Applied Statistics Group, University of the West of England, Bristol, BS16 1QY, UK.
MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, BS8 2BN, UK.
BMC Med. 2019 Nov 13;17(1):202. doi: 10.1186/s12916-019-1429-z.
It is not known whether segmentation of an in vitro fertilisation (IVF) cycle, with freezing of all embryos prior to transfer, increases the chance of a live birth after all embryos are transferred.
In a prospective study of UK Human Fertilisation and Embryology Authority data, we investigated the impact of segmentation, compared with initial fresh embryo followed by frozen embryo transfers, on live birth rate and perinatal outcomes. We used generalised linear models to assess the effect of segmentation in the whole cohort, with additional analyses within women who had experienced both segmentation and non-segmentation. We compared rates of live birth, low birthweight (LBW < 2.5 kg), preterm birth (< 37 weeks), macrosomia (> 4 kg), small for gestational age (SGA < 10th centile), and large for gestational age (LGA > 90th centile) for a given ovarian stimulation cycle accounting for all embryo transfers.
We assessed 202,968 women undergoing 337,148 ovarian stimulation cycles and 399,896 embryo transfer procedures. Live birth rates were similar in unadjusted analyses for segmented and non-segmented cycles (rate ratio 1.05, 95% CI 1.02-1.08) but lower in segmented cycles when adjusted for age, cycle number, cause of infertility, and ovarian response (rate ratio 0.80, 95% CI 0.78-0.83). Segmented cycles were associated with increased risk of macrosomia (adjusted risk ratio 1.72, 95% CI 1.55-1.92) and LGA (1.51, 1.38-1.66) but lower risk of LBW (0.71, 0.65-0.78) and SGA (0.64, 0.56-0.72). With adjustment for blastocyst/cleavage-stage embryo transfer in those with data on this (329,621 cycles), results were not notably changed. Similar results were observed comparing segmented to non-segmented within 3261 women who had both and when analyses were repeated excluding multiple embryo cycles and multiple pregnancies. When analyses were restricted to women with a single embryo transfer, the transfer of a frozen-thawed embryo in a segmented cycles was no longer associated with a lower risk of LBW (0.97, 0.71-1.33) or SGA (0.84, 0.61-1.15), but the risk of macrosomia (1.74, 1.39-2.20) and LGA (1.49, 1.20-1.86) persisted. When the analyses for perinatal outcomes were further restricted to solely frozen embryo transfers, there was no strong statistical evidence for associations.
Widespread application of segmentation and freezing of all embryos to unselected patient populations may be associated with lower cumulative live birth rates and should be restricted to those with a clinical indication.
目前尚不清楚体外受精（IVF）周期的分割，即在转移前冷冻所有胚胎，是否会增加所有胚胎转移后的活产机会。
在一项针对英国人类受精与胚胎管理局数据的前瞻性研究中，我们研究了分割与初始新鲜胚胎加冷冻胚胎转移相比，对活产率和围产期结局的影响。我们使用广义线性模型评估了整个队列中分割的影响，并在经历过分割和非分割的女性中进行了额外的分析。我们比较了给定卵巢刺激周期中所有胚胎转移的活产率、低出生体重（LBW < 2.5 公斤）、早产（< 37 周）、巨大儿（> 4 公斤）、小于胎龄儿（SGA < 第 10 百分位数）和大于胎龄儿（LGA > 第 90 百分位数）的发生率。
我们评估了 202968 名接受 337148 个卵巢刺激周期和 399896 个胚胎转移程序的女性。未调整分析显示，分割和非分割周期的活产率相似（比率比 1.05，95%置信区间 1.02-1.08），但调整年龄、周期数、不孕原因和卵巢反应后，分割周期的活产率较低（比率比 0.80，95%置信区间 0.78-0.83）。分割周期与巨大儿（调整风险比 1.72，95%置信区间 1.55-1.92）和 LGA（1.51，1.38-1.66）的风险增加有关，但与 LBW（0.71，0.65-0.78）和 SGA（0.64，0.56-0.72）的风险降低有关。在对有此数据的 329621 个周期进行囊胚/卵裂期胚胎转移的调整中，结果没有明显变化。在 3261 名经历过分割和非分割的女性中进行比较，以及当排除多胚胎周期和多胎妊娠时，也观察到类似的结果。当分析仅限于单胚胎转移的女性时，分割周期中冷冻解冻胚胎的转移不再与 LBW（0.97，0.71-1.33）或 SGA（0.84，0.61-1.15）的风险降低相关，但巨大儿（1.74，1.39-2.20）和 LGA（1.49，1.20-1.86）的风险仍然存在。当将围产期结局的分析进一步限制在仅冷冻胚胎转移时，没有强有力的统计学证据表明存在关联。
在未经选择的患者人群中广泛应用分割和冷冻所有胚胎可能与较低的累积活产率相关，并且应仅限于有临床指征的患者。
