STUDY QUESTION Is there a difference in clinical pregnancy rates (CPRs) in good prognosis patients after single embryo transfer (SET) on Day 5, in case of stable culture at 36.6°C or 37.1°C? SUMMARY ANSWER CPR (with heartbeat at 7 weeks) after blastocyst transfer do not differ after culturing at 36.6°C or 37.1°C. WHAT IS KNOWN ALREADY Since the beginning of IVF, embryo culture has been performed at 37.0°C; however, the optimal culture temperature remains unknown. Changes in incubator types have led to significant improvements in temperature control. Stable temperature control, i.e. with temperature differences of max. 0.1°C between chambers, is possible in some incubators. A previous prospective pilot study showed that embryo development on Day 5/6 was not affected when embryos were cultured at a stable temperature of 36.6°C or 37.1°C, but culture at 37.1°C resulted in an increased CPR when compared to culture at 36.6°C (74.2% vs 46.4%). STUDY DESIGN, SIZE, DURATION A prospective randomized controlled trial was performed in a tertiary fertility centre between February 2017 and November 26, 2022. A sample size of 89/89 patients with fresh single embryo transfer (SET) was required to achieve 80% power to detect a difference of 0.22 between group proportions (0.43–0.65) at a significance level of 0.05 using a two-sided z-test with continuity correction. PARTICIPANTS/MATERIALS, SETTING, METHODS Patients were recruited on the day of oocyte retrieval based on inclusion criteria with final randomization after denudation once six mature oocytes were present. The primary endpoint was CPR (heartbeat at 7 weeks); secondary endpoints were fertilization rate, blastocyst development, biochemical pregnancy rate, live birth rate (LBR), and cumulative live birth rate (CLBR). MAIN RESULTS AND THE ROLE OF CHANCE A total of 304 patients were eligible for the study; of these 268 signed the consent, 234 (intention-to-treat) were randomized and 181 (per-protocol) received a SET on Day 5: 90 received culture at 36.6°C and 91 at 37.1°C. Patients were on average 32.4 ± 3.5 versus 32.5 ± 4.2 years old, respectively. No differences were observed in embryological outcomes per cycle between culture at 36.6°C versus 37.1°C: 12.0 ± 3.8 vs 12.1 ± 3.8 COCs retrieved (P = 0.88), 10.0 ± 3.1 versus 9.9 ± 2.9 mature oocytes inseminated (P = 0.68), with a maturation rate of 84.2% (901/1083) versus 83.5% (898/1104) (P = 0.87); and 8.0 ± 3.1 versus 7.9 ± 2.7 normally fertilized oocytes with a fertilization rate of 79.7% (720/901) vs 80.5% (718/898) (P = 0.96), respectively. On average 1.5 ± 1.7 versus 1.4 ± 1.9 (P = 0.25) and 1.1 ± 1.1 versus 0.9 ± 1.0 (P = 0.45) supernumerary blastocysts were vitrified on Day 5 and Day 6, respectively. The utilization rate per fertilized oocyte was 46.1% vs 41.5% (P = 0.14). A SET was performed for 181 patients, leading to a biochemical pregnancy rate of 72.2% (65/90) versus 62.7% (57/91) (P = 0.17), respectively. The CPR per fresh transfer cycle was 51.1% (46/90) versus 48.4% (44/91) [OR (95% CI) 1.11 (0.59–2.08), P = 0.710]. To date, a CLBR of 73.3% (66/90) versus 67.0% (61/91) (P = 0.354) has been observed, respectively. In each group, seven patients without live birth have remaining blastocysts frozen. The CPR for the intention-to-treat groups were 38.3% vs 38.6% [OR (95% CI) 0.98 (0.56–1.73), P = 0.967], respectively, for culture at 36.6°C versus 37.1°C. LIMITATIONS, REASONS FOR CAUTION Only selected patients with expected good prognosis were eligible for the study. WIDER IMPLICATIONS OF THE FINDINGS Embryos tend to tolerate small changes in temperature deviations during culture to the blastocyst stage, as demonstrated by their similar implantation potential at two slightly different temperatures. STUDY FUNDING/COMPETING INTEREST(S) There is no funding or conflicts of interest to declare. TRIAL REGISTRATION NUMBER NCT03548532. TRIAL REGISTRATION DATE 23 October 2017 DATE OF FIRST PATIENT’S ENROLMENT 10 November 2017

中文翻译：

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在 36.6°C 和 37.1°C 的稳定温度下囊胚培养后的临床妊娠率：一项前瞻性随机对照试验


研究问题 在 36.6°C 或 37.1°C 稳定培养的情况下，第 5 天单胚胎移植 （SET） 后预后良好的患者的临床妊娠率 （CPR） 是否存在差异？总结 答案 囊胚移植后 CPR（7 周时有心跳）在 36.6°C 或 37.1°C 下培养后没有差异。已经知道的 自体外受精开始以来，胚胎培养一直在 37.0°C 下进行;然而，最佳培养温度仍然未知。培养箱类型的变化导致温度控制的显著改善。在一些培养箱中，可以进行稳定的温度控制，即腔室之间的温差最大为 0.1°C。之前的一项前瞻性试点研究表明，当胚胎在 36.6°C 或 37.1°C 的稳定温度下培养时，第 5/6 天的胚胎发育不受影响，但在 37.1°C 下培养导致 CPR 增加与 36.6°C 培养相比（74.2% 对 46.4%）。研究设计、规模、持续时间 2017 年 2 月至 2022 年 11 月 26 日期间，在三级生育中心进行了一项前瞻性随机对照试验。需要 89/89 名新鲜单胚胎移植 （SET） 患者的样本量才能达到 80% 的功效，才能在显着性水平为 0.05 的情况下检测组间比例之间的差异 （0.43-0.65），使用具有连续性校正的双侧 z 检验。参与者/材料、设置、方法 根据纳入标准在取卵当天招募患者，一旦存在 6 个成熟卵母细胞，剥脱后进行最终随机化。主要终点是 CPR（7 周时的心跳）;次要终点是受精率、囊胚发育、生化妊娠率、活产率 （LBR） 和累积活产率 （CLBR）。 主要结果和机会的作用 共有 304 名患者符合研究条件;在这 268 例签署同意书的病例中，234 例（意向治疗）是随机分配的，181 例（根据方案）在第 5 天接受了 SET：90 例在 36.6°C 下接受了培养，91 例在 37.1°C 下接受了培养。 患者平均分别为 32.4 岁± 3.5 岁和 32.5 岁± 4.2 岁。在 36.6°C 和 37.1°C 下培养的每个周期的胚胎学结果未观察到差异：12.0 ± 3.8 vs 12.1 ± 3.8 个回收的 COC （P = 0.88），10.0 ± 3.1 对 9.9 ± 2.9 个成熟卵母细胞受精 （P = 0.68），成熟率为 84.2% （901/1083） 对 83.5% （898/1104） （P = 0.87）;和 8.0 ± 3.1 对 7.9 ± 2.7 正常受精卵母细胞，受精率分别为 79.7% （720/901） 和 80.5% （718/898） （P = 0.96）。平均 1.5 ± 1.7 对 1.4 ± 1.9 （P = 0.25） 和 1.1 ± 1.1 对 0.9 ± 1.0 （P = 0.45） 多余囊胚分别在第 5 天和第 6 天玻璃化。每个受精卵母细胞的利用率为 46.1% vs 41.5% （P = 0.14）。对 181 例患者进行了 SET，生化妊娠率分别为 72.2% （65/90） 和 62.7% （57/91） （P = 0.17）。每个新鲜转移周期的 CPR 为 51.1% （46/90） 对 48.4% （44/91） [OR （95% CI） 1.11 （0.59–2.08），P = 0.710]。迄今为止，已观察到 CLBR 分别为 73.3% （66/90） 和 67.0% （61/91） （P = 0.354）。在每组中，7 名没有活产的患者有剩余的囊胚被冷冻。意向治疗组的 CPR 分别为 38.3% 和 38.6% [OR （95% CI） 0.98 （0.56–1.73），P = 0.967]，在 36.6°C 和 37.1°C 下培养。局限性，谨慎的原因 只有预期预后良好的选定患者才有资格参加该研究。 研究结果的更广泛意义 胚胎在培养到囊胚阶段倾向于容忍温度偏差的微小变化，正如它们在两个略有不同的温度下相似的着床电位所证明的那样。研究资金/竞争利益 无需申报资金或利益冲突。试验注册号 NCT03548532。试验注册日期 2017 年 10 月 23 日 首位患者入组日期 2017 年 11 月 10 日