Lee Malinda S, Cantonwine David, Little Sarah E, McElrath Thomas F, Parry Samuel I, Lim Kee-Hak, Wilkins-Haug Louise E
Brigham and Women's Hospital/Massachusetts General Hospital Integrated Residency Program in Obstetrics and Gynecology, Boston, MA; Harvard Medical School, Boston, MA.
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA; Harvard Medical School, Boston, MA.
Am J Obstet Gynecol. 2015 Aug;213(2):212.e1-8. doi: 10.1016/j.ajog.2015.03.032. Epub 2015 Mar 19.
Pregnancies that have been conceived through in vitro fertilization (IVF) have been associated with higher rates of preeclampsia and other complications that are associated with placental dysfunction. We evaluated whether IVF pregnancies, when compared with those conceived spontaneously, would be associated with alterations in serum angiogenic markers.
This was a retrospective cohort study from 3 US academic institutions (2006-2008). Women with singleton pregnancies who conceived via IVF or spontaneously were included. Placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured at 4 time points throughout gestation. Pregnancy outcomes that included diagnosis of preeclampsia or other obstetric complications were ascertained from the medical record. The relationship among IVF status, PlGF, and sFlt-1 were modeled over gestation and stratified by clinical pregnancy outcome.
Of the included 2392 singleton pregnancies, 4.5% (108 pregnancies) were conceived though IVF. IVF pregnancies were significantly more likely to be complicated by preeclampsia (15.7% vs 7.7%). IVF pregnancies had significantly higher levels of sFlt-1 at 18, 26, and 35 weeks of gestation (P = .04, P = .004, P < .0001, respectively) and lower levels of PlGF at 18 and 35 weeks of gestation (P = .007 and .0006, respectively). These differences persisted even after being controlled for maternal comorbidities or obstetric outcomes such as preeclampsia.
Pregnancies conceived via IVF were found to have an increased antiangiogenic profile (elevated sFlt-1 and decreased PlGF) at multiple time points throughout gestation when compared with spontaneously conceived pregnancies. Alterations in the angiogenic profile persisted even after we controlled for maternal comorbidities of clinically evident disorders of abnormal placentation such as preeclampsia. The increased antiangiogenic profile suggests fundamentally aberrant placentation related to in vitro fertilization, which may warrant closer fetal surveillance in these pregnancies.
通过体外受精（IVF）受孕的妊娠与子痫前期及其他与胎盘功能障碍相关并发症的发生率较高有关。我们评估了与自然受孕的妊娠相比，IVF妊娠是否与血清血管生成标志物的改变有关。
这是一项来自美国3家学术机构（2006 - 2008年）的回顾性队列研究。纳入通过IVF或自然受孕的单胎妊娠妇女。在整个孕期的4个时间点测量胎盘生长因子（PlGF）和可溶性fms样酪氨酸激酶-1（sFlt-1）。从病历中确定包括子痫前期诊断或其他产科并发症在内的妊娠结局。IVF状态、PlGF和sFlt-1之间的关系在整个孕期进行建模，并按临床妊娠结局分层。
在纳入的2392例单胎妊娠中，4.5%（108例妊娠）是通过IVF受孕的。IVF妊娠发生子痫前期的可能性显著更高（15.7%对7.7%）。IVF妊娠在妊娠18、26和35周时sFlt-1水平显著更高（分别为P = 0.04、P = 0.004、P < 0.0001），在妊娠18和35周时PlGF水平更低（分别为P = 0.007和0.0006）。即使在控制了母亲合并症或产科结局如子痫前期后，这些差异仍然存在。
与自然受孕的妊娠相比，发现通过IVF受孕的妊娠在整个孕期的多个时间点具有增加的抗血管生成特征（sFlt-1升高和PlGF降低）。即使在我们控制了母亲合并症或临床上明显的胎盘异常疾病如子痫前期后，血管生成特征的改变仍然存在。增加的抗血管生成特征提示与体外受精相关的胎盘形成存在根本异常，这可能需要对这些妊娠进行更密切的胎儿监测。
