Department of Obstetrics and Gynecology, IRCCS San Raffaele Hospital, Milan, Italy.
University Vita-Salute, Milan, Italy.
Ultrasound Obstet Gynecol. 2022 Jul;60(1):76-85. doi: 10.1002/uog.24806.
To compare, using a unified approach, standardized estimated fetal weight (EFW) trajectories from the second trimester to birth and birth-weight (BW) measurements in in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) pregnancies obtained after frozen-thawed vs fresh blastocyst transfer (BT).
This was a secondary analysis of a prospective longitudinal cohort study performed at the Fetal Medicine and Obstetric Departments of San Raffaele Hospital in Milan, Italy, from January 2016 to December 2020. Eligible for inclusion were singleton viable gestations conceived by autologous IVF/ICSI conception after fresh or frozen-thawed BT that underwent standard fetal biometry assessment at 19-41 weeks and had BW measurements available. All ultrasound assessments were performed by operators blinded to the employment of cryopreservation. Patients with twin gestation, significant pregestational disease, miscarriage, major fetal abnormalities and use of other types of medically assisted reproduction techniques were excluded. EFW and BW Z-scores and their trajectories were analyzed using general linear models (GLM) and logistic regression with a unified modeling methodology based on the Fetal Medicine Foundation fetal and neonatal population weight charts, adjusting for major confounders. Differences between prenatal EFW and postnatal BW centiles in the two groups were assessed and compared using contingency tables, χ test and conversion of prenatal to postnatal centiles.
A total of 631 IVF/ICSI pregnancies were considered, comprising 263 conceived following fresh BT and 368 after frozen-thawed BT. A total of 1795 EFW observations were available (n = 715 in fresh BT group and n = 1080 in frozen-thawed BT group; median of three observations per patient). EFW and BW < 10 centile were significantly more frequent in the fresh than in the frozen-thawed BT group (P = 0.003 and P < 0.001, respectively). EFW and BW > 90 centile were significantly more frequent in the frozen-thawed vs fresh BT group (P = 0.034 and P = 0.002, respectively). GLM showed significantly decreasing EFW Z-scores with advancing gestational age (GA) in both groups. The effect of GA was assumed to be equal in the two study groups, as no significant interaction effect was found. Smoothed mean EFW Z-scores from 19 weeks of gestation to term and smoothed mean BW Z-scores were both significantly higher in the frozen-thawed compared with the fresh BT group (EFW Z-score, 0.70 ± 1.29 vs 0.28 ± 1.43; P < 0.001; BW Z-score, 0.04 ± 1.08 vs -0.31 ± 1.28; P < 0.001). Mean smoothed EFW Z-score values in the frozen-thawed vs fresh BT groups were 1.01 ± 0.12 vs 0.60 ± 0.08 at 19-27 weeks, 0.36 ± 0.07 vs -0.06 ± 0.04 at 28-35 weeks and -0.66 ± 0.01 vs -0.88 ± 0.02 at 36-41 weeks. Mean smoothed BW Z-score values in the frozen-thawed vs fresh BT groups were -0.80 ± 0.14 vs -1.20 ± 0.10 at 28-35 weeks and 0.22 ± 0.16 vs -0.24 ± 0.14 at 36-41 weeks. Assessment of EFW and BW concordance showed a significantly greater rate of postnatal confirmation of prenatally predicted small-for-gestational age (SGA) < 10 centile in the fresh compared with the frozen-thawed BT group (P < 0.001), whereas the rate of postnatal confirmation of large-for-gestational age (LGA) > 90 centile was significantly higher in the frozen-thawed vs the fresh BT group (P < 0.001). Logistic regression analysis showed that the smoothed rate of EFW < 3 centile was about 6-fold higher in the fresh vs frozen-thawed BT group (P < 0.001), whereas the smoothed rates of EFW 90 -97 centile and > 97 centile were nearly double in the frozen-thawed compared with the fresh BT group (P < 0.05 and P < 0.001, respectively).
Robust novel unified prenatal-postnatal modeling in IVF/ICSI pregnancies after frozen-thawed or fresh BT from 19 weeks of gestation to birth showed non-divergent growth trajectories, with higher EFW and BW Z-scores in the frozen-thawed vs fresh BT group. The mean EFW Z-scores in both IVF/ICSI groups were greater than those expected for natural conceptions, being highest in the midtrimester and decreasing with advancing gestation in both groups, becoming negative after 32 weeks in the fresh and after 35 weeks in the frozen-thawed BT group. Mean BW Z-scores were negative in both groups, with lower values in preterm fetuses, and increased with advancing gestation, becoming positive at term in the frozen-thawed BT group. IVF/ICSI conceptions from frozen-thawed as compared to fresh BT presented increased rate of LGA and reduced rate of SGA both prenatally and postnatally. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
使用统一方法比较冷冻-解冻后与新鲜胚胎移植后体外受精/卵胞浆内单精子注射（IVF/ICSI）妊娠的妊娠中期至出生的标准化估计胎儿体重（EFW）轨迹和出生体重（BW）测量值。
这是一项在意大利米兰圣拉斐尔医院胎儿医学和妇产科进行的前瞻性纵向队列研究的二次分析。该研究纳入了 2016 年 1 月至 2020 年 12 月期间接受新鲜或冷冻解冻胚胎移植后，经标准胎儿生物测量评估在 19-41 周且 BW 测量值可用的单胎活胎妊娠。所有超声评估均由对冷冻保存的使用情况不知情的操作者进行。排除多胎妊娠、重大孕前疾病、流产、主要胎儿异常和使用其他类型的医学辅助生殖技术的患者。使用基于胎儿医学基金会胎儿和新生儿人群体重图表的统一建模方法，使用广义线性模型（GLM）和逻辑回归分析 EFW 和 BW Z 分数及其轨迹，并调整主要混杂因素。使用列联表、χ检验和产前到产后百分位数的转换评估和比较两组之间产前 EFW 和产后 BW 百分位数的差异。
共考虑了 631 例 IVF/ICSI 妊娠，其中 263 例为新鲜 BT 后受孕，368 例为冷冻解冻 BT 后受孕。共有 1795 次 EFW 观察值（新鲜 BT 组 715 次，冷冻解冻 BT 组 1080 次；每位患者的中位数为 3 次观察）。新鲜 BT 组中 EFW 和 BW <10 百分位的发生率显著高于冷冻解冻 BT 组（P=0.003 和 P<0.001），而冷冻解冻 BT 组中 EFW 和 BW >90 百分位的发生率显著高于新鲜 BT 组（P=0.034 和 P=0.002）。GLM 显示两组中 EFW Z 分数均随 GA 的增加而逐渐降低。两组间 GA 的影响被认为是相等的，因为没有发现显著的交互作用。冷冻解冻 BT 组的平滑平均 EFW Z 分数从 19 周妊娠至足月和平均 BW Z 分数均显著高于新鲜 BT 组（EFW Z 分数，0.70±1.29 对 0.28±1.43；P<0.001；BW Z 分数，0.04±1.08 对-0.31±1.28；P<0.001）。冷冻解冻 BT 组的平均平滑 EFW Z 分数值在 19-27 周时为 1.01±0.12，在 28-35 周时为 0.36±0.07，在 36-41 周时为-0.66±0.01，而新鲜 BT 组的平均平滑 EFW Z 分数值在 28-35 周时为 0.60±0.08，在 36-41 周时为-0.88±0.02。冷冻解冻 BT 组的平均平滑 BW Z 分数值在 28-35 周时为-0.80±0.14，在 36-41 周时为 0.22±0.16，而新鲜 BT 组的平均平滑 BW Z 分数值在 28-35 周时为-1.20±0.10，在 36-41 周时为-0.24±0.14。评估 EFW 和 BW 的一致性表明，新鲜 BT 组产前预测的小胎龄（SGA）<10 百分位的出生后确认率显著高于冷冻解冻 BT 组（P<0.001），而冷冻解冻 BT 组的大胎龄（LGA）>90 百分位的出生后确认率显著高于新鲜 BT 组（P<0.001）。逻辑回归分析显示，新鲜 BT 组 EFW <3 百分位的平滑率约为冷冻解冻 BT 组的 6 倍（P<0.001），而冷冻解冻 BT 组 EFW 90-97 百分位和>97 百分位的平滑率几乎是新鲜 BT 组的两倍（P<0.05 和 P<0.001）。
从 19 周妊娠至出生，对冷冻解冻后与新鲜胚胎移植后 IVF/ICSI 妊娠进行了稳健的新型产前-产后统一建模，结果显示两组的生长轨迹不一致，冷冻解冻 BT 组的 EFW 和 BW Z 分数较高。两组 IVF/ICSI 妊娠的平均 EFW Z 分数均高于自然妊娠的预期值，在中期妊娠时最高，在两组中均随 GA 的增加而降低，在新鲜 BT 组中在 32 周后变为负值，在冷冻解冻 BT 组中在 35 周后变为负值。两组 BW Z 分数均为负值，早产儿值较低，随 GA 的增加而增加，在冷冻解冻 BT 组中在足月时变为正值。与新鲜胚胎移植相比，冷冻解冻胚胎移植后 IVF/ICSI 妊娠的 LGA 发生率增加，SGA 发生率降低，无论是产前还是产后均如此。©2021 年国际超声协会。
