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Human embryo implantation failure

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
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
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...
July 22, 2016: Gynecological Endocrinology
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
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)
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
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
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...
2016: Reproductive Biology and Endocrinology: RB&E
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
Kara Turner, Katie Fowler, Gothami Fonseka, Darren Griffin, Dimitrios Ioannou
Fluorescence in-situ hybridization (FISH) revolutionized cytogenetics using fluorescently labelled probes with high affinity with target (nuclear) DNA. By the early 1990s FISH was adopted as a means of preimplantation genetic diagnosis (PGD) sexing for couples at risk of transmitting X-linked disorders and later for detection of unbalanced translocations. Following a rise in popularity of PGD by FISH for sexing and the availability of multicolor probes (5-8 colors), the use of FISH was expanded to the detection of aneuploidy and selective implantation of embryos more likely to be euploid, the rationale being to increase pregnancy rates (referral categories were typically advanced maternal age, repeated IVF failure, repeated miscarriage or severe male factor infertility)...
June 2016: Panminerva Medica
Khaled M Zohni, Itai Gat, Clifford Librach
Successful pregnancy involves a synchronized, coordinated cross-talk between an embryo capable of implanting, and an endometrium enabling implantation. Recurrent implantation failure (RIF) refers to unsuccessful implantation after repeated transfers of morphologically good quality embryos into a normal uterus. The etiology for RIF can be attributed to the embryo itself, the mother or, in some cases, both. Despite extensive research on underlying causes for RIF, our understanding of this condition is still limited...
December 2016: Minerva Ginecologica
Fabiola da Silva Nardi, Renata Slowik, Tatiana Michelon, Luis Felipe Dos Santos Manvailer, Bettina Wagner, Jorge Neumann, Peter Horn, Maria da Graça Bicalho, Vera Rebmann
PROBLEM: Human leukocyte antigen-G (HLA-G) expression is related to 14-bp insertion/deletion polymorphism at the 3'UTR of the HLA-G gene. Soluble forms of HLA-G are released as free molecules or via extracellular vesicles (EVs). Due to the crucial role of HLA-G during pregnancy, we analyzed the 14-bp polymorphism and the two secreted forms in implantation failure women (IF) and in fertile women (FW). METHOD OF STUDY: For the genetic analysis, 49 IF and 34 FW were genotyped...
June 2016: American Journal of Reproductive Immunology: AJRI
Katalin Kanyo, Jozsef Zeke, Rita Kriston, Zoltan Szücs, Sandor Cseh, Bence Somoskoi, Janos Konc
Biochemical modifications of zona pellucida (ZP) result in zona hardening. Zona hardening (ZH) is induced by several factors such as advancing maternal age, in vitro culture conditions and cryopreservation and adversely effects implantation. The objective of the clinical study was to determine whether or not laser-assisted hatching (LAH) applied on day 3 frozen embryos improves the outcome of frozen embryo transfer (FET) cycles in patients with recurrent implantation failure and/or advanced female age. In total, 413 patients of different ages with recurrent implantation failure (maximum three cycles) were involved into the study...
October 2016: Zygote: the Biology of Gametes and Early Embryos
Honami Ogoh, Nobuhiro Tanuma, Yasuhisa Matsui, Natsuki Hayakawa, Ayaka Inagaki, Mami Sumiyoshi, Yuki Momoi, Ayako Kishimoto, Mai Suzuki, Nozomi Sasaki, Tsukasa Ohuchi, Miyuki Nomura, Yuriko Teruya, Keiko Yasuda, Toshio Watanabe, Hiroshi Shima
Ppp6c, which encodes the catalytic subunit of phosphoprotein phosphatase 6 (PP6), is conserved among eukaryotes from yeast to humans. In mammalian cells, PP6 targets IκBε for degradation, activates DNA-dependent protein kinase to trigger DNA repair, and is reportedly required for normal mitosis. Recently, Ppp6c mutations were identified as candidate drivers of melanoma and skin cancer. Nonetheless, little is known about the physiological role of Ppp6c. To investigate this function in vivo, we established mice lacking the Ppp6c phosphatase domain by crossing heterozygous mutants...
February 2016: Mechanisms of Development
William A Pastor, Di Chen, Wanlu Liu, Rachel Kim, Anna Sahakyan, Anastasia Lukianchikov, Kathrin Plath, Steven E Jacobsen, Amander T Clark
Human embryonic stem cells (hESCs) typically exhibit "primed" pluripotency, analogous to stem cells derived from the mouse post-implantation epiblast. This has led to a search for growth conditions that support self-renewal of hESCs akin to hypomethylated naive epiblast cells in human pre-implantation embryos. We have discovered that reverting primed hESCs to a hypomethylated naive state or deriving a new hESC line under naive conditions results in the establishment of Stage Specific Embryonic Antigen 4 (SSEA4)-negative hESC lines with a transcriptional program resembling the human pre-implantation epiblast...
March 3, 2016: Cell Stem Cell
Hee-Jung Choi, Tae-Wook Chung, Mi-Ju Park, Kyu Sup Lee, Youngjin Yoon, Hyung Sik Kim, Jun Hee Lee, Sang-Mo Kwon, Syng-Ook Lee, Keuk-Jun Kim, Jin-Ho Baek, Ki-Tae Ha
In the present study, we investigated the role of Paeonia lactiflora Pall. extract on embryo implantation in vitro and in vivo. A polysaccharides depleted-water extract of P. lactiflora (PL-PP) increased LIF expression in human endometrial Ishikawa cells at non-cytotoxic doses. PL-PP significantly increased the adhesion of the human trophectoderm-derived JAr spheroids to endometrial Ishikawa cells. PL-PP-induced LIF expression was decreased in the presence of a p38 kinase inhibitor SB203580 and an MEK/ERK inhibitor U0126...
2016: PloS One
David R Meldrum, Robert F Casper, Antonio Diez-Juan, Carlos Simon, Alice D Domar, Rene Frydman
Optimal maturation of the oocyte depends on its environment and determines embryo competence, because the embryonic genome is not active until the cleavage stage and new mitochondria are not produced until blastulation. Adverse environmental factors include aging, andropause, oxidative stress, obesity, smoking, alcohol, and psychologic stress, whereas androgen supplementation, a prudent diet, exercise, nutritional supplements, and psychologic interventions have beneficial effects. Mitochondrial function and energy production deteriorate with age, adversely affecting ovarian reserve, chromosome segregation, and embryo competence...
March 2016: Fertility and Sterility
Camille Stora, Sylvie Epelboin, Emmanuel Devouche, Sophie Matheron, Loïc Epelboin, Chadi Yazbeck, Florence Damond, Pascale Longuet, Frederick Dzineku, Mandovi Rajguru, Lucie Delaroche, Laurent Mandelbrot, Dominique Luton, Catherine Patrat
OBJECTIVE: To compare the efficacy of assisted reproductive technology (ART) in women infected with human immunodeficiency virus type 1 (HIV-1) versus HIV-negative controls. DESIGN: Retrospective case-control study. SETTING: University hospital ART unit. PATIENT(S): Eighty-two women infected with HIV-1 and 82 women as seronegative controls. INTERVENTION(S): Ovarian stimulation, oocytes retrieval, standard in vitro fertilization (IVF) or intracytoplasmic sperm injection, embryo transfer...
May 2016: Fertility and Sterility
David A Clark
In an outbred mating typical of human reproduction, the embryo and feto-placental unit express paternal antigens to which the mother's immune system can react. However, the embryo and feto-placental unit can engineer the maternal immune defense system towards helpful rather than harmful reactions. Indeed, this begins with the prospective mother's exposure to paternal seminal plasma. In this review, the pregnancy complications of implantation failure (infertility), recurrent spontaneous abortion, pre-eclampsia and intrauterine growth restriction, and premature labor are examined to determine the degree of similarity between events in women and events in lab mouse models...
January 18, 2016: Seminars in Immunopathology
Laurence Bissonnette, Loubna Drissennek, Yannick Antoine, Laurent Tiers, Christophe Hirtz, Sylvain Lehmann, Hélène Perrochia, François Bissonnette, Isaac-Jacques Kadoch, Delphine Haouzi, Samir Hamamah
In assisted reproduction, about 30% of embryo implantation failures are related to inadequate endometrial receptivity. To identify molecules involved in endometrial receptivity acquisition, we investigated, using a SELDI-TOF approach, the protein expression profile of early-secretory and mid-secretory endometrium samples. Among the proteins upregulated in mid-secretory endometrium, we investigated the function of S100A10 in endometrial receptivity and implantation process. S100A10 was expressed in epithelial and stromal cells of the endometrium of fertile patients during the implantation windows...
May 3, 2016: Cell Adhesion & Migration
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