丹麦赫维多夫大学医院Sacha Stormlund团队比较了月经周期规律的女性在体外受精过程中全部囊胚冷冻和新鲜囊胚移植的效果。2020年8月5日，《英国医学杂志》在线发表了这一成果。

为了比较辅助生殖技术治疗中的“全部冷冻”策略和“新鲜移植”策略之间的持续妊娠率，研究组在丹麦、瑞典和西班牙的八家公立医院的门诊生育诊所进行了一项多中心、随机、对照、优势试验。研究组招募了460名年龄在18-39岁之间的女性，她们月经周期规律，开始进行体外受精或胞浆内精子注射的第一个、第二个或第三个治疗周期。

将这些女性在每个周期的第2、3天时随机分组，最终全部冷冻组（全部胚胎选择性冷冻）有223例，在随后的改良自然周期中接受促性腺激素释放激素激动剂诱导的单冻融囊胚移植；新鲜移植组有230例，在新鲜周期中接受人绒毛膜促性腺激素诱导和单个胚泡转移。新鲜移植组的女性若刺激出超过18个大于11mm的卵泡，则安全冷冻所有胚胎并推迟移植。

全部冷冻组和新鲜移植组之间的持续妊娠率（妊娠8周后可检测到胎心）分别为27.8％和29.6％，组间无显著差异。此外，全部冷冻组的活产率为27.4％，新鲜移植组为28.7％，组间差异不显著。

两组之间的绒毛膜促性腺激素阳性率或妊娠流产率均无显著差异，均未有女性患上严重的卵巢过度刺激综合征。全部冷冻组新生儿的平均出生体重较大，新鲜移植组的早产风险增加，除此之外，两组间的妊娠相关、产科和新生儿并发症的风险没有显著差异。全部冷冻组的怀孕时间更长。

总之，对于月经周期规律的女性，采用促性腺激素释放激素激动剂诱导终级卵母细胞成熟的全冷冻策略与新鲜移植策略相比，并未提高持续妊娠率和活产率。

附：英文原文

Title: Freeze-all versus fresh blastocyst transfer strategy during in vitro fertilisation in women with regular menstrual cycles: multicentre randomised controlled trial

Author: Sacha Stormlund, Negjyp Sopa, Anne Zedeler, Jeanette Bogstad, Lisbeth Prtorius, Henriette Svarre Nielsen, Margaretha Laczna Kitlinski, Sven O Skouby, Anne Lis Mikkelsen, Anne Lrke Spangmose, Janni Vikkels Jeppesen, Ali Khatibi, Nina la Cour Freiesleben, Sren Ziebe, Nikolaos P Polyzos, Christina Bergh, Peter Humaidan, Anders Nyboe Andersen, Kristine Lssl, Anja Pinborg

Issue&Volume: 2020/08/05

Abstract: Objective To compare the ongoing pregnancy rate between a freeze-all strategy and a fresh transfer strategy in assisted reproductive technology treatment.

Design Multicentre, randomised controlled superiority trial.

Setting Outpatient fertility clinics at eight public hospitals in Denmark, Sweden, and Spain.

Participants 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.

Interventions 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.

Main outcome measures 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.

Results Ongoing pregnancy rate did not differ significantly between the freeze-all and fresh transfer groups (27.8% (62/223) v 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.

Conclusions 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.

DOI: 10.1136/bmj.m2519

Source: https://www.bmj.com/content/370/bmj.m2519