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Human embryo implantation failure

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https://www.readbyqxmd.com/read/28402555/deregulation-of-the-endometrial-stromal-cell-secretome-precedes-embryo-implantation-failure
#1
Ruban Rex Peter Durairaj, Asma Aberkane, Lukasz Polanski, Yojiro Maruyama, Miriam Baumgarten, Emma S Lucas, Siobhan Quenby, Jerry K Y Chan, Nick Raine-Fenning, Jan J Brosens, Hilde Van de Velde, Yie Hou Lee
STUDY QUESTION: Is implantation failure following ART associated with a perturbed decidual response in endometrial stromal cells (EnSCs)? SUMMARY ANSWER: Dynamic changes in the secretome of decidualizing EnSCs underpin the transition of a hostile to a supportive endometrial microenvironment for embryo implantation; perturbation in this transitional pathway prior to ART is associated with implantation failure. WHAT IS KNOWN ALREADY: Implantation is the rate-limiting step in ART, although the contribution of an aberrant endometrial microenvironment in IVF failure remains ill defined...
April 10, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28360822/impact-of-blood-hypercoagulability-on-in-vitro-fertilization-outcomes-a-prospective-longitudinal-observational-study
#2
Grigoris T Gerotziafas, Patrick Van Dreden, Emmanuelle Mathieu d'Argent, Eleftheria Lefkou, Matthieu Grusse, Marjorie Comtet, Rabiatou Sangare, Hela Ketatni, Annette K Larsen, Ismail Elalamy
BACKGROUND: Blood coagulation plays a crucial role in the blastocyst implantation process and its alteration may be related to in vitro fertilization (IVF) failure. We conducted a prospective observational longitudinal study in women eligible for IVF to explore the association between alterations of coagulation with the IVF outcome and to identify the biomarkers of hypercoagulability which are related with this outcome. METHODS: Thirty-eight women eligible for IVF (IVF-group) and 30 healthy, age-matched women (control group) were included...
2017: Thrombosis Journal
https://www.readbyqxmd.com/read/28359310/increased-kr%C3%A3-ppel-like-factor-12-in-recurrent-implantation-failure-impairs-endometrial-decidualization-by-repressing-nur77-expression
#3
Chenyang Huang, Yue Jiang, Jianjun Zhou, Qiang Yan, Ruiwei Jiang, Xi Cheng, Jun Xing, Lijun Ding, Jianxin Sun, Guijun Yan, Haixiang Sun
BACKGROUND: Decidualization is a prerequisite for successful implantation and the establishment of pregnancy. A critical role of impaired decidualization in subfertility has been established. In human endometrial stromal cells (hESCs), Krüppel-like factor 12 (KLF12) and Nur77 are novel regulators of decidualization. We investigated whether KLF12 impaired the decidualization of hESCs in recurrent implantation failure (RIF) patients. METHODS: Endometrial tissues and hESCs were collected from RIF patients (n = 34) and fertile controls (n = 30) for in vitro analysis...
March 31, 2017: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/28259137/chronic-endometritis-modifies-decidualization-in-human-endometrial-stromal-cells
#4
Di Wu, Fuminori Kimura, Luyi Zheng, Mitsuaki Ishida, Yoko Niwa, Kimiko Hirata, Akie Takebayashi, Akiko Takashima, Kentaro Takahashi, Ryoji Kushima, Guangmei Zhang, Takashi Murakami
BACKGROUND: Chronic endometritis (CE) is a continuous inflammation of uterine endometrium, and it is usually symptomless. As CE has been thought not to affect the reproductive status and general health of affected women, its significance has not been explored. However, recent studies have shown that CE is related with repeated implantation failures after in vitro fertilization-embryo transfer, unexplained infertility, and recurrent miscarriages. As decidua differentiates to support the implantation process and maintains the pregnancy, we hypothesized that CE may influence the process of decidualization...
March 4, 2017: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/28253328/reprogramming-of-the-retinoic-acid-pathway-in-decidualizing-human-endometrial-stromal-cells
#5
Rie Ozaki, Keiji Kuroda, Yuko Ikemoto, Asako Ochiai, Akemi Matsumoto, Jun Kumakiri, Mari Kitade, Atsuo Itakura, Joanne Muter, Jan J Brosens, Satoru Takeda
Upon breaching of the endometrial surface epithelium, the implanting embryo embeds in the decidualizing stroma. Retinoic acid (RA), a metabolite of vitamin A, is an important morphogen during embryonic and fetal development, although the role of the RA pathway in the surrounding decidual cells is not understood. Here we show that decidual transformation of human endometrial stromal cells (HESCs) results in profound reprogramming of the RA signaling and metabolism pathways. Differentiating HESCs downregulate the intracellular carrier proteins CRABP2 and FABP5, responsible for transfer and binding of RA to the nuclear receptors RAR and PPARβ/δ, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28239559/gene-profiling-the-window-of-implantation-microarray-analyses-from-human-and-rodent-models
#6
Jennifer L Herington, Yan Guo, Jeff Reese, Bibhash C Paria
Poor uterine receptivity leads to implantation defects or failure. Identification of uterine molecules crucial to uterine receptivity and/or embryo implantation provides the opportunity to design a diagnostic screening toolkit for uterine receptivity or targeted drug discovery for treating implantation-based infertility. In this regard, gene-profiling studies performed in humans and rodents have identified numerous genes involved in the transcriptional regulation of uterine receptivity and embryo implantation...
December 2016: Journal of Reproductive Health and Medicine
https://www.readbyqxmd.com/read/28229988/endometrial-microrna-signature-during-the-window-of-implantation-changed-in-patients-with-repeated-implantation-failure
#7
Cheng Shi, Huan Shen, Li-Juan Fan, Jing Guan, Xin-Bang Zheng, Xi Chen, Rong Liang, Xiao-Wei Zhang, Qing-Hua Cui, Kun-Kun Sun, Zhu-Ran Zhao, Hong-Jing Han
BACKGROUND: At present, a diagnostic tool with high specificity for impaired endometrial receptivity, which may lead to implantation failure, remains to be developed. We aimed to assess the different endometrial microRNA (miRNA) signatures for impaired endometrial receptivity by microarray analysis. METHODS: A total of 12 repeated implantation failure (RIF) patients and 10 infertile patients, who conceived and delivered after one embryo transfer attempt, were recruited as RIF and control groups, respectively...
March 5, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28049832/forkhead-box-a2-foxa2-is-essential-for-uterine-function-and-fertility
#8
Andrew M Kelleher, Wang Peng, James K Pru, Cindy A Pru, Francesco J DeMayo, Thomas E Spencer
Establishment of pregnancy is a critical event, and failure of embryo implantation and stromal decidualization in the uterus contribute to significant numbers of pregnancy losses in women. Glands of the uterus are essential for establishment of pregnancy in mice and likely in humans. Forkhead box a2 (FOXA2) is a transcription factor expressed specifically in the glands of the uterus and is a critical regulator of postnatal uterine gland differentiation in mice. In this study, we conditionally deleted FOXA2 in the adult mouse uterus using the lactotransferrin Cre (Ltf-Cre) model and in the neonatal mouse uterus using the progesterone receptor Cre (Pgr-Cre) model...
February 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28003878/estimating-limits-for-natural-human-embryo-mortality
#9
Gavin E Jarvis
Natural human embryonic mortality is generally considered to be high. Values of 70% and higher are widely cited. However, it is difficult to determine accurately owing to an absence of direct data quantifying embryo loss between fertilisation and implantation. The best available data for quantifying pregnancy loss come from three published prospective studies (Wilcox, Zinaman and Wang) with daily cycle by cycle monitoring of human chorionic gonadotrophin (hCG) in women attempting to conceive. Declining conception rates cycle by cycle in these studies indicate that a proportion of the study participants were sub-fertile...
2016: F1000Research
https://www.readbyqxmd.com/read/27915038/intrauterine-administration-of-hcg-activated-autologous-human-peripheral-blood-mononuclear-cells-pbmc-promotes-live-birth-rates-in-frozen-thawed-embryo-transfer-cycles-of-patients-with-repeated-implantation-failure
#10
Saijiao Li, Jing Wang, Yan Cheng, Danni Zhou, Tailang Yin, Wangming Xu, Nan Yu, Jing Yang
Recurrent implantation failure refers to unsuccessful implantation after repeated transfers of morphologically good quality embryos into a normal uterus. Recently, accumulating evidence has suggested that local immune cells at the implantation site have actively contributed to embryo implantation. Our aim was to study the effects of intrauterine administration of hCG-activated autologous human PBMC on clinical pregnancy, implantation rates and live birth rate of patients who received frozen/thawed embryo transfer...
November 27, 2016: Journal of Reproductive Immunology
https://www.readbyqxmd.com/read/27810339/novel-immunotherapeutic-approaches-for-treatment-of-infertility
#11
REVIEW
Samaneh Abdolmohammadi-Vahid, Shahla Danaii, Kobra Hamdi, Farhad Jadidi-Niaragh, Majid Ahmadi, Mehdi Yousefi
One of the most important reasons of infertility and human reproductive failure is related to uncontrolled immunological response of maternal immune system to early embryo or fetus, that cause rejection of this semi-allograft. Therefore, a tolerance in the immune system is essential to modulate the reactions against the fetus to avoid rejection. The immune system imbalance during implantation or pregnancy may lead to implantation failure or miscarriage. So, use of immunosuppressive or immunomodulator agents can be helpful to prevent immunological attack...
December 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27783953/a-gata2-dependent-transcription-network-regulates-uterine-progesterone-responsiveness-and-endometrial-function
#12
Cory A Rubel, San-Pin Wu, Lin Lin, Tianyuan Wang, Rainer B Lanz, Xilong Li, Ramakrishna Kommagani, Heather L Franco, Sally A Camper, Qiang Tong, Jae-Wook Jeong, John P Lydon, Francesco J DeMayo
Altered progesterone responsiveness leads to female infertility and cancer, but underlying mechanisms remain unclear. Mice with uterine-specific ablation of GATA binding protein 2 (Gata2) are infertile, showing failures in embryo implantation, endometrial decidualization, and uninhibited estrogen signaling. Gata2 deficiency results in reduced progesterone receptor (PGR) expression and attenuated progesterone signaling, as evidenced by genome-wide expression profiling and chromatin immunoprecipitation. GATA2 not only occupies at and promotes expression of the Pgr gene but also regulates downstream progesterone responsive genes in conjunction with the PGR...
October 25, 2016: Cell Reports
https://www.readbyqxmd.com/read/27512152/uterine-histotroph-and-conceptus-development-ii-arginine-and-secreted-phosphoprotein-1-cooperatively-stimulate-migration-and-adhesion-of-ovine-trophectoderm-cells-via-focal-adhesion-mtorc2-mediated-cytoskeleton-reorganization
#13
Xiaoqiu Wang, Greg A Johnson, Robert C Burghardt, Guoyao Wu, Fuller W Bazer
In all mammalian species, critical events including uterine receptivity and development of the conceptus (embryo/fetus and its associated extra-embryonic membranes) must be intricately orchestrated and carefully timed during the window of implantation. Otherwise, failure of conceptuses to implant is inevitable which accounts for 50%-75% of failures to establish pregnancy. Unlike human and rodent blastocysts, the blastocysts of pigs and ruminants undergo rapid transitions from spherical to tubular and filamentous conceptuses in response to histotroph during the peri-implantation period of pregnancy...
August 10, 2016: Biology of Reproduction
https://www.readbyqxmd.com/read/27449969/a-study-of-intrauterine-infusion-of-human-chorionic-gonadotropin-hcg-before-frozen-thawed-embryo-transfer-after-two-or-more-implantation-failures
#14
Pinxiu Huang, Lihong Wei, Xinlin Li
OBJECTIVE: To investigate the effect of intrauterine infusion of human chorionic gonadotropin (hCG) before frozen-thawed embryo transfer (FET) after two or more implantation failures (TIFs). METHODS: The study was a prospective randomized single-blind study of 161 cycles in patients undergoing FET who had TIFs. The intervention group received an intrauterine injection of 1000 IU of hCG before embryo transfer (ET) (n = 62). A placebo group (n = 49) received an intrauterine injection of physiological saline before ET...
January 2017: Gynecological Endocrinology
https://www.readbyqxmd.com/read/27304912/integrative-analyses-of-uterine-transcriptome-and-micrornaome-reveal-compromised-lif-stat3-signaling-and-progesterone-response-in-the-endometrium-of-patients-with-recurrent-repeated-implantation-failure-rif
#15
Youngsok Choi, Hye-Ryun Kim, Eun Jin Lim, Miseon Park, Jung Ah Yoon, Yeon Sun Kim, Eun-Kyung Kim, Ji-Eun Shin, Ji Hyang Kim, Hwang Kwon, Haengseok Song, Dong-Hee Choi
Intimate two-way interactions between the implantation-competent blastocyst and receptive uterus are prerequisite for successful embryo implantation. In humans, recurrent/repeated implantation failure (RIF) may occur due to altered uterine receptivity with aberrant gene expression in the endometrium as well as genetic defects in embryos. Several studies have been performed to understand dynamic changes of uterine transcriptome during menstrual cycles in humans. However, uterine transcriptome of the patients with RIF has not been clearly investigated yet...
2016: PloS One
https://www.readbyqxmd.com/read/27141549/effect-of-adding-human-chorionic-gonadotropin-to-frozen-thawed-embryo-transfer-cycles-with-history-of-thin-endometrium
#16
Robab Davar, Sepideh Miraj, Maryam Farid Mojtahedi
BACKGROUND: Embryo implantation process is a complex phenomenon and depends on fetal and maternal factors interaction. Endometrial thickness is needed for successful implantation. OBJECTIVE: We designed this study in order to assess adding human chorionic gonadotropin (HCG) to the conventional protocol in endometrial preparation in women with thin endometrium and a history of in vitro fertilization-embryo transfer (IVF-ET) failure. MATERIALS AND METHODS: The non-randomized clinical trial study (quasi experimental design) was performed on 28 patients...
January 2016: International Journal of Reproductive Biomedicine (Yazd, Iran)
https://www.readbyqxmd.com/read/27132053/hysteroscopy-in-recurrent-in-vitro-fertilisation-failure-trophy-a-multicentre-randomised-controlled-trial
#17
RANDOMIZED CONTROLLED TRIAL
Tarek El-Toukhy, Rudi Campo, Yacoub Khalaf, Carla Tabanelli, Luca Gianaroli, Sylvie S Gordts, Stephan Gordts, Greet Mestdagh, Tonko Mardesic, Jan Voboril, Gian L Marchino, Chiara Benedetto, Talha Al-Shawaf, Luca Sabatini, Paul T Seed, Marco Gergolet, Grigoris Grimbizis, Hoda Harb, Arri Coomarasamy
BACKGROUND: The success rate of in-vitro fertilisation (IVF) remains low and many women undergo multiple treatment cycles. A previous meta-analysis suggested hysteroscopy could improve outcomes in women who have had recurrent implantation failure; however, studies were of poor quality and a definitive randomised trial was needed. In the TROPHY trial we aimed to assess whether hysteroscopy improves the livebirth rate following IVF treatment in women with recurrent failure of implantation...
June 25, 2016: Lancet
https://www.readbyqxmd.com/read/27068821/polymorphisms-in-the-mthfr-gene-influence-embryo-viability-and-the-incidence-of-aneuploidy
#18
María Enciso, Jonás Sarasa, Leoni Xanthopoulou, Sara Bristow, Megan Bowles, Elpida Fragouli, Joy Delhanty, Dagan Wells
MTHFR is an important enzyme in the metabolism of folic acid and is crucial for reproductive function. Variation in the sequence of MTHFR has been implicated in subfertility, but definitive data are lacking. In the present study, a detailed analysis of two common MTHFR polymorphisms (c.677C>T and c.1298A>C) was performed. Additionally, for the first time, the frequencies of different MTHFR alleles were assessed in preimplantation embryos. Several striking discoveries were made. Firstly, results demonstrated that maternal MTHFR c...
May 2016: Human Genetics
https://www.readbyqxmd.com/read/27059821/assessment-of-clinical-application-of-preimplantation-genetic-screening-on-cryopreserved-human-blastocysts
#19
Min Liu, Yu Su, Wei-Hua Wang
BACKGROUND: Recent advancement in both human embryology and preimplantation genetic screening has created a completely new situation for human assisted reproduction. Embryos, typically at blastocyst stage, are biopsied and screened by DNA microarray or next-generation sequencing before cryopreservation, and then euploid embryos are warmed for transfer. Increased embryo implantation rates have been reported after transfer of euploid embryos screened for all chromosomes. However, some patients may have frozen their embryos without doing embryo biopsy and screening, thus embryo biopsy and screening may be required after cryopreservation and warming...
April 8, 2016: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/27035670/the-promyelocytic-leukemia-zinc-finger-transcription-factor-is-critical-for-human-endometrial-stromal-cell-decidualization
#20
Ramakrishna Kommagani, Maria M Szwarc, Yasmin M Vasquez, Mary C Peavey, Erik C Mazur, William E Gibbons, Rainer B Lanz, Francesco J DeMayo, John P Lydon
Progesterone, via the progesterone receptor (PGR), is essential for endometrial stromal cell decidualization, a cellular transformation event in which stromal fibroblasts differentiate into decidual cells. Uterine decidualization supports embryo implantation and placentation as well as subsequent events, which together ensure a successful pregnancy. Accordingly, impaired decidualization results not only in implantation failure or early fetal miscarriage, but also may lead to potential adverse outcomes in all three pregnancy trimesters...
April 2016: PLoS Genetics
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