{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T02:30:43Z","timestamp":1792809043509,"version":"4.5.0"},"reference-count":82,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2020,12,29]],"date-time":"2020-12-29T00:00:00Z","timestamp":1609200000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,4,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>The aromatase inhibitor letrozole is increasingly recommended for ovulation induction, as it is more effective with fewer side-effects than other agents. But many clinicians are reluctant to use the drug for fertility treatment due to a strong-label warning against its use, which warns about congenital malformation risk to the foetus in women seeking pregnancy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>OBJECTIVE AND RATIONALE<\/jats:title>\n                    <jats:p>The aim of this study was to determine the risks of congenital malformations and pregnancy loss with letrozole compared with clomiphene primarily, and with other fertility drugs and natural conception.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>SEARCH METHODS<\/jats:title>\n                    <jats:p>A systematic review and meta-analysis using PRISMA harms guidelines. We searched MEDLINE, EMBASE and other sources from inception until January 2020, with the MeSH words for \u2018letrozole\u2019 and pregnancy OR foetal\/neonatal outcome. We included studies reported on congenital malformations in foetuses born to mothers conceived after fertility treatment, with letrozole versus clomiphene, placebo, gonadotrophins, metformin, natural conception or other agents, from randomised trials, comparative cohort studies and non-comparative observational cohorts. Quality of the studies was assessed using Cochrane risk of bias tool and Newcastle Ottawa Scale. The McMaster tool was used to assess the quality of reported harm for foetal congenital malformations in the studies. We compared the absolute risk of events using risk difference measures and pooled the findings using a fixed-effect model. We evaluated the statistical heterogeneity using forest plots and the I2 statistic and funnel plot to assess publication bias. We assessed the strength of evidence for congenital malformation and pregnancy loss as per the GRADE recommendations and with the Fragility index.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>OUTCOMES<\/jats:title>\n                    <jats:p>We included 46 studies (18 randomised trials; 21 comparative cohorts; 7 non-comparative cohorts). Overall 2.15% (101\/4697; 95% CI 1.7 to 2.5) of babies conceived on letrozole for fertility treatment had congenital foetal malformations. We did not observe a significant increase in congenital malformations with letrozole versus clomiphene in the randomised trials (risk difference (RD) 0.01, 95% CI \u22120.02, 0.03; I2 = 0%; 14 studies) and found a significant reduction in the cohort studies (RD \u22120.02, 95% CI \u22120.04, \u22120.01; I2 = 0%, 11 studies). The fragility index was 44% (7\/16) (either an increase in the intervention arm or a decrease in control arm was needed to alter the results). The risks of pregnancy loss were not increased with letrozole versus clomiphene in the 14 randomised trials (RD \u22120.01, 95% CI \u22120.06, 0.04; I2 = 0%), and the risks were reduced in the six cohort studies (RD \u22120.09, 95% CI \u22120.17, \u22120.00; I2 = 68%). The GRADE quality of evidence was low to moderate for congenital malformations and pregnancy loss. We did not find any increased congenital malformation risk with letrozole versus gonadotrophins, natural conception or natural cycle ART, but the number of studies was small.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WIDER IMPLICATIONS<\/jats:title>\n                    <jats:p>There is no evidence that letrozole increases the risk of congenital foetal malformation or pregnancy loss compared with clomiphene, natural conception or other fertility agents, to warrant warning against its use. Given its therapeutic benefits and lack of evidence of harm to the foetus, clinicians should consider letrozole as first-line agent for ovulation induction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/humupd\/dmaa055","type":"journal-article","created":{"date-parts":[[2020,11,25]],"date-time":"2020-11-25T23:12:48Z","timestamp":1606345968000},"page":"474-485","source":"Crossref","is-referenced-by-count":44,"title":["Risk of foetal harm with letrozole use in fertility treatment: a systematic review and meta-analysis"],"prefix":"10.1093","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4183-8048","authenticated-orcid":false,"given":"Jyotsna","family":"Pundir","sequence":"first","affiliation":[{"name":"Queen Mary University, London E1 4NS, UK"},{"name":"Centre for Reproductive Medicine, St. Bartholomew\u2019s Hospital, London EC1A 7BE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Achilli","sequence":"additional","affiliation":[{"name":"Hewitt Fertility Centre, Liverpool Women\u2019s Hospital, Liverpool L8 7SS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya","family":"Bhide","sequence":"additional","affiliation":[{"name":"Centre for Women\u2019s Health, Queen Mary University of London, E1 2AB, UK"},{"name":"Homerton University Hospital, London E9 6SR, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Sabatini","sequence":"additional","affiliation":[{"name":"Centre for Reproductive Medicine, St. Bartholomew\u2019s Hospital, London EC1A 7BE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard S","family":"Legro","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Penn State University College of Medicine, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luk","family":"Rombauts","sequence":"additional","affiliation":[{"name":"Monash University, Clayton, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Teede","sequence":"additional","affiliation":[{"name":"Monash Centre for Health Research and Implementation, Monash University, Clayton, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arri","family":"Coomarasamy","sequence":"additional","affiliation":[{"name":"Tommy\u2019s National Centre for Miscarriage Research, Institute of Metabolism and Systems Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK"},{"name":"Birmingham Women\u2019s and Children\u2019s NHS Foundation Trust, Birmingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Zamora","sequence":"additional","affiliation":[{"name":"CIBER Epidemiology and Public Health, Clinical Biostatistics Unit, Hospital Ramon y Cajal Ctra, Madrid 28034, Spain"},{"name":"Women's Health Research Unit, Queen Mary University of London"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shakila","family":"Thangaratinam","sequence":"additional","affiliation":[{"name":"Birmingham Women\u2019s and Children\u2019s NHS Foundation Trust, Birmingham, UK"},{"name":"Institute of Metabolism and Systems Research, University of Birmingham, Edgbaston, Birmingham B15 2TT UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,12,29]]},"reference":[{"key":"2021042605535025600_dmaa055-B1","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.ijgo.2010.11.026","article-title":"Reproductive outcome after letrozole versus laparoscopic ovarian drilling for clomiphene-resistant polycystic ovary syndrome","volume":"113","author":"Abdellah","year":"2011","journal-title":"Int J Gynaecol Obstet"},{"key":"2021042605535025600_dmaa055-B2","first-page":"29","article-title":"Comparing of letrozole versus clomiphene citrate combined with gonadotropins in intrauterine insemination cycles","volume":"10","author":"Akbari","year":"2012","journal-title":"Iran J Reprod Med"},{"key":"2021042605535025600_dmaa055-B3","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1093\/humrep\/dez272","article-title":"Harmonising research outcomes for polycystic ovary syndrome: an international multi-stakeholder core outcome set","volume":"35","author":"Al Wattar","year":"2020","journal-title":"Hum Reprod"},{"key":"2021042605535025600_dmaa055-B4","doi-asserted-by":"crossref","first-page":"83","DOI":"10.29252\/ijrm.15.2.83","article-title":"Can letrozole plus HMG protocol improve pregnancy outcomes in frozen-thawed embryo transfer? An RCT","volume":"15","author":"Aleyasin","year":"2017","journal-title":"Int J Reprod Biomed"},{"key":"2021042605535025600_dmaa055-B5","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1093\/humrep\/dex227","article-title":"Double-blind randomized controlled trial of letrozole versus clomiphene citrate in subfertile women with polycystic ovarian syndrome","volume":"32","author":"Amer","year":"2017","journal-title":"Hum Reprod"},{"key":"2021042605535025600_dmaa055-B6","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.jclinepi.2019.03.012","article-title":"The statistical significance of meta-analyses is frequently fragile: definition of a fragility index for meta-analyses","volume":"111","author":"Atal","year":"2019","journal-title":"J Clin Epidemiol"},{"key":"2021042605535025600_dmaa055-B7","first-page":"33","article-title":"Pregnancies following the use of sequential treatment of metformin and incremental doses of letrozole in clomiphen-resistant women with polycystic ovary syndrome","volume":"10","author":"Azargoon","year":"2012","journal-title":"Iran J Reprod Med"},{"key":"2021042605535025600_dmaa055-B8","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1080\/00016340802638199","article-title":"Pregnancy outcome after ovulation induction with aromatase inhibitors or clomiphene citrate in unexplained infertility","volume":"88","author":"Badawy","year":"2009","journal-title":"Acta Obstet Gynecol Scand"},{"key":"2021042605535025600_dmaa055-B9","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/j.fertnstert.2005.09.045","article-title":"Letrozole vs. clomiphene citrate in patients with ovulatory infertility","volume":"85","author":"Bayar","year":"2006","journal-title":"Fertil Steril"},{"key":"2021042605535025600_dmaa055-B10","doi-asserted-by":"crossref","first-page":"2838","DOI":"10.1093\/humrep\/del273","article-title":"Cost-effectiveness of aromatase inhibitor co-treatment for controlled ovarian stimulation","volume":"21","author":"Bedaiwy","year":"2006","journal-title":"Hum Reprod"},{"issue":"Suppl. 1","key":"2021042605535025600_dmaa055-B11","first-page":"O-231","article-title":"The outcome of 150 babies following the treatment with letrozole or letrozole and gonadotropins","volume":"84","author":"Biljan","year":"2005","journal-title":"Fertil Steril"},{"key":"2021042605535025600_dmaa055-B12","article-title":"Letrozole as first time treatment for infertility: a cost effective option in a non-mandated state","volume":"22","author":"Bocca","year":"2015","journal-title":"Reprod Sci"},{"key":"2021042605535025600_dmaa055-B13","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1093\/humrep\/dem046","article-title":"International estimates of infertility prevalence and treatment-seeking: potential need and demand for infertility medical care","volume":"22","author":"Boivin","year":"2007","journal-title":"Hum Reprod"},{"key":"2021042605535025600_dmaa055-B14","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.rbmo.2019.05.023","article-title":"The management of unexplained infertility: an evidence-based guideline from the Canadian Fertility and Andrology Society","volume":"39","author":"Buckett","year":"2019","journal-title":"Reprod Biomed Online"},{"key":"2021042605535025600_dmaa055-B15","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.jclinepi.2008.06.007","article-title":"AHRQ series paper 4: assessing harms when comparing medical interventions: AHRQ and the effective health-care program","volume":"63","author":"Chou","year":"2010","journal-title":"J Clin Epidemiol"},{"key":"2021042605535025600_dmaa055-B16"},{"key":"2021042605535025600_dmaa055-B17","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1111\/j.1479-828X.2004.00192.x","article-title":"Systematic review of the treatment of ovulatory infertility with clomiphene citrate and intrauterine insemination","volume":"44","author":"Costello","year":"2004","journal-title":"Aust N Z J Obstet Gynaecol"},{"key":"2021042605535025600_dmaa055-B18","first-page":"23","article-title":"Comparison of the effects of letrozole and clomiphene citrate on ovulation and pregnancy rate in patients with polycystic ovary syndrome","volume":"34","author":"Dehbashi","year":"2009","journal-title":"Iran J Med Sci"},{"key":"2021042605535025600_dmaa055-B19","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1056\/NEJMoa1414827","article-title":"Letrozole, gonadotropin, or clomiphene for unexplained infertility","volume":"373","author":"Diamond","year":"2015","journal-title":"N Engl J Med"},{"key":"2021042605535025600_dmaa055-B20","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1007\/978-90-481-9485-8_20","article-title":"The prevalence of congenital anomalies in Europe","volume":"686","author":"Dolk","year":"2010","journal-title":"Adv Exp Med Biol"},{"key":"2021042605535025600_dmaa055-B21","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1161\/CIRCULATIONAHA.110.958405","article-title":"Congenital heart defects in Europe: prevalence and perinatal mortality, 2000 to 2005","volume":"123","author":"Dolk","year":"2011","journal-title":"Circulation"},{"key":"2021042605535025600_dmaa055-B22","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.pedneo.2014.03.010","article-title":"Congenital malformations in the newborn population: a population study and analysis of the effect of sex and prematurity","volume":"56","author":"Egbe","year":"2015","journal-title":"Pediatr Neonatol"},{"key":"2021042605535025600_dmaa055-B23","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1093\/humrep\/deg459","article-title":"High singleton live birth rate following classical ovulation induction in normogonadotrophic anovulatory infertility (WHO 2)","volume":"18","author":"Eijkemans","year":"2003","journal-title":"Hum Reprod"},{"key":"2021042605535025600_dmaa055-B24","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.ijgo.2015.06.063","article-title":"A randomized controlled trial of clomifene citrate, metformin, and pioglitazone versus letrozole, metformin, and pioglitazone for clomifene-citrate-resistant polycystic ovary syndrome","volume":"132","author":"El-Khayat","year":"2016","journal-title":"Int J Gynaecol Obstet"},{"key":"2021042605535025600_dmaa055-B25","first-page":"CD010537","article-title":"Assisted reproductive technology: an overview of Cochrane Reviews","volume":"8","author":"Farquhar","year":"2018","journal-title":"Cochrane Database Syst Rev"},{"key":"2021042605535025600_dmaa055-B26","year":"2017"},{"key":"2021042605535025600_dmaa055-B27","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/S1701-2163(16)32551-8","article-title":"Fetal safety of letrozole and clomiphene citrate for ovulation induction","volume":"29","author":"Forman","year":"2007","journal-title":"J Obstet Gynaecol Can"},{"key":"2021042605535025600_dmaa055-B28","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/1477-7827-9-84","article-title":"Extended letrozole regimen versus clomiphene citrate for superovulation in patients with unexplained infertility undergoing intrauterine insemination: a randomized controlled trial","volume":"9","author":"Fouda","year":"2011","journal-title":"Reprod Biol Endocrinol"},{"key":"2021042605535025600_dmaa055-B29","first-page":"CD010287","article-title":"Aromatase inhibitors (letrozole) for subfertile women with polycystic ovary syndrome","volume":"5","author":"Franik","year":"2018","journal-title":"Cochrane Database Syst Rev"},{"key":"2021042605535025600_dmaa055-B30","author":"Gemmell","year":"2014"},{"key":"2021042605535025600_dmaa055-B31","first-page":"151","article-title":"Effects of inositol on ovarian function and metabolic factors in women with PCOS: a randomized double blind placebo-controlled trial","volume":"7","author":"Gerli","year":"2003","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"2021042605535025600_dmaa055-B32","doi-asserted-by":"crossref","first-page":"e13038","DOI":"10.1097\/MD.0000000000013038","article-title":"Letrozole for patients with polycystic ovary syndrome: a retrospective study","volume":"97","author":"Guang","year":"2018","journal-title":"Medicine (Baltimore)"},{"key":"2021042605535025600_dmaa055-B33","doi-asserted-by":"crossref","first-page":"4596","DOI":"10.12659\/MSM.898044","article-title":"Effect of natural cycle endometrial preparation for frozen-thawed embryo transfer in patients with advanced endometriosis","volume":"22","author":"Guo","year":"2016","journal-title":"Med Sci Monit"},{"key":"2021042605535025600_dmaa055-B34","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1136\/bmj.39489.470347.AD","article-title":"GRADE: an emerging consensus on rating quality of evidence and strength of recommendations","volume":"336","author":"Guyatt","year":"2008","journal-title":"BMJ"},{"key":"2021042605535025600_dmaa055-B35","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1111\/j.1600-0412.2011.01346.x","article-title":"Randomized comparison of superovulation with letrozole vs. clomiphene citrate in an IUI program for women with recently surgically treated minimal to mild endometriosis","volume":"91","author":"Hashim","year":"2012","journal-title":"Acta Obstet Gynecol Scand"},{"key":"2021042605535025600_dmaa055-B36","doi-asserted-by":"crossref","first-page":"173","DOI":"10.4103\/jhrs.JHRS_120_16","article-title":"A study of controlled ovarian stimulation with clomiphene citrate or letrozole in combination with gonadotropins and IUI in unexplained infertility","volume":"10","author":"Hembram","year":"2017","journal-title":"J Hum Reprod Sci"},{"key":"2021042605535025600_dmaa055-B37","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1002\/sim.1186","article-title":"Quantifying heterogeneity in a meta-analysis","volume":"21","author":"Higgins","year":"2002","journal-title":"Statist Med"},{"key":"2021042605535025600_dmaa055-B38","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1007\/s00404-018-4688-6","article-title":"Letrozole versus clomiphene citrate in polycystic ovary syndrome: a meta-analysis of randomized controlled trials","volume":"297","author":"Hu","year":"2018","journal-title":"Arch Gynecol Obstet"},{"key":"2021042605535025600_dmaa055-B39","doi-asserted-by":"crossref","first-page":"2857","DOI":"10.1016\/j.fertnstert.2010.06.008","article-title":"Aromatase inhibitors in women with clomiphene citrate resistance: a randomized, double-blind, placebo-controlled trial","volume":"94","author":"Kamath","year":"2010","journal-title":"Fertil Steril"},{"key":"2021042605535025600_dmaa055-B40","first-page":"CD008528","article-title":"Oral medications including clomiphene citrate or aromatase inhibitors with gonadotropins for controlled ovarian stimulation in women undergoing in vitro fertilisation","volume":"11","author":"Kamath","year":"2017","journal-title":"Cochrane Database Syst Rev"},{"key":"2021042605535025600_dmaa055-B41","article-title":"The effects of endometrial preparation regimen on pregnancy and neonatal outcomes following single vitrified warmed blastocyst transfer","volume":"31","author":"Kato","year":"2016","journal-title":"Hum Reprod"},{"key":"2021042605535025600_dmaa055-B42","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1007\/s00404-012-2579-9","article-title":"Is letrozole superior to clomiphene for ovarian stimulation prior to intrauterine insemination?","volume":"287","author":"Khanna","year":"2013","journal-title":"Arch Gynecol Obstet"},{"key":"2021042605535025600_dmaa055-B43","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.fertnstert.2013.09.007","article-title":"Luteal-phase ovarian stimulation is feasible for producing competent oocytes in women undergoing in vitro fertilization\/intracytoplasmic sperm injection treatment, with optimal pregnancy outcomes in frozen-thawed embryo transfer cycles","volume":"101","author":"Kuang","year":"2014","journal-title":"Fertil Steril"},{"key":"2021042605535025600_dmaa055-B44","first-page":"264","article-title":"Efficacy of letrozole and clomiphene in patients with multiple-cause infertility undergoing intrauterine insemination","volume":"4","author":"Lee","year":"2012","journal-title":"Int J Pharm Pharmaceut Sci"},{"key":"2021042605535025600_dmaa055-B45","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1056\/NEJMoa1313517","article-title":"Letrozole versus clomiphene for infertility in the polycystic ovary syndrome","volume":"371","author":"Legro","year":"2014","journal-title":"N Engl J Med"},{"key":"2021042605535025600_dmaa055-B46","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1136\/bmj.322.7300.1479","article-title":"Forest plots: trying to see the wood and the trees","volume":"322","author":"Lewis","year":"2001","journal-title":"BMJ"},{"key":"2021042605535025600_dmaa055-B47","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1080\/09513590.2017.1332174","article-title":"Comparison of clomiphene citrate and letrozole for ovulation induction in women with polycystic ovary syndrome: a prospective randomized trial","volume":"33","author":"Liu","year":"2017","journal-title":"Gynecol Endocrinol"},{"issue":"4 Suppl 14","key":"2021042605535025600_dmaa055-B48","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0093-7754(03)00305-1","article-title":"Pharmacokinetics of third-generation aromatase inhibitors","volume":"30","author":"L\u00f8nning","year":"2003","journal-title":"Semin Oncol"},{"key":"2021042605535025600_dmaa055-B49","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/S0960-0760(03)00358-3","article-title":"Use of letrozole as a chemopreventive agent in aromatase overexpressing transgenic mice","volume":"86","author":"Luthra","year":"2003","journal-title":"J Steroid Biochem Mol Biol"},{"key":"2021042605535025600_dmaa055-B50","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1016\/j.fertnstert.2013.08.040","article-title":"An assessment of current clinical attitudes toward letrozole use in reproductive endocrinology practices","volume":"100","author":"Malloch","year":"2013","journal-title":"Fertil Steril"},{"key":"2021042605535025600_dmaa055-B51","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/humupd\/3.3.235","article-title":"Current and future status of ovulation induction in polycystic ovary syndrome","volume":"3","author":"Messinis","year":"1997","journal-title":"Hum Reprod Update"},{"key":"2021042605535025600_dmaa055-B52","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/S0015-0282(00)01705-2","article-title":"Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate","volume":"75","author":"Mitwally","year":"2001","journal-title":"Fertil Steril"},{"key":"2021042605535025600_dmaa055-B53","article-title":"Pregnancy and neonatal outcome following ovulation induction with the aromatase inhibitor letrozole and clomiphene","volume":"29","author":"Nakamura","year":"2014","journal-title":"Hum Reprod"},{"key":"2021042605535025600_dmaa055-B54"},{"key":"2021042605535025600_dmaa055-B55","doi-asserted-by":"crossref","first-page":"2424","DOI":"10.1200\/JCO.2014.59.3723","article-title":"Fertility preservation success subsequent to concurrent aromatase inhibitor treatment and ovarian stimulation in women with breast cancer","volume":"33","author":"Oktay","year":"2015","journal-title":"J Clin Oncol"},{"key":"2021042605535025600_dmaa055-B56","first-page":"32","article-title":"Letrozole ovulation induction in clomiphene resistant women, experience from a DGH","volume":"14","author":"Opoku","year":"2011","journal-title":"Hum Fertil"},{"key":"2021042605535025600_dmaa055-B57","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1136\/bmj.328.7454.1490","article-title":"Grading quality of evidence and strength of recommendations GRADE Working Group","volume":"328","author":"Oxman","year":"2004","journal-title":"BMJ"},{"key":"2021042605535025600_dmaa055-B58","article-title":"Oocyte cryopreservation after ovarian stimulation with gonadotropin and letrozole to save fertility in breast cancer","volume":"29","author":"Porcu","year":"2014","journal-title":"Hum Reprod"},{"key":"2021042605535025600_dmaa055-B59","first-page":"81","article-title":"Letrozole as an ovulation induction agent: safe or unsafe?","volume":"121","author":"Rajesh","year":"2014","journal-title":"BJOG"},{"key":"2021042605535025600_dmaa055-B60","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1007\/s00404-011-2091-7","article-title":"Comparison of efficacy of letrozole and clomiphene citrate in ovulation induction in Indian women with polycystic ovarian syndrome","volume":"285","author":"Ray","year":"2012","journal-title":"Arch Gynecol Obstet"},{"key":"2021042605535025600_dmaa055-B61","doi-asserted-by":"crossref","first-page":"20","DOI":"10.4103\/0974-1208.97789","article-title":"A prospective randomized trial comparing the efficacy of Letrozole and Clomiphene citrate in induction of ovulation in polycystic ovarian syndrome","volume":"5","author":"Roy","year":"2012","journal-title":"J Hum Reprod Sci"},{"key":"2021042605535025600_dmaa055-B62","first-page":"24","volume-title":"Infecundity, Infertility, and Childlessness in Developing Countries. DHS Comparative Reports No. 9","author":"Rutstein","year":"2004"},{"key":"2021042605535025600_dmaa055-B63","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1111\/jog.13644","article-title":"Comparison of the pregnancy outcomes and the incidence of fetal congenital abnormalities in infertile women treated with letrozole and clomiphene citrate","volume":"44","author":"Sene","year":"2018","journal-title":"J Obstet Gynaecol Res"},{"key":"2021042605535025600_dmaa055-B64","doi-asserted-by":"crossref","first-page":"e108219","DOI":"10.1371\/journal.pone.0108219","article-title":"Congenital malformations among babies born following letrozole or clomiphene for infertility treatment","volume":"9","author":"Sharma","year":"2014","journal-title":"PLoS One"},{"key":"2021042605535025600_dmaa055-B65","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/1471-2288-11-15","article-title":"Methodology in conducting a systematic review of systematic reviews of healthcare interventions","volume":"11","author":"Smith","year":"2011","journal-title":"BMC Med Res Methodol"},{"key":"2021042605535025600_dmaa055-B66","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1093\/humrep\/del020","article-title":"Efficacy of combined metformin-letrozole in comparison with metformin-clomiphene citrate in clomiphene-resistant infertile women with polycystic ovarian disease","volume":"21","author":"Sohrabvand","year":"2006","journal-title":"Hum Reprod"},{"key":"2021042605535025600_dmaa055-B67","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1093\/oxfordjournals.humrep.a136353","article-title":"Epidemiology of human reproduction","volume":"1","author":"Spira","year":"1986","journal-title":"Hum Reprod"},{"key":"2021042605535025600_dmaa055-B68","first-page":"125","article-title":"No increased risk of major congenital anomalies or adverse pregnancy or neonatal outcomes following letrozole use in assisted reproductive technology","volume":"32","author":"Tatsumi","year":"2016","journal-title":"Hum Reprod"},{"key":"2021042605535025600_dmaa055-B69","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1093\/humrep\/dex066","article-title":"Pregnancy and neonatal outcomes following letrozole use in frozen-thawed single embryo transfer cycles","volume":"32","author":"Tatsumi","year":"2017","journal-title":"Hum Reprod"},{"key":"2021042605535025600_dmaa055-B70","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1093\/humrep\/dey256","article-title":"Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome","volume":"33","author":"Teede","year":"2018","journal-title":"Hum Reprod"},{"key":"2021042605535025600_dmaa055-B71","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1016\/j.fertnstert.2006.03.014","article-title":"Congenital malformations among 911 newborns conceived after infertility treatment with letrozole or clomiphene citrate","volume":"85","author":"Tulandi","year":"2006","journal-title":"Fertil Steril"},{"key":"2021042605535025600_dmaa055-B72","doi-asserted-by":"crossref","first-page":"j138","DOI":"10.1136\/bmj.j138","article-title":"Treatment strategies for women with WHO group II anovulation: systematic review and network meta-analysis","volume":"356","author":"Wang","year":"2017","journal-title":"BMJ"},{"key":"2021042605535025600_dmaa055-B73","volume-title":"The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-Analyses","author":"Wells","year":"2011"},{"key":"2021042605535025600_dmaa055-B74","year":"2014"},{"key":"2021042605535025600_dmaa055-B75","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.fertnstert.2016.05.022","article-title":"Randomized controlled trial of letrozole, berberine, or a combination for infertility in the polycystic ovary syndrome","volume":"106","author":"Wu","year":"2016","journal-title":"Fertil Steril"},{"key":"2021042605535025600_dmaa055-B76","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1007\/s00404-016-4164-0","article-title":"A comparison among different methods of letrozole combined with gonadotropin in an antagonist protocol and high-dose gonadotropin ovarian stimulation antagonist protocol in poor ovarian responders undergoing in vitro fertilization","volume":"294","author":"Yang","year":"2016","journal-title":"Arch Gynecol Obstet"},{"key":"2021042605535025600_dmaa055-B77","first-page":"105","article-title":"Evaluation of long-term results of treatment with aromatase inhibitors","volume":"32","author":"Yarmolinskaya","year":"2016","journal-title":"Gynecol Endocrinol"},{"key":"2021042605535025600_dmaa055-B78","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.fertnstert.2017.10.033","article-title":"Low dosing of gonadotropins in in vitro fertilization cycles for women with poor ovarian reserve: systematic review and meta-analysis","volume":"109","author":"Youssef","year":"2018","journal-title":"Fertil Steril"},{"key":"2021042605535025600_dmaa055-B79","doi-asserted-by":"crossref","first-page":"653","DOI":"10.3109\/09513590.2014.920002","article-title":"Comparison of estradiol and progesterone priming\/antagonist\/letrozole and microdose flare-up protocols for poor responders undergoing intracytoplasmic sperm injection","volume":"30","author":"Yucel","year":"2014","journal-title":"Gynecol Endocrinol"},{"key":"2021042605535025600_dmaa055-B80","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.reprotox.2018.10.006","article-title":"Comparison of congenital malformations among babies born after administration of letrozole or clomiphene citrate for infertility treatment in a Korean cohort","volume":"82","author":"Yun","year":"2018","journal-title":"Reprod Toxicol"},{"key":"2021042605535025600_dmaa055-B81","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.fertnstert.2019.09.042","article-title":"Gonadotropins versus oral ovarian stimulation agents for unexplained infertility: a systematic review and meta-analysis","volume":"113","author":"Zolton","year":"2020","journal-title":"Fertil Steril"},{"key":"2021042605535025600_dmaa055-B82","doi-asserted-by":"crossref","first-page":"i157","DOI":"10.1136\/bmj.i157","article-title":"PRISMA harms checklist: improving harms reporting in systematic reviews","volume":"352","author":"Zorzela","year":"2016","journal-title":"BMJ"}],"container-title":["Human Reproduction Update"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/humupd\/article-pdf\/27\/3\/474\/37248770\/dmaa055.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/humupd\/article-pdf\/27\/3\/474\/37248770\/dmaa055.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T17:29:48Z","timestamp":1669742988000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/humupd\/article\/27\/3\/474\/6055043"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,29]]},"references-count":82,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,12,29]]},"published-print":{"date-parts":[[2021,4,21]]}},"URL":"https:\/\/doi.org\/10.1093\/humupd\/dmaa055","relation":{},"ISSN":["1355-4786","1460-2369"],"issn-type":[{"value":"1355-4786","type":"print"},{"value":"1460-2369","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,6,1]]},"published":{"date-parts":[[2020,12,29]]}}}