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The proteome of IVF-induced aberrant embryo-maternal crosstalk by implantation stage in ewes.

ABSTRACT: Background:Implantation failure limits the success of in vitro fertilization and embryo transfer (IVF-ET). Well-organized embryo-maternal crosstalk is essential for successful implantation. Previous studies mainly focused on the aberrant development of in vitro fertilized (IVF) embryos. In contrast, the mechanism of IVF-induced aberrant embryo-maternal crosstalk is not well defined. Results:In the present study, using ewes as the model, we profiled the proteome that features aberrant IVF embryo-maternal crosstalk following IVF-ET. By comparing in vivo (IVO) and IVF conceptuses, as well as matched endometrial caruncular (C) and intercaruncular (IC) areas, we filtered out 207, 295, and 403 differentially expressed proteins (DEPs) in each comparison. Proteome functional analysis showed that the IVF conceptuses were characterized by the increased abundance of energy metabolism and proliferation-related proteins, and the decreased abundance of methyl metabolism-related proteins. In addition, IVF endometrial C areas showed the decreased abundance of endometrial remodeling and redox homeostasis-related proteins; while IC areas displayed the aberrant abundance of protein homeostasis and extracellular matrix (ECM) interaction-related proteins. Based on these observations, we propose a model depicting the disrupted embryo-maternal crosstalk following IVF-ET: Aberrant energy metabolism and redox homeostasis of IVF embryos, might lead to an aberrant endometrial response to conceptus-derived pregnancy signals, thus impairing maternal receptivity. In turn, the suboptimal uterine environment might stimulate a compensation effect of the IVF conceptuses, which was revealed as enhanced energy metabolism and over-proliferation. Conclusion:Systematic proteomic profiling provides insights to understand the mechanisms that underlie the aberrant IVF embryo-maternal crosstalk. This might be helpful to develop practical strategies to prevent implantation failure following IVF-ET.

SUBMITTER: Yang Q

PROVIDER: S-EPMC6958772 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The proteome of IVF-induced aberrant embryo-maternal crosstalk by implantation stage in ewes.

Yang Qianying Q Fu Wei W Wang Yue Y Miao Kai K Zhao Haichao H Wang Rui R Guo Min M Wang Zhilong Z Tian Jianhui J An Lei L

Journal of animal science and biotechnology 20200114

<h4>Background</h4>Implantation failure limits the success of <i>in vitro</i> fertilization and embryo transfer (IVF-ET). Well-organized embryo-maternal crosstalk is essential for successful implantation. Previous studies mainly focused on the aberrant development of <i>in vitro</i> fertilized (IVF) embryos. In contrast, the mechanism of IVF-induced aberrant embryo-maternal crosstalk is not well defined.<h4>Results</h4>In the present study, using ewes as the model, we profiled the proteome that ...[more]

PMID: 31956410

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Project description:Embryo quality is associated with successful implantation and live births. Our retrospective study was carried out to determine whether or not cleavage stage embryo quality affects the miscarriage rate, pregnancy complications and neonatal outcomes of singletons conceived with assisted reproduction technology.The current study included 11,721 In Vitro Fertilization-Embryo Transfer cycles (IVF-ET) between January 2009 (the date at which electronic medical records were implemented at our center) and March 2013. Only women?<?40 years of age undergoing their first fresh embryo transfer cycle using non-donor oocytes were included.Our study indicated that the transfer of poor-quality embryos resulted in higher miscarriage (19.77% vs. 13.28%, p?=?0.02) and lower ongoing pregnancy rates (15.33% vs. 48.06%, p?<?0.001). Logistic regression analysis performed on data derived from 744 cycles culminating in miscarriages versus 4,333 cycles culminating in live births, suggested that embryo quality (p?=?0.04) is significantly associated with miscarriage rate after adjusting for other confounding factors. Moreover, there were no differences in the mean birth weight, low birth weight (<2,500 g), very low birth weight (<1,500 g), gestational age, preterm delivery (<37 weeks), very preterm delivery (<32 weeks), congenital malformations, small-for-gestational-age singletons (SGA), and large-for-gestational-age singleton (LGA) rate (p?>?0.05). Similarly, pregnancy complications resulting from poor-quality embryos were not different from good-quality embryos (4.04% vs. 2.57 %, p?=?0.33). Finally, logistic regression suggested that embryo quality was not significantly associated with pregnancy complications after adjusting for other confounding factors (p?=?0.40).Our study suggests that transfer of poor-quality embryos did not increase the risk of adverse outcomes; however, the quality of cleavage stage embryos significantly affected the miscarriage rate and ongoing pregnancies.

Project description:IntroductionAlthough the majority of singleton births after in vitro fertilization (IVF) are uncomplicated, studies have suggested that IVF pregnancies may be independently associated with low birth weight (LBW), preterm birth (PTB), and perinatal mortality. These outcomes complicate multiple gestations as expected, but have also been reported in singletons. A multiple embryo implantation model allows for assessment of the early in utero environment, and therefore, assessment of any maternal constraints on developing fetuses. We question whether adverse perinatal outcomes associated with assisted reproductive techniques (ART) occur as a result of maternal physiologic adaptations.Patients and methodsThis is a retrospective, single center study of ART cycles, specifically intracytoplasmic sperm injection (ICSI) cycles during a 16-year period. For each positive pregnancy test 9-11 days after embryo transfer, an ultrasonogram was performed at 7 weeks of gestation to record the number of implanted fetal poles with cardiac activity. Controlled ovarian stimulation (COS), hCG trigger, oocyte retrieval and sperm injection were performed as per our standard protocols. First trimester implantation sites that resulted in live births were defined as "true" to distinguish them from those that spontaneously reduced called "virtual." Birth outcomes analyzed included birth weight and gestational age at delivery.ResultsA total of 17,415 cycles were analyzed. The average maternal age was 36.9 (±5.0) years. An overall fertilization rate of 73.4% generated approximately 48,708 good quality cleavage-stage embryos. In most patients (92.8%), an average of 3 embryos were transferred. The clinical pregnancy rate was 39.2% (n = 6,281). The overall occurrence of multiple gestations was 38.2% (n = 2,608) consisting of 2,038 twin, 511 triplet, and 59 quadruplet pregnancies. Of these multiple gestations, 18.6% of twin, 54.2% of triplet and 76.3% of quadruplet gestations spontaneously reduced. Failure of the implanted embryo to progress was not related to maternal age. Singleton newborns resulting from multiple implantation sites had lower birth weights (P<0.01) and shorter gestational ages (P<0.01) than those from a single implanted embryo. The number of embryos transferred did not affect the gestational length of singleton newborns. Although the birth weights of singletons from multiple implantation sites (virtual singletons) were lower than true singletons, the birth weight of virtual singletons were comparable to the birth weights of true twin, triplet, and quadruplet live births. Multiple logistic regression revealed that virtual singletons were an independent risk factor for PTB (odds ratio: 4.55, 95% CI 2.23-9.29) and LBW (odds ratio: 3.61, 95% CI 1.78-7.32), even after controlling for the number of oocytes, stimulation protocol type, sperm source, total gonadotropins administered, age, embryo quality, and day of embryo transfer.ConclusionsOur study highlights that embryonic implantation sites during early gestation set the growth profile of each embryo, dictating later growth patterns. Specifically, spontaneous reduction of an embryo after multiple embryo implantations can confer greater perinatal risk in the form of LBW and PTB to the surviving fetus. Our findings suggest that maternal constraints or physiologic adaptations maybe one of the mechanisms mediating adverse perinatal outcomes when multiple embryo implantation occurs.

Project description:BACKGROUND:With improvements in in vitro culture techniques there has been a steady shift in practice to transfer embryos at the blastocyst stage (post fertilization day (p.f.d.) 5-7), when embryos reach the endometrial cavity during natural conception. For patients with >?5 zygotes on day 1 of embryo development, fresh blastocyst embryo transfer (ET) increases live birth rates when compared to cleavage stage (p.f.d. 3) transfer. In poorer prognosis patients (? 5 zygotes) cleavage stage ET is commonly performed to reduce the risk of cycle cancellation if no embryo survives to the blastocyst stage. However, there is a dearth of randomized controlled trial (RCT) data demonstrating improved live birth rates per cycle for cleavage vs blastocyst stage ET in this subgroup of patients. The hypothesis of the PRECiSE (PooR Embryo Yield Cleavage Stage Versus blaStocyst Embryo Transfer) trial is that blastocyst ET is not inferior to cleavage stage ET with regard to live birth rates per retrieval in poorer prognosis patients. The adoption of routine blastocyst culture for all patients would result in higher rates of single embryo transfers (SET), reduced incidence of multiple pregnancies and simplified laboratory protocols, thereby reducing costs. METHODS/DESIGN:Multicenter, non-inferiority randomized controlled trial (RCT) comparing blastocyst to cleavage stage embryo transfer in poorer prognosis patients with ?5 zygotes on day 1 after fertilization. The primary outcome is live birth per retrieval. Secondary outcomes include: time to pregnancy, clinical pregnancy, ongoing pregnancy, miscarriage and multiple pregnancy rate (per retrieval). This trial will enroll 658 women with ?5 zygotes on day 1 at 6 IVF centers over the course of 22?months. DISCUSSION:If the hypothesis is proven true, the data from this trial may facilitate the adoption of uniform blastocyst culture in all IVF patients. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT03764865. Registered 5 December 2019, Protocol issue date: 4 December 2018, Original.

Dataset Information

The proteome of IVF-induced aberrant embryo-maternal crosstalk by implantation stage in ewes.

Publications

The proteome of IVF-induced aberrant embryo-maternal crosstalk by implantation stage in ewes.

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