Fertility Clinic, Department of Obstetrics and Gynaecology, Hvidovre University Hospital, Hvidovre, Kettegaard Allé 30, Copenhagen DK-2650, Denmark
Fertility Clinic, Department of Obstetrics and Gynaecology, Hvidovre University Hospital, Hvidovre, Kettegaard Allé 30, Copenhagen DK-2650, Denmark.
BMJ. 2020 Aug 5;370:m2519. doi: 10.1136/bmj.m2519.
To compare the ongoing pregnancy rate between a freeze-all strategy and a fresh transfer strategy in assisted reproductive technology treatment.
Multicentre, randomised controlled superiority trial.
Outpatient fertility clinics at eight public hospitals in Denmark, Sweden, and Spain.
460 women aged 18-39 years with regular menstrual cycles starting their first, second, or third treatment cycle of in vitro fertilisation or intracytoplasmic sperm injection.
Women were randomised at baseline on cycle day 2 or 3 to one of two treatment groups: the freeze-all group (elective freezing of all embryos) who received gonadotropin releasing hormone agonist triggering and single frozen-thawed blastocyst transfer in a subsequent modified natural cycle; or the fresh transfer group who received human chorionic gonadotropin triggering and single blastocyst transfer in the fresh cycle. Women in the fresh transfer group with more than 18 follicles larger than 11 mm on the day of triggering had elective freezing of all embryos and postponement of transfer as a safety measure.
The primary outcome was the ongoing pregnancy rate defined as a detectable fetal heart beat after eight weeks of gestation. Secondary outcomes were live birth rate, positive human chorionic gonadotropin rate, time to pregnancy, and pregnancy related, obstetric, and neonatal complications. The primary analysis was performed according to the intention-to-treat principle.
Ongoing pregnancy rate did not differ significantly between the freeze-all and fresh transfer groups (27.8% (62/223) 29.6% (68/230); risk ratio 0.98, 95% confidence interval 0.87 to 1.10, P=0.76). Additionally, no significant difference was found in the live birth rate (27.4% (61/223) for the freeze-all group and 28.7% (66/230) for the fresh transfer group; risk ratio 0.98, 95% confidence interval 0.87 to 1.10, P=0.83). No significant differences between groups were observed for positive human chorionic gonadotropin rate or pregnancy loss, and none of the women had severe ovarian hyperstimulation syndrome; only one hospital admission related to this condition occurred in the fresh transfer group. The risks of pregnancy related, obstetric, and neonatal complications did not differ between the two groups except for a higher mean birth weight after frozen blastocyst transfer and an increased risk of prematurity after fresh blastocyst transfer. Time to pregnancy was longer in the freeze-all group.
In women with regular menstrual cycles, a freeze-all strategy with gonadotropin releasing hormone agonist triggering for final oocyte maturation did not result in higher ongoing pregnancy and live birth rates than a fresh transfer strategy. The findings warrant caution in the indiscriminate application of a freeze-all strategy when no apparent risk of ovarian hyperstimulation syndrome is present.
Clinicaltrials.gov NCT02746562.
比较辅助生殖技术治疗中冷冻保存策略与新鲜胚胎移植策略的持续妊娠率。
多中心、随机对照优效性试验。
丹麦、瑞典和西班牙 8 家公立医院的门诊生育诊所。
460 名年龄在 18-39 岁、月经周期规律的女性，她们正在进行第一次、第二次或第三次体外受精或胞浆内单精子注射治疗周期。
女性在基线时按周期第 2 或 3 天随机分为两组治疗：冷冻组（选择冷冻所有胚胎）接受促性腺激素释放激素激动剂触发和随后的改良自然周期中的单个冷冻解冻囊胚移植；新鲜胚胎移植组接受人绒毛膜促性腺激素触发和新鲜周期中的单个囊胚移植。新鲜胚胎移植组中，在触发日有超过 18 个大于 11mm 的卵泡的女性，选择冷冻所有胚胎，并作为安全措施推迟移植。
主要结局指标为妊娠 8 周后可检测到胎心的持续妊娠率。次要结局指标为活产率、人绒毛膜促性腺激素阳性率、妊娠时间和妊娠相关、产科和新生儿并发症。主要分析按照意向治疗原则进行。
冷冻组和新鲜胚胎移植组的持续妊娠率无显著差异（27.8%（62/223）与 29.6%（68/230）；风险比 0.98，95%置信区间 0.87-1.10，P=0.76）。活产率也无显著差异（27.4%（61/223）与 28.7%（66/230）；风险比 0.98，95%置信区间 0.87-1.10，P=0.83）。两组间人绒毛膜促性腺激素阳性率或妊娠丢失率无显著差异，且无严重卵巢过度刺激综合征患者；仅在新鲜胚胎移植组中发生 1 例与该病症相关的住院治疗。两组妊娠相关、产科和新生儿并发症的风险无差异，但冷冻囊胚移植后平均出生体重较高，新鲜囊胚移植后早产风险增加。冷冻组妊娠时间较长。
在月经周期规律的女性中，与新鲜胚胎移植策略相比，使用促性腺激素释放激素激动剂触发进行最终卵母细胞成熟的冷冻保存策略并未导致更高的持续妊娠率和活产率。这些发现提示，在没有明显卵巢过度刺激综合征风险的情况下，盲目应用冷冻保存策略需谨慎。
Clinicaltrials.gov NCT02746562。
