Peak serum estradiol level during controlled ovarian hyperstimulation is associated with increased risk of small for gestational age and preeclampsia in singleton pregnancies after in vitro fertilization

Imudia, Anthony N.; Awonuga, Awoniyi O.; Doyle, J.; Kaimal, Anjali J; Wright, Donald R.; Toth, Thomas L.; Styer, Aaron K.

doi:10.1016/j.fertnstert.2012.03.028

Cited by 231 publications

(193 citation statements)

References 52 publications

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“…High E 2 level above 3,450 pg/mL on the day of hCG administration during COH, was found to be associated with greater odds of developing preeclampsia and delivery of a small for gestational age infant in singleton pregnancies resulting from IVF cycles [34]. In another recent retrospective database analysis, extended culture of embryos from cleavage stage to blastocyst stage has been shown to increase the risk of preterm delivery [35].…”

Section: Discussionmentioning

confidence: 97%

Reduced protein C Global assay level in infertile women prior to IVF-ET treatment

Younis

Ben‐Ami

Izhaki

et al. 2013

J Assist Reprod Genet

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Purpose In the last few years more robust evidence is emerging to point out at an increased rate of prematurity and low birth weight in singleton pregnancies following ART. Whether this increased rate is related to ART practice or to infertility per se, is still an open question. Our aim in this study was to explore this question by evaluating Protein C (ProC) Global assay in infertile women before ART treatment. Methods A cohort of 95 unselected and consecutive infertile women, eligible for ART, was prospectively recruited for the study. The control group included 77 matched healthy fertile women with a history of spontaneous conceptions. Pro C Global assay was evaluated in both groups. A full thrombophilic work-up was performed in the study group.Results ProC Global assay level was found to be significantly lower in the study as compared to the control group, corresponding to 0.78 ± 0.16 and 0.88 ± 0.16, respectively (P <0.01). As well, abnormal ProC Global assay level of ≤0.8 was significantly higher in the study as compared to control group corresponding to 53 % and 29 %, respectively. ProC Global assay level was significantly lower in women within the study group found to have APCR, factor V Leiden and high factor VIII level, any thrombophilia or combined thrombophilia when compared to women without these thrombophilic risk factors. Conclusions Reduced ProC Global assay level is encountered in infertile women prior to ART treatment. This finding may suggest a unique anticoagulation Protein C pathway in infertile as compared to fertile women. Further studies are encouraged to explore this finding.

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Section: Discussionmentioning

confidence: 97%

Reduced protein C Global assay level in infertile women prior to IVF-ET treatment

Younis

Ben‐Ami

Izhaki

et al. 2013

J Assist Reprod Genet

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“…Recent reports suggest that EE 2 levels have a negative downstream effect on obstetrical outcomes (preeclampsia and small for gestational age) following IVF conception [12,13]. However, the upstream effects on early reproductive outcomes have not been clearly established.…”

Section: Discussionmentioning

confidence: 99%

“…Cycles with elevated estradiol levels greater than the 90th percentile comprised the study group, while cycles with levels less than the 90th percentile served as the control. The 90th percentile threshold was chosen based on published data that suggested that patients with extremes of serum estradiol levels measured on the day of hCG trigger were more likely to develop preeclampsia and deliver small for gestational age infants [12,13]. To test the hypothesis whether high estradiol levels were associated with worse oocyte, fertilization and peri-implantation parameters and early pregnancy outcomes in IVF, we decided to use similar methodology to establish our cut off to discriminate between the study (high estradiol) and control (lower estradiol) groups.…”

Section: Methodsmentioning

confidence: 99%

“…Recent studies have suggested that the supraphysiologic h o r m o n a l m i l i e u u n iq u e t o c o n t r o l l e d o v a r i a n hyperstimulation during ART may be responsible for adverse outcomes such as preeclampsia and delivery of small fetuses [11][12][13]. In 1998, Barker became the first to link maternal malnutrition during the pre-implantation period to low birth weight and showed that affected individuals are at greater risk of developing coronary heart disease, hypertension, and diabetes [14].…”

Section: Introductionmentioning

confidence: 99%

“…It is theorized that if aberrant trophoblastic invasion due to elevated serum estradiol (EE 2 ) mediates reported adverse obstetrical outcomes such as preeclampsia and small for gestational age infants following in vitro fertilization (IVF) conception [12,13], such aberrant invasion may also be associated with decreased implantation and higher miscarriage rates in these patients. In addition, oocyte quality and fertilization rates, as well as embryo quality and development rates may also be affected.…”

Section: Introductionmentioning

confidence: 99%

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The impact of supraphysiologic serum estradiol levels on peri-implantation embryo development and early pregnancy outcome following in vitro fertilization cycles

Imudia

Goldman

Awonuga

et al. 2013

J Assist Reprod Genet

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Purpose To determine the impact of elevated serum estradiol levels (EE 2 -defined as levels>90th percentile) on the day of hCG administration during IVF on oocyte fertilization, embryo development, implantation, clinical pregnancy and miscarriage rates. Methods A total of 2,995 consecutive IVF cycles in 1,889 patients with non-donor oocyte retrieval resulting in fresh embryo transfer between 1/1/2005 and 12/31/2011 were analyzed. Cycles were stratified by serum E 2 level on the day of hCG administration into those with levels >90th percentile and≤90th percentile. Rates of normal fertilization, embryo development, positive pregnancy test, implantation, clinical pregnancy and spontaneous miscarriage were compared. Results Serum estradiol above the 90th percentile on the day of hCG administration was associated with a significantly lower rate of normal fertilization (68.6±20 vs. 71.6±21, p = 0.02) when compared with patients with a lower serum estradiol threshold. The proportion of embryos that progressed from 2PN to 6-8 cell on day 3 was not different between the two groups. Although rates of positive pregnancy test (55.2 % vs. 57 %), implantation (26.4 % vs. 28.5 %) and clinical pregnancy (45.5 % vs. 49.4 %) were lower in patients with a higher estradiol threshold, these differences were not statistically significant. Similarly, there was no difference in the spontaneous miscarriage rates between the two groups (8.4 % vs. 7.1 %). Conclusions Serum estradiol levels above the 90th percentile on the day of hCG administration is associated with lower oocyte fertilization rate; however, such levels do not impact embryo development, implantation, clinical pregnancy or spontaneous miscarriage rates.

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Neonatal outcomes following fresh as compared to frozen/thawed embryo transfer in in vitro fertilization

Heertum

Weinerman

2018

Birth Defects Research

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In vitro fertilization (IVF) and embryo cryopreservation have become increasingly common in recent years. As utilization increases, it is important to understand the clinical effects these technologies have on offspring, as well as the mechanisms behind these effects. Many epidemiologic studies have observed that pregnancies following IVF are more likely to be affected by obstetric complications such as pre‐eclampsia, preterm birth, and small for gestational age neonates compared with naturally conceived pregnancies. There has been a great deal of research emerging suggesting that these differences are related to the supraphysiologic hormonal environment that results from ovarian superovulation. While pregnancies resulting from frozen embryo transfer are less likely to experience these complications, babies born after frozen transfer are more likely to be large for gestational age. Epigenetic studies point toward differential methylation of genes critical for growth that may be responsible for the increased incidence of larger neonates following transfer of vitrified embryos. Although it does appear that perinatal outcomes are improved by transferring frozen embryos instead of fresh, it would be premature at this time to recommend universal freeze‐all protocols in all patients. This article, as part of the “IVF Reviews” special issue of this journal, aims to expound on the issues outlined above.

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Peak serum estradiol level during controlled ovarian hyperstimulation is associated with increased risk of small for gestational age and preeclampsia in singleton pregnancies after in vitro fertilization

Cited by 231 publications

References 52 publications

Reduced protein C Global assay level in infertile women prior to IVF-ET treatment

Reduced protein C Global assay level in infertile women prior to IVF-ET treatment

The impact of supraphysiologic serum estradiol levels on peri-implantation embryo development and early pregnancy outcome following in vitro fertilization cycles

Neonatal outcomes following fresh as compared to frozen/thawed embryo transfer in in vitro fertilization

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