Letrozole-induced frozen embryo transfer cycles are associated with a lower risk of hypertensive disorders of pregnancy among women with polycystic ovary syndrome
Letrozole-induced frozen embryo transfer cycles are associated with a lower risk of hypertensive disorders of pregnancy among women with polycystic ovary syndrome
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DOI：
10.1016/j.ajog.2021.01.024
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发表时间：
2021-06-30
影响因子：
9.8
通讯作者：
Wang, Bian
中科院分区：
文献类型：
--
作者：
Zhang, Jie;Wei, Mengjie;Wang, Bian
背景：回顾性观察数据显示，在有规律排卵周期的女性中，人工周期冷冻胚胎移植可能比自然周期冷冻胚胎移植更有可能导致妊娠高血压疾病的风险增加。黄体在人工冷冻周期中不存在，这至少是造成这种不良产科结局的部分原因。然而，对于接受冷冻胚胎移植的多囊卵巢综合征妇女来说，人工周期是最常用的方案。目前尚不清楚在多囊卵巢综合征患者中采用生理性冷冻胚胎移植方案能否降低妊娠高血压疾病的风险，目前尚不清楚。目的：本研究旨在探讨在冷冻胚胎移植周期中使用来曲唑与人工冷冻周期相比对单胎和双胞胎妊娠的产科和围产儿结局的影响。STUDY设计：这项回顾性队列研究涉及2010至2018年间在三级护理中心接受人工冷冻周期或来曲唑刺激的冷冻周期的多囊卵巢综合征妇女。主要结果是妊娠期高血压疾病的发生率。对相关因素进行多因素Logistic回归分析。结果：2427例多囊卵巢综合征患者进入最终分析。在这些妇女中，有1168人接受了人工周期，1259人接受了来曲唑治疗，其中25%的妇女单独接受来曲唑治疗，75%的妇女接受来曲唑和促性腺激素的联合治疗。在控制了母体特征和治疗变量后，在单胎妊娠和双胎妊娠中，妊娠期糖尿病、胎盘异常和胎膜早破在两组之间没有显著差异。对于出生结果，无论是单胞胎还是双胞胎，早产、围产期死亡和出生体重结果的患病率都是相似的。然而，来曲唑刺激周期导致的单胎妊娠患高血压疾病的风险低于人工周期妊娠(调整后的优势比，0.63；95%可信区间，0.40-0.98)。此外，莱曲唑刺激周期与人工周期相比，双胎分娩的孕妇患妊娠高血压疾病的风险降低(调整后的优势比为0.52；95%可信区间为0.30-0.87)。此外，与人工周期组相比，来曲唑组单胎剖宫产率显著降低(调整后优势比0.63；95%可信区间0.50~0.78；调整后优势比1.20；95%可信区间0.65~2.23)。结论：在接受冷冻胚胎移植的多囊卵巢综合征患者中，来曲唑用于子宫内膜准备的妊娠高血压疾病风险低于人工周期子宫内膜准备。我们的发现提供了一个基础，即通过使用导致黄体发育的生理子宫内膜准备方案，例如对少排卵或无排卵妇女进行温和的卵巢刺激周期，可以减轻与冷冻胚胎移植相关的妊娠高血压疾病的风险。
BACKGROUND: Observational retrospective data suggest that an artificial cycle frozen embryo transfer may be associated with a higher risk of hypertensive disorder of pregnancy than a natural cycle frozen embryo transfer among women with regular ovulatory cycles. The corpus luteum, which is not present in the artificial frozen cycles, is at least partly responsible for this poor obstetrical outcome. However, an artificial cycle is the most frequently used regimen for women with polycystic ovary syndrome undergoing frozen embryo transfer. Whether the risk of hypertensive disorder of pregnancy could be mitigated by employing physiological frozen embryo transfer protocols that lead to the development of a corpus luteum in patients with polycystic ovary syndrome remains unknown.OBJECTIVE: This study aimed to investigate the impact of letrozole use during frozen embryo transfer cycles on obstetrical and perinatal outcomes of singleton and twin pregnancies compared with artificial frozen cycles among women with polycystic ovary syndrome.STUDY DESIGN: This retrospective cohort study involved women with polycystic ovary syndrome who had undergone artificial frozen cycles or letrozole-stimulated frozen cycles during the period from 2010 to 2018 at a tertiary care center. The primary outcome was the incidence of hypertensive disorder of pregnancy. A multivariable logistic regression analysis was performed to control for the relevant confounders.RESULTS: A total of 2427 women with polycystic ovary syndrome were included in the final analysis. Of these women, 1168 underwent artificial cycles and 1259 underwent letrozole treatment, of which 25% of women treated with letrozole alone and 75% of women receiving letrozole combined with gonadotropins. After controlling for maternal characteristics and treatment variables, no significant difference was noticed regarding gestational diabetes mellitus, abnormal placentation, and preterm premature rupture of membranes between groups in both singleton and twin pregnancies. For birth outcomes, the prevalence rates of preterm birth, perinatal death, and birthweight outcomes were all comparable between groups in both singletons and twins. However, singleton pregnancies resulting from letrozole-stimulated cycles had a lower risk of hypertensive disorder of pregnancy than those conceived by artificial cycles (adjusted odds ratio, 0.63; 95% confidence interval, 0.40-0.98). Furthermore, a decreased risk of hypertensive disorder of pregnancy was seen among women with twin deliveries resulting from letrozole-stimulated cycles vs artificial cycles (adjusted odds ratio, 0.52; 95% confidence interval, 0.30-0.87). In addition, the cesarean delivery rate was significantly lower for singletons but not for twins in the letrozole group compared with pregnancies from the artificial cycle group (adjusted odds ratio, 0.63; 95% confidence interval, 0.50-0.78, and adjusted odds ratio, 1.20; 95% confidence interval, 0.65-2.23, respectively).CONCLUSION: In women with polycystic ovary syndrome undergoing frozen embryo transfer, letrozole use for endometrial preparation was associated with a lower risk of hypertensive disorder of pregnancy than artificial cycles for endometrial preparation. Our findings provided a foundation that the increased risk of hypertensive disorder of pregnancy associated with frozen embryo transfer might be mitigated by utilizing physiological endometrial preparation protocols that lead to the development of a corpus luteum, such as a mild ovarian stimulation cycle for oligoor anovulatory women.