Prospective longitudinal cohort study of uterine arteries Doppler in singleton pregnancies obtained by IVF/ICSI with oocyte donation or natural conception
Prospective longitudinal cohort study of uterine arteries Doppler in singleton pregnancies obtained by IVF/ICSI with oocyte donation or natural conception
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DOI：
10.1093/humrep/deaa235
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发表时间：
2020-11-01
影响因子：
6.1
通讯作者：
Candiani, M.
中科院分区：
文献类型：
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作者：
Cavoretto, P., I;Farina, A.;Candiani, M.
研究问题：与自然受孕相比，子宫动脉多普勒研究是否显示IVF/ICSI捐赠卵母细胞（OD）妊娠的脉动指数（UtA-PI）测量值不同？简要答复：在IVF/ICSI妊娠OD，UtA-PI是减少了平均约40%的怀孕相比，自然conception.What是已知的：OD妊娠目前更糟糕的妊娠结局相比，自然conception，特别是对于先兆子痫（PE）的发病率增加.最近的证据表明，IVF/ICSI妊娠冷冻囊胚移植也呈现出较高的患病率PE和15%的UtA-PI降低相比，新鲜囊胚transfers.Study设计，大小，持续时间：前瞻性，纵向匹配队列研究在米兰的圣拉斐尔医院的胎儿医学和产科部门，在2013年和2018年之间进行。该分析基于从296名不同受孕方法的妇女（OD n = 122;自然受孕n = 174）收集的584个多普勒观察结果（OD n = 122;自然受孕n = 174）。参与者/材料，设置，方法：IVF/ICSI存活的单胎妊娠与OD和自然受孕对照妊娠匹配BMI和吸烟，在11-34周进行重复UtA-PI测量。排除流产、畸形、双胞胎、重大母体疾病和其他类型的ART。使用对数平均左右UtA-PI进行线性混合模型（LMM）分析，并校正显著混杂因素。主要结果和机会的作用：OD后的参与者年龄较大，更频繁地未经产（平均年龄：OD 43.4，95% CI从42.3到44.6;自然受孕35.1，95% CI从34.5到35.7; P值< 0.001;未经产：OD 96.6%;自然受孕56.2%; P值< 0.001）。OD组的平均搏动指数较低（UtA-PI：自然受孕1.22; 95% CI从1.11至1.28; OD 1.04; 95% CI从0.96至1.12; P值< 0.001）。在LMM中描述了产次、用三次多项式建模的胎龄（GA）和BMI的显著影响。与LMM时的自然受孕妊娠相比，OD时的平均Log UtA-PI平均低37%（P值< 0.001）。我们还发现了纵向UtA-PI多普勒和GA之间的显着相互作用。因此，在妊娠11周时，Log UtA-PI降低42%，在34周时，差异降低至32%。OD组分娩时GA和出生体重在统计学上较低;然而，出生体重百分位数无统计学差异。先兆子痫在OD组中的发生率高11倍（0.6%和6.6%，P值= 0.003）。研究组中未显示妊娠结局的其他显著差异（妊娠期糖尿病，GA为小或大）。限制，预防原因：由于队列之间的主要差异，不可能适当匹配母亲年龄和盲化评估;然而，我们没有发现与母亲年龄相关的显著组内效应。未来的研究需要重新评估结果并根据母体特征（例如心血管功能）对其进行校正。研究结果的更广泛意义：这一发现再现了我们之前发现的冷冻囊胚移植比新鲜囊胚移植的UtA-PI低。绝大多数OD是通过使用冷冻保存获得的。我们推测子宫灌注增加可能是对母体和胎盘功能障碍的生理反应。
STUDY QUESTION: Do uterine arteries Doppler studies show different pulsatility index (UtA-PI) measurements in IVF/ICSI pregnancies with oocyte donation (OD) as compared to natural conceptions?SUMMARY ANSWER: In IVF/ICSI pregnancies with OD, UtA-PI is reduced by an average of about 40% as compared to pregnancies with natural conception.WHAT IS KNOWN ALREADY: OD pregnancies present worse pregnancy outcomes as compared to natural conception, particularly for increased incidence of pre-eclampsia (PE). Recent evidence shows that IVF/ICSI pregnancies with frozen blastocyst transfer also present higher prevalence of PE and 15% lower UtA-PI as compared to pregnancies after fresh blastocyst transfers.STUDY DESIGN, SIZE, DURATION: Prospective, longitudinal matched cohort study performed in the Fetal Medicine and Obstetric Departments of San Raffaele Hospital in Milan, between 2013 and 2018. The analysis is based on 584 Doppler observations collected from 296 women with different method of conception (OD n = 122; natural conception n = 174).PARTICIPANTS/MATERIALS, SETTING, METHODS: IVF/ICSI viable singleton pregnancies with OD and natural conception control pregnancies matched for BMI and smoking, performing repeated UtA-PI measurements at 11-34 weeks. Miscarriages, abnormalities, twins, significant maternal diseases and other types of ARTs were excluded. Log mean left-right UtA-PI was used for analysis with linear mixed model (LMM) and correction for significant confounders. Pregnancy outcome was also analyzed.MAIN RESULTS AND THE ROLE OF CHANCE: Participants after OD were older and more frequently nulliparous (mean age: OD 43.4, 95% CI from 42.3 to 44.6; natural conception 35.1, 95% CI from 34.5 to 35.7; P-value < 0.001; nulliparous: OD 96.6%; natural conception 56.2%; P-value < 0.001). Mean pulsatility index was lower in OD (UtA-PI: natural conception 1.22; 95% CI from 1.11 to 1.28; OD 1.04; 95% CI from 0.96 to 1.12; P-value < 0.001). A significant effect of parity, gestational age (GA) modeled with a cubic polynomial and BMI was described in the LMM. The mean Log UtA-PI was on average 37% lower in OD as compared to natural conception pregnancies at LMM (P-value < 0.001). We also found a significant interaction between longitudinal UtA-PI Doppler and GA. Therefore, at 11 weeks' gestation the Log UtA-PI was 42% lower and, at 34 weeks, the differences reduced to 32%. GA at delivery and birth weight were statistically lower in OD group; however, birthweight centile was not statistically different. Preeclampsia was 11-fold more common in the OD group (0.6% and 6.6%, P-value = 0.003). No other significant difference in pregnancy outcome was shown in the study groups ( gestational diabetes mellitus, small or large for GA).LIMITATIONS, REASONS FOR CAUTION: It was not possible to properly match for maternal age and to blind the assessment given the major differences between cohorts; however, we did not find significant within-groups effects related to maternal age. Future research is needed to reassess outcomes and correct them for maternal characteristics (e.g. cardiovascular function).WIDER IMPLICATIONS OF THE FINDINGS: This finding reproduces our previous discovery of lower UtA-PI in frozen as compared to fresh blastocyst transfer. The vast majority of OD is obtained by the use of cryopreservation. We speculate that increased uterine perfusion may be the physiological response to compensate dysfunctions both in the mother and in the placenta.