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Inhibitory aromatazy (letrozol) w indukcji owulacji u niepłodnych kobiet z zespołem policystycznych jajników

Appendices

Appendix 1. The Cochrane Gynaecology and Fertility specialised register search strategy

ProCite platform

Searched from inception to 4 November 2021

Keywords CONTAINS "Polycystic Ovary Syndrome"or "PCOS" or "*Ovulation Induction" or "ovulation stimulation" or "ovarian hyperstimulation" or "superovulation" or Title CONTAINS "Polycystic Ovary Syndrome"or "PCOS" or "*Ovulation Induction" or "ovulation stimulation" or "ovarian hyperstimulation" or "superovulation"

AND

Keywords CONTAINS "aromatase inhibition" or "aromatase inhibitor" or "aromatase P450" or "Anastrozole" or "letozole" or "letrozole" or "Exemestane" or "arimidex" or Title CONTAINS "aromatase inhibition" or "aromatase inhibitor" or "aromatase P450" or "Anastrozole" or "letozole" or "letrozole" or "Exemestane" or "arimidex"

(206 records)

Appendix 2. CENTRAL via the Cochrane Register of Studies Online (CRSO) search strategy

Web platform

Searched from inception to 4 November 2021

#1 MESH DESCRIPTOR Polycystic Ovary Syndrome EXPLODE ALL TREES 1599

#2 (Polycystic Ovar*):TI,AB,KY 3955

#3 (PCOS or PCOD):TI,AB,KY 3221

#4 (stein leventh*):TI,AB,KY 33

#5 PCO:TI,AB,KY 718

#6 MESH DESCRIPTOR Ovulation Induction EXPLODE ALL TREES 1405

#7 (ovulat* adj2 induc*):TI,AB,KY 2848

#8 superovulation:TI,AB,KY 220

#9 (ovari* adj2 hyperstimulat*):TI,AB,KY 1503

#10 (ovar* adj2 stimulat*):TI,AB,KY 2503

#11 #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 9066

#12 MESH DESCRIPTOR Aromatase Inhibitors EXPLODE ALL TREES 1460

#13 MESH DESCRIPTOR Aminoglutethimide EXPLODE ALL TREES 80

#14 MESH DESCRIPTOR Fadrozole EXPLODE ALL TREES 24

#15 (aromatase inhibitor*):TI,AB,KY 2256

#16 aminoglutethimide:TI,AB,KY 178

#17 Anastrozole:TI,AB,KY 1226

#18 Arimidex:TI,AB,KY 256

#19 Letrozole:TI,AB,KY 2187

#20 Femara:TI,AB,KY 118

#21 Exemestane:TI,AB,KY 940

#22 Aromasin:TI,AB,KY 56

#23 Vorozole:TI,AB,KY 18

#24 Rivizor:TI,AB,KY 3

#25 Formestane:TI,AB,KY 41

#26 Lentaron:TI,AB,KY 8

#27 Fadrozole:TI,AB,KY 38

#28 Afema:TI,AB,KY 0

#29 #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28 4782

#30 #11 AND #29 562

Appendix 3. MEDLINE search strategy

Ovid platform

Searched from 1946 to 4 November 2021

1 exp Polycystic Ovary Syndrome/ (15766)
2 Polycystic Ovar$.tw. (18537)
3 PCOS.tw. (12806)
4 PCOD.tw. (302)
5 stein leventh$.tw. (626)
6 (ovar$ adj2 sclerocystic).tw. (105)
7 (ovar$ adj2 degeneration).tw. (154)
8 PCO.tw. (4908)
9 exp ovulation induction/ or exp superovulation/ (13918)
10 (ovulat$ adj2 induc$).tw. (8049)
11 superovulation.tw. (2132)
12 (ovari$ adj2 hyperstimulat$).tw. (5435)
13 (ovari$ adj2 stimulat$).tw. (7765)
14 or/1‐13 (48358)
15 exp aromatase inhibitors/ or exp aminoglutethimide/ or exp fadrozole/ (9337)
16 aromatase inhibitor$.tw. (7829)
17 aminoglutethimide.tw. (1400)
18 Anastrozole.tw. (1880)
19 Arimidex.tw. (258)
20 Letrozole.tw. (3202)
21 Femara.tw. (87)
22 Exemestane.tw. (1390)
23 Aromasin.tw. (33)
24 Vorozole.tw. (127)
25 Rivizor.tw. (5)
26 Formestane.tw. (167)
27 Lentaron.tw. (15)
28 Fadrozole.tw. (377)
29 Afema.tw. (6)
30 or/15‐29 (13775)
31 14 and 30 (921)
32 randomized controlled trial.pt. (549418)
33 controlled clinical trial.pt. (94513)
34 randomized.ab. (539225)
35 placebo.tw. (228833)
36 clinical trials as topic.sh. (197987)
37 randomly.ab. (369070)
38 trial.ti. (250408)
39 (crossover or cross‐over or cross over).tw. (91109)
40 or/32‐39 (1437766)
41 exp animals/ not humans.sh. (4909657)
42 40 not 41 (1321608)
43 31 and 42 (265)

Appendix 4. Embase search strategy

Ovid platform

Searched from 1980 to 4 November 2021

1 exp ovary polycystic disease/ (29828)
2 Polycystic Ovar$.tw. (25622)
3 PCOS.tw. (19277)
4 PCOD.tw. (431)
5 stein leventh$.tw. (135)
6 (ovar$ adj2 sclerocystic).tw. (48)
7 (ovar$ adj2 degeneration).tw. (150)
8 PCO.tw. (4782)
9 exp ovulation induction/ (15520)
10 (ovulat$ adj2 induc$).tw. (9450)
11 (ovari$ adj2 hyperstimulat$).tw. (7977)
12 superovulation.tw. (2501)
13 (ovari$ adj2 stimulat$).tw. (12123)
14 or/1‐13 (66109)
15 exp aromatase inhibitor/ (34277)
16 aromatase inhibitor$.tw. (12717)
17 aminoglutethimide.tw. (1310)
18 Anastrozole.tw. (3249)
19 Arimidex.tw. (1750)
20 Letrozole.tw. (6067)
21 Femara.tw. (1170)
22 Exemestane.tw. (2646)
23 Aromasin.tw. (546)
24 Vorozole.tw. (160)
25 Rivizor.tw. (28)
26 Formestane.tw. (210)
27 Lentaron.tw. (129)
28 Fadrozole.tw. (404)
29 Afema.tw. (28)
30 or/15‐29 (35982)
31 14 and 30 (2179)
32 Clinical Trial/ (1007849)
33 Randomized Controlled Trial/ (677700)
34 exp randomization/ (92216)
35 Single Blind Procedure/ (44143)
36 Double Blind Procedure/ (186128)
37 Crossover Procedure/ (68417)
38 Placebo/ (359368)
39 Randomi?ed controlled trial$.tw. (269387)
40 Rct.tw. (43953)
41 random allocation.tw. (2228)
42 randomly allocated.tw. (39371)
43 allocated randomly.tw. (2698)
44 (allocated adj2 random).tw. (832)
45 Single blind$.tw. (27447)
46 Double blind$.tw. (217387)
47 ((treble or triple) adj blind$).tw. (1418)
48 placebo$.tw. (327421)
49 prospective study/ (721072)
50 or/32‐49 (2424186)
51 case study/ (81682)
52 case report.tw. (454480)
53 abstract report/ or letter/ (1167318)
54 or/51‐53 (1691117)
55 50 not 54 (2365980)
56 31 and 55 (699)

Appendix 5. PsycINFO search strategy

Ovid platform

Searched from 1806 to 4 November 2021

1 exp Endocrine Sexual Disorders/ (1855)
2 Polycystic Ovar$.tw. (468)
3 PCOS.tw. (324)
4 PCOD.tw. (8)
5 or/1‐4 (2158)
6 aromatase inhibitor$.tw. (277)
7 Anastrozole.tw. (32)
8 Arimidex.tw. (3)
9 Letrozole.tw. (90)
10 Femara.tw. (0)
11 Exemestane.tw. (16)
12 or/6‐11 (328)
13 5 and 12 (7)

Appendix 6. Trial registries search strategy

The ClinicalTrials database, a service of the US National Institutes of Health (clinicaltrials.gov/ct2/home) and the World Health Organization International Trials Registry Platform search portal (www.who.int/trialsearch/Default.aspx.

Web Platform

Searched from inception to 4 November 2021

1 polycystic ovary syndrome (490)

2 PCOS (560)

3 letrozole (438)

4 aromatase inhibitor* (897)

5 (1 OR 2) AND (3 OR 4) (26)

Appendix 7. Google Scholar search strategy

Web Platform

Searched from inception to 4 November 2021

Keywords included: polycystic ovary syndrome, PCOS, letrozole, aromatase inhibitor, anastrozole, ovulation induction

Study flow diagram for update 2021

Figuras y tablas -
Figure 1

Study flow diagram for update 2021

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

Figuras y tablas -
Figure 2

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

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

Figuras y tablas -
Figure 3

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

Forest plot of comparison: 2 Aromatase inhibitors compared to selective oestrogen receptor modulators (SERMs), outcome: 2.1 Live birth rate.

Figuras y tablas -
Figure 4

Forest plot of comparison: 2 Aromatase inhibitors compared to selective oestrogen receptor modulators (SERMs), outcome: 2.1 Live birth rate.

Funnel plot of comparison: 2 AIs compared to SERMs with or without adjuncts, followed by timed intercourse, outcome: 2.1 Live birth rate.

Figuras y tablas -
Figure 5

Funnel plot of comparison: 2 AIs compared to SERMs with or without adjuncts, followed by timed intercourse, outcome: 2.1 Live birth rate.

Forest plot of comparison: 2 Aromatase inhibitors compared to selective oestrogen receptor modulators SERMs, outcome: 2.6 Ovarian hyperstimulation syndrome rate.

Figuras y tablas -
Figure 6

Forest plot of comparison: 2 Aromatase inhibitors compared to selective oestrogen receptor modulators SERMs, outcome: 2.6 Ovarian hyperstimulation syndrome rate.

Forest plot of comparison: 2 Aromatase inhibitors compared to selective oestrogen receptor modulators SERMs, outcome: 2.5 Multiple pregnancy rate.

Figuras y tablas -
Figure 7

Forest plot of comparison: 2 Aromatase inhibitors compared to selective oestrogen receptor modulators SERMs, outcome: 2.5 Multiple pregnancy rate.

Comparison 1: Letrozole compared to placebo, Outcome 1: Live birth rate

Figuras y tablas -
Analysis 1.1

Comparison 1: Letrozole compared to placebo, Outcome 1: Live birth rate

Comparison 1: Letrozole compared to placebo, Outcome 2: Ovarian hyperstimulation syndrome rate

Figuras y tablas -
Analysis 1.2

Comparison 1: Letrozole compared to placebo, Outcome 2: Ovarian hyperstimulation syndrome rate

Comparison 1: Letrozole compared to placebo, Outcome 3: Clinical pregnancy rate

Figuras y tablas -
Analysis 1.3

Comparison 1: Letrozole compared to placebo, Outcome 3: Clinical pregnancy rate

Comparison 1: Letrozole compared to placebo, Outcome 4: Miscarriage rate per woman

Figuras y tablas -
Analysis 1.4

Comparison 1: Letrozole compared to placebo, Outcome 4: Miscarriage rate per woman

Comparison 1: Letrozole compared to placebo, Outcome 5: Miscarriage rate per pregnancy

Figuras y tablas -
Analysis 1.5

Comparison 1: Letrozole compared to placebo, Outcome 5: Miscarriage rate per pregnancy

Comparison 1: Letrozole compared to placebo, Outcome 6: Multiple pregnancy rate

Figuras y tablas -
Analysis 1.6

Comparison 1: Letrozole compared to placebo, Outcome 6: Multiple pregnancy rate

Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 1: Live birth rate

Figuras y tablas -
Analysis 2.1

Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 1: Live birth rate

Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 2: Live birth rate by BMI

Figuras y tablas -
Analysis 2.2

Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 2: Live birth rate by BMI

Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 3: Live birth rate by first‐ or second‐line treatment

Figuras y tablas -
Analysis 2.3

Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 3: Live birth rate by first‐ or second‐line treatment

Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 4: Impact of allocation bias for live birth rate

Figuras y tablas -
Analysis 2.4

Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 4: Impact of allocation bias for live birth rate

Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 5: Impact of detection bias for live birth rate

Figuras y tablas -
Analysis 2.5

Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 5: Impact of detection bias for live birth rate

Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 6: Impact of attrition bias for live birth rate

Figuras y tablas -
Analysis 2.6

Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 6: Impact of attrition bias for live birth rate

Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 7: Ovarian hyperstimulation syndrome rate

Figuras y tablas -
Analysis 2.7

Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 7: Ovarian hyperstimulation syndrome rate

Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 8: Ovarian hyperstimulation syndrome rate by BMI

Figuras y tablas -
Analysis 2.8

Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 8: Ovarian hyperstimulation syndrome rate by BMI

Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 9: Clinical pregnancy rate

Figuras y tablas -
Analysis 2.9

Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 9: Clinical pregnancy rate

Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 10: Impact of allocation bias for clinical pregnancy rate

Figuras y tablas -
Analysis 2.10

Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 10: Impact of allocation bias for clinical pregnancy rate

Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 11: Miscarriage rate per woman

Figuras y tablas -
Analysis 2.11

Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 11: Miscarriage rate per woman

Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 12: Miscarriage rate per pregnancy

Figuras y tablas -
Analysis 2.12

Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 12: Miscarriage rate per pregnancy

Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 13: Multiple pregnancy rate

Figuras y tablas -
Analysis 2.13

Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 13: Multiple pregnancy rate

Comparison 3: Letrozole compared to SERMs with our without adjuncts, followed by IUI, Outcome 1: Ovarian hyperstimulation syndrome rate

Figuras y tablas -
Analysis 3.1

Comparison 3: Letrozole compared to SERMs with our without adjuncts, followed by IUI, Outcome 1: Ovarian hyperstimulation syndrome rate

Comparison 3: Letrozole compared to SERMs with our without adjuncts, followed by IUI, Outcome 2: Clinical pregnancy rate

Figuras y tablas -
Analysis 3.2

Comparison 3: Letrozole compared to SERMs with our without adjuncts, followed by IUI, Outcome 2: Clinical pregnancy rate

Comparison 3: Letrozole compared to SERMs with our without adjuncts, followed by IUI, Outcome 3: Miscarriage rate per woman

Figuras y tablas -
Analysis 3.3

Comparison 3: Letrozole compared to SERMs with our without adjuncts, followed by IUI, Outcome 3: Miscarriage rate per woman

Comparison 3: Letrozole compared to SERMs with our without adjuncts, followed by IUI, Outcome 4: Miscarriage rate per pregnancy

Figuras y tablas -
Analysis 3.4

Comparison 3: Letrozole compared to SERMs with our without adjuncts, followed by IUI, Outcome 4: Miscarriage rate per pregnancy

Comparison 3: Letrozole compared to SERMs with our without adjuncts, followed by IUI, Outcome 5: Multiple pregnancy rate

Figuras y tablas -
Analysis 3.5

Comparison 3: Letrozole compared to SERMs with our without adjuncts, followed by IUI, Outcome 5: Multiple pregnancy rate

Comparison 4: Letrozole compared to laparoscopic ovarian drilling, Outcome 1: Live birth rate

Figuras y tablas -
Analysis 4.1

Comparison 4: Letrozole compared to laparoscopic ovarian drilling, Outcome 1: Live birth rate

Comparison 4: Letrozole compared to laparoscopic ovarian drilling, Outcome 2: Clinical pregnancy rate

Figuras y tablas -
Analysis 4.2

Comparison 4: Letrozole compared to laparoscopic ovarian drilling, Outcome 2: Clinical pregnancy rate

Comparison 4: Letrozole compared to laparoscopic ovarian drilling, Outcome 3: Miscarriage rate per woman

Figuras y tablas -
Analysis 4.3

Comparison 4: Letrozole compared to laparoscopic ovarian drilling, Outcome 3: Miscarriage rate per woman

Comparison 4: Letrozole compared to laparoscopic ovarian drilling, Outcome 4: Miscarriage rate per pregnancy

Figuras y tablas -
Analysis 4.4

Comparison 4: Letrozole compared to laparoscopic ovarian drilling, Outcome 4: Miscarriage rate per pregnancy

Comparison 4: Letrozole compared to laparoscopic ovarian drilling, Outcome 5: Multiple pregnancy rate

Figuras y tablas -
Analysis 4.5

Comparison 4: Letrozole compared to laparoscopic ovarian drilling, Outcome 5: Multiple pregnancy rate

Comparison 5: Letrozole compared to FSH, Outcome 1: Live birth

Figuras y tablas -
Analysis 5.1

Comparison 5: Letrozole compared to FSH, Outcome 1: Live birth

Comparison 5: Letrozole compared to FSH, Outcome 2: Ovarian hyperstimulation syndrome rate

Figuras y tablas -
Analysis 5.2

Comparison 5: Letrozole compared to FSH, Outcome 2: Ovarian hyperstimulation syndrome rate

Comparison 5: Letrozole compared to FSH, Outcome 3: Clinical pregnancy rate

Figuras y tablas -
Analysis 5.3

Comparison 5: Letrozole compared to FSH, Outcome 3: Clinical pregnancy rate

Comparison 5: Letrozole compared to FSH, Outcome 4: Miscarriage rate per woman

Figuras y tablas -
Analysis 5.4

Comparison 5: Letrozole compared to FSH, Outcome 4: Miscarriage rate per woman

Comparison 5: Letrozole compared to FSH, Outcome 5: Miscarriage rate per pregnancy

Figuras y tablas -
Analysis 5.5

Comparison 5: Letrozole compared to FSH, Outcome 5: Miscarriage rate per pregnancy

Comparison 5: Letrozole compared to FSH, Outcome 6: Multiple pregnancy rate

Figuras y tablas -
Analysis 5.6

Comparison 5: Letrozole compared to FSH, Outcome 6: Multiple pregnancy rate

Comparison 6: Letrozole compared to anastrozole, Outcome 1: Clinical pregnancy rate

Figuras y tablas -
Analysis 6.1

Comparison 6: Letrozole compared to anastrozole, Outcome 1: Clinical pregnancy rate

Comparison 6: Letrozole compared to anastrozole, Outcome 2: Multiple pregnancy rate

Figuras y tablas -
Analysis 6.2

Comparison 6: Letrozole compared to anastrozole, Outcome 2: Multiple pregnancy rate

Comparison 7: Letrozole compared to berberine, followed by timed intercourse, Outcome 1: Live birth rate

Figuras y tablas -
Analysis 7.1

Comparison 7: Letrozole compared to berberine, followed by timed intercourse, Outcome 1: Live birth rate

Comparison 7: Letrozole compared to berberine, followed by timed intercourse, Outcome 2: Clinical pregnancy rate

Figuras y tablas -
Analysis 7.2

Comparison 7: Letrozole compared to berberine, followed by timed intercourse, Outcome 2: Clinical pregnancy rate

Comparison 7: Letrozole compared to berberine, followed by timed intercourse, Outcome 3: Miscarriage rate per woman

Figuras y tablas -
Analysis 7.3

Comparison 7: Letrozole compared to berberine, followed by timed intercourse, Outcome 3: Miscarriage rate per woman

Comparison 7: Letrozole compared to berberine, followed by timed intercourse, Outcome 4: Miscarriage rate per pregnancy

Figuras y tablas -
Analysis 7.4

Comparison 7: Letrozole compared to berberine, followed by timed intercourse, Outcome 4: Miscarriage rate per pregnancy

Comparison 7: Letrozole compared to berberine, followed by timed intercourse, Outcome 5: Multiple pregnancy rate

Figuras y tablas -
Analysis 7.5

Comparison 7: Letrozole compared to berberine, followed by timed intercourse, Outcome 5: Multiple pregnancy rate

Comparison 8: Different administration protocols of letrozole, Outcome 1: Clinical pregnancy rate

Figuras y tablas -
Analysis 8.1

Comparison 8: Different administration protocols of letrozole, Outcome 1: Clinical pregnancy rate

Comparison 9: Dosage studies of letrozole, Outcome 1: Ovarian hyperstimulation syndrome rate

Figuras y tablas -
Analysis 9.1

Comparison 9: Dosage studies of letrozole, Outcome 1: Ovarian hyperstimulation syndrome rate

Comparison 9: Dosage studies of letrozole, Outcome 2: Clinical pregnancy rate

Figuras y tablas -
Analysis 9.2

Comparison 9: Dosage studies of letrozole, Outcome 2: Clinical pregnancy rate

Comparison 9: Dosage studies of letrozole, Outcome 3: Miscarriage rate per woman

Figuras y tablas -
Analysis 9.3

Comparison 9: Dosage studies of letrozole, Outcome 3: Miscarriage rate per woman

Comparison 9: Dosage studies of letrozole, Outcome 4: Miscarriage rate per pregnancy

Figuras y tablas -
Analysis 9.4

Comparison 9: Dosage studies of letrozole, Outcome 4: Miscarriage rate per pregnancy

Comparison 9: Dosage studies of letrozole, Outcome 5: Multiple pregnancy rate

Figuras y tablas -
Analysis 9.5

Comparison 9: Dosage studies of letrozole, Outcome 5: Multiple pregnancy rate

Summary of findings 1. Letrozole with or without adjuncts compared to SERMs with or without adjuncts followed by timed intercourse for infertile women with polycystic ovary syndrome

Letrozole with or without adjuncts compared to SERMs with or without adjuncts followed by timed intercourse for infertile women with polycystic ovary syndrome

Patient or population: infertile women with polycystic ovary syndrome
Setting: (fertility) clinics or outpatient settings
Intervention: letrozole with or without adjuncts followed by timed intercourse
Comparison: SERMs (clomiphene citrate) with or without adjuncts followed by timed intercourse

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

No. of participants
(trials)

Certainty of the evidence
(GRADE)

Comments

Risk with SERMs with or without adjuncts

Risk with letrozole with or without adjuncts

Live birth rate

204 per 1000

307 per 1000
(265 to 352)

OR 1.72
(1.40 to 2.11)

2060
(11 RCTs)

⊕⊕⊕⊕
High

 

Ovarian hyperstimulation syndrome rate

7 per 1000

5 per 1000
(5 to 5)

RD −0.00
(−0.01 to 0.01)

1848
(10 RCTs)

⊕⊕⊕⊕
High

 

Clinical pregnancy rate

242 per 1000

350 per 1000
(316 to 387)

OR 1.69
(1.45 to 1.98)

3321
(23 RCTs)

⊕⊕⊕⊕
High

 

Miscarriage rate per pregnancy

252 per 1000

240 per 1000
(182 to 307)

OR 0.94
(0.66 to 1.32)

736
(15 RCTs)

⊕⊕⊕⊕
High

 

Multiple pregnancy rate

22 per 1000

16 per 1000
(9 to 28)

OR 0.74
(0.42 to 1.32)

2247
(14 RCTs)

⊕⊕⊕⊕
High

 

*The risk in the intervention group (and its 95% confidence interval) is based on the mean risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: confidence interval; OR: odds ratio; RD: risk difference; RCT: randomised controlled trial

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.

Figuras y tablas -
Summary of findings 1. Letrozole with or without adjuncts compared to SERMs with or without adjuncts followed by timed intercourse for infertile women with polycystic ovary syndrome
Summary of findings 2. Letrozole compared to laparoscopic ovarian drilling for infertile women with polycystic ovary syndrome

Letrozole compared to laparoscopic ovarian drilling compared to placebo for infertile women with polycystic ovary syndrome

Patient or population: infertile women with polycystic ovary syndrome
Setting: (fertility) clinics or outpatient settings
Intervention: letrozole with or without adjuncts followed by timed intercourse
Comparison: laparoscopic ovarian drilling (LOD) followed by timed intercourse

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

No. of participants
(trials)

Certainty of the evidence
(GRADE)

Comments

Risk with LOD

Risk with letrozole

Live birth rate

229 per 1000

380 per 1000
(227 to 561)

OR 2.07
(0.99 to 4.32)

141
(1 RCT)

⊕⊝⊝⊝
Very Lowa,b,c

 

Ovarian hyperstimulation syndrome rate

No trials reported on this outcome

Clinical pregnancy rate

290 per 1000

375 per 1000
(279 to 482)

OR 1.47
(0.95 to 2.28)

376
(3 RCTs)

⊕⊕⊝⊝
Lowa,b

 

Miscarriage rate per pregnancy

151 per 1000

104 per 1000
(38 to 254)

OR 0.65
(0.22 to 1.92)

122
(3 RCTs)

⊕⊕⊝⊝
Lowa,b

 

Multiple pregnancy rate

0 per 1000

0 per 1000
(0 to 0)

OR 3.00
(0.12 to 74.90)

141
(1 RCT)

⊕⊝⊝⊝
Very Lowa,b,c

 

*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; OR: odds ratio; RCT: randomised controlled trial

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.

aInsufficient data to allow judgement of risk of bias in some trials ‐ downgraded one level for serious risk of bias.
bThere is insufficient data to determine if there is a difference as opposed to no evidence of a difference ‐ downgraded one level for imprecision.
cAnalysis is based on only one trial ‐ downgraded one additional level for imprecision.
 

Figuras y tablas -
Summary of findings 2. Letrozole compared to laparoscopic ovarian drilling for infertile women with polycystic ovary syndrome
Comparison 1. Letrozole compared to placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1.1 Live birth rate Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.2 Ovarian hyperstimulation syndrome rate Show forest plot

2

167

Risk Difference (M‐H, Fixed, 95% CI)

0.00 [‐0.05, 0.05]

1.3 Clinical pregnancy rate Show forest plot

2

167

Odds Ratio (M‐H, Fixed, 95% CI)

2.88 [1.08, 7.66]

1.4 Miscarriage rate per woman Show forest plot

2

167

Odds Ratio (M‐H, Fixed, 95% CI)

1.60 [0.26, 9.89]

1.5 Miscarriage rate per pregnancy Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.6 Multiple pregnancy rate Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

Figuras y tablas -
Comparison 1. Letrozole compared to placebo
Comparison 2. Letrozole compared to SERM with or without adjuncts, followed by timed intercourse

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

2.1 Live birth rate Show forest plot

11

2060

Odds Ratio (M‐H, Fixed, 95% CI)

1.72 [1.40, 2.11]

2.1.1 AIs versus clomiphene citrate

8

1646

Odds Ratio (M‐H, Fixed, 95% CI)

1.79 [1.42, 2.25]

2.1.2 Aromatase inhibitor + metformin compared to clomiphene + metformin

2

194

Odds Ratio (M‐H, Fixed, 95% CI)

1.70 [0.89, 3.23]

2.1.3 Aromatase inhibitor + FSH compared to clomiphene + FSH

1

120

Odds Ratio (M‐H, Fixed, 95% CI)

1.18 [0.53, 2.61]

2.1.4 AIs versus clomiphene + estradiol valerate

1

100

Odds Ratio (M‐H, Fixed, 95% CI)

1.48 [0.54, 4.06]

2.2 Live birth rate by BMI Show forest plot

9

1880

Odds Ratio (M‐H, Fixed, 95% CI)

1.74 [1.41, 2.15]

2.2.1 BMI > 25

6

1428

Odds Ratio (M‐H, Fixed, 95% CI)

1.84 [1.44, 2.35]

2.2.2 BMI < 25

3

452

Odds Ratio (M‐H, Fixed, 95% CI)

1.49 [0.98, 2.25]

2.3 Live birth rate by first‐ or second‐line treatment Show forest plot

11

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.3.1 No previous ovulation induction

4

1089

Odds Ratio (M‐H, Fixed, 95% CI)

1.61 [1.22, 2.14]

2.3.2 CC‐resistant women

4

344

Odds Ratio (M‐H, Fixed, 95% CI)

1.78 [1.08, 2.93]

2.3.3 Unclear or mixed study cohort

3

627

Odds Ratio (M‐H, Fixed, 95% CI)

1.88 [1.31, 2.69]

2.4 Impact of allocation bias for live birth rate Show forest plot

11

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.4.1 Unclear risk of allocation

8

1031

Odds Ratio (M‐H, Fixed, 95% CI)

1.90 [1.42, 2.54]

2.4.2 Low risk of allocation

3

1029

Odds Ratio (M‐H, Fixed, 95% CI)

1.57 [1.18, 2.08]

2.5 Impact of detection bias for live birth rate Show forest plot

11

2060

Odds Ratio (M‐H, Fixed, 95% CI)

1.72 [1.40, 2.11]

2.5.1 High risk of detection

1

64

Odds Ratio (M‐H, Fixed, 95% CI)

2.60 [0.83, 8.13]

2.5.2 Low risk of detection

5

1189

Odds Ratio (M‐H, Fixed, 95% CI)

1.65 [1.26, 2.16]

2.5.3 Unclear risk of detection

5

807

Odds Ratio (M‐H, Fixed, 95% CI)

1.76 [1.27, 2.44]

2.6 Impact of attrition bias for live birth rate Show forest plot

11

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.6.1 Unclear risk of attrition

1

147

Odds Ratio (M‐H, Fixed, 95% CI)

2.04 [0.93, 4.50]

2.6.2 Low risk of attrition

9

1645

Odds Ratio (M‐H, Fixed, 95% CI)

1.75 [1.39, 2.19]

2.6.3 High risk of attrition

1

268

Odds Ratio (M‐H, Fixed, 95% CI)

1.46 [0.85, 2.50]

2.7 Ovarian hyperstimulation syndrome rate Show forest plot

10

1848

Risk Difference (M‐H, Fixed, 95% CI)

‐0.00 [‐0.01, 0.01]

2.7.1 AIs versus clomiphene citrate

8

1572

Risk Difference (M‐H, Fixed, 95% CI)

‐0.00 [‐0.01, 0.00]

2.7.2 Aromatase inhibitor + hMG versus clomiphene + hMG

2

276

Risk Difference (M‐H, Fixed, 95% CI)

0.00 [‐0.04, 0.04]

2.8 Ovarian hyperstimulation syndrome rate by BMI Show forest plot

9

Risk Difference (M‐H, Fixed, 95% CI)

Subtotals only

2.8.1 BMI > 25

4

1163

Risk Difference (M‐H, Fixed, 95% CI)

‐0.01 [‐0.01, 0.00]

2.8.2 BMI < 25

5

605

Risk Difference (M‐H, Fixed, 95% CI)

0.00 [‐0.02, 0.02]

2.9 Clinical pregnancy rate Show forest plot

23

3321

Odds Ratio (M‐H, Fixed, 95% CI)

1.69 [1.45, 1.98]

2.9.1 Aromatase inhibitor versus clomiphene citrate

17

2516

Odds Ratio (M‐H, Fixed, 95% CI)

1.70 [1.42, 2.03]

2.9.2 Aromatase inhibitor + metformin versus clomiphene + metformin

3

294

Odds Ratio (M‐H, Fixed, 95% CI)

1.86 [1.05, 3.29]

2.9.3 Aromatase inhibitor + hMG versus clomiphene + hMG

2

276

Odds Ratio (M‐H, Fixed, 95% CI)

1.37 [0.82, 2.27]

2.9.4 AIs versus tamoxifen

2

135

Odds Ratio (M‐H, Fixed, 95% CI)

1.58 [0.64, 3.90]

2.9.5 AIs versus clomiphene + estradiol valerate

1

100

Odds Ratio (M‐H, Fixed, 95% CI)

2.47 [0.94, 6.46]

2.10 Impact of allocation bias for clinical pregnancy rate Show forest plot

21

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.10.1 Unclear risk of allocation

17

1931

Odds Ratio (M‐H, Fixed, 95% CI)

1.74 [1.41, 2.14]

2.10.2 Low risk of allocation

4

580

Odds Ratio (M‐H, Fixed, 95% CI)

1.56 [1.10, 2.21]

2.11 Miscarriage rate per woman Show forest plot

15

2422

Odds Ratio (M‐H, Fixed, 95% CI)

1.37 [1.01, 1.87]

2.11.1 AIs versus clomiphene citrate

10

1752

Odds Ratio (M‐H, Fixed, 95% CI)

1.40 [0.98, 1.99]

2.11.2 Aromatase inhibitor + metformin versus clomiphene + metformin

3

294

Odds Ratio (M‐H, Fixed, 95% CI)

1.21 [0.52, 2.82]

2.11.3 Aromatase inhibitor + hMG versus clomiphene + hMG

2

276

Odds Ratio (M‐H, Fixed, 95% CI)

0.84 [0.31, 2.27]

2.11.4 AIs versus clomiphene + estradiol valerate

1

100

Odds Ratio (M‐H, Fixed, 95% CI)

12.21 [0.66, 226.97]

2.12 Miscarriage rate per pregnancy Show forest plot

15

736

Odds Ratio (M‐H, Fixed, 95% CI)

0.94 [0.66, 1.32]

2.12.1 AIs versus clomiphene citrate

10

529

Odds Ratio (M‐H, Fixed, 95% CI)

0.94 [0.63, 1.42]

2.12.2 Aromatase inhibitor + metformin versus clomiphene + metformin

3

79

Odds Ratio (M‐H, Fixed, 95% CI)

0.80 [0.32, 2.02]

2.12.3 Aromatase inhibitor + hMG versus clomiphene + hMG

2

104

Odds Ratio (M‐H, Fixed, 95% CI)

0.67 [0.23, 1.96]

2.12.4 AIs versus clomiphene + estradiol valerate

1

24

Odds Ratio (M‐H, Fixed, 95% CI)

8.13 [0.39, 167.90]

2.13 Multiple pregnancy rate Show forest plot

14

2247

Odds Ratio (M‐H, Fixed, 95% CI)

0.74 [0.42, 1.32]

2.13.1 Aromatase inhibitor versus clomiphene citrate

12

1971

Odds Ratio (M‐H, Fixed, 95% CI)

0.69 [0.35, 1.34]

2.13.2 Aromatase inhibitor + hMG versus clomiphene + hMG

2

276

Odds Ratio (M‐H, Fixed, 95% CI)

0.94 [0.29, 3.05]

Figuras y tablas -
Comparison 2. Letrozole compared to SERM with or without adjuncts, followed by timed intercourse
Comparison 3. Letrozole compared to SERMs with our without adjuncts, followed by IUI

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

3.1 Ovarian hyperstimulation syndrome rate Show forest plot

2

1494

Risk Difference (M‐H, Fixed, 95% CI)

‐0.00 [‐0.01, 0.00]

3.1.1 AI versus clomiphene

1

107

Risk Difference (M‐H, Fixed, 95% CI)

‐0.02 [‐0.07, 0.03]

3.1.2 AI versus clomiphene + rFSH and rFSH only

1

1387

Risk Difference (M‐H, Fixed, 95% CI)

‐0.00 [‐0.01, 0.00]

3.2 Clinical pregnancy rate Show forest plot

3

1597

Odds Ratio (M‐H, Fixed, 95% CI)

1.71 [1.30, 2.25]

3.2.1 AI versus clomiphene

2

210

Odds Ratio (M‐H, Fixed, 95% CI)

2.09 [0.97, 4.53]

3.2.2 AI versus clomiphene + rFSH and rFSH only

1

1387

Odds Ratio (M‐H, Fixed, 95% CI)

1.66 [1.23, 2.22]

3.3 Miscarriage rate per woman Show forest plot

2

1490

Odds Ratio (M‐H, Fixed, 95% CI)

1.22 [0.62, 2.40]

3.3.1 AI versus clomiphene

1

103

Odds Ratio (M‐H, Fixed, 95% CI)

0.32 [0.01, 8.06]

3.3.2 AI versus clomiphene + rFSH and rFSH only

1

1387

Odds Ratio (M‐H, Fixed, 95% CI)

1.32 [0.66, 2.65]

3.4 Miscarriage rate per pregnancy Show forest plot

2

260

Odds Ratio (M‐H, Fixed, 95% CI)

0.76 [0.37, 1.57]

3.4.1 AI versus clomiphene

1

15

Odds Ratio (M‐H, Fixed, 95% CI)

0.10 [0.00, 3.09]

3.4.2 AI versus clomiphene + rFSH and rFSH only

1

245

Odds Ratio (M‐H, Fixed, 95% CI)

0.85 [0.40, 1.79]

3.5 Multiple pregnancy rate Show forest plot

3

1597

Odds Ratio (M‐H, Fixed, 95% CI)

1.03 [0.49, 2.13]

3.5.1 AI versus clomiphene

2

210

Odds Ratio (M‐H, Fixed, 95% CI)

3.48 [0.14, 87.49]

3.5.2 AI versus clomiphene + rFSH and rFSH only

1

1387

Odds Ratio (M‐H, Fixed, 95% CI)

0.94 [0.44, 2.03]

Figuras y tablas -
Comparison 3. Letrozole compared to SERMs with our without adjuncts, followed by IUI
Comparison 4. Letrozole compared to laparoscopic ovarian drilling

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

4.1 Live birth rate Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

4.2 Clinical pregnancy rate Show forest plot

3

367

Odds Ratio (M‐H, Fixed, 95% CI)

1.47 [0.95, 2.28]

4.2.1 AI versus LOD

2

221

Odds Ratio (M‐H, Fixed, 95% CI)

1.69 [0.96, 2.97]

4.2.2 AI + metformin versus LOD

1

146

Odds Ratio (M‐H, Fixed, 95% CI)

1.20 [0.60, 2.39]

4.3 Miscarriage rate per woman Show forest plot

3

367

Odds Ratio (M‐H, Fixed, 95% CI)

0.87 [0.31, 2.44]

4.3.1 AI versus LOD

2

221

Odds Ratio (M‐H, Fixed, 95% CI)

0.58 [0.14, 2.50]

4.3.2 AI + metformin versus LOD

1

146

Odds Ratio (M‐H, Fixed, 95% CI)

1.35 [0.29, 6.27]

4.4 Miscarriage rate per pregnancy Show forest plot

3

122

Odds Ratio (M‐H, Fixed, 95% CI)

0.65 [0.22, 1.92]

4.4.1 AI versus LOD

2

73

Odds Ratio (M‐H, Fixed, 95% CI)

0.38 [0.08, 1.72]

4.4.2 AI + metformin versus LOD

1

49

Odds Ratio (M‐H, Fixed, 95% CI)

1.21 [0.24, 6.09]

4.5 Multiple pregnancy rate Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Figuras y tablas -
Comparison 4. Letrozole compared to laparoscopic ovarian drilling
Comparison 5. Letrozole compared to FSH

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

5.1 Live birth Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5.2 Ovarian hyperstimulation syndrome rate Show forest plot

2

236

Risk Difference (M‐H, Fixed, 95% CI)

‐0.03 [‐0.08, 0.01]

5.3 Clinical pregnancy rate Show forest plot

2

236

Odds Ratio (M‐H, Fixed, 95% CI)

0.81 [0.46, 1.43]

5.4 Miscarriage rate per woman Show forest plot

2

236

Odds Ratio (M‐H, Fixed, 95% CI)

0.61 [0.19, 1.92]

5.5 Miscarriage rate per pregnancy Show forest plot

2

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

5.6 Multiple pregnancy rate Show forest plot

2

236

Odds Ratio (M‐H, Fixed, 95% CI)

0.22 [0.04, 1.32]

Figuras y tablas -
Comparison 5. Letrozole compared to FSH
Comparison 6. Letrozole compared to anastrozole

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

6.1 Clinical pregnancy rate Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

6.2 Multiple pregnancy rate Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Figuras y tablas -
Comparison 6. Letrozole compared to anastrozole
Comparison 7. Letrozole compared to berberine, followed by timed intercourse

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

7.1 Live birth rate Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

7.2 Clinical pregnancy rate Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

7.3 Miscarriage rate per woman Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

7.4 Miscarriage rate per pregnancy Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

7.5 Multiple pregnancy rate Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Figuras y tablas -
Comparison 7. Letrozole compared to berberine, followed by timed intercourse
Comparison 8. Different administration protocols of letrozole

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

8.1 Clinical pregnancy rate Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

8.1.1 Letrozole day 3‐7 administration versus day 5‐9 administration

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

Figuras y tablas -
Comparison 8. Different administration protocols of letrozole
Comparison 9. Dosage studies of letrozole

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

9.1 Ovarian hyperstimulation syndrome rate Show forest plot

1

Risk Difference (M‐H, Fixed, 95% CI)

Totals not selected

9.1.1 5 mg versus 7.5 mg letrozole

1

Risk Difference (M‐H, Fixed, 95% CI)

Totals not selected

9.2 Clinical pregnancy rate Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

9.2.1 5 mg versus 7.5 mg letrozole

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

9.3 Miscarriage rate per woman Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

9.3.1 5 mg versus 7.5 mg letrozole

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

9.4 Miscarriage rate per pregnancy Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

9.4.1 5 mg versus 7.5 mg letrozole

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

9.5 Multiple pregnancy rate Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

9.5.1 5 mg versus 7.5 mg letrozole

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

Figuras y tablas -
Comparison 9. Dosage studies of letrozole