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. 2022 Sep 27;9(9):CD010287.
doi: 10.1002/14651858.CD010287.pub4.

Aromatase inhibitors (letrozole) for ovulation induction in infertile women with polycystic ovary syndrome

Sebastian Franik  1 , Quang-Khoi Le  1 , Jan Am Kremer  2 , Ludwig Kiesel  1 , Cindy Farquhar  3
Affiliations

Aromatase inhibitors (letrozole) for ovulation induction in infertile women with polycystic ovary syndrome

Sebastian Franik et al. Cochrane Database Syst Rev. .

Abstract

Background: Polycystic ovary syndrome (PCOS) is the most common cause of infrequent periods (oligomenorrhoea) and absence of periods (amenorrhoea). It affects about 5% to 20% of women worldwide and often leads to anovulatory infertility. Aromatase inhibitors (AIs) are a class of drugs that were introduced for ovulation induction in 2001. Since about 2001 clinical trials have reached differing conclusions as to whether the AI, letrozole, is at least as effective as the first-line treatment clomiphene citrate (CC), a selective oestrogen receptor modulator (SERM).

Objectives: To evaluate the effectiveness and safety of AIs (letrozole) (with or without adjuncts) compared to SERMs (with or without adjuncts) for infertile women with anovulatory PCOS for ovulation induction followed by timed intercourse or intrauterine insemination.

Search methods: We searched the following sources, from their inception to 4 November 2021, to identify relevant randomised controlled trials (RCTs): the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase and PsycINFO. We also checked reference lists of relevant trials, searched the trial registers and contacted experts in the field for any additional trials. We did not restrict the searches by language or publication status.

Selection criteria: We included all RCTs of AIs used alone or with other medical therapies for ovulation induction in women of reproductive age with anovulatory PCOS.

Data collection and analysis: Two review authors independently selected trials, extracted the data and assessed risks of bias using RoB 1. We pooled trials where appropriate using a fixed-effect model to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for most outcomes, and risk differences (RDs) for ovarian hyperstimulation syndrome (OHSS). The primary outcomes were live birth rate and OHSS rate. Secondary outcomes were clinical pregnancy, miscarriage and multiple pregnancy rates. We assessed the certainty of the evidence for each comparison using GRADE methods.

Main results: This is a substantive update of a previous review; of six previously included trials, we excluded four from this update and moved two to 'awaiting classification' due to concerns about validity of trial data. We included five additional trials for this update that now includes a total of 41 RCTs (6522 women). The AI, letrozole, was used in all trials. Letrozole compared to SERMs with or without adjuncts followed by timed intercourse Live birth rates were higher with letrozole (with or without adjuncts) compared to SERMs followed by timed intercourse (OR 1.72, 95% CI 1.40 to 2.11; I2 = 0%; number needed to treat for an additional beneficial outcome (NNTB) = 10; 11 trials, 2060 participants; high-certainty evidence). This suggests that in women with a 20% chance of live birth using SERMs, the live birth rate in women using letrozole with or without adjuncts would be 27% to 35%. There is high-certainty evidence that OHSS rates are similar with letrozole or SERMs (0.5% in both arms: risk difference (RD) -0.00, 95% CI -0.01 to 0.01; I2 = 0%; 10 trials, 1848 participants; high-certainty evidence). There is evidence for a higher pregnancy rate in favour of letrozole (OR 1.69, 95% CI 1.45 to 1.98; I2 = 0%; NNTB = 10; 23 trials, 3321 participants; high-certainty evidence). This suggests that in women with a 24% chance of clinical pregnancy using SERMs, the clinical pregnancy rate in women using letrozole with or without adjuncts would be 32% to 39%. There is little or no difference between treatment groups in the rate of miscarriage per pregnancy (25% with SERMs versus 24% with letrozole: OR 0.94, 95% CI 0.66 to 1.32; I2 = 0%; 15 trials, 736 participants; high-certainty evidence) and multiple pregnancy rate (2.2% with SERMs versus 1.6% with letrozole: OR 0.74, 95% CI 0.42 to 1.32; I2 = 0%; 14 trials, 2247 participants; high-certainty evidence). However, a funnel plot showed mild asymmetry, indicating that some trials in favour of SERMs might be missing. Letrozole compared to laparoscopic ovarian drilling (LOD) One trial reported very low-certainty evidence that live birth rates may be higher with letrozole compared to LOD (OR 2.07, 95% CI 0.99 to 4.32; 1 trial, 141 participants; very low-certainty evidence). This suggests that in women with a 22% chance of live birth using LOD with or without adjuncts, the live birth rate in women using letrozole with or without adjuncts would be 24% to 47%. No trial reported OHSS rates. Due to the low-certainty evidence we are uncertain if letrozole improves pregnancy rates compared to LOD (OR 1.47, 95% CI 0.95 to 2.28; I² = 0%; 3 trials, 367 participants; low-certainty evidence). This suggests that in women with a 29% chance of clinical pregnancy using LOD with or without adjuncts, the clinical pregnancy rate in women using letrozole with or without adjuncts would be 28% to 45%. There seems to be no evidence of a difference in miscarriage rates per pregnancy comparing letrozole to LOD (OR 0.65, 95% CI 0.22 to 1.92; I² = 0%; 3 trials, 122 participants; low-certainty evidence). This also applies to multiple pregnancies (OR 3.00, 95% CI 0.12 to 74.90; 1 trial, 141 participants; very low-certainty evidence).

Authors' conclusions: Letrozole appears to improve live birth rates and pregnancy rates in infertile women with anovulatory PCOS, compared to SERMs, when used for ovulation induction, followed by intercourse. There is high-certainty evidence that OHSS rates are similar with letrozole or SERMs. There was high-certainty evidence of no difference in miscarriage rate and multiple pregnancy rate. We are uncertain if letrozole increases live birth rates compared to LOD. In this update, we added good quality trials and removed trials with concerns over data validity, thereby upgrading the certainty of the evidence base.

Trial registration: ClinicalTrials.gov NCT03455426 NCT01315912 NCT03135301 NCT02703649 NCT03664050 NCT03625531 NCT03009838.

PubMed Disclaimer

Conflict of interest statement

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.

Figures

1
1
Study flow diagram for update 2021
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
4
4
Forest plot of comparison: 2 Aromatase inhibitors compared to selective oestrogen receptor modulators (SERMs), outcome: 2.1 Live birth rate.
5
5
Funnel plot of comparison: 2 AIs compared to SERMs with or without adjuncts, followed by timed intercourse, outcome: 2.1 Live birth rate.
6
6
Forest plot of comparison: 2 Aromatase inhibitors compared to selective oestrogen receptor modulators SERMs, outcome: 2.6 Ovarian hyperstimulation syndrome rate.
7
7
Forest plot of comparison: 2 Aromatase inhibitors compared to selective oestrogen receptor modulators SERMs, outcome: 2.5 Multiple pregnancy rate.
1.1
1.1. Analysis
Comparison 1: Letrozole compared to placebo, Outcome 1: Live birth rate
1.2
1.2. Analysis
Comparison 1: Letrozole compared to placebo, Outcome 2: Ovarian hyperstimulation syndrome rate
1.3
1.3. Analysis
Comparison 1: Letrozole compared to placebo, Outcome 3: Clinical pregnancy rate
1.4
1.4. Analysis
Comparison 1: Letrozole compared to placebo, Outcome 4: Miscarriage rate per woman
1.5
1.5. Analysis
Comparison 1: Letrozole compared to placebo, Outcome 5: Miscarriage rate per pregnancy
1.6
1.6. Analysis
Comparison 1: Letrozole compared to placebo, Outcome 6: Multiple pregnancy rate
2.1
2.1. Analysis
Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 1: Live birth rate
2.2
2.2. Analysis
Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 2: Live birth rate by BMI
2.3
2.3. Analysis
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
2.4
2.4. Analysis
Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 4: Impact of allocation bias for live birth rate
2.5
2.5. Analysis
Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 5: Impact of detection bias for live birth rate
2.6
2.6. Analysis
Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 6: Impact of attrition bias for live birth rate
2.7
2.7. Analysis
Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 7: Ovarian hyperstimulation syndrome rate
2.8
2.8. Analysis
Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 8: Ovarian hyperstimulation syndrome rate by BMI
2.9
2.9. Analysis
Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 9: Clinical pregnancy rate
2.10
2.10. Analysis
Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 10: Impact of allocation bias for clinical pregnancy rate
2.11
2.11. Analysis
Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 11: Miscarriage rate per woman
2.12
2.12. Analysis
Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 12: Miscarriage rate per pregnancy
2.13
2.13. Analysis
Comparison 2: Letrozole compared to SERM with or without adjuncts, followed by timed intercourse, Outcome 13: Multiple pregnancy rate
3.1
3.1. Analysis
Comparison 3: Letrozole compared to SERMs with our without adjuncts, followed by IUI, Outcome 1: Ovarian hyperstimulation syndrome rate
3.2
3.2. Analysis
Comparison 3: Letrozole compared to SERMs with our without adjuncts, followed by IUI, Outcome 2: Clinical pregnancy rate
3.3
3.3. Analysis
Comparison 3: Letrozole compared to SERMs with our without adjuncts, followed by IUI, Outcome 3: Miscarriage rate per woman
3.4
3.4. Analysis
Comparison 3: Letrozole compared to SERMs with our without adjuncts, followed by IUI, Outcome 4: Miscarriage rate per pregnancy
3.5
3.5. Analysis
Comparison 3: Letrozole compared to SERMs with our without adjuncts, followed by IUI, Outcome 5: Multiple pregnancy rate
4.1
4.1. Analysis
Comparison 4: Letrozole compared to laparoscopic ovarian drilling, Outcome 1: Live birth rate
4.2
4.2. Analysis
Comparison 4: Letrozole compared to laparoscopic ovarian drilling, Outcome 2: Clinical pregnancy rate
4.3
4.3. Analysis
Comparison 4: Letrozole compared to laparoscopic ovarian drilling, Outcome 3: Miscarriage rate per woman
4.4
4.4. Analysis
Comparison 4: Letrozole compared to laparoscopic ovarian drilling, Outcome 4: Miscarriage rate per pregnancy
4.5
4.5. Analysis
Comparison 4: Letrozole compared to laparoscopic ovarian drilling, Outcome 5: Multiple pregnancy rate
5.1
5.1. Analysis
Comparison 5: Letrozole compared to FSH, Outcome 1: Live birth
5.2
5.2. Analysis
Comparison 5: Letrozole compared to FSH, Outcome 2: Ovarian hyperstimulation syndrome rate
5.3
5.3. Analysis
Comparison 5: Letrozole compared to FSH, Outcome 3: Clinical pregnancy rate
5.4
5.4. Analysis
Comparison 5: Letrozole compared to FSH, Outcome 4: Miscarriage rate per woman
5.5
5.5. Analysis
Comparison 5: Letrozole compared to FSH, Outcome 5: Miscarriage rate per pregnancy
5.6
5.6. Analysis
Comparison 5: Letrozole compared to FSH, Outcome 6: Multiple pregnancy rate
6.1
6.1. Analysis
Comparison 6: Letrozole compared to anastrozole, Outcome 1: Clinical pregnancy rate
6.2
6.2. Analysis
Comparison 6: Letrozole compared to anastrozole, Outcome 2: Multiple pregnancy rate
7.1
7.1. Analysis
Comparison 7: Letrozole compared to berberine, followed by timed intercourse, Outcome 1: Live birth rate
7.2
7.2. Analysis
Comparison 7: Letrozole compared to berberine, followed by timed intercourse, Outcome 2: Clinical pregnancy rate
7.3
7.3. Analysis
Comparison 7: Letrozole compared to berberine, followed by timed intercourse, Outcome 3: Miscarriage rate per woman
7.4
7.4. Analysis
Comparison 7: Letrozole compared to berberine, followed by timed intercourse, Outcome 4: Miscarriage rate per pregnancy
7.5
7.5. Analysis
Comparison 7: Letrozole compared to berberine, followed by timed intercourse, Outcome 5: Multiple pregnancy rate
8.1
8.1. Analysis
Comparison 8: Different administration protocols of letrozole, Outcome 1: Clinical pregnancy rate
9.1
9.1. Analysis
Comparison 9: Dosage studies of letrozole, Outcome 1: Ovarian hyperstimulation syndrome rate
9.2
9.2. Analysis
Comparison 9: Dosage studies of letrozole, Outcome 2: Clinical pregnancy rate
9.3
9.3. Analysis
Comparison 9: Dosage studies of letrozole, Outcome 3: Miscarriage rate per woman
9.4
9.4. Analysis
Comparison 9: Dosage studies of letrozole, Outcome 4: Miscarriage rate per pregnancy
9.5
9.5. Analysis
Comparison 9: Dosage studies of letrozole, Outcome 5: Multiple pregnancy rate
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References

References to studies included in this review

Al‐Omari 2004 {published data only}
    1. Al-Omari WR, Sulaiman WR, Al-Hadithi N. Comparison of two aromatase inhibitors in women with clomiphene-resistant polycystic ovary syndrome. International Journal of Gynecology & Obstetrics 2004;85(3):289-91. - PubMed
Amer 2017 {published data only}
    1. Amer SA, Smith J, Mahran A, Fox P, Fakis A. Double-blind randomized controlled trial of letrozole versus clomiphene citrate in subfertile women with polycystic ovarian syndrome. Human Reproduction 2017;32(8):1631-8. [CENTRAL: 01405506] - PMC - PubMed
Ashfaq 2018 {published data only}
    1. Ashfaq A, Tahseen H, Noreen Z, Alam N. Clomiphene citrate vs letrozole in PCO's patient's for ovulation induction. Pakistan Journal of Medical and Health Sciences 2018;12(2):781-3.
Atay 2006 {published data only}
    1. Atay V, Cam C, Muhcu M, Cam M, Karateke A. Comparison of letrozole and clomiphene citrate in women with polycystic ovaries undergoing ovarian stimulation. Journal of International Medical Research 2006;34(1):73-6. - PubMed
Bayar 2006 {published data only}
    1. Bayar U, Basaran M, Kiran S, Coskun A, Gezer S. Use of an aromatase inhibitor in patients with polycystic ovary syndrome: a prospective randomized trial. Fertility and Sterility 2006;86(5):1447-51. - PubMed
Begum 2009 {published and unpublished data}
    1. Begum MR, Ferdous J, Begum A, Quadir E. Comparison of efficacy of aromatase inhibitor and clomiphene citrate in induction of ovulation in polycystic ovarian syndrome. Fertility and Sterility 2009;92(3):853-7. - PubMed
Behnoud 2019 {published data only}
    1. Behnoud N, Farzaneh F, Ershadi S. The effect of clomiphene citrate versus letrozole on pregnancy rate in women with polycystic ovary syndrome: a randomized clinical trial. Crescent Journal of Medical and Biological Sciences 2019;6(3):335-40.
Chen 2016 {published data only}
    1. Chen Z, Zhang M, Qiao Y, Yang J. Effects of letrozole in combination with low-dose intramuscular injection of human menopausal gonadotropin on ovulation and pregnancy of 156 patients with polycystic ovary syndrome. Pakistanian Journal of Medical Sciences 2016;32(6):1434-8. - PMC - PubMed
Davar 2011 {published data only}
    1. Davar R, Javedani M, Fallahzadeh MH. Metformin-letrozole in comparison with metformin-clomiphene citrate in clomiphene-resistance PCOS patients undergoing IUI. Iranian Journal of Reproductive Medicine 2011;9(1):31-6. - PMC - PubMed
Dehbashi 2009 {published data only}
    1. Dehbashi S, Kazerooni T, Robati M, Alborzi S, Parsanezhad ME, Shadman A. Comparison of the effects of letrozole and clomiphene citrate on ovulation and pregnancy rate in patients with polycystic ovary syndrome. Iranian Journal of Medical Sciences 2009;34:23-8.
Elgafor 2013 {published data only}
    1. Elgafor IA. Efficacy of combined metformin–letrozole in comparison with bilateral ovarian drilling in clomiphene-resistant infertile women with polycystic ovarian syndrome. Archives of Gynecology and Obstetrics 2013;288(1):119-23. [DOI: 10.1007/s00404-013-2714-2] - DOI - PubMed
El‐Gharib 2015 {published data only}
    1. EL-Gharib MN, Mahfouz AE, Farahat MA. Comparison of letrozole versus tamoxifen effects in clomiphene citrate resistant women with polycystic ovarian syndrome. Journal of Reproduction and Infertility 2015;16(1):30-5. - PMC - PubMed
El‐Khayat 2016 {published data only}
    1. El-Khayat W, Abdel Moety G, Mohammady MA, Hamed D. A randomized controlled trial of clomifene citrate, metformin, and pioglitazone versus letrozole, metformin, and pioglitazone for clomifene-citrate resistant polycystic ovary syndrome. International Journal of Gynaecology and Obstetrics 2016;132(2):206-9. - PubMed
Foroozanfard 2011 {published data only}
    1. Foroozanfard F, Mahdian M, Mousavi Gl, Pejmanmanesh M, Soleimani A. Use of letrozole versus clomiphene citrate combined with gonadotropins in patients with clomiphene resistant polycystic ovarian syndrome: A comparative study. Pakistan Journal of Medical Sciences 2011;27(5):967-70.
Ganesh 2009 {published data only}
    1. Ganesh A, Goswami SK, Chattopadhyay R, Chaudhury K, Chakravarty B. Comparison of letrozole with continuous gonadotropins and clomiphene-gonadotropin combination for ovulation induction in 1387 PCOS women after clomiphene citrate failure: a randomized prospective clinical trial. Journal of Assisted Reproduction and Genetics 2009;26(1):19-24. - PMC - PubMed
Ghahiri 2016 {published data only}
    1. Ghahiri A, Mogharehabed N, Mamourian M. Letrozole as the first-line treatment of infertile women with poly cystic ovarian syndrome (PCOS) compared with clomiphene citrate: a clinical trial. Advanced Biomedical Research 2016;5(6):1-4. - PMC - PubMed
Ghomian 2015 {published data only}
    1. Ghomian N, Khosravi A, Mousavifar N. A randomized clinical trial on comparing the cycle characteristics of two different initiation days of letrozole treatment in clomiphene citrate resistant PCOS patients in IUI cycles. International Journal of Fertility and Sterility 2015;9(1):17-26. - PMC - PubMed
Hassan 2017 {published data only}
    1. Hassan A, Shehata N, Wahba A. Cost effectiveness of letrozole and purified urinary FSH in treating women with clomiphene citrate-resistant polycystic ovarian syndrome: a randomized controlled trial. Human Fertility 2017;20(1):37-42. - PubMed
Hendawy 2011 {published data only}
    1. Hendawy SF, Samaha HE, Elkholy MF. Letrozole versus clomiphene citrate for induction of ovulation in patients with polycystic ovarian syndrome undergoing intrauterine insemination. Clinical Medicine Insights: Reproductive Health 2011;5:11-16. - PMC - PubMed
Ibrahim 2017 {published data only}
    1. Ibrahim MH, Tawfic M, Hassan MM, Sedky OH. Letrozole versus laparoscopic ovarian drilling in infertile women with PCOS resistant to clomiphene citrate. Middle East Fertility Society Journal 2017;22(4):251-4.
Kamath 2010 {published and unpublished data}
    1. Kamath MS, Aleyamma TK, Chandy A, George K. Aromatase inhibitors in women with clomiphene citrate resistance: a randomized, double-blind, placebo-controlled trial. Fertility and Sterility 2010;94(7):2857-9. - PubMed
Kar 2012 {published data only}
    1. Kar S. Clomiphene citrate or letrozole as first-line ovulation induction drug in infertile PCOS women: a prospective randomized trial. Journal of Human Reproductive Sciences 2012;5(3):262-5. [DOI: 10.4103/0974-1208.106338] - DOI - PMC - PubMed
Legro 2014 {published and unpublished data}
    1. Legro RS, Brzyski RG, Diamond MP, Coutifaris C, Schlaff WD, Casson P, et al, NICHD Reproductive Medicine Network. Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. New England Journal of Medicine 2014;371(2):119-29. - PMC - PubMed
    1. Legro RS, Kunselman AR, Brzyski RG, Casson PR, Diamond MP, Schlaff WD, et al. Effect of letrozole versus clomiphene on live birth in women with anovulatory infertility due to polycystic ovary syndrome (PCOS): A randomized double-blind multi-center trial. Fertility and Sterility 2013;100(3):Suppl 51.
Liu 2015 {published data only}
    1. Liu W, Dong S, Li Y, Shi L, Zhou W, Liu Y, et al. Randomized controlled trial comparing letrozole with laparoscopic ovarian drilling in women with clomiphene citrate-resistant polycystic ovary syndrome. Experimental and Therapeutic Medicine 2015;10(4):1297-1302. - PMC - PubMed
Liu 2017 {published data only}
    1. Liu C, Feng G, Huang W, Wang Q, Yang S, Tan J, et al. Comparison of clomiphene citrate and letrozole for ovulation induction in women with polycystic ovary syndrome: a prospective randomized trial. Gynecological Endocrinology 2017;33(11):872-6. - PubMed
Moussa 2016 {published data only}
    1. Moussa AA, Torky H, Dief O, Elwahed AA, Senna HA. The effect of clomiphene citrate versus tamoxifen versus letrozole on endometrial thickness and blood flow in ovulation induction in women with polycystic ovaries. Acta Medica International 2016;3(2):88-92.
Najafi 2020 {published data only}
    1. Najafi PZ, Noghabi SP, Afzali N, Mohammadzadeh S. Comparing the effect of clomiphene citrate and letrozole on ovulation induction in infertile women with polycystic ovary syndrome. Journal of the Pakistan Medical Association 2020;70(2):268-71. - PubMed
Nazik 2012 {published data only}
    1. Nazik H, Kumtepe Y. Comparison of efficacy of letrozole and clomiphene citrate in ovulation induction for women with polycystic ovarian syndrome. HealthMED Journal 2012;6(3):879-83.
Ramezanzadeh 2011 {published data only}
    1. Ramezanzadeh F, Nasiri R, Yazdi MS, Baghrei M. A randomized trial of ovulation induction with two different doses of Letrozole in women with PCOS. Archives of Gynecology and Obstetrics 2011;284(4):1029-34. - PubMed
Ray 2012 {published data only}
    1. Ray PB, Ray A, Chakraborti PS. Comparison of efficacy of letrozole and clomiphene citrate in ovulation induction in Indian women with polycystic ovarian syndrome. Archives of Gynecology and Obstetrics 2012;285(3):873-7. - PubMed
Roy 2012 {published data only}
    1. Roy K, Baruah J, Singla S, Sharma JB, Singh N, Jain SK, et al. A prospective randomized trial comparing the efficacy of letrozole and clomiphene citrate in induction of ovulation in polycystic ovarian syndrome. Journal of Human Reproductive Sciences 2012;5(1):20-5. - PMC - PubMed
Salazar‐Ortiz 2016 {published data only}
    1. Salazar-Ortiz DY, Rodriguez-Antonio M, Contreras-Carreto NA. Comparison of clomiphene citrate and letrozole for induction of ovulation and pregnancy and its effectiveness in patients with infertility [Comparación de la eficacia decitrato de clomifeno vs letrozolen mujeres con infertilidad porsíndrome de ovario poliquístico]. Ginecologia y Obstetricia de Mexico 2016;84(11):696-703.
Selim 2012 {published data only}
    1. Selim MF, Borg TF. Letrozole and clomiphene citrate effect on endometrial and subendometrial vascularity in treating infertility in women with polycystic ovary syndrome. Journal of Gynaecologic Surgery 2012;28(6):405-10. [DOI: 10.1089/gyn.2012.0033] - DOI
Seyedoshohadaei 2016 {published data only}
    1. Seyedoshohadaei F, Tangestani L, Zandvakili F, Rashadmanesh N. Comparison of the effect of clomiphene- estradiol valerate vs letrozole on endometrial thickness, abortion and pregnancy rate in infertile women with polycystic ovarian syndrome. Journal of Clinical and Diagnostic Research 2016;10(8):QC10-13. - PMC - PubMed
Sharief 2015 {published data only}
    1. Sharief M, Nafee NR. Comparison of letrozole and clomiphene citrate in women with polycystic ovaries undergoing ovarian stimulation. Journal of Pakistani Medical Association 2015;65(11):1149-52. - PubMed
Sh‐El‐Arab Elsedeek 2011 {published data only}
    1. Sheikh-El-Arab Elsedeek M, Elmaghraby HA. Predictors and characteristics of letrozole induced ovulation in comparison with clomiphene induced ovulation in anovulatory PCOS women. Middle East Fertility Society Journal 2011;16(2):125-30.
Shi 2019 {published data only}
    1. Shi S, Hong T, Jiang F, Zhuang Y, Chen L, Huang X. Letrozole and human menopausal gonadotropin for ovulation induction in clomiphene resistance polycystic ovary syndrome patients: A randomized controlled study. Medicine 2020;99(4):e18383. - PMC - PubMed
Sohrabvand 2006 {published data only}
    1. Sohrabvand F, Ansari SH, Bagheri M. Efficacy of combined metformin-letrozole in comparison with metformin-clomiphene citrate in clomiphene-resistant infertile women with polycystic ovarian disease. Human Reproduction 2006;21(6):1432-5. - PubMed
Wu 2016 {published data only}
    1. Wu X, Wang Y, Liu J, Liang R, Xue H, Ma H, et al. Randomized controlled trial of letrozole, berberine, or a combination for infertility in the polycystic ovary syndrome. Fertility and Sterility 2016;106(3):757-66. - PubMed
Zarei 2015 {published data only}
    1. Zarei A, Shabahrami TB, Dadras N. Effects of letrozole in prevention of premature luteinizing hormone (LH) surge in infertile women with clomiphene citrate resistant polycystic ovary syndrome (PCOS) undergoing intrauterine insemination. Galen Medical Journal 2015;4(3):104-11.
Zeinalzadeh 2010 {published data only}
    1. Zeinalzadeh M, Basirat Z, Esmailpour M. Efficacy of letrozole in ovulation induction compared to that of clomiphene citrate in patients with polycystic ovarian syndrome. Journal of Reproductive Medicine 2010;55(1-2):36-40. - PubMed

References to studies excluded from this review

Abu Hashim 2010 {published data only}8527269
    1. Abu Hashim H, Shokeir T, Badawy A. RETRACTED: Letrozole versus combined metformin and clomiphene citrate for ovulation induction in clomiphene-resistant women with polycystic ovary syndrome: a randomized controlled trial. Fertility and Sterility 2010;94(4):1405-9. 8527270 - PubMed
Akbari 2012 {published data only}
    1. Akbari S, Ayazi Roozbahani M, Ayazi Roozbahani F. Comparing letrozole versus clomiphene citrate combined with gonadotropins in intrauterine insemination cycles. Iranian Journal of Reproductive Medicine 2012;10(1):29-32. - PMC - PubMed
Al‐Hussaini 2014 {published data only}
    1. Al-Hussaini T, Mohammed S, Abdellah M, Abdel Aleem A. Letrozole versus combined clomiphene citrate and metformin as a first line treatment in women with polycystic ovarian syndrome. British Journal of Obstetrics and Gynaecology 2014;E-Posters:EP6.13.
Al‐Obaidi 2018 {published data only}
    1. Al-Obaidi MT, Ali ZH, Al-Saadi WI, Al-Wasiti EA, Al-Aubaidy H. Impact of letrozole versus clomiphene citrate on endometrial receptivity in Iraqi women with polycystic ovarian syndrome. Journal of Clinical Pharmacy and Therapeutics 2019;44:618-22. - PubMed
Al‐Shaikh 2017 {published data only}
    1. Al-Shaikh SF, Al-Mukhatar EJ, Al-Zubaid AA, Al-Rubaie BJ, Al-Khuzaee L. Use of clomiphene or letrozole for treating women with polycystic ovary syndrome related subfertility in Hilla city. Middle East Fertility Society Journal 2017;22:105-10.
Angel 2014 {published data only}
    1. Angel M, Ghose S, Gowda M. A randomized trial comparing the ovulation induction efficacy of clomiphene citrate and letrozole. Journal of Natural Science Biology & Medicine 2014;5(2):450-2. - PMC - PubMed
Anwary 2012 {published data only}
    1. Anwary SA, Alfazzaman M, Bar, N, Islam MR. Outcome of metformin treatment in polycystic ovary syndrome. Mymensingh Medical Journal 2012;21(1):60-5. - PubMed
Azargoon 2012 {published data only}
    1. Azargoon A, Toussy JA, Darbanan FF. Pregnancies following the use of sequential treatment of metformin and incremental doses of letrozole in clomiphene-resistant women with polycystic ovary syndrome. Iranian Journal of Reproductive Medicine 2012;10(1):33-40. - PMC - PubMed
Azmoodeh 2015 {published data only}
    1. Azmoodeh A, Pejman Manesh M, Akbari Asbagh F, Ghaseminejad A, Hamzehgardeshi Z. Effects of letrozole-HMG and clomiphene-HMG on incidence of luteinized unruptured follicle syndrome in infertile women undergoing induction ovulation and intrauterine insemination: a randomised trial. Global Journal of Health Science 2015;8(4):244-52. - PMC - PubMed
Badawy 2008 {published data only}
    1. Badawy A, Mosbah A, Shady M. RETRACTED: Anastrozole or letrozole for ovulation induction in clomiphene-resistant women with polycystic ovarian syndrome: a prospective randomized trial. Fertility and Sterility 2008;89(5):1209-12. - PubMed
Badawy 2009a {published data only}
    1. Badawy A, Mosbah A, Tharwat A, Eid M. EXPRESSION OF CONCERN: Extended letrozole therapy for ovulation induction in clomiphene-resistant women with polycystic ovary syndrome: a novel protocol. Fertility and Sterility 2009;92(1):236-9. - PubMed
Badawy 2009b {published and unpublished data}
    1. Badawy A, Abdel Aal I, Abulatta M. RETRACTED: Clomiphene citrate or letrozole for ovulation induction in women with polycystic ovarian syndrome: a prospective randomized trial. Fertility and Sterility 2009;92(3):849-52. - PubMed
Badawy 2009c {published data only}
    1. Badawy A, Abdel Aal I, Abulatta M. Clomiphene citrate or anastrozole for ovulation induction in women with polycystic ovary syndrome? A prospective controlled trial. Fertility and Sterility 2009;92:860-3. - PubMed
Baruah 2009 {published data only}
    1. Baruah J, Roy KK, Rahman SM, Kumar S, Sharma JB, Karmakar D. Endometrial effects of letrozole and clomiphene citrate in women with polycystic ovary syndrome using spiral artery Doppler. Archives of Gynecology & Obstetrics 2009;279(3):311-14. - PubMed
El Bigawy 2008 {published data only}
    1. El Bigawy AF, Fouda UMF, Wahab HAE. A randomized trial of letrozole versus clomiphene citrate in induction of ovulation in patients with polycystic ovary syndrome (PCOS). Middle East Fertility Society Journal 2008;13(1):52-6.
Foroozanfard 2013 {published data only}
    1. Foroozanfard F, Saberi H, Moravvegi A, Kazemi M. Pregnancy rate following luteal phase support in polycystic ovarian syndrome using combination therapies for ovulation induction: A randomized clinical trial.. Human Reproduction 2013;28(Suppl 1):i311-56.
Huang 2019 {published data only}
    1. Huang S, Wang R, Li R, Yan H, Li N, Wang H, et al. Intrauterine insemination (IUI) with or without letrozole for unexplained or mild male factor infertility: a randomized pilot study. Human Reproduction 2019;34(Suppl 1):i149. [https://clinicaltrials.gov/show/NCT03455426] - PubMed
IRCT6517 {published data only}
    1. IRCT6517. The effect of metformin in different phenotypes of poly cystic ovary syndrome according to Rotterdam criteria. en.irct.ir/trial/6517 2010. [IRCT201103146063N1]
Khanna 2013 {published data only}
    1. Khanna SC, Kumar A, Joy SG, Tanwar R, Sharma S, Prasad S. Is letrozole superior to clomiphene for ovarian stimulation prior to intrauterine insemination? Archives of Gynaecology and Obstetrics 2013;287(3):571-5. - PubMed
Li 2016 {published data only}
    1. Li J, Ng EH, Stener-Victorin E, Hu Z, Wu W, Ai M, et al. Comparison of acupuncture pre-treatment followed by letrozole versus letrozole alone on live birth in anovulatory infertile women with polycystic ovary syndrome:a study protocol for a randomised controlled trial. BMJ Open 2016;6(10):e010955. - PMC - PubMed
Mittal 2004 {published data only}
    1. Mittal S, Kamthane VP, Goswami SK, Ghosh S, Chakravarty BN. Comparative evaluation of different stimulation protocols in CC resistant P.C.O women undergoing IUI. In: 20th Annual Meeting of the ESHRE, Berlin, Germany, 2004 06 27-30. 2004:i122.
Nahid 2012 {published data only}
    1. Nahid L, Sirous K. Comparison of the effects of letrozole and clomiphene citrate for ovulation induction in infertile women with polycystic ovary syndrome. Minerva Ginecologica 2012;64(3):253-8. - PubMed
NCT00610077 {published data only}
    1. NCT00610077. An open, randomized, parallel-group, multicentric, comparative study of letrozole with clomiphene citrate for induction of ovulation in anovulatory infertility. clinicaltrials.gov/ct2/show/NCT00610077 (first received 7 February 2008). [NCT00610077]
NCT01315912 {published data only}
    1. NCT01315912. Dosage optimization for letrozole treatment. clinicaltrials.gov/ct2/show/NCT01315912 (first received 16 March 2011). [NCT01315912]
NCT01431352 {published data only}
    1. NCT01431352. Letrozole versus chinese herbal medicine on polycystic ovary syndrome (PCOS). clinicaltrials.gov/ct2/show/NCT01431352 (first received 9 September 2011). [NCT01431352]
NCT01577017 {published data only}
    1. NCT01577017. The effects of letrozole and clomiphene citrate for induction of ovulation in polycystic ovarian syndrome (PCOS). clinicaltrials.gov/ct2/show/NCT01577017 (first received 13 April 2012).
NCT01679574 {published data only}
    1. NCT01679574. Letrozole or combined clomiphene citrate metformin as a first line treatment in women with polycystic ovary syndrome. clinicaltrials.gov/ct2/show/NCT01679574 (first received 6 September 2012). [NCT01679574]
NCT01793038 {published data only}
    1. NCT01793038. Clomiphene citrate plus uFSH versus aromatase inhibitor plus uFSH in clomiphene resistant infertile PCOS women. clinicaltrials.gov/ct2/show/NCT01793038 (first received 15 February 2013). [NCT01793038]
NCT03135301 {published data only}
    1. Abbas AM. Letrozole in clomiphene resistant infertile women with polycystic ovarian syndrome. clinicaltrials.gov/ct2/show/NCT03135301 (first received 1 May 2017).
Ozdemir 2013 {published data only}
    1. Ozdemir U, Ozaksit G, Cakir Gungor AN, Aydogan M. Letrozole usage adjuvant to gonadotropins for ovulation induction for patients with clomiphene citrate failure. Archives of Gynecology and Obstetrics 2013;288(2):445-8. - PubMed
Pakrashi 2014 {published data only}
    1. Pakrashi T, Baydoun H, Bocca S, Oehninger S, Stadtmauer L. Luteral phase supplementation with vaginal progesterone in women with Polycystic ovary syndrome and ovulatory Dysfunction undergoing ovulation induction with letrozole: a randomized controlled trial. Fertility and Sterility 2014;102(3):Suppl e237.
Palihawadana 2015 {published data only}
    1. Palihawadana TS, Wijesinghe PS, Seneviratne HR. A comparison of endometrial thickness following augmentation of ovulation with clomifene citrate or letrozole in women with ovulatory infertility. Ceylon Medical Journal 2015;60(2):48-52. - PubMed
Pourali 2017 {published data only}
    1. Pourali L, Ayati S, Tavakolizadeh S, Soleimani H, Sani FT. Clomiphene citrate versus letrozole with gonadotropins in intrauterine insemination cycles: a randomized trial. International Journal of Reproductive Biomedicine 2017;15(1):49-54. - PMC - PubMed
Sharma 2010 {published data only}
    1. Sharma S, Goswami SK, Rajani S, Mukherjee S. Efficacy of letrozole-gonadotropin, clomiphene-gonadotropin and only gonadotropin in clomiphene and letrozole resistant PCOS women undergoing IUI. Human Reproduction 2010;25(Suppl 1):i46.
Wang 2019 {published data only}
    1. Wang L, Wen X, Lv S, Zhao J, Yang T, Yang X. Comparison of endometrial receptivity of clomiphene citrate versus letrozole in women with polycystic ovary syndrome: a randomized controlled study. Gynecological Endocrinology 2019;35(10):862-5. - PubMed
Xi 2015 {published data only}
    1. Xi W, Liu S, Mao H, Yang Y, Xue X, Lu X. Use of letrozole and clomiphene citrate combined with gonadotropins in clomiphene-resistant infertile women with polycystic ovary syndrome: a prospective study. Drug Design, Development and Therapy 2015;9:6001-8. - PMC - PubMed
Yang 2008 {published data only}
    1. Yang M, Quan S, Li H, Song Y, Xing F. Effect of two different doses of letrozole in promoting ovulation in infertile women with polycystic ovarian syndrome. Journal of Southern Medical University 2008;28(11):2060-2. - PubMed
Yun 2015 {published data only}
    1. Yun BH, Chon SJ, Park JH, Seo SK, Cho S, Choi YS, et al. Minimal stimulation using gonadotropin combined with clomiphene citrate or letrozole for intrauterine insemination. Yonsei Medical Journal 2015;56:490-6. - PMC - PubMed

References to studies awaiting assessment

Abdellah 2011 {published data only}
    1. Abdellah MS. Reproductive outcome after letrozole versus laparoscopic ovarian drilling for clomiphene-resistant polycystic ovary syndrome. International Journal of Gynecology and Obstetrics 2011;113(3):218-21. - PubMed
Abu Hashim 2010a {published data only}
    1. Abu Hashim H, Mashaly AM, Badawy A. Letrozole versus laparoscopic ovarian diathermy for ovulation induction in clomiphene-resistant women with polycystic ovary syndrome: a randomized controlled trial. Archives of Gynecology and Obstetrics 2010;282(5):567-71. - PubMed
Aygen 2007 {published data only}
    1. Aygen EM, Guzel Z, Ozgun T, Atakul T, Sahin Y. The use of letrozole for ovulation induction in infertile women with polycystic ovarian syndrome. Erciyes Tip Dergisi 2007;29:195-200.
Ghoneim 2020 {published data only}
    1. Ghoneim BM, Farahat MA, El-Badry AM, El-Gharib MN. Clomiphene-metformin in comparison with letrozole-metformin in overweight infertile women with PCOS. Obstetrics Genecology and Reproductive Sciences 2020;4(1):1-8. [DOI: 10.31579/2578-8965/037] - DOI
Jindal 2019 {published data only}
    1. Jindal PC, Singh R, Singh M. Letrozole versus Clomiphene Citrate for induction of ovulation in PCOS Infertile patients for IUI: a comparative study. Human Reproduction 2019;34:Suppl 1.
Kamel 2019 {published data only}
    1. Kamel MA, Amin AF, Farghaly TA, Farag NA. Clomiphene citrate plus N-acetyl cysteine versus letrozole for induction of ovulation in infertile patients with polycystic ovarian disease: a randomized clinical trial. Internatinal Journal of Reproduction, Contraception, Obstetrics and Gynecology 2019;8(10):3959-63.
Lorzadeh 2011 {published data only}
    1. Lorzadeh N, Kazemirad S, Mohammadi Z. Comparison of effects letrozole and clomiphene citrate for ovulation induction in women with polycystic ovary syndrome. Iranian Journal of Obstetrics, Gynecology and Infertility 2011;14(3):13-19.
NCT02551367 {published data only}
    1. NCT02551367. Letrozole versus clomiphene citrate for ovulation induction in women with polycystic ovary syndrome (PCOS). clinicaltrials.gov/ct2/show/NCT02551367 (first received 16 September 2015). [NCT02551367]
NCT02703649 {published data only}
    1. NCT02703649. Administration of single high dose letrozole for ovulation induction. clinicaltrials.gov/ct2/show/NCT02703649 (first received 9 March 2016). [NCT02703649]
NCT03664050 {published data only}
    1. NCT03664050. Laparoscopic ovarian drilling versus letrozole in clomiphene citrate resistant polycystic ovary. clinicaltrials.gov/ct2/show/NCT03664050 (first received 10 September 2018).
Rezk 2018 {published data only}
    1. Rezk M, Shaheen A, El-Nasr IS. Clomiphene citrate combined with metformin versus letrozole for induction of ovulation in clomiphene-resistant polycystic ovary syndrome: a randomized clinical trial. Gynecological Endocrinlogy 2018;34(4):298-300. - PubMed
Safdarian 2012 {published data only}
    1. Safdarian L, Dibazar NS, Ahmadzadeh A, Yekta BG. Comparing two ovulation induction methods by brachial artery ultrasonography in infertile women with polycystic ovary syndrome. Tehran University Medical Journal 2012;70:242-9.
Saha 2020 {published data only}
    1. Saha S, Shirazee HH. Cost effective protocol with letrozole and 3 doses of gonadotropin combination as an alternative to continuous gonadotropin for ovulation induction for IUI in clomiphene resistant PCOS patients - a RCT. Fertility & Sterility 2020;114(3):e520.
Shirin 2009 {published data only}
    1. Shirin G, Mehran A, Maryam B, Maryam G, Masoumeh M. Comparing the effects of clomiphene-HMG and letrozole-HMG on ovulation Induction in infertile women. Journal of Reproduction and Infertility 2009;10(2):109-14.

References to ongoing studies

ChiCTR2100042082 {published data only}ChiCTR2100042082
    1. ChiCTR2100042082. Comparison of the clinical outcomes with different doses of letrozole in PCOS patients undergoing ovulation induction: a prospective, randomized, controlled trial. www.chictr.org.cn/searchprojen.aspx (first received 13 January 2021).
CTRI/2018/04/013343 {published data only}
    1. CTRI/2018/04/013343. A randomized controlled trial comparing the effect of letrozole and clomiphene citrate on endometrial development in infertile women with polycystic ovarian disease [A Randomized Controlled Trial comparing the effect of Letrozole and Clomiphene Citrate on endometrial development in infertile women with Polycystic Ovarian Disease]. www.ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=25010&EncHid... (first received 20 April 2018). [CTRI/2018/04/013343]
Cutler 2018 {published data only}
    1. Cutler DA, Shaw AK, Pride SM, Bedaiwy MA, Cheung AP. A randomized controlled trial comparing lifestyle intervention to letrozole for ovulation in women with polycystic ovary syndrome: a study protocol. Trials 2018;19:632. [https://doi.org/10.1186/s13063-018-3009-5] - PMC - PubMed
Huang 2020 {published data only}
    1. Huang S, Hu M, Ng EH, Stener-Victorin E, Zheng Y, Wen Q, et al. A multicenter randomized trial of personalized acupuncture, fixed acupuncture, letrozole, and placebo letrozole on live birth in infertile women with polycystic ovary syndrome. Trials 2020;4(21):239. [DOI: DOI: 10.1186/s13063-020-4154-1] - PMC - PubMed
IRCT2016030926962N2 {published data only}
    1. IRCT2016030926962N2. Comparing the efficacy of long-term and short-term doses of letrozole in ovulation induction among patients with polycystic ovary syndrome. en.irct.ir/trial/22224 (first received 8 May 2016).
NCT03009838 {published data only}
    1. NCT03009838. Letrozole versus laparoscopic ovarian drilling in polycystic ovary syndrome. clinicaltrials.gov/ct2/show/NCT03009838 (first received 4 January 2017).
Priest 2019 {published data only}
    1. Priest L. Letrozole or clomifene, with or without metformin, for ovulation induction in women with polycystic ovary syndrome: a 2x2 factorial design randomised trial (the LOCI trial). ISRCTN registry 2019. [ISRCTN11828358]

Additional references

Abu 2012
    1. Abu Hashim H. Clomiphene citrate alternatives for the initial management of polycystic ovary syndrome: an evidence-based approach. Archives of Gynecology and Obstetrics 2012;285(6):1737-45. - PubMed
Azziz 2006
    1. Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, et al, Androgen Excess Society. Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an androgen excess society guideline. Journal of Clinical Endocrinology and Metabolism 2006;91(11):4237-45. - PubMed
Azziz 2009
    1. Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, et al, Task Force on the Phenotype of the Polycystic Ovary Syndrome of The Androgen Excess and PCOS Society. The androgen excess and PCOS society criteria for the polycystic ovary syndrome: the complete task force report. Fertility and Sterility 2009;91(2):456. [PMID: ] - PubMed
Biljan 2005
    1. Biljan MM, Hemmings R, Brassard N. The outcome of 150 babies following the treatment with letrozole or letrozole and gonadotropins. Fertility and Sterility 2005;84(Suppl 1):s95.
Brown 2016
    1. Brown J, Farquhar C. Clomiphene and other antioestrogens for ovulation induction in polycystic ovarian syndrome. Cochrane Database of Systematic Reviews 2016, Issue 12. Art. No: CD002249. [DOI: 10.1002/14651858.CD002249.pub5] - DOI - PMC - PubMed
Casper 2006
    1. Casper RF, Mitwally MF. Review: aromatase inhibitors for ovulation induction. Journal of Clinical Endocrinology and Metabolism 2006;91(3):760-71. - PubMed
Casper 2011
    1. Casper RF, Mitwally MF. Use of the aromatase inhibitor letrozole for ovulation induction in women with polycystic ovarian syndrome. Clinical Obstetrics and Gynaecology 2011;54(4):685-95. - PubMed
Cole 1990
    1. Cole PA, Robinson CH. Mechanism and inhibition of cytochrome P-450 aromatase. Journal of Medical Chemistry 1990;33(11):2933-44. - PubMed
Duffy 2020
    1. Duffy JM, AlAhwany H, Bhattacharya S, Collura B, Curtis C, Evers JL, et al, Core Outcome Measure for Infertility Trials (COMMIT) initiative. Developing a core outcome set for future infertility research: an international consensus development study. Human Reproduction 2020;35(12):2725–34. [DOI: ] - PMC - PubMed
Farquhar 2002
    1. Farquhar CM, Williamson K, Gudex G, Johnson NP, Garland J, Sadler L. A randomized controlled trial of laparoscopic ovarian diathermy versus gonadotropin therapy for women with clomiphene citrate-resistant polycystic ovary syndrome. Fertility and Sterility 2002;78(2):404. - PubMed
Farquhar 2012
    1. Farquhar C, Brown J, Marjoribanks J. Laparoscopic drilling by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome. Cochrane Database of Systematic Reviews 2012, Issue 6. Art. No: CD001122. [DOI: 10.1002/14651858.CD001122.pub4] - DOI - PubMed
Forman 2007
    1. Forman R, Gill S, Moretti M, Tulandi T, Koren G, Casper R. Fetal safety of letrozole and clomiphene citrate for ovulation induction. Journal of Obstetrics and Gynaecology Canada 2007;29(8):668. - PubMed
GRADEpro GDT [Computer program]
    1. GRADEpro GDT. Version accessed prior to 26 September 2022. Hamilton (ON): McMaster University (developed by Evidence Prime). Available at gradepro.org.
Higgins 2017
    1. Higgins JP, Altman DG, Sterne JA, editor(s). Chapter 8: Assessing risk of bias in included studies. In: Higgins JP, Churchill R, Chandler J, Cumpston MS, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.2.0 (updated June 2017). Cochrane, 2017. Available from www.training.cochrane.org/handbook/archive/v5.2.
Higgins 2021
    1. Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.2 (updated February 2021). Cochrane, 2021. Available from training.cochrane.org/handbook. - PMC - PubMed
Homburg 2011
    1. Homburg R, Hendriks ML, König TE, Anderson RA, Balen AH, Brincat M, et al. Clomifene citrate or low-dose FSH for the first-line treatment of infertile women with anovulation associated with polycystic ovary syndrome: a prospective randomized multinational study. Human Reproduction 2011;27(2):468-73. - PubMed
Jirge 2010
    1. Jirge PR, Patil RS. Comparison of endocrine and ultrasound profiles during ovulation induction with clomiphene citrate and letrozole in ovulatory volunteer women. Fertility and Sterility 2010;93(1):174-83. - PubMed
Lee 2011
    1. Lee VC, Ledger W. Aromatase inhibitors for ovulation induction and ovarian stimulation. Clinical Endocrinology 2011;74(5):537-46. - PubMed
Lefebvre 2021
    1. Lefebvre C, Glanville J, Briscoe S, Littlewood A, Marshall C, Metzendorf M-I, et al. Chapter 4: Searching for and selecting studies. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.2 (updated February 2021). Cochrane, 2021. Available from training.cochrane.org/handbook.
Lizneva 2016
    1. Lizneva D, Suturina L, Walker W, Brakta S, Gavrilova-Jordan L, Azziz R. Criteria, prevalence, and phenotypes of polycystic ovary syndrome. Fertility and Sterility 2016;106(1):6-15. [DOI: 10.1016/j.fertnstert.2016.05.003] - DOI - PubMed
Lunenfeld 2004
    1. Lunenfeld B. Historical perspectives in gonadotrophin therapy. Human Reproduction Update 2004;10(6):453-67. - PubMed
Misso 2012
    1. Misso ML, Wong JL, Teede HJ, Hart R, Rombauts L, Melder AM, et al. Aromatase inhibitors for PCOS: a systematic review and meta-analysis. Human Reproduction Update 2012;18(3):301-12. - PubMed
Mitwally 2001
    1. Mitwally MF, Casper RF. Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate. Fertility and Sterility 2001;75(2):305-9. - PubMed
Nahuis 2011
    1. Nahuis MJ, Kose N, Bayram N, Van Dessel HJ, Braat DD, Hamilton CJ, et al. Long-term outcomes in women with polycystic ovary syndrome initially randomized to receive laparoscopic electrocautery of the ovaries or ovulation induction with gonadotrophins. Human Reproduction 2011;26(7):1889-1904. - PubMed
Reproductive Medicine Network 2013
    1. Reproductive Medicine Network. Letrozole versus clomiphene citrate in anovulatory PCOS women: A cost-effectiveness analysis. Fertility and Sterility 2013;100(3):Suppl 128.
Review Manager 2020 [Computer program]
    1. Review Manager 5 (RevMan 5). Version 5.4. Copenhagen: The Cochrane Collaboration, 2020.
Roque 2015
    1. Roque M, Tostes AC, Valle M, Sampaio M, Geber S. Letrozole versus clomiphene citrate in polycystic ovary syndrome: systematic review and meta-analysis. Gynaecological Endocrinology 2015;31(12):917-21. [DOI: 10.3109/09513590.2015.1096337] - DOI - PubMed
Rotterdam 2003
    1. Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Human Reproduction 2004;19(1):41. - PubMed
Samani 2009
    1. Samani FG, Farzadi L, Nezami N, Tarzamni MK, Soleimani F. Endometrial and follicular development following letrozole intervention in unexplained infertile patients failed to get pregnant with clomiphene citrate. Archives of Gynecology and Obstetrics 2009;280(2):201-5. - PubMed
Schünemann 2013
    1. Schünemann H, Brożek J, Guyatt G, Oxman A, editor(s). Handbook for grading the quality of evidence and the strength of recommendations using the GRADE approach (updated October 2013). GRADE Working Group, 2013. Available from gdt.guidelinedevelopment.org/app/handbook/handbook.html.
Soares 2008
    1. Soares SR, Gomez R, Simon C, Garcia-Velasco JA, Pellicer A. Targeting the vascular endothelial growth factor system to prevent ovarian hyperstimulation syndrome. Human Reproduction Update 2008;14:321-33. [DOI: ] - PubMed
Tulandi 2006
    1. Tulandi T, Martin J, Al-Fadhli R, Kabli N, Forman R, Hitkari J, et al. Congenital malformations among 911 newborns conceived after infertility treatment with letrozole or clomiphene citrate. Fertility and Sterility 2006;85(6):1761-5. - PubMed
Velázquez 1997
    1. Velázquez E, Acosta A, Mendoza SG. Menstrual cyclicity after metformin therapy in polycystic ovary syndrome. Obstetrics and Gynecology 1997;90(3):392-5. - PubMed
Von Hofe 2015
    1. Von Hofe J, Wright Bates G. Ovulation Induction. Obstetrics and Gynecoly Clinics of North America 2015;42:27-37. - PubMed
White 1996
    1. White DM, Polson DW, Kiddy D, Sagle P, Watson H, Gilling-Smith C, et al. Induction of ovulation with low-dose gonadotropins in polycystic ovary syndrome: an analysis of 109 pregnancies in 225 women. Journal of Clinical Endocrinology and Metabolism 1996;81(11):3821-4. - PubMed
Zawadski 1992
    1. Zawadski JK, Dunaif A. Diagnostic criteria for polycystic ovary syndrome: Towards a rational approach. Boston: Blackwell Scientific Publications 1992:377-84.

References to other published versions of this review

Franik 2012
    1. Franik S, Kremer JA, Nelen WL, Farquhar C. Aromatase inhibitors for subfertile women with polycystic ovary syndrome. Cochrane Database of Systematic Reviews 2012, Issue 12. Art. No: CD010287. [DOI: 10.1002/14651858.CD010287] - DOI - PubMed
Franik 2014
    1. Franik S, Kremer JA, Nelen WL, Farquhar C. Aromatase inhibitors for subfertile women with polycystic ovary syndrome. Cochrane Database of Systematic Reviews 2014, Issue 2. Art. No: CD010287. [DOI: 10.1002/14651858.CD010287.pub2] - DOI - PubMed
Franik 2018
    1. Franik S, Eltrop SM, Kremer JA, Kiesel L, Farquhar C. Aromatase inhibitors (letrozole) for subfertile women with polycystic ovary syndrome. Cochrane Database of Systematic Reviews 2018, Issue 5. Art. No: CD010287. [DOI: 10.1002/14651858.CD010287.pub3] - DOI - PMC - PubMed

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