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      Increased Preeclampsia Risk and Reduced Aortic Compliance With In Vitro Fertilization Cycles in the Absence of a Corpus Luteum

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          Abstract

          In vitro fertilization involving frozen embryo transfer (FET) and donor oocytes increases preeclampsia risk. These IVF protocols typically yield pregnancies without a corpus luteum (CL), which secretes vasoactive hormones. We investigated whether IVF pregnancies without a CL disrupt maternal circulatory adaptations and increase preeclampsia risk. Women with 0 (n=26), 1 (n=23), or >1 (n=22) CL were serially evaluated before, during and after pregnancy. Because increasing arterial compliance is a major physiological adaptation in pregnancy, we assessed carotid-femoral pulse wave velocity (cfPWV) and transit time (cfPWTT). In a parallel, prospective cohort study, obstetric outcomes for singleton livebirths achieved with autologous oocytes were compared between groups by CL number (n=683). The expected decline in cfPWV and rise in cfPWTT during the first trimester were attenuated in the 0 CL compared to combined single/multiple CL cohorts, which were similar (group-time interaction: p=0.06 and 0.03, respectively). The blunted changes of cfPWV and cfPWTT from pre-pregnancy in the 0 CL cohort were most striking at 10–12 weeks gestation (p=0.01 and 0.006, respectively, versus 1 and >1 CL). 0 CL was predictive of preeclampsia (adjusted odds ratio 2.73; 95%CI 1.14–6.49) and preeclampsia with severe features (6.45; 95%CI 1.94–25.09) compared to 1 CL. Programmed FET cycles (0 CL) were associated with higher rates of preeclampsia (12.8% vs 3.9%, p=0.02) and preeclampsia with severe features (9.6% vs 0.8%, p=0.002) compared with modified natural FET cycles (1 CL). In common IVF protocols, absence of the CL perturbed the maternal circulation in early pregnancy, and increased the incidence of preeclampsia.

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          Most cited references35

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          Circulating angiogenic factors and the risk of preeclampsia.

          The cause of preeclampsia remains unclear. Limited data suggest that excess circulating soluble fms-like tyrosine kinase 1 (sFlt-1), which binds placental growth factor (PlGF) and vascular endothelial growth factor (VEGF), may have a pathogenic role. We performed a nested case-control study within the Calcium for Preeclampsia Prevention trial, which involved healthy nulliparous women. Each woman with preeclampsia was matched to one normotensive control. A total of 120 pairs of women were randomly chosen. Serum concentrations of angiogenic factors (total sFlt-1, free PlGF, and free VEGF) were measured throughout pregnancy; there were a total of 655 serum specimens. The data were analyzed cross-sectionally within intervals of gestational age and according to the time before the onset of preeclampsia. During the last two months of pregnancy in the normotensive controls, the level of sFlt-1 increased and the level of PlGF decreased. These changes occurred earlier and were more pronounced in the women in whom preeclampsia later developed. The sFlt-1 level increased beginning approximately five weeks before the onset of preeclampsia. At the onset of clinical disease, the mean serum level in the women with preeclampsia was 4382 pg per milliliter, as compared with 1643 pg per milliliter in controls with fetuses of similar gestational age (P<0.001). The PlGF levels were significantly lower in the women who later had preeclampsia than in the controls beginning at 13 to 16 weeks of gestation (mean, 90 pg per milliliter vs. 142 pg per milliliter, P=0.01), with the greatest difference occurring during the weeks before the onset of preeclampsia, coincident with the increase in the sFlt-1 level. Alterations in the levels of sFlt-1 and free PlGF were greater in women with an earlier onset of preeclampsia and in women in whom preeclampsia was associated with a small-for-gestational-age infant. Increased levels of sFlt-1 and reduced levels of PlGF predict the subsequent development of preeclampsia. Copyright 2004 Massachusetts Medical Society
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            Obstetric and perinatal outcomes in singleton pregnancies resulting from IVF/ICSI: a systematic review and meta-analysis.

            Earlier reviews have suggested that IVF/ICSI pregnancies are associated with higher risks. However, there have been recent advances in the way IVF/ICSI is done, leading to some controversy as to whether IVF/ICSI singletons are associated with higher perinatal risks. The objective of this systematic review was to provide an up-to-date comparison of obstetric and perinatal outcomes of the singletons born after IVF/ICSI and compare them with those of spontaneous conceptions. Extensive searches were done by two authors. The protocol was agreed a priori. PRISMA guidance was followed. The data were extracted in 2 × 2 tables. Risk ratio and risk difference were calculated on pooled data using Rev Man 5.1. Quality assessment of studies was performed using Critical Appraisal Skills programme. Sensitivity analysis was performed when the heterogeneity was high (I(2) > 50%). There were 20 matched cohort studies and 10 unmatched cohort studies included in this review. IVF/ICSI singleton pregnancies were associated with a higher risk (95% confidence interval) of ante-partum haemorrhage (2.49, 2.30-2.69), congenital anomalies (1.67, 1.33-2.09), hypertensive disorders of pregnancy (1.49, 1.39-1.59), preterm rupture of membranes (1.16, 1.07-1.26), Caesarean section (1.56, 1.51-1.60), low birthweight (1.65, 1.56-1.75), perinatal mortality (1.87, 1.48-2.37), preterm delivery (1.54, 1.47-1.62), gestational diabetes (1.48, 1.33-1.66), induction of labour (1.18, 1.10-1.28) and small for gestational age (1.39, 1.27-1.53). Singletons pregnancies after IVF/ICSI are associated with higher risks of obstetric and perinatal complications when compared with spontaneous conception. Further research is needed to determine which aspect of assisted reproduction technology poses most risk and how this risk can be minimized.
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              Obstetric outcome in singletons after in vitro fertilization with cryopreserved/thawed embryos.

              There is increasing use of cryopreservation in IVF. This study compared singletons born after cryopreservation with singletons born after fresh IVF cycles and singletons born to women in the general population. Data were collected for Swedish IVF treatments during the years 2002-2006. All singletons from single embryo transfer (SET) and double embryo transfer (DET) after cryopreserved (n = 2348) and fresh cycles (n = 8944) were included and cross-linked with the Swedish Medical Birth Registry and compared with all singletons born after spontaneous conception (n = 571 914). Main outcomes were preterm and very preterm birth and low and very low birthweight (VLBW). Other outcomes were small for gestational age, large for gestational age (LGA), perinatal mortality and maternal outcomes. Singletons from cryopreserved SET/DET or cryopreserved SET had increased rates of extreme preterm birth compared with singletons from the general population. A lower rate of LBW was found for cryopreserved SET/DET singletons compared with singletons from fresh cycles; however, a higher rate of perinatal mortality was detected. The rates of LGA and macrosomia were increased for cryopreserved SET/DET singletons when compared with those from fresh cycles and the general population. For maternal outcomes, a higher rate of pre-eclampsia was noted for pregnancies from cryopreserved cycles compared with those from fresh cycles or the general population, but the rate of placenta praevia was lower in pregnancies from cryopreserved cycles compared with those from fresh cycles. The obstetric outcome of singletons after cryopreservation was slightly poorer when compared with the general population. In comparison with fresh cycles, the outcome varied. The finding of an increased rate of LGA after cryopreservation requires further study.
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                Author and article information

                Journal
                Hypertension
                Hypertension
                Ovid Technologies (Wolters Kluwer Health)
                0194-911X
                1524-4563
                March 2019
                March 2019
                : 73
                : 3
                : 640-649
                Affiliations
                [1 ]From the Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology (F.v.V.-H., R.R.F., W.Z., V.L.B.), Stanford University School of Medicine, Sunnyvale, CA
                [2 ]Department of Obstetrics and Gynecology, Hannover Medical School, Lower Saxony, Germany (F.v.V.-H.), University of Florida, Gainesville.
                [3 ]Department of Obstetrics and Gynecology (A.M.S., R.S.W., A.R.-V., K.P.C.), University of Florida, Gainesville.
                [4 ]Department of Biostatistics (Y.-Y.C., K.-H.C., J.L.), University of Florida, Gainesville.
                [5 ]Division of Nephrology, Hypertension, and Renal Transplantation (M.L., M.S.S.), University of Florida, Gainesville.
                [6 ]Division of Cardiology (W.W.N.), University of Florida, Gainesville.
                [7 ]Division of Reproductive, Stem Cell, and Perinatal Biology, Department of Obstetrics and Gynecology (V.D.W.), Stanford University School of Medicine, Sunnyvale, CA
                [8 ]Department of Medicine, and Department of Physiology and Functional Genomics, D.H. Barron Reproductive and Perinatal Biology Research Program (K.P.C.), University of Florida, Gainesville.
                Article
                10.1161/HYPERTENSIONAHA.118.12043
                6434532
                30636552
                43502b7e-90ff-4e05-aae5-961d5e8f38b6
                © 2019
                History

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