Tighe Jack, Broughton Sophie, Roberts Rachel, Kasaven Lorraine S, Cutting Rachel, Bridges Elliot, Ng Abigail, Evans Amanda, Theodorou Efstathios, Ben Nagi Jara, Jones Benjamin P
Department of Gynaecology, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK.
Department of Metabolism, Digestion and Reproduction, Institute of Reproductive & Developmental Biology, Imperial College London, Hammersmith Hospital Campus, London, UK.
Hum Reprod. 2025 May 1;40(5):885-894. doi: 10.1093/humrep/deaf028.
How does two-consecutive single embryo transfer (2xSET) affect reproductive outcomes of IVF and ICSI compared to double embryo transfer (DET)?
Two-consecutive SET may provide greater or comparable live birth rate (LBR); with lower multiple birth, preterm birth, and pregnancy loss or neonatal death rates compared to DET.
Elective SET in IVF/ICSI is widely encouraged over DET to minimize the risk of multiple births and associated morbidities. Despite this, multiple birth rates following IVF remain higher than the 10% target across Europe and the USA. Currently, the majority of evidence regarding SET and DET is based on various studies assessing outcomes such as LBR per treatment cycle, as opposed to per oocyte retrieval. As such, the representation of SET is mostly unfavourable. Analysis of cumulative LBR following the transfer of two embryos over consecutive cycles, rather than in one transfer event (DET) is more effective at distinguishing the two methods and will therefore provide more valuable information relevant to clinical practice.
STUDY DESIGN, SIZE, DURATION: This retrospective cohort study was conducted using Human Fertilisation and Embryology Authority (HFEA) register data, which encompasses national data from all IVF clinics in the UK. All women who underwent their first oocyte retrieval and IVF or ICSI treatment cycle with subsequent SET, DET, or 2xSET between 2010 and 2019 using blastocyst embryos were included (N = 71 807).
PARTICIPANTS/MATERIALS, SETTING, METHODS: The rate of live birth, liveborn baby rate, multiple birth, preterm birth, and pregnancy loss or neonatal death was compared between SET, DET, and 2xSET IVF/ICSI pregnancies using blastocyst-stage embryos, where data were stratified by maternal age. Data analysis was conducted in RStudio v4.2, alpha equals 0.05.
Blastocyst-stage 2xSET achieved a greater median LBR of 0.47 (interquartile range [IQR] 0.13) than SET, 0.41 (IQR 0.13), and DET, 0.38 (IQR 0.13) (P < 0.05). Using SET as the reference standard, 2xSET was associated with a significantly lower odds of multiple births compared to DET ((odds ratio [OR] 6.87, 95% CI 6.14-7.68) vs 28.20, 95% CI 25.20-31.57). The odds of preterm birth were also lower following 2xSET (OR 1.11, 95% CI 1.06-1.15) compared to DET (OR 2.80, 95% CI 2.67-2.94). Similarly, the odds of pregnancy loss or neonatal death were lower following 2xSET (OR 1.14, 95% CI 1.08-1.21) compared to DET (OR 2.11, 95% CI 1.98-2.24). LBR was consistently higher following 2xSET than DET and SET in women aged 39 years and under (P < 0.05). However, results were comparable in women over 39 years (P > 0.05). Across all age groups, DET pregnancies had the highest multiple birth rate (P < 0.05). In women aged 39 years and under, DET was associated with the highest preterm birth rate (P < 0.05), whereas the rate was comparable across cohorts in women over 39 (P > 0.05). Moreover, pregnancy loss and neonatal death rates were highest following DET in women aged 37 years and under (P < 0.05), and comparable to SET and 2xSET in women over 37 years (P > 0.05).
LIMITATIONS, REASONS FOR CAUTION: Certain confounders are not recorded within HFEA registry data, including patient BMI, evaluation of embryo quality, and endometrial thickness at embryo transfer. Consequently, while our analysis identifies broad trends in embryo transfer success and morbidity, results may differ within certain patient populations.
Blastocyst-stage 2xSET may provide greater LBR in women aged 39 years and under, and comparable LBR in women over 39 years old, with overall lower multiple birth and morbidity than DET. 2xSET should be considered first-line among certain patient cohorts, including women with advanced maternal age to improve reproductive outcomes and reduce the risk of morbidity following ART.
STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for this study. None of the authors has any conflicts of interest.
This cohort study did not require registration. Following consultation with the Institutional Review Board at Imperial College London, ethical approval was not deemed necessary.
与双胚胎移植（DET）相比，连续两次单胚胎移植（2xSET）如何影响体外受精（IVF）和卵胞浆内单精子注射（ICSI）的生殖结局？
与DET相比，连续两次SET可能提供更高或相当的活产率（LBR）；多胎妊娠、早产、妊娠丢失或新生儿死亡率更低。
在IVF/ICSI中，广泛鼓励选择性SET而非DET，以将多胎妊娠及相关发病风险降至最低。尽管如此，IVF后的多胎妊娠率在欧洲和美国仍高于10%的目标。目前，关于SET和DET的大多数证据基于各种评估每个治疗周期（而非每个取卵周期）LBR等结局的研究。因此，SET的表现大多不利。分析连续周期（而非一次移植事件（DET））移植两个胚胎后的累积LBR，在区分这两种方法时更有效，因此将提供与临床实践相关的更有价值信息。
研究设计、规模、持续时间：这项回顾性队列研究使用了人类受精与胚胎学管理局（HFEA）的登记数据，该数据涵盖了英国所有IVF诊所的全国数据。纳入了2010年至2019年间所有首次进行取卵及IVF或ICSI治疗周期，随后使用囊胚胚胎进行SET、DET或2xSET的女性（N = 71807）。
参与者/材料、设置、方法：比较了使用囊胚期胚胎的SET、DET和2xSET IVF/ICSI妊娠之间的活产率、活产婴儿率、多胎妊娠、早产以及妊娠丢失或新生儿死亡率，数据按产妇年龄分层。在RStudio v4.2中进行数据分析，α等于0.05。
囊胚期2xSET的LBR中位数为0.47（四分位间距[IQR] 0.13），高于SET的0.41（IQR 0.13）和DET的0.38（IQR 0.13）（P < 0.05）。以SET作为参考标准，与DET相比，2xSET的多胎妊娠几率显著更低（优势比[OR] 6.87，95%置信区间[CI] 6.14 - 7.68），而DET为28.20，95% CI 25.20 - 31.57）。与DET相比，2xSET后的早产几率也更低（OR 1.11，95% CI 1.06 - 1.15），而DET为（OR 2.80，95% CI 2.67 - 2.94）。同样，与DET相比，2xSET后的妊娠丢失或新生儿死亡几率更低（OR 1.14，95% CI 1.08 - 1.21），而DET为（OR 2.11，95% CI 1.98 - 2.24）。在39岁及以下女性中，2xSET后的LBR始终高于DET和SET（P < 0.05）。然而，在39岁以上女性中结果相当（P > 0.05）。在所有年龄组中，DET妊娠的多胎妊娠率最高（P < 0.05）。在39岁及以下女性中，DET与最高的早产率相关（P < 0.05），而在39岁以上女性中各队列的早产率相当（P > 0.05）。此外，在37岁及以下女性中，DET后的妊娠丢失和新生儿死亡率最高（P < 0.05），在37岁以上女性中与SET和2xSET相当（P > 0.05）。
局限性、谨慎原因：HFEA登记数据中未记录某些混杂因素，包括患者体重指数、胚胎质量评估以及胚胎移植时的子宫内膜厚度。因此，虽然我们的分析确定了胚胎移植成功和发病的总体趋势，但在某些患者群体中结果可能不同。
囊胚期2xSET可能在39岁及以下女性中提供更高的LBR，在39岁以上女性中提供相当的LBR，总体多胎妊娠和发病率低于DET。在某些患者队列中，包括高龄产妇，2xSET应被视为一线方案，以改善生殖结局并降低辅助生殖技术后的发病风险。
研究资金/利益冲突：本研究未使用外部资金。作者均无利益冲突。
本队列研究无需注册。经与伦敦帝国理工学院机构审查委员会协商，认为无需伦理批准。
