First Trimester Intrauterine Hematoma And The Risk Of Pregnancy Complications In IVF-Pregnancies

Background: Intrauterine hematomas(IUHs) are frequent in a normal pregnancy on ultrasound examination, especially in the first trimester of gestation. The reported incidence of first-trimester IUHs ranged from 0.46% to 39.5% in spontaneous pregnancy. Some studies have proved that the presence of IUHs are associated with an increased risk for gestational hypertensive disorders, placental abruption, preterm delivery(PTD), small for gestational age(SGA), low 5-min Apgar score and other abnormal pregnancy outcomes in ongoing pregnancies. However, others refute the concept that women presenting with IUHs are at more risk for adverse pregnancy outcomes than those without. To our knowledge, little is known on the outcome of ongoing pregnancies after in vitro fertilization-embryo transfer(IVF-ET) when first-trimester IUHs have occurred. Moreover, the specific mechanism between hematomas and pregnancy complications remains unknown until now. Natural killer(NK) cells are a type of large granular lymphocyte that belongs to the innate immune system. Multiple studies have shown that NK cells are involved in some pregnancy complications, such as spontaneous abortion and PE; Antiphospholipid antibodies(APAs) are a heterogeneous family of autoantibodies that are often found in patients with autoimmune rheumatic disease. Elevated circulating APA levels are reported to increase the risk of recurrent early pregnancy loss as well as late obstetrical complications associated with impaired placental function. However, few studies describing those two changes have been reported in the pregnancies with an IUH. Objective: To evaluate the clinical significance of first-trimester IUHs detected in the pregnancies achieved by IVF-ET; to investigate cellular(NK cell) and auto- immune(APA) abnormalities in the IVF-pregnancies with an IUH. Methods:(1) The retrospective case-control study was designed to compare the obstetric and perinatal outcomes between 350 pregnancies with IUHs and 350 matched controls without hematomas;(2)A case-control study of 208 IVF-pregnancies, including 104 women with an IUH and 104 controls without matched for number of fetuses and way to achieve pregnancy, was designed to compare NK cells by flow cytometric analysis and APAs by enzyme-linked immunosorbent assay(ELISA). Results:(1) Compared with normal IVF pregnancies, the incidence of gestational hypertension(OR, 2.6; 95% CI, 1.5-4.6), preeclampsia(OR, 2.8; 95% CI, 1.5-5.0), postpartum hemorrhage(OR, 3.1; 95% CI, 1.8-5.3), placenta previa(OR, 8.7; 95% CI, 3.4-22.2) and oligohydramnion(OR, 5.8; 95% CI, 2.4-14.0) were significantly higher in the hematoma group. The incidence of PTD(<37 weeks’ gestation) increased significantly in the hematoma group(OR, 2.1; 95% CI, 1.4-3.0), but not for the incidence of PTD(before 34 weeks’ gestation). No differences were observed in pregnancy complications(including gestational diabetes mellitus, premature rupture of membranes and low birth weight);(2) NK cells as a percentage of total peripheral lymphocytes were similar between the IUH population and normal pregnancies. However, the prevalence of APAs was found to be significantly more prevalent in IVF-pregnancies with an IUH, regardless of singleton or twin pregnancies(singleton, p=0.015; twin, p<0.001). Conclusions:The presence of first-trimester IUHs in the pregnancies achieved by IVF-ET associated a higher risk for several pregnancy complications. Moreover, IUH in the IVF-pregnancies may lead to adverse pregnancy outcome by increasing APA levels.