Letrozole, Gonadotropin, or Clomiphene for Unexplained Infertility

被引:205
作者
Diamond, M. P. [1 ,2 ]
Legro, R. S. [3 ]
Coutifaris, C. [4 ]
Alvero, R. [5 ]
Robinson, R. D. [6 ]
Casson, P. [7 ]
Christman, G. M. [8 ]
Ager, J. [2 ]
Huang, H. [9 ]
Hansen, K. R. [10 ]
Baker, V. [11 ]
Usadi, R. [12 ]
Seungdamrong, A. [13 ]
Bates, G. W. [14 ]
Rosen, R. M. [15 ]
Haisenleder, D. [16 ]
Krawetz, S. A. [2 ]
Barnhart, K. [4 ]
Trussell, J. C. [17 ]
Ohl, D. [8 ]
Jin, Y. [9 ]
Santoro, N. [5 ]
Eisenberg, E. [18 ]
Zhang, H. [9 ]
机构
[1] Georgia Regents Univ, Dept Obstet & Gynecol, Augusta, GA 30912 USA
[2] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA
[3] Penn State Univ, Dept Obstet & Gynecol, Hershey, PA USA
[4] Univ Penn, Sch Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA
[5] Univ Colorado, Dept Obstet & Gynecol, Denver, CO 80202 USA
[6] Univ Texas Hlth Sci Ctr San Antonio, Dept Obstet & Gynecol, San Antonio, TX 78229 USA
[7] Univ Vermont, Dept Obstet & Gynecol, Burlington, VT 05405 USA
[8] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA
[9] Yale Univ, Sch Publ Hlth, Dept Biostat, New Haven, CT USA
[10] Univ Oklahoma, Coll Med, Dept Obstet & Gynecol, Oklahoma City, OK 73190 USA
[11] Stanford Univ, Med Ctr, Stanford, CA 94305 USA
[12] Carolinas Med Ctr, Charlotte, NC 28203 USA
[13] Univ Med & Dent New Jersey, Newark, NJ 07103 USA
[14] Univ Alabama Birmingham, Birmingham, AL 35487 USA
[15] Univ Calif San Francisco, Dept Reprod Endocrinol & Infertil, San Francisco, CA 94143 USA
[16] Univ Virginia, Ctr Res Reprod, Ligand Core Lab, Charlottesville, VA USA
[17] Upstate Univ Hosp, Syracuse, NY USA
[18] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Fertil & Infertil Branch, Rockville, MD USA
基金
美国国家卫生研究院;
关键词
ASSISTED REPRODUCTIVE TECHNOLOGY; MULTIPLE INTRAUTERINE GESTATIONS; OVARIAN STIMULATION; AROMATASE INHIBITORS; FERTILITY TREATMENTS; OVULATION INDUCTION; RANDOMIZED-TRIAL; INSEMINATION; CITRATE; SUPEROVULATION;
D O I
10.1056/NEJMoa1414827
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BACKGROUND The standard therapy for women with unexplained infertility is gonadotropin or clomiphene citrate. Ovarian stimulation with letrozole has been proposed to reduce multiple gestations while maintaining live birth rates. METHODS We enrolled couples with unexplained infertility in a multicenter, randomized trial. Ovulatory women 18 to 40 years of age with at least one patent fallopian tube were randomly assigned to ovarian stimulation (up to four cycles) with gonadotropin (301 women), clomiphene (300), or letrozole (299). The primary outcome was the rate of multiple gestations among women with clinical pregnancies. RESULTS After treatment with gonadotropin, clomiphene, or letrozole, clinical pregnancies occurred in 35.5%, 28.3%, and 22.4% of cycles, and live birth in 32.2%, 23.3%, and 18.7%, respectively; pregnancy rates with letrozole were significantly lower than the rates with standard therapy (gonadotropin or clomiphene) (P = 0.003) or gonadotropin alone (P<0.001) but not with clomiphene alone (P = 0.10). Among ongoing pregnancies with fetal heart activity, the multiple gestation rate with letrozole (9 of 67 pregnancies, 13%) did not differ significantly from the rate with gonadotropin or clomiphene (42 of 192, 22%; P = 0.15) or clomiphene alone (8 of 85, 9%; P = 0.44) but was lower than the rate with gonadotropin alone (34 of 107, 32%; P = 0.006). All multiple gestations in the clomiphene and letrozole groups were twins, whereas gonadotropin treatment resulted in 24 twin and 10 triplet gestations. There were no significant differences among groups in the frequencies of congenital anomalies or major fetal and neonatal complications. CONCLUSIONS In women with unexplained infertility, ovarian stimulation with letrozole resulted in a significantly lower frequency of multiple gestation but also a lower frequency of live birth, as compared with gonadotropin but not as compared with clomiphene. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01044862.)
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收藏
页码:1230 / 1240
页数:11
相关论文
共 25 条
[1]   A randomized trial of superovulation with two different doses of letrozole [J].
Al-Fadhli, R ;
Sylvestre, C ;
Buckett, W ;
Tan, SL ;
Tulandi, T .
FERTILITY AND STERILITY, 2006, 85 (01) :161-164
[2]   A randomized trial of letrozole versus clomiphene citrate in women undergoing superovulation [J].
Al-Fozan, H ;
Al-Khadouri, M ;
Tan, SL ;
Tulandi, T .
FERTILITY AND STERILITY, 2004, 82 (06) :1561-1563
[3]   RETRACTED: Clomiphene citrate or aromatase inhibitors for superovulation in women with unexplained infertility undergoing intrauterine insemination: a prospective randomized trial (Retracted article. See vol. 114, pg. 670, 2020) [J].
Badawy, Ahmed ;
Elnashar, Abubaker ;
Totongy, Mohamed .
FERTILITY AND STERILITY, 2009, 92 (04) :1355-1359
[4]   Letrozole vs. clomiphene citrate in patients with ovulatory infertility [J].
Bayar, Ü ;
Tanriverdi, HA ;
Barut, A ;
Ayoglu, F ;
Özcan, O ;
Kaya, E .
FERTILITY AND STERILITY, 2006, 85 (04) :1045-1048
[5]   Multiple Births Associated With Assisted Human Reproduction in Canada [J].
Cook, Jocelynn L. ;
Geran, Leslie ;
Rotermann, Michelle .
JOURNAL OF OBSTETRICS AND GYNAECOLOGY CANADA, 2011, 33 (06) :609-616
[6]   Assessment of multiple intrauterine gestations from ovarian stimulation (AMIGOS) trial: baseline characteristics [J].
Diamond, Michael P. ;
Legro, Richard S. ;
Coutifaris, Christos ;
Alvero, Ruben ;
Robinson, Randal D. ;
Casson, Peter ;
Christman, Gregory M. ;
Ager, Joel ;
Huang, Hao ;
Hansen, Karl R. ;
Baker, Valerie ;
Usadi, Rebecca ;
Seungdamrong, Aimee ;
Bates, G. Wright ;
Rosen, R. Mitchell ;
Haisonleder, Daniel ;
Krawetz, Stephen A. ;
Barnhart, Kurt ;
Trussell, J. C. ;
Jin, Yufeng ;
Santoro, Nanette ;
Eisenberg, Esther ;
Zhang, Heping .
FERTILITY AND STERILITY, 2015, 103 (04) :962-U143
[7]   Estimating rates of multiple gestation pregnancies: Sample size calculation from the assessment of multiple intrauterine gestations from ovarian stimulation (AMIGOS) trial [J].
Diamond, Michael P. ;
Mitwally, Mohamed ;
Casper, Robert ;
Ager, Joel ;
Legro, Richard S. ;
Brzyski, Robert ;
Casson, Peter ;
Eisenberg, Esther ;
Zhang, Heping .
CONTEMPORARY CLINICAL TRIALS, 2011, 32 (06) :902-908
[8]   Comparison of the sperm quality necessary for successful intrauterine insemination with World Health Organization threshold values for normal sperm [J].
Dickey, RP ;
Pyrzak, R ;
Lu, PY ;
Taylor, SN ;
Rye, PH .
FERTILITY AND STERILITY, 1999, 71 (04) :684-689
[9]  
FISCH P, 1989, FERTIL STERIL, V51, P828
[10]   Extended letrozole regimen versus clomiphene citrate for superovulation in patients with unexplained infertility undergoing intrauterine insemination: A randomized controlled trial [J].
Fouda, Usama M. ;
Sayed, Ahmed M. .
REPRODUCTIVE BIOLOGY AND ENDOCRINOLOGY, 2011, 9