Aromatase inhibitors (letrozole) for ovulation induction in infertile women with polycystic ovary syndrome
Information
- DOI:
- https://doi.org/10.1002/14651858.CD010287.pub4Copy DOI
- Database:
-
- Cochrane Database of Systematic Reviews
- Version published:
-
- 27 September 2022see what's new
- Type:
-
- Intervention
- Stage:
-
- Review
- Cochrane Editorial Group:
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Cochrane Gynaecology and Fertility Group
- Copyright:
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- Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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Cited by:
Authors
Contributions of authors
SF wrote the protocol and drafted the full review.
JK and CF acted as clinical experts and commented on the protocol and full review.
SF and QL updated the 2021 version of the review.
CF, JK and LK acted as clinical expert and commented on the full review update in 2021.
Sources of support
Internal sources
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Cochrane Gynaecology and Fertility Group, New Zealand
editorial support
External sources
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None, Other
This review was written without external support.
Declarations of interest
SF has nothing to declare
QL has nothing to declare
JK has nothing to declare
LK has received payment for consulting/lectures from Ferring Pharmaceuticals A/S, Mithra Pharmaceuticals SA, AstraZeneca, Dr KADE/Besins, Actavis, Abvie; consulting fees from Roche, Pantarhei, Gideon Richter, Dr KADE/Besins, payment participation on a data safety monitoring board from Palleos Pharma GmbH
CF is a co‐ordinating editor of CGF group and has not participated in the editorial process. CF has nothing further to declare.
Acknowledgements
We would like to thank Marian Showell (Information Specialist) for writing and running the search, Vanessa Jordan for assistance with methodological questions, Helen Nagels (Managing Editor of CGFG) for helping us to develop the protocol and answering our questions, and Julie Brown for assistance with writing the full review.
The authors of the 2018 update thank Dr Willianne Nelen for her contributions to the previous version of this review.
The authors of the 2021 update thank Dr Stefanie Eltrop for her contribution to the previous version of this review.
We would like to thank the peer reviewers for the valuable comments:
Wentao Li, Monash University
Dr Katie Stocking, University of Manchester
Charalampos S Siristatidis, Professor of Obstetrics Gynaecology and Reproductive Medicine, 2nd Department of Obstetrics and Gynaecology, National and Kapodistrian University of Athens, Greece
Madelon van Wely, Satellite CGF, Amsterdam UMC
Michelle Shwarz, PhD, PCOS Challenge: The National Polycystic Ovary Syndrome Association
We would like thank Clare Dooley for copy‐editing the review update.
Version history
| Published | Title | Stage | Authors | Version |
| 2022 Sep 27 | Aromatase inhibitors (letrozole) for ovulation induction in infertile women with polycystic ovary syndrome | Review | Sebastian Franik, Quang-Khoi Le, Jan AM Kremer, Ludwig Kiesel, Cindy Farquhar | |
| 2018 May 24 | Aromatase inhibitors (letrozole) for subfertile women with polycystic ovary syndrome | Review | Sebastian Franik, Stephanie M Eltrop, Jan AM Kremer, Ludwig Kiesel, Cindy Farquhar | |
| 2014 Feb 24 | Aromatase inhibitors for subfertile women with polycystic ovary syndrome | Review | Sebastian Franik, Jan AM Kremer, Willianne LDM Nelen, Cindy Farquhar | |
| 2012 Dec 12 | Aromatase inhibitors for subfertile women with polycystic ovary syndrome | Protocol | Sebastian Franik, Jan AM Kremer, Willianne LDM Nelen, Cindy Farquhar | |
Differences between protocol and review
In the 2021 update, we changed the title from 'Aromatase inhibitors (letrozole) for subfertile women with polycystic ovary syndrome' to 'Aromatase inhibitors (letrozole) for ovulation induction in infertile women with polycystic ovary syndrome' for clarity.
Notes
In the 2021 update, we changed the title from 'Aromatase inhibitors (letrozole) for subfertile women with polycystic ovary syndrome' to 'Aromatase inhibitors (letrozole) for ovulation induction in infertile women with polycystic ovary syndrome' for clarity.
Keywords
MeSH
Medical Subject Headings (MeSH) Keywords
- *Abortion, Spontaneous [epidemiology];
- *Anovulation [complications, drug therapy];
- Aromatase Inhibitors [adverse effects];
- Clomiphene [adverse effects];
- Fertility Agents, Female [adverse effects];
- *Infertility, Female [drug therapy, etiology];
- Letrozole [therapeutic use];
- Live Birth [epidemiology];
- *Ovarian Hyperstimulation Syndrome;
- Ovulation Induction [methods];
- *Polycystic Ovary Syndrome [drug therapy];
- Pregnancy Rate;
- Selective Estrogen Receptor Modulators [therapeutic use];
Medical Subject Headings Check Words
Female; Humans; Pregnancy;
PICOs
Study flow diagram for update 2021
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.
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.
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.
Comparison 1: Letrozole compared to placebo, Outcome 1: Live birth rate
Comparison 1: Letrozole compared to placebo, Outcome 2: Ovarian hyperstimulation syndrome rate
Comparison 1: Letrozole compared to placebo, Outcome 3: Clinical pregnancy rate
Comparison 1: Letrozole compared to placebo, Outcome 4: Miscarriage rate per woman
Comparison 1: Letrozole compared to placebo, Outcome 5: Miscarriage rate per pregnancy
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
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
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
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
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
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
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
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
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
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
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
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
Comparison 5: Letrozole compared to FSH, Outcome 1: Live birth
Comparison 5: Letrozole compared to FSH, Outcome 2: Ovarian hyperstimulation syndrome rate
Comparison 5: Letrozole compared to FSH, Outcome 3: Clinical pregnancy rate
Comparison 5: Letrozole compared to FSH, Outcome 4: Miscarriage rate per woman
Comparison 5: Letrozole compared to FSH, Outcome 5: Miscarriage rate per pregnancy
Comparison 5: Letrozole compared to FSH, Outcome 6: Multiple pregnancy rate
Comparison 6: Letrozole compared to anastrozole, Outcome 1: Clinical pregnancy rate
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
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
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
Comparison 8: Different administration protocols of letrozole, Outcome 1: Clinical pregnancy rate
Comparison 9: Dosage studies of letrozole, Outcome 1: Ovarian hyperstimulation syndrome rate
Comparison 9: Dosage studies of letrozole, Outcome 2: Clinical pregnancy rate
Comparison 9: Dosage studies of letrozole, Outcome 3: Miscarriage rate per woman
Comparison 9: Dosage studies of letrozole, Outcome 4: Miscarriage rate per pregnancy
Comparison 9: Dosage studies of letrozole, Outcome 5: Multiple pregnancy rate
| 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 | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | No. of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with SERMs with or without adjuncts | Risk with letrozole with or without adjuncts | |||||
| Live birth rate | 204 per 1000 | 307 per 1000 | OR 1.72 | 2060 | ⊕⊕⊕⊕ |
|
| Ovarian hyperstimulation syndrome rate | 7 per 1000 | 5 per 1000 | RD −0.00 | 1848 | ⊕⊕⊕⊕ |
|
| Clinical pregnancy rate | 242 per 1000 | 350 per 1000 | OR 1.69 | 3321 | ⊕⊕⊕⊕ |
|
| Miscarriage rate per pregnancy | 252 per 1000 | 240 per 1000 | OR 0.94 | 736 | ⊕⊕⊕⊕ |
|
| Multiple pregnancy rate | 22 per 1000 | 16 per 1000 | OR 0.74 | 2247 | ⊕⊕⊕⊕ |
|
| *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). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 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 | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | No. of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with LOD | Risk with letrozole | |||||
| Live birth rate | 229 per 1000 | 380 per 1000 | OR 2.07 | 141 | ⊕⊝⊝⊝ |
|
| Ovarian hyperstimulation syndrome rate | No trials reported on this outcome | |||||
| Clinical pregnancy rate | 290 per 1000 | 375 per 1000 | OR 1.47 | 376 | ⊕⊕⊝⊝ |
|
| Miscarriage rate per pregnancy | 151 per 1000 | 104 per 1000 | OR 0.65 | 122 | ⊕⊕⊝⊝ |
|
| Multiple pregnancy rate | 0 per 1000 | 0 per 1000 | OR 3.00 | 141 | ⊕⊝⊝⊝ |
|
| *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). | ||||||
| GRADE Working Group grades of evidence | ||||||
| aInsufficient data to allow judgement of risk of bias in some trials ‐ downgraded one level for serious risk of bias. | ||||||
| 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 | |
| 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] |
| 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] |
| 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 | |
| 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] |
| 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 | |
| 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 | |
| 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 | |
| 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 | |
