PDF(Pubmed)
Abstract：
OBJECTIVE: Can an extended letrozole (LE) regimen result in a higher ovulatory rate than a conventional regimen in patients with polycystic ovary syndrome (PCOS) undergoing their first ovulation induction cycle?
CONCLUSIONS: There was no statistical difference in ovulation rate between patients with PCOS using the extended LE regimen and those using the conventional LE regimen.
BACKGROUND: LE has become the first-line agent for ovulation induction. However, there is still a proportion of non-responsive cycles in patients with PCOS undergoing ovulation induction therapy with LE alone, and the extended LE regimen has been demonstrated to be a feasible method for inducing ovulation in these non-responders. Nevertheless, whether the extended regimen could be applied to all patients with PCOS as a first choice for the induction of ovulation remains to be explored.
UNASSIGNED: This was a prospective randomized controlled trial that included 148 female patients with PCOS who underwent their first ovulation induction cycle with LE from January 2021 to October 2022.
METHODS: Participants were randomly assigned to receive an extended (5 mg LE daily for 7 days) or conventional regimen (5 mg LE daily for 5 days) for one treatment cycle. The ovulation rate was the primary outcome. Secondary outcomes included the clinical pregnancy rate, the number of preovulatory follicles, and the rate of multiple pregnancies.
RESULTS: The ovulation rate among patients receiving an extended LE regimen was slightly higher than the rate with a conventional LE regimen, but the difference did not reach statistical significance in either the intention-to-treat analysis (90.54% [67/74] vs 79.73% [59/74], P = 0.065; relative risk [95% CI]: 0.881 [0.768-1.009]) or the per-protocol analysis (90.54% [67/74] vs 84.29% [59/70], P = 0.257; relative risk [95% CI]: 0.931 [0.821-1.055]). The number of preovulatory follicles was nearly identical in the two groups (1.39 ± 0.62 vs 1.37 ± 0.59, P = 0.956), and no cases of ovarian hyperstimulation syndrome were observed. With regards to the endometrial parameters, the mean endometrium thickness was slightly thicker with the conventional LE regimen compared to that with the extended LE regimen, though with no statistical difference (9.27 ± 1.72 mm vs 9.57 ± 2.28 mm, P = 0.792). In the per-protocol analysis, the rates of clinical pregnancy (20.27% [15/74] vs 14.29% [10/70], P = 0.343; relative risk [95% CI]: 0.705 [0.34-1.463]) and live birth (13.51% [10/74] vs 11.43% [8/70], P = 0.705; relative risk [95% CI]: 0.846 [0.354-2.019]) did not differ significantly between treatment groups. Moreover, all conceptions were singletons without neonatal defects.
CONCLUSIONS: The major concerns regarding this study are its single-center and open-label nature. Additionally, the limited number of lean patients with PCOS with a mean body mass index of 23-25 kg/m2 enrolled in our trial also restricted the generalizability of our findings.
CONCLUSIONS: A change from the standard strategy of ovulation induction in patients with PCOS is not advisable, because a statistically superior effect of the extended LE regimen over a conventional regimen was not detected. The extended LE regimen could be applied with caution in a specific population who failed to respond to a conventional regimen rather than all the patients with PCOS during ovulation induction. Additional prospective trials with larger sample sizes and different PCOS subgroups are needed to assess the ovulatory effects of various LE treatment durations.
BACKGROUND: This study was funded by the Shanghai First Maternity and Infant Hospital, affiliated with Tongji University School of Medicine (grant numbers: 2023B03 to Y.F., 2023B18 to X.Z., and 2020RC02 to Y.F.). The authors report no conflicts of interest.
BACKGROUND: Chinese Clinical Trial Registry (ChiCTR2100042082).
UNASSIGNED: 13 January 2021.
UNASSIGNED: 21 January 2021.
CONCLUSIONS: There was no statistical difference in ovulation rate between patients with PCOS using the extended LE regimen and those using the conventional LE regimen.
BACKGROUND: LE has become the first-line agent for ovulation induction. However, there is still a proportion of non-responsive cycles in patients with PCOS undergoing ovulation induction therapy with LE alone, and the extended LE regimen has been demonstrated to be a feasible method for inducing ovulation in these non-responders. Nevertheless, whether the extended regimen could be applied to all patients with PCOS as a first choice for the induction of ovulation remains to be explored.
UNASSIGNED: This was a prospective randomized controlled trial that included 148 female patients with PCOS who underwent their first ovulation induction cycle with LE from January 2021 to October 2022.
METHODS: Participants were randomly assigned to receive an extended (5 mg LE daily for 7 days) or conventional regimen (5 mg LE daily for 5 days) for one treatment cycle. The ovulation rate was the primary outcome. Secondary outcomes included the clinical pregnancy rate, the number of preovulatory follicles, and the rate of multiple pregnancies.
RESULTS: The ovulation rate among patients receiving an extended LE regimen was slightly higher than the rate with a conventional LE regimen, but the difference did not reach statistical significance in either the intention-to-treat analysis (90.54% [67/74] vs 79.73% [59/74], P = 0.065; relative risk [95% CI]: 0.881 [0.768-1.009]) or the per-protocol analysis (90.54% [67/74] vs 84.29% [59/70], P = 0.257; relative risk [95% CI]: 0.931 [0.821-1.055]). The number of preovulatory follicles was nearly identical in the two groups (1.39 ± 0.62 vs 1.37 ± 0.59, P = 0.956), and no cases of ovarian hyperstimulation syndrome were observed. With regards to the endometrial parameters, the mean endometrium thickness was slightly thicker with the conventional LE regimen compared to that with the extended LE regimen, though with no statistical difference (9.27 ± 1.72 mm vs 9.57 ± 2.28 mm, P = 0.792). In the per-protocol analysis, the rates of clinical pregnancy (20.27% [15/74] vs 14.29% [10/70], P = 0.343; relative risk [95% CI]: 0.705 [0.34-1.463]) and live birth (13.51% [10/74] vs 11.43% [8/70], P = 0.705; relative risk [95% CI]: 0.846 [0.354-2.019]) did not differ significantly between treatment groups. Moreover, all conceptions were singletons without neonatal defects.
CONCLUSIONS: The major concerns regarding this study are its single-center and open-label nature. Additionally, the limited number of lean patients with PCOS with a mean body mass index of 23-25 kg/m2 enrolled in our trial also restricted the generalizability of our findings.
CONCLUSIONS: A change from the standard strategy of ovulation induction in patients with PCOS is not advisable, because a statistically superior effect of the extended LE regimen over a conventional regimen was not detected. The extended LE regimen could be applied with caution in a specific population who failed to respond to a conventional regimen rather than all the patients with PCOS during ovulation induction. Additional prospective trials with larger sample sizes and different PCOS subgroups are needed to assess the ovulatory effects of various LE treatment durations.
BACKGROUND: This study was funded by the Shanghai First Maternity and Infant Hospital, affiliated with Tongji University School of Medicine (grant numbers: 2023B03 to Y.F., 2023B18 to X.Z., and 2020RC02 to Y.F.). The authors report no conflicts of interest.
BACKGROUND: Chinese Clinical Trial Registry (ChiCTR2100042082).
UNASSIGNED: 13 January 2021.
UNASSIGNED: 21 January 2021.
摘要：
目的：多囊卵巢综合征（PCOS）患者在第一次排卵诱导周期中，延长来曲唑（LE）方案的排卵率是否比常规方案高？
结论：使用延长LE方案的PCOS患者与使用常规LE方案的PCOS患者的排卵率没有统计学差异。
背景：LE已成为促排卵的一线剂。然而,在接受单纯LE诱导排卵治疗的PCOS患者中，仍有一定比例的无反应周期，并且已证明延长LE方案是在这些无应答者中诱导排卵的可行方法。然而，延长方案是否可以作为诱导排卵的首选方案应用于所有PCOS患者,还有待探索.
■这是一项前瞻性随机对照试验，包括148名PCOS女性患者，他们在2021年1月至2022年10月期间接受了LE的第一个排卵诱导周期。
方法：参与者被随机分配接受一个治疗周期的延长方案（每天5mgLE，持续7天）或常规方案（每天5mgLE，持续5天）。排卵率是主要结果。次要结局包括临床妊娠率，排卵前卵泡的数量，和多胎妊娠率。
结果：接受延长LE方案的患者的排卵率略高于常规LE方案的排卵率。但是在意向治疗分析中差异均未达到统计学意义（90.54％[67/74]vs79.73％[59/74]，P=0.065；相对风险[95%CI]：0.881[0.768-1.009]）或符合方案分析（90.54%[67/74]vs84.29%[59/70]，P=0.257；相对风险[95%CI]：0.931[0.821-1.055]）。两组排卵前卵泡数几乎相同(1.39±0.62vs1.37±0.59,P=0.956),无卵巢过度刺激综合征病例。关于子宫内膜参数，与延长LE方案相比,常规LE方案的平均子宫内膜厚度稍厚,虽然没有统计学差异(9.27±1.72毫米vs9.57±2.28毫米，P=0.792）。在符合方案的分析中，临床妊娠率（20.27%[15/74]vs14.29%[10/70]，P=0.343；相对危险度[95%CI]：0.705[0.34-1.463]）和活产（13.51%[10/74]vs11.43%[8/70]，P=0.705；相对风险[95%CI]：0.846[0.354-2.019]）在治疗组之间没有显着差异。此外，所有概念都是没有新生儿缺陷的单胎。
结论：这项研究的主要关注点是它的单中心和开放标签性质。此外,我们的试验纳入的平均体重指数为23~25kg/m2的PCOS瘦肉患者数量有限,这也限制了我们研究结果的普遍性.
结论：不建议改变PCOS患者的标准促排卵策略，因为未检测到延长LE方案在统计学上优于常规方案的效果.延长LE方案可谨慎应用于对常规方案无反应的特定人群，而不是排卵诱导期间的所有PCOS患者。需要更大样本量和不同PCOS亚组的其他前瞻性试验来评估不同LE治疗持续时间的排卵效果。
背景：本研究由上海市第一妇产医院资助，附属于同济大学医学院(资助号：2023B03至Y.F.，2023B18至X.Z.,和2020RC02至Y.F.）。作者报告没有利益冲突。
背景：中国临床试验注册中心(ChiCTR2100042082)。
■2021年1月13日。
■2021年1月21日。
结论：使用延长LE方案的PCOS患者与使用常规LE方案的PCOS患者的排卵率没有统计学差异。
背景：LE已成为促排卵的一线剂。然而,在接受单纯LE诱导排卵治疗的PCOS患者中，仍有一定比例的无反应周期，并且已证明延长LE方案是在这些无应答者中诱导排卵的可行方法。然而，延长方案是否可以作为诱导排卵的首选方案应用于所有PCOS患者,还有待探索.
■这是一项前瞻性随机对照试验，包括148名PCOS女性患者，他们在2021年1月至2022年10月期间接受了LE的第一个排卵诱导周期。
方法：参与者被随机分配接受一个治疗周期的延长方案（每天5mgLE，持续7天）或常规方案（每天5mgLE，持续5天）。排卵率是主要结果。次要结局包括临床妊娠率，排卵前卵泡的数量，和多胎妊娠率。
结果：接受延长LE方案的患者的排卵率略高于常规LE方案的排卵率。但是在意向治疗分析中差异均未达到统计学意义（90.54％[67/74]vs79.73％[59/74]，P=0.065；相对风险[95%CI]：0.881[0.768-1.009]）或符合方案分析（90.54%[67/74]vs84.29%[59/70]，P=0.257；相对风险[95%CI]：0.931[0.821-1.055]）。两组排卵前卵泡数几乎相同(1.39±0.62vs1.37±0.59,P=0.956),无卵巢过度刺激综合征病例。关于子宫内膜参数，与延长LE方案相比,常规LE方案的平均子宫内膜厚度稍厚,虽然没有统计学差异(9.27±1.72毫米vs9.57±2.28毫米，P=0.792）。在符合方案的分析中，临床妊娠率（20.27%[15/74]vs14.29%[10/70]，P=0.343；相对危险度[95%CI]：0.705[0.34-1.463]）和活产（13.51%[10/74]vs11.43%[8/70]，P=0.705；相对风险[95%CI]：0.846[0.354-2.019]）在治疗组之间没有显着差异。此外，所有概念都是没有新生儿缺陷的单胎。
结论：这项研究的主要关注点是它的单中心和开放标签性质。此外,我们的试验纳入的平均体重指数为23~25kg/m2的PCOS瘦肉患者数量有限,这也限制了我们研究结果的普遍性.
结论：不建议改变PCOS患者的标准促排卵策略，因为未检测到延长LE方案在统计学上优于常规方案的效果.延长LE方案可谨慎应用于对常规方案无反应的特定人群，而不是排卵诱导期间的所有PCOS患者。需要更大样本量和不同PCOS亚组的其他前瞻性试验来评估不同LE治疗持续时间的排卵效果。
背景：本研究由上海市第一妇产医院资助，附属于同济大学医学院(资助号：2023B03至Y.F.，2023B18至X.Z.,和2020RC02至Y.F.）。作者报告没有利益冲突。
背景：中国临床试验注册中心(ChiCTR2100042082)。
■2021年1月13日。
■2021年1月21日。
