Use of Letrozole in Assisted Reproduction: a Systematic Review and Meta-analysis

Overview

Journal Hum Reprod Update

Specialty Reproductive Medicine

Date 2008 Sep 25

PMID 18812422

Citations 42

Authors

Antonio Requena

Julio Herrero

Jose Landeras

Esperanza Navarro

Jose L Neyro

Cristina Salvador

Rosa Tur

Justo Callejo

Miguel A Checa

Magi Farre

Juan J Espinos

Francesc Fabregues

Maria Grana-Barcia

Affiliations

Soon will be listed here.

Abstract

Background: Letrozole is the third-generation aromatase inhibitor (AI) most widely used in assisted reproduction. AIs induce ovulation by inhibiting estrogen production; the consequent hypoestrogenic state increases GnRH release and pituitary follicle-stimulating hormone (FSH) synthesis.

Methods: A systematic search of the literature was performed for both prospective and retrospective studies. Meta-analyses of randomized clinical trials (RCTs) were performed for three comparisons: letrozole versus clomiphene citrate (CC), letrozole + FSH versus FSH in intrauterine insemination (IUI) and letrozole + FSH versus FSH in IVF. In the absence of RCTs, non-randomized studies were pooled.

Results: Nine studies were included in the meta-analysis. Four RCTs compared the overall effect of letrozole with CC in patients with polycystic ovary syndrome. The pooled result was not significant for ovulatory cycles (OR = 1.17; 95% CI 0.66-2.09), or for pregnancy rate per cycle (OR = 1.47; 95% CI 0.73-2.96) or for pregnancy rate per patient (OR = 1.37; 95% CI 0.70-2.71). In three retrospective studies which compared L + FSH with FSH in ovarian stimulation for IUI, the pooled OR was 1.15 (95% CI 0.78-1.71). A final meta-analysis included one RCT and one cohort study that compared letrozole + gonadotrophin versus gonadotrophin alone: the pooled pregnancy rate per patient was not significantly different (OR = 1.40; 95% CI 0.67-2.91).

Conclusions: Letrozole is as effective as other methods of ovulation induction. Further randomized-controlled studies are warranted to define more clearly the efficacy and safety of letrozole in human reproduction.

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References

Bedaiwy M, Forman R, Mousa N, Al Inany H, Casper R . Cost-effectiveness of aromatase inhibitor co-treatment for controlled ovarian stimulation. Hum Reprod. 2006; 21(11):2838-44. DOI: 10.1093/humrep/del273. View

Oktay K, Hourvitz A, Sahin G, Oktem O, Safro B, Cil A . Letrozole reduces estrogen and gonadotropin exposure in women with breast cancer undergoing ovarian stimulation before chemotherapy. J Clin Endocrinol Metab. 2006; 91(10):3885-90. DOI: 10.1210/jc.2006-0962. View

Guzick D . Ovulation induction management of PCOS. Clin Obstet Gynecol. 2007; 50(1):255-67. DOI: 10.1097/GRF.0b013e31802f361e. View

Bedaiwy M, Mousa N, Esfandiari N, Forman R, Casper R . Follicular phase dynamics with combined aromatase inhibitor and follicle stimulating hormone treatment. J Clin Endocrinol Metab. 2006; 92(3):825-33. DOI: 10.1210/jc.2006-1673. View

Wu H, Wang N, Cheng M, Hsieh J . A randomized comparison of ovulation induction and hormone profile between the aromatase inhibitor anastrozole and clomiphene citrate in women with infertility. Gynecol Endocrinol. 2007; 23(2):76-81. DOI: 10.1080/09513590601137509. View

Azim A, Oktay K . Letrozole for ovulation induction and fertility preservation by embryo cryopreservation in young women with endometrial carcinoma. Fertil Steril. 2007; 88(3):657-64. DOI: 10.1016/j.fertnstert.2006.12.068. View

Schoolcraft W, Surrey E, Minjarez D, Stevens J, Gardner D . Management of poor responders: can outcomes be improved with a novel gonadotropin-releasing hormone antagonist/letrozole protocol?. Fertil Steril. 2007; 89(1):151-6. DOI: 10.1016/j.fertnstert.2007.02.013. View

Gregoriou O, Vlahos N, Konidaris S, Papadias K, Botsis D, Creatsas G . Randomized controlled trial comparing superovulation with letrozole versus recombinant follicle-stimulating hormone combined with intrauterine insemination for couples with unexplained infertility who had failed clomiphene citrate stimulation and.... Fertil Steril. 2007; 90(3):678-83. DOI: 10.1016/j.fertnstert.2007.06.099. View

Badawy A, Aal I, Abulatta M . RETRACTED: Clomiphene citrate or letrozole for ovulation induction in women with polycystic ovarian syndrome: a prospective randomized trial. Fertil Steril. 2007; 92(3):849-852. DOI: 10.1016/j.fertnstert.2007.02.062. View

10.

Plourde P, Reiter E, Jou H, Desrochers P, Rubin S, B Bercu B . Safety and efficacy of anastrozole for the treatment of pubertal gynecomastia: a randomized, double-blind, placebo-controlled trial. J Clin Endocrinol Metab. 2004; 89(9):4428-33. DOI: 10.1210/jc.2004-0082. View

11.

Garcia J, Jones G, Wentz A . The use of clomiphene citrate. Fertil Steril. 1977; 28(7):707-17. DOI: 10.1016/s0015-0282(16)42670-1. View

12.

Kurl R, Morris I . Differential depletion of cytoplasmic high affinity oestrogen receptors after the in vivo administration of the antioestrogens, clomiphene, MER-25 and tamoxifen. Br J Pharmacol. 1978; 62(4):487-93. PMC: 1668047. DOI: 10.1111/j.1476-5381.1978.tb07752.x. View

13.

Kerin J, Liu J, Phillipou G, Yen S . Evidence for a hypothalamic site of action of clomiphene citrate in women. J Clin Endocrinol Metab. 1985; 61(2):265-8. DOI: 10.1210/jcem-61-2-265. View

14.

Cole P, Robinson C . Mechanism and inhibition of cytochrome P-450 aromatase. J Med Chem. 1990; 33(11):2933-42. DOI: 10.1021/jm00173a001. View

15.

Gonen Y, Casper R . Sonographic determination of a possible adverse effect of clomiphene citrate on endometrial growth. Hum Reprod. 1990; 5(6):670-4. DOI: 10.1093/oxfordjournals.humrep.a137165. View

16.

Bhatnagar A, Hausler A, Schieweck K, Lang M, Bowman R . Highly selective inhibition of estrogen biosynthesis by CGS 20267, a new non-steroidal aromatase inhibitor. J Steroid Biochem Mol Biol. 1990; 37(6):1021-7. DOI: 10.1016/0960-0760(90)90460-3. View

17.

Fritz M, Holmes R, Keenan E . Effect of clomiphene citrate treatment on endometrial estrogen and progesterone receptor induction in women. Am J Obstet Gynecol. 1991; 165(1):177-85. DOI: 10.1016/0002-9378(91)90247-o. View

18.

Plourde P, Dyroff M, Dukes M . Arimidex: a potent and selective fourth-generation aromatase inhibitor. Breast Cancer Res Treat. 1994; 30(1):103-11. DOI: 10.1007/BF00682745. View

19.

. Anovulatory infertility. The ESHRE Capri Workshop Group. Hum Reprod. 1995; 10(6):1549-53. View

20.

Kousta E, White D, Franks S . Modern use of clomiphene citrate in induction of ovulation. Hum Reprod Update. 1997; 3(4):359-65. DOI: 10.1093/humupd/3.4.359. View