Emulating a target trial of the comparative effectiveness of clomiphene citrate and letrozole for ovulation induction.
Emulating a target trial of the comparative effectiveness of clomiphene citrate and letrozole for ovulation induction.
复制标题
模拟克罗米芬柠檬酸盐和来曲唑诱导排卵效果比较的目标试验。
DOI：
10.1093/humrep/deac005
复制
发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Hernández-Díaz,Sonia
中科院分区：
文献类型：
--
作者：
Yland,JenniferJ;Chiu,Yu-Han;Rinaudo,Paolo;Hsu,John;Hernán,MiguelA;Hernández-Díaz,Sonia
研究问题：接受连续6个周期来曲唑与克罗米芬诱导排卵的妇女的妊娠结局比较如何？在多囊卵巢综合征（PCOS）患者中，来曲唑组的妊娠、活产、多胎妊娠、早产、新生儿重症监护室（NICU）入院和先天性畸形的风险高于克罗米芬组，尽管在不明原因的不孕症患者中没有观察到治疗差异。已知的随机试验报告了来曲唑与克罗米酚相比更高的妊娠率和活产率在PCOS患者中，但在不明原因不孕症患者中没有差异。研究设计、规模、持续时间我们模拟了一个假设性的试验，比较来曲唑与克罗米芬在所有妇女中诱导排卵的有效性，然后按PCOS和不明原因的不孕状态分层。我们使用了来自美国大型医疗索赔数据库的真实世界数据（2011-2015）。参与者/材料，设置，方法我们分析了2011-2014年期间18 120 名开始来曲唑的女性和49 647名开始克罗米酚的女性的数据，这些女性年龄在18-45岁之间，没有糖尿病，甲状腺疾病，肝病或乳腺癌，并且在试验开始前3个月内未接受生育治疗。治疗方案为克罗米芬或来曲唑，连续6个周期。结局包括妊娠、活产、多胎妊娠、早产、小于胎龄儿（SGA）、NICU住院和严重先天性畸形。我们估计每个结果的概率，根据每个策略，通过汇总logistic回归和使用标准化调整混杂和选择偏差，由于损失follow-up.Main结果和作用的机会估计的概率怀孕，活产和新生儿的结果是相似的每个策略下，无论是整体和个人之间的原因不明的不孕症。在PCOS患者中，意向治疗分析中，来曲唑组的妊娠概率为43%，克罗米芬组为37%（风险差异[RD] = 6.0%; 95%CI：4.4，7.7）。相应的活产概率为32% vs 29%（RD = 3.1%; 95% CI：1.5，4.8）。在符合方案分析中，多胎妊娠风险为19% vs 9%，早产风险为20% vs 15%，SGA风险为5% vs 3%，NICU入院风险为22% vs 16%，先天性畸形风险为8% vs 2%。排除的原因我们不能完全排除体重指数或不孕持续时间的可能性。然而，我们对管理数据中确定的代理进行了调整，结果并没有改变。更广泛的研究结果我们的研究结果表明，对于不明原因不孕症的妇女，两种治疗方法导致活产的概率相当。对于患有PCOS的女性，来曲唑似乎对获得活产稍微更有效。在不明原因不孕的妇女中，两种治疗的新生儿结局相似;我们没有证实克罗米酚与来曲唑相比，新生儿不良结局的假设风险更高。不良新生儿结局的风险在有...
STUDY QUESTIONWhat are the comparative pregnancy outcomes in women who receive up to six consecutive cycles of ovulation induction with letrozole versus clomiphene citrate?SUMMARY ANSWERThe risks of pregnancy, livebirth, multiple gestation, preterm birth, neonatal intensive care unit (NICU) admission and congenital malformations were higher for letrozole compared with clomiphene in participants with polycystic ovarian syndrome (PCOS), though no treatment differences were observed in those with unexplained infertility.WHAT IS KNOWN ALREADYRandomized trials have reported higher pregnancy and livebirth rates for letrozole versus clomiphene among individuals with PCOS, but no differences among those with unexplained infertility. None of these trials were designed to study maternal or neonatal complications.STUDY DESIGN, SIZE, DURATIONWe emulated a hypothetical trial of the comparative effectiveness of letrozole versus clomiphene citrate for ovulation induction among all women, then stratified by PCOS and unexplained infertility status. We used real-world data from a large healthcare claims database in the USA (2011–2015).PARTICIPANTS/MATERIALS, SETTING, METHODSWe analyzed data from 18 120 women who initiated letrozole and 49 647 women who initiated clomiphene during 2011–2014, and who were aged 18–45 years with no history of diabetes, thyroid disease, liver disease or breast cancer and had no fertility treatments for 3 months before trial initiation. The treatment strategies were clomiphene citrate or letrozole for six consecutive cycles. The outcomes were pregnancy, livebirth, multiple gestation, preterm birth, small for gestational age (SGA), NICU admission and major congenital malformations. We estimated the probability of each outcome under each strategy via pooled logistic regression and used standardization to adjust for confounding and selection bias due to loss to follow-up.MAIN RESULTS AND THE ROLE OF CHANCEThe estimated probabilities of pregnancy, livebirth and neonatal outcomes were similar under each strategy, both overall and among individuals with unexplained infertility. Among women with PCOS, the probability of pregnancy was 43% for letrozole vs 37% for clomiphene (risk difference [RD] = 6.0%; 95% CI: 4.4, 7.7) in the intention-to-treat analyses. The corresponding probability of livebirth was 32% vs 29% (RD = 3.1%; 95% CI: 1.5, 4.8). In per protocol analyses, the risk of multiple gestation was 19% vs 9%, the risk of preterm birth was 20% vs 15%, the risk of SGA was 5% vs 3%, the risk of NICU admission was 22% vs 16% and the risk of congenital malformation was 8% vs 2% among those with a livebirth.LIMITATIONS, REASONS FOR CAUTIONWe cannot completely rule out the possibility of residual confounding by body mass index or duration of infertility. However, we adjusted for proxies identified in administrative data and results did not change.WIDER IMPLICATIONS OF THE FINDINGSOur findings suggest that for women with unexplained infertility, the two treatments result in comparable probabilities of a livebirth. For women with PCOS, letrozole appears slightly more effective for attaining a livebirth. Neonatal outcomes were similar for the two treatments among women with unexplained infertility; we did not confirm the hypothesized higher risk of adverse neonatal outcomes for clomiphene versus letrozole. The risks of adverse neonatal outcomes were slightly greater among women with …
登录
查看更多内容
内皮源性舒张因子控制正常大鼠肾脏中的肾血流动力学。
DOI：
10.1681/asn.v16875
发表时间：
1990
期刊：
Journal of the American Society of Nephrology : JASN
影响因子：
--
作者：
Baylis,C;Harton,P;Engels,K
通讯作者：
Engels,K
DOI：
10.1073/pnas.87.2.682
发表时间：
1990-01-01
影响因子：
11.1
作者：
BREDT, DS;SNYDER, SH
通讯作者：
SNYDER, SH
内皮源性舒张因子在调节肾血流动力学反应中的作用。
影响因子：
--
作者：
J. P. Tolins;R. Palmer;S. Moncada;L. Raij
通讯作者：
L. Raij
梗阻对肾功能的影响
DOI：
--
发表时间：
1983
期刊：
影响因子：
--
作者：
J. Roberts;Ronald W. Lewis
通讯作者：
Ronald W. Lewis
衰老大鼠肾脏对静脉注射甘氨酸的肾血管舒张反应。
DOI：
10.1016/s0272-6386(12)80769-4
发表时间：
1990
期刊：
American journal of kidney diseases : the official journal of the National Kidney Foundation
影响因子：
--
作者：
Baylis,C;Fredericks,M;Wilson,C;Munger,K;Collins,R
通讯作者：
Collins,R