Mesh : Female Pregnancy Humans Child, Preschool Pregnancy Outcome / epidemiology Aneuploidy Embryo Transfer Gonadotropins / therapeutic use Infertility

来  源:   DOI:10.1001/jamanetworkopen.2024.4438   PDF(Pubmed)

Abstract:
UNASSIGNED: The safety of exogenous gonadotropin treatment, based on its effect on embryos and pregnancy outcomes, remains inconclusive.
UNASSIGNED: To evaluate the associations of different doses and durations of gonadotropins with embryonic genetic status and pregnancy outcomes after euploid embryo transfer in couples with infertility.
UNASSIGNED: This study was a post hoc analysis of a multicenter randomized clinical trial (RCT) conducted at 14 reproductive centers throughout China from July 2017 to June 2018 that evaluated the cumulative live birth rate with or without preimplantation genetic testing for aneuploidy (PGT-A) among couples with infertility and good prognosis. The PGT-A group from the original RCT was selected for secondary analysis. Patients were divided into 4 groups according to the total dosage of exogenous gonadotropins and treatment duration: group 1 (≤1500 IU and <10 days), group 2 (≤1500 IU and ≥10 days), group 3 (>1500 IU and <10 days), and group 4 (>1 500 IU and ≥10 days). Group 1 served as the control group. Data were analyzed from June through August 2023.
UNASSIGNED: Blastocyst biopsy and PGT-A.
UNASSIGNED: The primary outcomes were embryonic aneuploidy, embryonic mosaicism, and cumulative live birth rates after euploid embryo transfer.
UNASSIGNED: A total of 603 couples (mean [SD] age of prospective mothers, 29.13 [3.61] years) who underwent PGT-A were included, and 1809 embryos were screened using next-generation sequencing. The embryo mosaicism rate was significantly higher in groups 2 (44 of 339 embryos [13.0%]; adjusted odds ratio [aOR], 1.69 [95% CI, 1.09-2.64]), 3 (27 of 186 embryos [14.5%]; aOR, 1.98 [95% CI, 1.15-3.40]), and 4 (82 of 651 embryos [12.6%]; aOR, 1.60 [95% CI, 1.07-2.38]) than in group 1 (56 of 633 embryos [8.8%]). There were no associations between gonadotropin dosage or duration and the embryo aneuploidy rate. The cumulative live birth rate was significantly lower in groups 2 (83 of 113 couples [73.5%]; aOR, 0.49 [95% CI, 0.27-0.88]), 3 (42 of 62 couples [67.7%]; aOR, 0.41 [95% CI, 0.21-0.82]), and 4 (161 of 217 couples [74.2%]; aOR, 0.53 [95% CI, 0.31-0.89]) than in group 1 (180 of 211 couples [85.3%]).
UNASSIGNED: In this study, excessive exogenous gonadotropin administration was associated with increased embryonic mosaicism and decreased cumulative live birth rate after euploid embryo transfer in couples with a good prognosis. These findings suggest that consideration should be given to minimizing exogenous gonadotropin dosage and limiting treatment duration to improve embryo outcomes and increase the live birth rate.
UNASSIGNED: ClinicalTrials.gov Identifier: NCT03118141.
摘要:
外源性促性腺激素治疗的安全性,基于它对胚胎和妊娠结局的影响,仍然没有定论。
评估不同剂量和持续时间的促性腺激素与不育症夫妇整倍体胚胎移植后胚胎遗传状态和妊娠结局的关系。
这项研究是对2017年7月至2018年6月在中国14个生殖中心进行的多中心随机临床试验(RCT)的事后分析,该试验评估了患有不育症和预后良好的夫妇中有无非整倍体植入前遗传检测(PGT-A)的累积活产率。从原始RCT中选择PGT-A组进行二次分析。根据外源性促性腺激素的总剂量和治疗时间将患者分为4组:第1组(≤1500IU和<10天),第2组(≤1500IU,≥10天),第3组(>1500IU和<10天),和第4组(>1500IU和≥10天)。第1组作为对照组。数据从2023年6月到8月进行了分析。
囊胚活检和PGT-A。
主要结果是胚胎非整倍体,胚胎镶嵌,整倍体胚胎移植后的累积活产率。
共有603对夫妇(准母亲的平均年龄[SD],29.13[3.61]年)接受PGT-A的人被包括在内,和1809个胚胎使用下一代测序进行筛选。第2组的胚胎镶嵌率显着较高(339个胚胎中有44个[13.0%];调整后的比值比[aOR],1.69[95%CI,1.09-2.64]),3(186个胚胎中的27个[14.5%];aOR,1.98[95%CI,1.15-3.40]),和4(651个胚胎中的82个[12.6%];aOR,1.60[95%CI,1.07-2.38])比第1组(633个胚胎中的56个[8.8%])。促性腺激素剂量或持续时间与胚胎非整倍体率之间没有关联。第2组的累积活产率显着降低(113对夫妇中的83对[73.5%];aOR,0.49[95%CI,0.27-0.88]),3(62对夫妇中的42对[67.7%];或,0.41[95%CI,0.21-0.82]),和4(217对夫妇中的161对[74.2%];或,0.53[95%CI,0.31-0.89])高于第1组(211对夫妇中的180对[85.3%])。
在这项研究中,在预后良好的夫妇中,过度施用外源性促性腺激素与整倍体胚胎移植后胚胎镶嵌性增加和累积活产率降低相关.这些结果表明,应考虑尽量减少外源性促性腺激素剂量和限制治疗持续时间,以改善胚胎结局并提高活产率。
ClinicalTrials.gov标识符:NCT03118141。
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