.61)	351 (4 studies)	⊕⊕⊝⊝ Low^{1, 2, 3,4}
Ongoing pregnancy per woman	494 per 1000	416 per 1000 (328 to 508)	OR 0.72 (0.5 to 1.05)	485 (3 studies)	⊕⊕⊕⊝ Moderate^1,2
Multiple pregnancy per woman	26 per 1000	20 per 1000 (7 to 58)	OR 0.76 (0.25 to 2.31)	527 (2 studies)	⊕⊝⊝⊝ Very low²
The basis for the assumed risk* is the median control group risk across studies. 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; OR: Odds 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.
¹ Serious imprecision: confidence intervals compatible with no difference between the interventions or with substantial benefit from standard IVF ² Very serious imprecision, did not describe methods of allocation concealment or sequence generation in all cases ³ High risk of attrition bias in one study ⁴ Substantial inconsistency (I²=63%), findings sensitive to choice of statistical model

Summary of findings for the main comparison. Natural cycle IVF versus standard IVF for subfertile couples

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Table 1. Number of articles

	Initial search result	After screening
CENTRAL	151	16
EMBASE	127	2
MEDLINE	110	3
PsycINFO	15	0
MDSG	28	3
Clinicaltrials	114	2
CINAHL	7	1
WEBOFKN	66	9
TOTAL	617	36

Table 1. Number of articles

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Table 2. Additional data

	Ingerslev 2001		Levy 1991
	Natural cycle	Stimulated cycle	Natural cycle	Stimulated cycle
Cycles	114	111	22	26
Clinical pregnancy rate	4	20	0	6
Oocytes retrieved	68 (0.92 ± 0.40)	174 (1.83 ± 1.15)
Cycle cancellations	40	16	6	1

Table 2. Additional data

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Comparison 1. Natural cycle IVF versus standard IVF

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Live births Show forest plot	2	425	Odds Ratio (M‐H, Fixed, 95% CI)	0.68 [0.46, 1.01]

2 OHSS Show forest plot	1	60	Odds Ratio (M‐H, Fixed, 95% CI)	0.19 [0.01, 4.06]

3 Clinical pregnancy Show forest plot	4	351	Odds Ratio (M‐H, Random, 95% CI)	0.52 [0.17, 1.61]

3.1 Cumulative rate over up to 3 cycles	2	261	Odds Ratio (M‐H, Random, 95% CI)	0.44 [0.06, 3.25]
3.2 Single cycle	2	90	Odds Ratio (M‐H, Random, 95% CI)	0.84 [0.30, 2.37]
4 Ongoing pregnancy Show forest plot	3	485	Odds Ratio (M‐H, Fixed, 95% CI)	0.72 [0.50, 1.05]

5 Oocytes retrieved Show forest plot	1	60	Mean Difference (IV, Fixed, 95% CI)	‐4.40 [‐7.87, ‐0.93]

8 Multiple pregnancies Show forest plot	2	527	Odds Ratio (M‐H, Fixed, 95% CI)	0.76 [0.25, 2.31]

9 Gestational abnormalities Show forest plot	1	18	Odds Ratio (M‐H, Fixed, 95% CI)	0.44 [0.03, 5.93]

11 Cycle cancellations Show forest plot	2		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

11.1 NC‐IVF versus stimulated cycle IVF	2	159	Odds Ratio (M‐H, Random, 95% CI)	8.98 [0.20, 393.66]
12 Costs Show forest plot	1	60	Std. Mean Difference (IV, Fixed, 95% CI)	‐5.59 [‐6.75, ‐4.44]

13 Subgroup analysis: Clinical pregnancy rate by intervention Show forest plot	4	351	Odds Ratio (M‐H, Random, 95% CI)	0.52 [0.17, 1.61]

13.1 NC IVF versus stimulated cycle IVF	3	291	Odds Ratio (M‐H, Random, 95% CI)	0.39 [0.08, 1.89]
13.2 MNC‐IVF versus stimulated cycle IVF	1	60	Odds Ratio (M‐H, Random, 95% CI)	1.0 [0.33, 3.02]

Comparison 1. Natural cycle IVF versus standard IVF

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