Letrozole: ovulation or superovulation?
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Aromatase inhibitors theoretically avoid adverse effects of clomiphene citrate as they do not affect oestrogen receptors centrally or thin the endometrium.
“These agents theoretically avoid adverse effects of clomiphene citrate, 238,239 as they do not affect oestrogen receptors centrally or thin the endometrium. 237”
From Assessment and management of polycystic ovary syndrome: Summary of an evidence-based guideline (2011) · cites this paper as [239]
Cites
Aromatase inhibition improves ovarian response to follicle-stimulating hormone in poor responders
Mitwally, M. F. M., & Casper, R. F. (2002) · Fertility and Sterility · doi:10.1016/s0015-0282(01)03280-0 · Cited by 407 · see citing works
Self-citationHealey, S., Tan, S. L., Tulandi, T., & Biljan, M. M. (2003) · Fertility and Sterility · doi:10.1016/j.fertnstert.2003.03.001 · Cited by 132 · see citing works
Aromatase inhibitors for the treatment of infertility
Mitwally, M. F., & Casper, R. F. (2003) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.12.3.353 · Cited by 120 · see citing works
Self-citationYoung, S. L., Opsahl, M. S., & Fritz, M. A. (1999) · Fertility and Sterility · doi:10.1016/s0015-0282(98)00537-8 · Cited by 111 · see citing works
Ohno, Y. (1998) · Human Reproduction Update · doi:10.1093/humupd/4.5.560 · Cited by 34 · see citing works
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Oktay, K., Hourvitz, A., Şahin, G., Öktem, Ö., Safro, B., Çil, A. P., & Bang, H. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-0962 · Cited by 418 · see citing works
“Furthermore, when used for ovulation induction, letrozole is expected to be cleared from the circulation by the time embryos implant because it has a 48-h half-life (31); and when embryos are cryopreserved, they cannot practically be exposed to letrozole because the fertilization takes place in vitro.”
BackgroundAssessment and management of polycystic ovary syndrome: Summary of an evidence-based guideline
Teede, H. J., Misso, M. L., Deeks, A. A., Moran, L. J., Stuckey, B. G. A., Wong, J. L. A., Norman, R. J., Costello, M. F., & Groups, O. B. O. T. G. D. (2011) · Medical Journal of Australia · doi:10.5694/mja11.10915 · Cited by 379 · see citing works
Aromatase Inhibitors for Ovulation Induction
Casper, R. F., & Mitwally, M. F. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-1923 · Cited by 272 · see citing works
Self-citationOktay, K., Turan, V., Bedoschi, G., Pacheco, F. S., & MOY, F. H. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2014.59.3723 · Cited by 221 · see citing works
Use of letrozole in assisted reproduction: a systematic review and meta-analysis
Requena, A., Herrero, J. C., Landeras, J., Navarro, E., Neyro, J. L., Salvador, C., Tur, R., Callejo, J., Checa, M. Á., Farré, M., et al. (2008) · Human Reproduction Update · doi:10.1093/humupd/dmn033 · Cited by 197 · see citing works
“Finally, nine studies were included with a total of 2573 women.”
BackgroundMethodInfluentialPregnancy outcome after the use of an aromatase inhibitor for ovarian stimulation
Mitwally, M. F., Biljan, M. M., & Casper, R. F. (2005) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2004.08.013 · Cited by 186 · see citing works
“25 Clomiphene treatment was associated with the highest rate of multiple gestations, whereas gonadotropins treatment was associated with much lower multiple gestation rates than expected.”
BackgroundSelf-citationPregnancy outcome after the use of an aromatase inhibitor for ovarian stimulation
Mitwally, M. F., & Casper, R. F. (2002) · Fertility and Sterility · doi:10.1016/s0015-0282(02)03975-4 · Cited by 178 · see citing works
Self-citationOvulation induction: a mini review
Messinis, I. E. (2005) · Human Reproduction · doi:10.1093/humrep/dei128 · Cited by 140 · see citing works
“Before the onset of letrozole administration, early pregnancy should be ruled out, since information regarding possible teratogenic effects of this drug is limited (Casper, 2003).”
BackgroundMethodAtay, V., Çam, Ç., Muhçu, M., Cam, M., & Karateke, A. (2006) · Journal of International Medical Research · doi:10.1177/147323000603400109 · Cited by 138 · see citing works
Costello, M., Misso, M. L., Balen, A. H., Boyle, J., Devoto, L., Garad, R. M., Hart, R. J., Johnson, L., Jordan, C., Legro, R. S., et al. (2018) · Human Reproduction Open · doi:10.1093/hropen/hoy021 · Cited by 125 · see citing works
“These agents were originally used to improve pregnancy rates and limit adverse effects (Casper, 2003; Healey et al., 2003), especially with clomiphene resistance and failure (Imani et al., 1999; Imani et al., 2002 January, Casper, 2003; Legro et al., 2007).”
BackgroundAzim, A. A., & Oktay, K. (2007) · Fertility and Sterility · doi:10.1016/j.fertnstert.2006.12.068 · Cited by 108 · see citing works
Pirard, C., Donnez, J., & Loumaye, E. (2005) · Human Reproduction · doi:10.1093/humrep/deh830 · Cited by 96 · see citing works
“Different doses and different durations of administration would need to be tested, however, before reaching any conclusion on the ability of this specific aromatase inhibitor to stimulate multiple follicular development (Casper, 2003; Healy et al., 2003).”
BackgroundAromatase inhibitors for PCOS: a systematic review and meta-analysis
Misso, M. L., Wong, J. L. A., Teede, H. J., Hart, R. J., Rombauts, L. J. F., Melder, A., Norman, R. J., & Costello, M. (2012) · Human Reproduction Update · doi:10.1093/humupd/dms003 · Cited by 96 · see citing works
Letrozole: Pharmacology, toxicity and potential therapeutic effects
Mukherjee, A. G., Wanjari, U. R., Nagarajan, D., Vibhaa, K. K., Anagha, V., Joshua Paul, P., Thirumoorthy, T. P., Chakraborty, R., Renu, K., Dey, A., et al. (2022) · Life Sciences · doi:10.1016/j.lfs.2022.121074 · Cited by 76 · see citing works
Ebert, A. D., Bartley, J., & David, M. (2005) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2005.04.017 · Cited by 73 · see citing works
Predictive factors for intrauterine insemination outcomes: a review
Starosta, A., Gordon, C. E., & Hornstein, M. D. (2020) · Fertility Research and Practice · doi:10.1186/s40738-020-00092-1 · Cited by 71 · see citing works
Aromatase inhibitors in ovarian stimulation for IVF/ICSI: a pilot study
Verpoest, W., Kolibianakis, E. M., Papanikolaou, E. G. E., Smitz, J. E. J., Steirteghem, A. V., & Devroey, P. (2006) · Reproductive BioMedicine Online · doi:10.1016/s1472-6483(10)60611-6 · Cited by 70 · see citing works
“However, there does not appear to be depletion of the central oestrogen receptors, as opposed to what happens when clomiphene citrate is used, thus allowing normal central feedback mechanisms, and therefore monofollicular rather than multifollicular development in most cases (Casper, 2003).”
BackgroundFouda, U. M., & Sayed, A. M. (2011) · Reproductive Biology and Endocrinology · doi:10.1186/1477-7827-9-84 · Cited by 65 · see citing works
“about ten days), Casper suggested that letrozole administration in early follicular phase is not associated with any teratogenic effects because it is completely cleared before implantation[35].”
BackgroundStrategies to reduce multiple pregnancies due to ovulation stimulation
Dickey, R. P. (2008) · Fertility and Sterility · doi:10.1016/j.fertnstert.2008.08.008 · Cited by 64 · see citing works
Jee, B. C., Ku, S., Suh, C. S., Kim, K. C., Lee, W. D., & Kim, S. H. (2006) · Fertility and Sterility · doi:10.1016/j.fertnstert.2006.02.070 · Cited by 57 · see citing works
Hu, Y., Chen, Y., Zhu, Y., & Huang, H. (2013) · Clinical Endocrinology · doi:10.1111/cen.12280 · Cited by 52 · see citing works
Aromatase inhibitors and teratogenesis
Tiboni, G. M. (2004) · Fertility and Sterility · doi:10.1016/j.fertnstert.2004.01.006 · Cited by 50 · see citing works
Nejad, E. S. T., Abediasl, Z., Rashidi, B. H., Nekoo, E. A., Shariat, M., & Amirchaghmaghi, E. (2008) · Journal of Assisted Reproduction and Genetics · doi:10.1007/s10815-008-9209-2 · Cited by 37 · see citing works
Polyzos, N. P., Tsappi, M., Mauri, D., Atay, V., Cortinovis, I., & Casazza, G. (2008) · Fertility and Sterility · doi:10.1016/j.fertnstert.2007.10.016 · Cited by 37 · see citing works
A randomized trial of ovulation induction with two different doses of Letrozole in women with PCOS
Ramezanzadeh, F., Nasiri, R., Yazdi, M. S., & Baghrei, M. (2011) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-011-1951-5 · Cited by 33 · see citing works
“Due to its short half life (45 h) and the lack of down-regulation of estrogen receptors [ 12 ] Letrozole may have less negative effects on the endometrium and cervix in the late follicular phase [13, 14].”
BackgroundDehbashi, S., Dehbashi, S., Kazerooni, T., Robati, M., Alborzi, S., & Shadman, A. (2009) · DOAJ (DOAJ: Directory of Open Access Journals) · Cited by 32 · see citing works
Hendawy, S. F., Samaha, H. E., & Elkholy, M. K. A. (2011) · Clinical Medicine Insights Reproductive Health · doi:10.4137/cmrh.s6598 · Cited by 29 · see citing works
Wang, J. G., Guarnaccia, M. M., Weiss, S. F., Sauer, M. V., & Choi, J. M. (2006) · Fertility and Sterility · doi:10.1016/j.fertnstert.2005.12.065 · Cited by 27 · see citing works
EL-Gharib, M. N., Mahfouz, A. E., & Farahat, M. A. (2015) · Europe PMC (PubMed Central) · Cited by 25 · see citing works
Bedaiwy, M. A., Shokry, M., Mousa, N. A., Claessens, A., Esfandiari, N., Gotleib, L., & Casper, R. F. (2008) · Fertility and Sterility · doi:10.1016/j.fertnstert.2008.03.020 · Cited by 22 · see citing works
Self-citationEffects of a non-steroidal aromatase inhibitor on ovarian function in cattle
Yapura, J., Mapletoft, R. J., Singh, J. K., Pierson, R. A., Naile, J. E., Giesy, J. P., Chang, H., Higley, E. B., Hecker, M., & Adams, G. P. (2011) · Reproduction Fertility and Development · doi:10.1071/rd11239 · Cited by 16 · see citing works
“Letrozole has been used for several years for ovarian stimulation and induction of ovulation in women [42-47, 128-130, 132, 150]; however, there are apparently no reports on the use of letrozole to control ovarian function in cattle.”
BackgroundHembram, M., Biswas, R., & Jain, A. (2017) · Journal of Human Reproductive Sciences · doi:10.4103/jhrs.jhrs_120_16 · Cited by 15 · see citing works
Al-Shaikh, S. F., Al-Mukhatar, E. J., Al-Zubaidy, A. A., Al-Rubaie, B. J. U., & Al-Khuzaee, L. M. (2016) · Middle East Fertility Society Journal · doi:10.1016/j.mefs.2016.12.003 · Cited by 15 · see citing works
Costello, M., & Ledger, W. J. (2012) · Women s Health · doi:10.2217/whe.12.14 · Cited by 13 · see citing works
Aromatase inhibitors for ovulation induction
ElDaly, A. A., Al-Fozan, H. M., Al-Inany, H. G., Bedaiwy, M. A., & Saleh, W. F. (2015) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd005635.pub2 · Cited by 13 · see citing works
Effect of vehicle and route of administration of letrozole on ovarian function in a bovine model
Yapura, J., Mapletoft, R. J., Pierson, R. A., Singh, J. K., & Adams, G. P. (2013) · Reproduction Fertility and Development · doi:10.1071/rd13100 · Cited by 13 · see citing works
Fouda, U. M., & Sayed, A. M. (2011) · Gynecological Endocrinology · doi:10.3109/09513590.2011.579661 · Cited by 13 · see citing works
Tang, L., Xu, L., Pan, X., Zhang, J., Wu, T., & Liu, G. J. (2010) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd008583 · Cited by 12 · see citing works
Zhang, J., Tang, L., Kong, L., Wu, T., Xu, L., Pan, X., & Liu, G. J. (2019) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd008583.pub2 · Cited by 11 · see citing works
“It was originally used to improve pregnancy rates and limit adverse eGects, especially with clomiphene resistance and failure (Casper 2003; Legro 2014).”
BackgroundMethodAromatase inhibitors for ovulation induction
ElDaly, A. A., Al-Fozan, H. M., Al-Inany, H. G., Bedaiwy, M. A., & Saleh, W. F. (2006) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd005635 · Cited by 11 · see citing works
RetractedThe potential of letrozole use for priming in vitro maturation cycles.
Rose, B. I. (2014) · PubMed Central · Cited by 9 · see citing works
L'apoptose des cellules folliculaires : son implication dans les protocoles de stimulation ovarienne
Maillet, G., Féral, C., & Benhaïm, A. (2005) · Gynécologie Obstétrique & Fertilité · doi:10.1016/j.gyobfe.2005.06.016 · Cited by 8 · see citing works
Ovulation induction in polycystic ovary syndrome
Gupta, S., Metterle, L., Thakkar, P., Surti, N., Chandra, A., & Agarwal, A. K. (2009) · Cited by 8 · see citing works
Zhang, J., Tang, L., Kong, L., Wu, T., Xu, L., Pan, X., & Liu, G. J. (2021) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd008583.pub3 · Cited by 7 · see citing works
Ozdemir, U., Özakşit, G., Güngör, A. N. Ç., & Aydogan, M. (2013) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-013-2780-5 · Cited by 6 · see citing works
Athwal, A., Chakravorty, R., Sur, D., & Saha, R. (2017) · International Journal of Reproduction Contraception Obstetrics and Gynecology · doi:10.18203/2320-1770.ijrcog20174068 · Cited by 3 · see citing works
Hatırnaz, Ş., Hatırnaz, E. S., Ürkmez, S. S., Çelik, S., Ürkmez, Y. C., Cao, M., Tan, S. L., & Dahan, M. H. (2023) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2023.103648 · Cited by 4 · see citing works
Letrozole in Fertility Therapy
Marguerie, M., & Bedaiwy, M. A. (2020) · Springer eBooks · doi:10.1007/978-981-15-2377-9_7 · Cited by 3 · see citing works
Najim, H. D., Al-khfajy, W. S., Albasry, Z., & Al‐Taie, A. (2023) · International Journal of Academic Medicine · doi:10.4103/ijam.ijam_90_22 · Cited by 2 · see citing works
Luk, J., & Patrizio, P. (2013) · Cambridge University Press eBooks · doi:10.1017/cbo9781139192736.027 · Cited by 1 · see citing works
ART: skills, techniques and present status
Coward, K., & Wells, D. (2013) · Cambridge University Press eBooks · doi:10.1017/cbo9781139192736.025 · Cited by 1 · see citing works
The Role of Assisted Reproduction in the Cancer Patient
Patrizio, P., & Levi-Setti, P. E. (2016) · Current clinical urology · doi:10.1007/978-3-319-27711-0_15 · Cited by 1 · see citing works
Letrozole versus Tamoxifen in Treatment of Clomiphene Citrate Resistant Polycystic Ovarian Syndrome
EL-Gharib, M. N., Mahfouz, A., & Farahat, M. A. (2014) · Enliven Gynecology and Obstetrics · doi:10.18650/2377-5351.12003 · Cited by 1 · see citing works
Kishk, E. A. (2019) · Evidence Based Women s Health Journal · doi:10.21608/ebwhj.2019.33487 · Cited by 1 · see citing works
“One of the most important advantages of both agents is very low rates of multiple pregnancies[1, 12, 21].”
BackgroundYapura, M. J. (2013) · HARVEST (University of Saskatchewan) · Cited by 1 · see citing works
Physiologic Basis of Ovulation Induction
Casper, R. F. (2011) · doi:10.1002/9781444393958.ch11
Self-citationPossible additional therapeutic uses of aromatase inhibitors
Furr, B. J. A. (2008) · Birkhäuser Basel eBooks · doi:10.1007/978-3-7643-8693-1_9
“Taking the half-life of letrozole into consideration, it seems likely that therapeutically active concentrations of the drug were present at the time of hCG administration that might account for reduced oestrogen production and impaired endometrial thickness [ 34 ].”
BackgroundOvulation induction: once bitten, twice shy?
Casper, R. F. (2014) · Fertility and Sterility · doi:10.1016/j.fertnstert.2014.11.010
Self-citationMonofollicular Stimulation in PCOS Patients
Kuang, Y., Hong, Q., & Chen, Q. (2015) · Springer eBooks · doi:10.1007/978-81-322-1118-1_8
Aromataseinhibitoren bei Endometriose?
Ebert, A. D. (2004) · Gynäkologische Endokrinologie · doi:10.1007/s10304-004-0085-2
Possible additional therapeutic uses of aromatase inhibitors
Furr, B. J. A. (2006) · Birkhäuser Basel eBooks · doi:10.1007/3-7643-7418-7_9
Hatırnaz, Ş., Hatırnaz, E. S., Ürkmez, S. S., Çalışkan, C. S., Çelik, S., Hatırnaz, K., Cao, M., Tan, S. L., & Dahan, M. H. (2023) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2023.103620
Ovulation induction with gonadotropins
Cooman, M. D., & Delbaere, A. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-13825-6.00165-5
Ovarian stimulation with clomiphene citrate
Peigné, M., Sonigo, C., & Robin, G. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-13825-6.00268-5
- Authors
- Casper, R. F.
- Affiliations
- Mount Sinai Hospital (CA)
- Corresponding author
- Casper, Robert F
- ORCID
- Casper, Robert F
- Venue
- Fertility and Sterility
- Publisher
- Elsevier BV
- Published
- 2003-12
- Volume
- 80
- Issue
- 6
- Pages
- 1335-1337
- ISSN
- 0015-0282 (ISSN-L)
- OpenAlex
- W2163690844
- Cited by
- 64
- References
- 5
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 4 · 2014: 3 · 2013: 6 · 2012: 2
- FWCI
- 4.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Fertility and Sterility (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Health Sciences › Medicine › Reproductive Medicine › Reproductive Health and Technologies
- Keywords
- letrozole, aromatase inhibitors, superovulation, ovulation induction, intrauterine insemination, follicle-stimulating hormone, endometrial thickness, controlled ovarian stimulation, pregnancy rate
- MeSH terms
- Letrozole, Aromatase, Enzyme Inhibitors, Female, Humans, Models, Biological, Nitriles, Ovulation, Superovulation, Triazoles
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