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Journal articles on the topic 'Embryo implantation'
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1
Koot, Yvonne E. M., and Nick S. Macklon. "Embryo implantation." Current Opinion in Obstetrics and Gynecology 25, no. 4 (August 2013): 274–79. http://dx.doi.org/10.1097/gco.0b013e3283630d94.
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Carson, Daniel D., Indrani Bagchi, Sudhandsu K. Dey, Allen C. Enders, Asgerally T. Fazleabas, Bruce A. Lessey, and Koji Yoshinaga. "Embryo Implantation." Developmental Biology 223, no. 2 (July 2000): 217–37. http://dx.doi.org/10.1006/dbio.2000.9767.
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Mustafa, Snoor Jalal, and Kameel Mate Naoum. "EFFECT OF ACYCLOVIR ON EMBRYO IMPLANTATION IN MICE." Journal of Sulaimani Medical College 3, no. 2 (December 1, 2013): 103–7. http://dx.doi.org/10.17656/jsmc.10038.
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Gou, Jinhai, Tingwenyi Hu, Lin Li, Luqi Xue, Xia Zhao, Tao Yi, and Zhengyu Li. "Role of epithelial–mesenchymal transition regulated by twist basic helix-loop-helix transcription factor 2 (Twist2) in embryo implantation in mice." Reproduction, Fertility and Development 31, no. 5 (2019): 932. http://dx.doi.org/10.1071/rd18314.
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In a previous study we found the expression of epithelial–mesenchymal transition (EMT) biomarkers, including E-cadherin and N-cadherin, was significantly altered in uterine endometrium during embryo implantation via regulation by microRNA (miRNA)-429 and protocadherin-8 (Pcdh8). As a natural continuation of the previous study, the aim of the present study was to explore the role of EMT during embryo implantation and the potential activity of twist basic helix-loop-helix transcription factor 2 (Twist2) in regulating embryo implantation. A pregnancy model was established by naturally mating adult female ICR mice with fertile males. A pseudopregnancy model was established by mating fertile female ICR mice with vasectomised males. An invitro model of embryo implantation was established by the coculture of Ishikawa and JAR spheroids. Endometrial tissue during the peri-implantation period was collected, as were Ishikawa cells, JAR cells and cocultured cells. The expression of EMT markers (E-cadherin, N-cadherin, vimentin and cytokeratin) and Twist2 was detected invivo and invitro using the western blot analysis during embryo implantation. The expression of N-cadherin and vimentin (mesenchymal markers) was upregulated in the invitro implantation model, with downregulation of E-cadherin and cytokeratin (epithelial markers) expression. The expression of N-cadherin, vimentin and Twist2 increased significantly at the implantation sites at the time of implantation (Day 5), whereas the expression of E-cadherin and cytokeratin decreased. Location of Twist2 during embryo implantation was detected by immunohistochemistry (IHC), which revealed that it was extensively expressed in endometrial glandular epithelium and luminal epithelium at implantation sites on Day 5. The effect of the expression of Twist2 on embryo implantation was evaluated by suppressing Twist2 using Twist2-short interference (si) RNA in invivo and invitro models. The numbers of implanted embryos and the implantation rate were compared invivo and invitro. Western blot analysis showed that suppression of Twist2 led to upregulation of E-cadherin and cytokeratin, accompanied by downregulation of N-cadherin and vimentin (P<0.05). The number of implanted embryos after Twist2-siRNA interference was lower than in normal pregnancy (mean (±s.d.) 2.4±0.5 vs 6.8±1.3 respectively; P<0.05). These findings suggest the involvement of EMT in embryo implantation. The suppression of Twist2 could suppress embryo implantation by regulating EMT.
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Flores, Diana, Manoj Madhavan, Savannah Wright, and Ripla Arora. "Mechanical and signaling mechanisms that guide pre-implantation embryo movement." Development 147, no. 24 (November 6, 2020): dev193490. http://dx.doi.org/10.1242/dev.193490.
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ABSTRACTHow a mammalian embryo determines and arrives at its attachment site has been studied for decades, but our understanding of this process is far from complete. Using confocal imaging and image analysis, we evaluate embryo location along the longitudinal oviductal-cervical axis of murine uteri. Our analysis reveals three distinct pre-implantation phases: embryo entry, unidirectional movement of embryo clusters and bidirectional scattering and spacing of embryos. We show that unidirectional clustered movement is facilitated by a mechanical stimulus of the embryo and is regulated by adrenergic uterine smooth muscle contractions. Embryo scattering, on the other hand, depends on embryo-uterine communication reliant on the LPAR3 signaling pathway and is independent of adrenergic muscle contractions. Finally, we demonstrate that uterine implantation sites in mice are neither random nor predetermined but are guided by the number of embryos entering the uterine lumen. These studies have implications for understanding how embryo-uterine communication is key to determining an optimal implantation site necessary for the success of a pregnancy.
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Huang, Z. P., H. Yu, Z. M. Yang, W. X. Shen, J. Wang, and Q. X. Shen. "Uterine expression of implantation serine proteinase 2 during the implantation period and in vivo inhibitory effect of its antibody on embryo implantation in mice." Reproduction, Fertility and Development 16, no. 3 (2004): 379. http://dx.doi.org/10.1071/rd03102.
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The aim of the present study was to examine the uterine expression pattern of implantation serine proteinase 2 (ISP2) protein during early pregnancy in mice and the effects of anti-ISP2 antibody on embryo implantation. Expression of ISP2 protein was found to be specifically up-regulated in mouse uterine endometrial glands following the initiation of embryo implantation. Similarly, ISP2 protein expression was observed during pseudopregnancy, indicating that its expression is not embryo dependent. In other experiments, rabbit anti-ISP2 IgG was infused into the mouse uterine lumen on Day 3 or 4 of pregnancy to examine its effects on embryo implantation, whereas vehicle (saline) or unspecific rabbit IgG served as controls. The mean number of implanted embryos from anti-ISP2-IgG-treated mice was significantly lower than that from control mice. These results suggest that ISP2 may play an important role during embryo implantation.
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Gao, Weina, Xiao Tang, Zhenyan Chen, Yue Guo, Lijun Wang, Mingmin Zhang, and Guangying Huang. "Effects of Acupuncture on CCL2 and CXCL8 Expression and the Subset of uNK Cells in Rats with Embryo Implantation Failure." Evidence-Based Complementary and Alternative Medicine 2013 (2013): 1–12. http://dx.doi.org/10.1155/2013/678390.
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The present study was designed to investigate the efficacy and mechanism of acupuncture treatment on embryo implantation failure in rats. The pregnant rats were randomized into normal group (N), implantation failure group (M), acupuncture treatment group (A), and progestin treatment group (W). The embryo implantation failure model was established by mifepristone. Efficacy of acupuncture treatment was evaluated by the number of implanted embryos. The expression of CCL2 and CXCL8 and the subset of uterine natural killer cells in the endometrium were detected. We demonstrated that the number of implanted embryos was dramatically reduced after mifepristone (M group) treatment, while the acupuncture (A group) and progestin (W group) treatments significantly rescued impaired embryo implantation. The protein and mRNA expressions of CCL2 and CXCL8 were significantly reduced by mifepristone treatment, but the attenuated expression of CCL2 and CXCL8 was markedly reversed by acupuncture or progestin treatment. More importantly, acupuncture and progestin could markedly increase the subset of uNK cells in rats with embryo implantation failure. These evidences suggest that acupuncture is able to modulate the endometrial immune microenvironment and thus improve embryo implantation in pregnant rats, which provides solid experimental evidence for the curative effect of acupuncture treatment on infertility.
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Benkhalifa, M., A. Demirol, T. Sari, E. Balashova, M. Tsouroupaki, Y. Giakoumakis, and T. Gurgan. "Autologous embryo–cumulus cells co-culture and blastocyst transfer in repeated implantation failures: a collaborative prospective randomized study." Zygote 20, no. 2 (April 7, 2011): 173–80. http://dx.doi.org/10.1017/s0967199411000062.
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SummaryIn repeated implantation failure, the co-culture of human embryos with somatic cells has been reported to promote the improvement of embryos quality, implantation and pregnancy rate. It was reported that feeder cells can be more beneficial to the oocyte and embryo by detoxifying the culture medium and supporting embryo development via different pathways. In this study, 432 patients, each with a minimum of three repeated implantation failures, were accepted for a prospective randomized study with or without autologous cumulus cell embryo co-culture and transfer at day 3 or day 5–6. We also investigated the expression of leukaemia inhibitor factor (LIF) and platelet activating factor receptor (PAF-R) on day 3 confluent cumulus cells. The statistic analysis of the data showed significant difference of implantation and clinical pregnancy rates between classical culture and day 3 compared with co-culture and day 5–6 transfer. The molecular analysis showed that cumulus cells express the LIF and the PAF-R genes and confirmed the possible positive role of growth factors and cytokines in early embryo development. Embryo co-culture systems with autologous cells can be beneficial in routine in vitro fertilization for embryo selection and implantation improvement. More molecular investigations need to be done to improve elucidation of the complex dialogue between the embryo and feeder cells prior to implantation and to understand the involved biological function and molecular process during embryo development.
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Zorina, I. M., C. M. Eldarov, S. A. Yarigina, N. P. Makarova, D. Yu Trofimov, V. Yu Smolnikova, E. A. Kalinina, and M. Yu Bobrov. "Metabolomic profiling in culture media of day-5 human embryos." Biomeditsinskaya Khimiya 63, no. 5 (2017): 385–91. http://dx.doi.org/10.18097/pbmc20176305385.
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The aim of this study was to determine the changes of metabolomic profiles in embryonic culture media (ECM) for the evaluation of quality and implantation potential of human embryos. ECM (n=163) were collected on day 5 before transfer or cryopreservation. Some embryos were used in preimplantation genetic screening for detection of aneuploidy karyotypes. Samples were subdivided into groups according to embryo morphological classification (by Gardner), genetic analysis and implantation data. ECM were extracted with methanol, precipitates were separated by centrifugation and metabolite production of individual embryo was analysed by LC-MS (the positive ion mode). After peak detection and retention time alignment, data were analysed using the PCA algorithm. MS fingerprinting analysis of embryo culture medium showed significant differences between morphologically divided groups. Intragroup comparisons did not reveal differences between subclasses. Genetic screening of embryos revealed 33 aneuploid karyotypes. It was shown that chromosome number did not affect the metabolite profiles comparing with the normal group. The culture media of embryos that were positive or negative for successful implantation showed specific signatures that allowed to distinguish embryos with different outcomes.The characterization of ECMs by LC-MS may facilitate more accurate selection of the best embryo for the implantation, improving single-embryo transfer and thus eliminating the risk and undesirable effects of multiple pregnancies.
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Bahgat, Nagwan Ahmed, and Waleed Said. "Personalized embryo transfer after endometrial receptivity array test in patients with recurrent unexplained implantation failure." International Journal of Reproduction, Contraception, Obstetrics and Gynecology 11, no. 3 (February 25, 2022): 657. http://dx.doi.org/10.18203/2320-1770.ijrcog20220380.
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Background: Unexplained recurrent implantation failure is a devastating situation for both patients and the doctor treating them, with transfer of high grade euploid embryos this situation became more related to the endometrial receptivity and the interaction between the embryo and the endometrium. Till now the best way of detecting endometrial receptivity was through endometrial receptivity array of gene in endometrial tissue.Methods: A retrospective study was carried out in large IVF center in Abu Dhabi in period from 2017-2021. Patients included in the study were infertile patients with age limit of 43 years old with history of repeated IVF failure after multiple transfer trials of high grade embryos. All patients had ERA test then frozen embryo transfer of Euploid high grade embryos obtained through stimulated cycle of each patient according to Era test results.Results: 45 patients included in our study. Patients divided into 2 major groups according to Era test result. First group included patients with receptive endometrium. The second group was the patients with displaced window of implantation. Patients with receptive endometrium were 12 (26.7%) and the displaced window of implantation was found in 33 patients (73.3%). Higher pregnancy and cumulative pregnancy rate in the patients with displaced window of implantation more than the receptive group 19 (57.7%) versus 5 (41.6%) and 27 (81,8%) versus 6 (50%), but lower implantation rate in the displaced window of implantation group 6/12 (50%) versus 25/53 (47.2%) with higher miscarriage rate in the receptive group 2/6 (33.3%) versus 4/26 (14.8%), live birth and take home baby rate in the patients with displaced window of implantation 3 babies delivered to the receptive group 3/12 (25%), 24 babies to the group of displaced window of implantation 24/53 (45.3%).Conclusions: Patients with recurrent unexplained implantation failure may benefit from personalized embryo transfer after determining their window of implantations with endometrial receptivity array testing.
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Savostina, G. V., S. G. Perminova, A. V. Timofeeva, and M. A. Veyukova. "Modern Methods for Assessment of the Implantation Potential of Embryos in Assisted Reproductive Programs." Doctor.Ru 20, no. 8 (2021): 12–18. http://dx.doi.org/10.31550/1727-2378-2021-20-8-12-18.
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Objective of the Review: To analyse the modern methods for assessment of the implantation potential of embryos in assisted reproductive programs. Key Points. We present the study results for selection of a most optimal embryo for transfer, using visual assessment of embryo quality, preimplantation genetic aneuploidy testing, analysis of metabolomic, proteomic, transcriptomic profiles of culture media and embryo blastocele. We have paid special attention to assessment of small non-coding RNA (sncRNA) in embryo culture medium. Conclusion. Due to the high sensitivity, objectivity and biomarker resistance to degradation, the most promising non-invasive method to assess the implantation potential of an embryo is analysis of the sncRNA profile in embryo culture media. Keywords: aneuploidy, pre-implantation genetic testing, small non-coding RNAs, proteomic analysis, metabolomic analysis.
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Gurung, S., D. W. Greening, S. Catt, L. Salamonsen, and J. Evans. "Exosomes and soluble secretome from hormone-treated endometrial epithelial cells direct embryo implantation." Molecular Human Reproduction 26, no. 7 (May 13, 2020): 510–20. http://dx.doi.org/10.1093/molehr/gaaa034.
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Abstract A successful pregnancy requires a synchronous dialogue between endometrium and embryo within the endometrial milieu. The aim of this study was to assess the role in the implantation of mediators in the endometrial milieu. Total secretome (TS), soluble secretome (SS) and small extracellular vesicles (containing exosomes) were generated from hormonally primed human endometrial epithelial cell culture medium. Human trophectoderm stem cell-derived spheroids were cultured with TS, SS or exosomes (30 µg/ml) on hormonally primed epithelial cells, with exosomes significantly increasing cell adhesion and outgrowth. Furthermore, F1 mouse 2-cell embryos were cultured in groups for 48 h followed by culture with each secretome fraction (30 µg/ml) for 48 h. Blastocyst cell number and hatching were quantified. In addition, blastocysts were further cultured on a fibronectin matrix for 72 h or transferred to recipient mice (with corresponding secretomes) with embryo implantation assessed after 6 days. Exosomes significantly increased total cell number in mouse embryos and complete hatching from zona pellucida, with both exosomes and SS significantly enhancing mouse embryo outgrowth. Importantly, exosomes increased the embryo implantation rate in comparison to other secretome fractions (normalized based on treatment amount) from the endometrial epithelia. These data indicate that endometrial epithelial exosomes support embryo growth, development and implantation while the SS has selective involvement specifically on mouse embryo outgrowth. This finding provides new insights into the molecular differences of endometrial secretome components in implantation and early embryo development and may implicate endometrial exosomes in the pathophysiology of implantation failure in infertility.
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Eldarov, Chupalav, Alina Gamisonia, Vitaliy Chagovets, Luiza Ibragimova, Svetlana Yarigina, Veronika Smolnikova, Elena Kalinina, et al. "LC-MS Analysis Revealed the Significantly Different Metabolic Profiles in Spent Culture Media of Human Embryos with Distinct Morphology, Karyotype and Implantation Outcomes." International Journal of Molecular Sciences 23, no. 5 (February 28, 2022): 2706. http://dx.doi.org/10.3390/ijms23052706.
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In this study we evaluated possible differences in metabolomic profiles of spent embryo culture media (SECM) of human embryos with distinct morphology, karyotype, and implantation outcomes. A total of 153 samples from embryos of patients undergoing in vitro fertilization (IVF) programs were collected and analyzed by HPLC-MS. Metabolomic profiling and statistical analysis revealed clear clustering of day five SECM from embryos with different morphological classes and karyotype. Profiling of day five SECM from embryos with different implantation outcomes showed 241 significantly changed molecular ions in SECM of successfully implanted embryos. Separate analysis of paired SECM samples on days three and five revealed 46 and 29 molecular signatures respectively, significantly differing in culture media of embryos with a successful outcome. Pathway enrichment analysis suggests certain amino acids, vitamins, and lipid metabolic pathways to be crucial for embryo implantation. Differences between embryos with distinct implantation potential are detectable on the third and fifth day of cultivation that may allow the application of culture medium analysis in different transfer protocols for both fresh and cryopreserved embryos. A combination of traditional morphological criteria with metabolic profiling of SECM may increase implantation rates in assisted reproductive technology programs as well as improve our knowledge of the human embryo metabolism in the early stages of development.
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Cortezzi, Sylvia Sanches, Elaine Cristina Cabral, Marcello Garcia Trevisan, Christina Ramires Ferreira, Amanda Souza Setti, Daniela Paes de Almeida Ferreira Braga, Rita de Cássia Sávio Figueira, Assumpto Iaconelli, Marcos Nogueira Eberlin, and Edson Borges. "Prediction of embryo implantation potential by mass spectrometry fingerprinting of the culture medium." REPRODUCTION 145, no. 5 (May 2013): 453–62. http://dx.doi.org/10.1530/rep-12-0168.
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This study has evaluated the performance of a multivariate statistical model to predict embryo implantation potential by processing data from the chemical fingerprinting of culture medium samples used for human embryo culture. The culture medium for 113 embryos from 55 patients undergoing ICSI was collected after embryo transfer. The samples were split into positive (n=29) and negative (n=84) implantation groups according their implantation outcomes (100% or 0% implantation). The samples were individually diluted and analyzed by electrospray ionization mass spectrometry (ESI-MS). Them/zratios and relative abundances of the major ions in each spectrum were considered for partial least square discriminant analysis. Data were divided into two subsets (calibration and validation), and the models were evaluated and applied to the validation set. A total of 5987 ions were observed in the groups. The multivariate statistical model described more than 82% of the data variability. Samples of the positive group were correctly identified with 100% probability and negative samples with 70%. The culture media used for embryos that were positive or negative for successful implantation showed specific biochemical signatures that could be detected in a fast, simple, and noninvasive way by ESI-MS. To our knowledge, this is the first report that uses MS fingerprinting to predict human embryo implantation potential. This biochemical profile could help the selection of the most viable embryo, improving single-embryo transfer and thus eliminating the risk and undesirable outcomes of multiple pregnancies.
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Gou, Jinhai, Jia Jia, Juntao Feng, Xia Zhao, Tao Yi, Tao Cui, and Zhengyu Li. "Stathmin 1 plays a role in endometrial decidualisation by regulating hypoxia inducible factor-1α and vascular endothelial growth factor during embryo implantation." Reproduction, Fertility and Development 29, no. 8 (2017): 1530. http://dx.doi.org/10.1071/rd15539.
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The aim of the present study was to explore the potential mechanism underlying stathmin 1 (Stmn1) regulation of embryo implantation, as a continuation of previous proteomic research. Adult healthy female mice were mated naturally with fertile males. Murine uterine tissue was collected during the peri-implantation period. Local expression of Stmn1 during embryo implantation was detected by immunohistochemistry (IHC), which showed that Stmn1 was extensively expressed in endometrial glandular epithelium, vascular endothelium, luminal epithelium and the underlying stromal cells at the implantation site on Day 5. The role of Stmn1 during embryo implantation was evaluated by transient knockdown of Stmn1 in vivo using short interference (si) RNA, and some associated factors including Akt, phosphorylated (p-) Akt, hypoxia-inducible factor (HIF)-1α, prolactin (PRL), insulin-like growth factor binding protein (IGFBP) 1 and vascular endothelial growth factor (VEGF) were examined by western blotting analysis and ELISA. The number of embryos implanted after Stmn1-siRNA infusion into the lumen of one uterine horn was lower than that with normal pregnancies (2.2 ± 1.5 vs 8.6 ± 0.5 respectively; P < 0.05). The expression of VEGF, HIF-1α, p-Akt and the decidualisation biomarkers PRL and IGFBP 1 was upregulated at the implantation site on Day 5, but downregulated after Stmn1-siRNA infusion. These findings suggest that during embryo implantation, knockdown of Stmn1 suppresses decidualisation by inhibiting the expression of p-Akt, HIF-1α and VEGF, thus leading to impaired embryo implantation. These findings provide clues for understanding the complicated process of embryo implantation and the potential role of Stmn1 during embryo implantation.
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Kim, Jihyun, Jaewang Lee, and Jin Hyun Jun. "Identification of differentially expressed microRNAs in outgrowth embryos compared with blastocysts and non-outgrowth embryos in mice." Reproduction, Fertility and Development 31, no. 4 (2019): 645. http://dx.doi.org/10.1071/rd18161.
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Recurrent implantation failure (RIF) is one of the main causes for the repeated failure of IVF, and the major reason for RIF is thought to be a miscommunication between the embryo and uterus. However, the exact mechanism underlying embryo–uterus cross-talk is not fully understood. The aim of the present study was to identify differentially expressed microRNAs (miRNAs) among blastocysts, non-outgrowth and outgrowth embryos in mice using microarray analysis. A bioinformatics analysis was performed to predict the potential mechanisms of implantation. The miRNA expression profiles differed significantly between non-outgrowth and outgrowth embryos. In all, 3163 miRNAs were detected in blastocysts and outgrowth embryos. Of these, 10 miRNA candidates (let-7b, miR-23a, miR-27a, miR-92a, miR-183, miR-200c, miR-291a, miR-425, miR-429 and miR-652) were identified as significant differentially expressed miRNAs of outgrowth embryos by in silico analysis. The expression of the miRNA candidates was markedly changed during preimplantation embryo development. In particular, let-7b-5p, miR-200c-3p and miR-23a-3p were significantly upregulated in outgrowth embryos compared with non-outgrowth blastocysts. Overall, differentially expressed miRNAs in outgrowth embryos compared with blastocysts and non-outgrowth embryos could be involved in embryo attachment, and interaction between the embryo proper and maternal endometrium during the implantation process.
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Stafford-Bell, M. A., and C. M. Copeland. "Surrogacy in Australia: implantation rates have implications for embryo quality and uterine receptivity." Reproduction, Fertility and Development 13, no. 1 (2001): 99. http://dx.doi.org/10.1071/rd00044.
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Since the passage, in November 1995, of the ACT Substitute Parents Agreement Act, The Canberra Fertility Centre has added a true gestational carrier pregnancy programme to its established infertility and IVF services. Embryos generated are transferred as frozen–thawed embryos to the carrier in an average of 2.2 embryos per transfer. Between 1 January 1996 and 31 December 1999 the results of 49 frozen embryo transfers to 25 gestational carriers were compared with 849 frozen embryo transfers on a routine IVF programme. In the carrier group, the embryo implantation rate of 13.8% per embryo transferred is double that of an exactly comparable group of patients undergoing routine frozen–thawed embryo transfer on the same IVF programme and considerably higher than those reported in large series of frozen–thawed embryo transfers. Exclusion from the carrier pregnancy programme of patients with incipient ovarian failure results in an implantation rate of 16.7%, a clinical pregnancy rate of 29.0% and a live birth rate of 19.4% per embryo transfer procedure.
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Vinijsanun, A., and L. Martin. "Effect of early ovariectomy and steroid hormone replacement of embryo transport, development and implantation in mice." Reproduction, Fertility and Development 3, no. 1 (1991): 35. http://dx.doi.org/10.1071/rd9910035.
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Bilateral ovariectomy on Day 1 of pregnancy increased abnormal embryo numbers on Day 4 and delayed passage of embryos to the uterus. Progestins given on Day 1 reversed these effects; given on Day 3 they reduced numbers of abnormal embryos, but did not restore normal transport. Oestrogen given alone after ovariectomy increased embryo loss, but restored preimplantation embryo development to normal when given on Day 3 after progestins on Day 1. The results suggested that both oestrogen and progesterone were necessary for normal preimplantation embryo development in vivo. However, although Day-1 progestins produced the greatest improvement in embryo transport and preimplantation development, they supported only low implantation rates compared with progestins starting on Day 3, and no progestin treatment returned implantation rates to normal. Sham ovariectomy on Day 1 also reduced implantation rate, suggesting that surgical stress of Day-1 ovariectomy had major adverse effects on embryo viability. This view was supported by experiments involving unilateral ovariectomy, which produced abnormalities in embryo transport, development and implantation, but only on the operated side. Furthermore, the major abnormality induced in embryo development by unilateral and bilateral ovariectomy, viz embryonic autolysis, was not increased in experiments in which pregnancy was blocked by non-surgical antagonism of progesterone. It is concluded that abnormalities in embryo development induced by early ovariectomy are not caused by a deficit of endogenous hormones, but result largely from effects of surgical trauma on oviduct function which can be reversed by treatment with exogenous hormones.
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Asfarova, Gunai R., Veronika I. Smol'nikova, Natalia P. Makarova, Iuliia S. Drapkina, Anastasiia P. Sysoeva, Nataliia N. Lobanova, and Elena A. Kalinina. "The birth of a healthy child in the assisted reproductive technologies program after autologous co-culture of embryo with cumulus cells and a new CAT transfer technology. Case report." Gynecology 23, no. 3 (August 13, 2021): 270–74. http://dx.doi.org/10.26442/20795696.2021.3.200876.
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Cumulus cells are essential during oocytes growth and development, as well as during their maturation and fertilization. Research results have shown that embryo co-cultivation with autologous cumulus cells increases the frequency of blastocyst formation, and also improves the effectiveness of ART programs. Embryo transfer in such programs is recommended to be carried out using the CAT technology (Cumulus-Aided embryo Transfer), which includes embryo cultivation on a layer of cumulus cells and embryo transfer with a certain amount of diluted cumulus cells. Patient G., 38 years old, came to the department with infertility for 15 years and recurrent implantation failure in history. The patient had ART program with autologous co-cultivation of embryos with cumulus cells and a new CAT transfer technology. The patient fell pregnant and gave birth to a healthy child. Autologous cumulus cells can be a source of biologically active substances and improve embryological parameters and implantation rate in ART programs. Embryo co-cultivation with cumulus cells is especially important for patients with recurrent implantation failure. This technique can become an alternative for optimizing human embryos culturing.
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Guajardo-Correa, Emanuel, Denisse Mena-Silva, Patricia Diaz, Carlos Godoy-Guzmán, Hugo Cardenas, and Pedro A. Orihuela. "2-Methoxyoestradiol impairs mouse embryo implantation via F-spondin." Reproduction, Fertility and Development 31, no. 4 (2019): 689. http://dx.doi.org/10.1071/rd18114.
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The anti-implantation effects of high oestradiol (E2) concentrations could be mediated by E2 metabolites. Herein, we examined whether 2-methoxyoestradiol (2ME) impairs embryo implantation via its target protein F-spondin. Mice on Day 3 of pregnancy were treated with E2 concomitantly with the cathecol-O-methyl transferase inhibitor OR486 and the number of implanted embryos was recorded 5 days later. The effect of 2ME or 4-methoxyoestradiol (4ME) on embryo implantation was also investigated. Plasma and uterine levels of 2ME were measured 0.5, 1 or 3h after E2 treatment while the mRNA for spondin 1 (Spon1) and F-spondin were determined in the uterus 3, 6, 12 or 24h after 2ME treatment. Finally, the effect of a neutralising F-spondin antibody on the anti-implantation effect of 2ME was explored. OR486 blocked the anti-implantation effect of E2; 2ME, but not 4ME, affected embryo implantation. The 2ME concentration was increased after 0.5 and 1h in plasma and 3h in uterine fluid following E2 treatment. 2ME increased levels of Spon1 at 12 and 24h although F-spondin was increased at 12h. F-spondin antibody blocked the effect of 2ME on embryo implantation. We conclude that 2ME impairs mouse embryo implantation via activation of F-spondin in the uterus.
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Raef, Behnaz, Masoud Maleki, and Reza Ferdousi. "Computational prediction of implantation outcome after embryo transfer." Health Informatics Journal 26, no. 3 (December 12, 2019): 1810–26. http://dx.doi.org/10.1177/1460458219892138.
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The aim of this study is to develop a computational prediction model for implantation outcome after an embryo transfer cycle. In this study, information of 500 patients and 1360 transferred embryos, including cleavage and blastocyst stages and fresh or frozen embryos, from April 2016 to February 2018, were collected. The dataset containing 82 attributes and a target label (indicating positive and negative implantation outcomes) was constructed. Six dominant machine learning approaches were examined based on their performance to predict embryo transfer outcomes. Also, feature selection procedures were used to identify effective predictive factors and recruited to determine the optimum number of features based on classifiers performance. The results revealed that random forest was the best classifier (accuracy = 90.40% and area under the curve = 93.74%) with optimum features based on a 10-fold cross-validation test. According to the Support Vector Machine-Feature Selection algorithm, the ideal numbers of features are 78. Follicle stimulating hormone/human menopausal gonadotropin dosage for ovarian stimulation was the most important predictive factor across all examined embryo transfer features. The proposed machine learning-based prediction model could predict embryo transfer outcome and implantation of embryos with high accuracy, before the start of an embryo transfer cycle.
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Tvrdonova, Katerina, Silvie Belaskova, Tatana Rumpikova, Alice Malenovska, David Rumpik, Alena Myslivcova Fucikova, and Frantisek Malir. "Differences in Morphokinetic Parameters and Incidence of Multinucleations in Human Embryos of Genetically Normal, Abnormal and Euploid Embryos Leading to Clinical Pregnancy." Journal of Clinical Medicine 10, no. 21 (November 5, 2021): 5173. http://dx.doi.org/10.3390/jcm10215173.
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The selection of the best embryo for embryo transfer (ET) is one of the most important steps in IVF (in vitro fertilisation) treatment. Preimplantation genetic testing (PGT) is an invasive method that can greatly facilitate the decision about the best embryo. An alternative way to select the embryo with the greatest implantation potential is by cultivation in a time-lapse system, which can offer several predictive factors. Non-invasive time-lapse monitoring can be used to select quality embryos with high implantation potential under stable culture conditions. The embryo for ET can then be selected based on the determined morphokinetic parameters and morphological features, which according to our results predict a higher implantation potential. This study included a total of 1027 morphologically high-quality embryos (552 normal and 475 abnormal PGT-tested embryos) from 296 patients (01/2016–06/2021). All embryos were cultivated in a time-lapse incubator and PGT biopsy of trophectoderm cells on D5 or D6 was performed. Significant differences were found in the morphological parameters cc2, t5 and tSB and the occurrence of multinucleations in the stage of two-cell and four-cell embryos between the group of genetically normal embryos and abnormal embryos. At the same time, significant differences in the morphological parameters cc2, t5 and tSB and the occurrence of multinucleations in the two-cell and four-cell embryo stage were found between the group of genetically normal embryos that led to clinical pregnancy after ET and the group of abnormal embryos. From the morphokinetic data found in the PGT-A group of normal embryos leading to clinical pregnancy, time intervals were determined based on statistical analysis, which should predict embryos with high implantation potential. Out of a total of 218 euploid embryos, which were transferred into the uterus after thawing (single frozen embryo transfer), clinical pregnancy was confirmed in 119 embryos (54.6%). Our results show that according to the morphokinetic parameters (cc2, t5, tSB) and the occurrence of multinucleations during the first two cell divisions, the best euploid embryo for ET can be selected with high probability.
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Fadhil, Salwa, Mohammad Selman, and Manal Al-Obaidi. "EMBRYO GLUE AND CLINICAL PREGNANCY RATES IN ICSI EMBRYO TRANSFER CYCLES: A PROSPECTIVE STUDY." Journal of Health, Medicine and Nursing 7, no. 4 (December 16, 2021): 1–12. http://dx.doi.org/10.47604/jhmn.1429.
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Purpose: One of the reasons for failed implantation after transferring good quality embryos in an intracytoplasmic sperm injection cycle is the failure of creation a viscid layer between the embryo and the endometrium. Many modifications have been made in embryo transfer medium to improve implantation and increase pregnancy rates such as adding albumin as a source of energy and adding hyaluronic acid in high concentrations such as in Embryo Glue medium: a human embryo transfer medium. To investigate whether the use of Embryo Glue had any effect on clinical pregnancy rates in intracytoplasmic sperm injection-fresh embryo transfer cycles.
Methods: A prospective study included one hundred and twenty-eight infertile Iraqi women who were selected and subjected to a stimulation protocol in an intracytoplasmic sperm injection-fresh embryo transfer cycle. All patients were considered to be eligible for embryo transfer (no visible causes could prevent implantation) and only good quality embryos were transferred to them. Those women were divided randomly into two groups according to type of embryo transfer medium: group A: Embryo Glue medium. group B: Conventional medium. Then group A was subdivided according to age into: AI (34 women with age < 35 years and represented 50.7%) AII (33 women with age ≥ 35 years and represented 49.3%) While group B was subdivided into: BI (41women with age < 35 years and represented 67.3%) BII (20 women with age ≥ 35 years and represented 32.7%).
Results: Although there was no significant difference between all groups in causes of infertility, the pregnancy rate was significantly higher in subgroup AII (18 pregnant from 33 women) while only 5 patients became pregnant from 20 patients in subgroup BII. In all women no more than four good quality embryos were transferred, and when total number of transferred embryos was significantly more in group B than group A (P=0.013), the significant increase in pregnancy rates was only observed in subgroup AII (P=0.048). Even though a highly significant difference in number of repeated implantation failure was in group A than group B (P=0.027), the pregnancy rates were significantly higher in group A (P=0.038).
Conclusion: This study concluded that using Embryo Glue has a beneficial effect on old women and increase pregnancy rates, also it has a positive effect on pregnancy rates in repeated implantation failure and increases pregnancy rates even if the women is old.
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Rajhans, R., G. S. Kumar, and G. T. Sharma. "292 EXPRESSION PROFILES OF STRESS AND METABOLIC MARKER GENES DURING IN VITRO PRODUCTION OF BUFFALO (BUBALUS BUBALIS) EMBRYOS." Reproduction, Fertility and Development 18, no. 2 (2006): 253. http://dx.doi.org/10.1071/rdv18n2ab292.
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An increased understanding of the pre-implantation embryo developmental stage, with respect to physiological interaction of embryo with its micromilieu both in vivo and in vitro, is imperative to comprehend the events of pre-implantation development.The objective of the present study was to examine the temporal expression of heat shock protein 70 (Hsp-70) and glucose transporter 1 (Glut1) genes in pre-implantation-stage buffalo embryos produced under the standard in vitro production (IVP) system. Embryos were produced from slaughterhouse ovaries employing standard in vitro embryo production protocol, and presumptive zygotes produced following IVM/IVF were cultured in vitro in mSOF under mineral oil; FCS (10%) was added at 48 h post-insemination (hpi).The time series of development at stages being zygote (18-20 hpi), 2-1 cell (48 hpi), 8-16 cell (94-96 hpi), morula (120-144 hpi), and blastocyst (168-192 hpi), pre-implantation embryos conforming to the above developmental pattern were considered as 'fast-cleaving embryos', and all the embryos that did not conform to the above developmental timing were regarded as 'slow-cleaving embryos'. Pools of immature oocytes (IM, 120), Matured oocytes (MO, 120), 8-16 cell stages (8-16, 70), morula (M, 28), and blastocyst (B, 9) were collected and prepared for total RNA isolation and RT-PCR for the specific transcripts, with �-actin as loading control. The total RNA content ranged from 2.5 to 5.0 ng per oocyte/embryo. Presence of Hsp 70 and Glut1 gene transcripts was assessed in different stages of buffalo pre-implantation embryos using primers designed from bovine Hsp 70 and Glut1 by using the OLIGO program. RT was standardized using the embryo equivalent of 1-10 oocytes/embryo as the template as described by Arcellana-Panlilio and Schultz 1993 (Methods Enzymol. 225, 303-328) with PCR conditions being 59�C and 62�C for 45 s with 39 cycles for Glut1 and Hsp 70 gene transcripts, respectively. Amplicons were subjected to restriction digestion and sequencing (Acc. No. AJ812563, AJ812564). The expression of Hsp 70 throughout pre-implantation development in the fast-cleaving embryos indicated their maternal and zygotic origin, but transcripts of the Hsp 70 gene, represented by a single 488-bp amplicon, were not detected in slow-cleaving embryos, suggesting altered zygotic expression. Glut1 expression was prominent from the 8-16 cell stage, indicating a metabolic shift from pyruvate to glucose after the pre-compaction stage. For slow-cleaving embryos, transcripts of the Glut1 gene, represented by a single 327-bp amplicon, were absent during morula- and blastocyst-stage embryos, indicating the poor developmental competence of these embryos, which morphologically appeared normal. These transcription patterns reflect the embryonic response to the in vitro culture conditions and also correlate with the embryo quality and the speed of development of the pre-implantation buffalo (Bubalus bubalis) embryos.
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Chang, T., G. I. Bondarenko, M. Durning, K. Vielhuber, M. A. Garthwaite, and T. G. Golos. "124 A THREE-DIMENSIONAL IN VITRO IMPLANTATION MODEL WITH NONHUMAN PRIMATE EMBRYOS AND EXTRACELLULAR MATRIX UNDER VARIOUS CULTURE CONDITIONS." Reproduction, Fertility and Development 20, no. 1 (2008): 142. http://dx.doi.org/10.1071/rdv20n1ab124.
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The need for blastocyst culture and post-implantation embryo research has emerged in the past few years. Our objective is to evaluate a novel in vitro model to study implantation and placenta formation in vitro with rhesus macaque embryos under various culture conditions. A novel nonhuman primate in vitro 3-D system can provide cues for implantation and interaction with the extracellular environment not available in 2-D planar models. Optimization of such a model can be tested with diverse culture environments. We developed and evaluated an in vitro 3-D implantation model utilizing IVF-derived, blastocyst-stage rhesus macaque embryos embedded in 3-D Matrigel droplets cultured with different feeder cells and media. Signs of implantation including enlargement of the embryo mass, invasion and proliferation of trophectoderm cell layers, cystic formation, and cellular outgrowths derived from the embryo were initiated within the first week post-embedding. Trophoblast structures with protrusion and branches growing from the surface of embryo implants were observed. Immunohistochemical staining for chorionic gonadotropin (CG) combined with immunoassays for CG and progesterone indicated differentiation of trophoblastic cell lineages. In addition, we found morphological factors, such as proliferation of embryonic and extraembryonic structures, as well as initiation of protrusions interacting with the extracellular matrix, to predict successful establishment of prolonged embryo development. We further evaluated effects of different types of feeder cells and media combinations, and found that a combination of BRL, Ishikawa cells, and human uterine fibroblasts, provided an optimized culture microenvironment to promote peri-implantation embryo development and hormone secretion including CG and progesterone. In conclusion, we have established a 3-D in vitro system modeling implantation initiation, and demonstrating the capability of the embryo to interact with the extracellular matrix. Further studies will facilitate the methodology of peri-implantation blastocyst culture and accelerate our understanding of nonhuman primate embryo development, with potential for insights into early pregnancy loss and related pathologies. The present study and future directions may be extended to provide retrospective views on blastocyst selection for embryo transfer in assisted reproductive technology. This study was funded by NIH grants RR000167, RR21876, and HD053926.
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Morris, D. G., P. Humpherson, H. J. Leese, and J. M. Sreenan. "Protein and energy metabolism in the pre-implantation cattle embryo." BSAP Occasional Publication 26, no. 2 (September 2001): 443–46. http://dx.doi.org/10.1017/s0263967x0003408x.
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AbstractThere is no information on the metabolism of the cattle embryo during the period from day 8 to 16 a period of greatest embryonic loss. In this study the rate of protein synthesis and phosphorylation was measured in 13 to 15 day old cattle embryos. The rate of glucose utilisation and amino acid uptake/efflux by day 14 to 16 embryos was also measured. Protein synthesis and phosphorylation activity when expressed per unit of protein decreased with increasing embryo size and age. Similarly the rate of glucose utilisation was greatest for the earlier day 14 embryos. Embryos differed in their requirement for different amino acids. The pattern of uptake/efflux was similar to that of the earlier day 7 embryo. This study suggests that the metabolic rate of cattle embryos expressed per unit of protein content tends to decrease with increasing age and size from the initial burst of activity at day 13 around the time that expansion of the embryo begins.
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Gonzalez Fernandez, Javier, Javier Moncayo Arlandi, Ana Ochando, Carlos Simon, and Felipe Vilella. "The role of extracellular vesicles in intercellular communication in human reproduction." Clinical Science 137, no. 3 (February 2023): 281–301. http://dx.doi.org/10.1042/cs20220793.
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Abstract Embryo–maternal cross-talk has emerged as a vitally important process for embryo development and implantation, which is driven by secreted factors and extracellular vesicles (EVs). The EV cargo of bioactive molecules significantly influences target cells and primes them for critical stages of reproductive biology, including embryo development, adhesion, and implantation. Recent research has suggested that EVs and their cargo represent a powerful non-invasive tool that can be leveraged to assess embryo and maternal tissue quality during assisted reproduction treatments. Here, we review the current scientific literature regarding the intercellular cross-talk between embryos and maternal tissues from fertilization to implantation, focusing on human biology and signaling mechanisms identified in animal models.
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Grasa, Patricia, Heidy Kaune, and Suzannah A. Williams. "Embryos generated from oocytes lacking complex N- and O-glycans have compromised development and implantation." REPRODUCTION 144, no. 4 (October 2012): 455–65. http://dx.doi.org/10.1530/rep-12-0084.
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Female mice generating oocytes lacking complexN- andO-glycans (double mutants (DM)) produce only one small litter before undergoing premature ovarian failure (POF) by 3 months. Here we investigate the basis of the small litter by evaluating ovulation rate and embryo development in DM (Mgat1F/FC1galt1F/F:ZP3Cre) and Control (Mgat1F/FC1galt1F/F) females. Surprisingly, DM ovulation rate was normal at 6 weeks, but declined dramatically by 9 weeks.In vitrodevelopment of zygotes to blastocysts was equivalent to Controls although all embryos from DM females lacked a normal zona pellucida (ZP) and ∼30% lacked a ZP entirely. In contrast,in vivopreimplantation development resulted in less embryos recovered from DM females compared with Controls at 3.5 days post coitum (dpc) (3.2±1.3 vs 7.0±0.6). Furthermore, only 45% of mated DM females contained embryos at 3.5 dpc. Of the preimplantation embryos collected from DM females, approximately half were morulae unlike Controls where the majority were blastocysts, indicating delayed embryo development in DM females. Post-implantation development in DM females was analysed to determine whether delayed preimplantation development affected subsequent development. In DM females at 5.5 dpc, only ∼40% of embryos found at 3.5 dpc had implanted. However, at 6.5 dpc, implantation sites in DM females corresponded to embryo numbers at 3.5 dpc indicating delayed implantation. At 9.5 dpc, the number of decidua corresponded to embryo numbers 6 days earlier indicating that all implanted embryos progress to midgestation. Therefore, a lack of complexN- andO-glycans in oocytes during development impairs early embryo development and viabilityin vivoleading to delayed implantation and a small litter.
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Kamrava, M., and M. Yin. "177HYSTEROSCOPIC BLASTOCYST IMPLANTATION A NOVEL EMBRYO TRANSFER PROCEDURE." Reproduction, Fertility and Development 16, no. 2 (2004): 210. http://dx.doi.org/10.1071/rdv16n1ab177.
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Various techniques using different types of catheters have been advocated to increase pregnancy rates while reducing side effects from the embryo transfer procedure. However, all of these techniques are ‘blind’ procedures of catheter introduction into the uterus, and the problems of ‘lost embryos’ and the occurrence of ectopic pregnancies persist. A novel hysteroscopic-guided direct embryo transfer procedure with visually directed embryo implantation was developed to improve the current ‘blind’ embryo transfer procedures by increasing chances of success while eliminating tubal pregnancies and decreasing high-order multiple pregnancies from IVF related techniques. At West Coast Infertility Medical Clinic, 57 patients with average age of 28.43±4.54 were analyzed. Stimulation method: controlled ovarian hyperstimulation was initiated with Follitropin β; (Follistim®, Organon Pharmaceuticals, Inc.). Premature endogenous gonadotropin surge (i.e. the prevention of an LH surge) was controlled with ganirelix acitate (AntagonTM, Organon Pharmaceuticals, Inc., West Orange, NJ, USA.). Oocyte retrieval was performed in an office setting under local anesthesia and mild sedation, followed by routine IVF/ICSI, IVC. By Day 5–6, up to 2 best quality blastocyst stage embryos were transferred to patient’s uterus by ‘hysteroscopic embryo implantation’ procedure: a lightweight hybrid (rigid/flexible) mini hysteroscope (Napoli, Inc., Los Angeles, CA, USA) was used for visualization of the endometrial cavity. The scope incorporates a flexible distal end of 3mm in diameter with a straight-through operating channel. In addition, the optic filter is directly connected to a light source, decreasing the weight of the scope and giving a better feel for the scope. The transfer catheter (Napoli, Inc.) is polycarbon based with a tapered tip (to 500μm), beveled to 60°. During embryo transfer procedure, the catheter tip was inserted into a depth of 1mm from the surface of the endometrium under direct hysteroscopic visualization. The loaded embryos with 10μL medium was released underneath the endometrium to produce a ‘bubble’ cushion. Luteal phase support was provided (3000IU of hCG at Day 3 and Day 6 post-retrieval, separately). Pregnancies were determined by serum hCG concentration of 5IUmL−1 or more at Day 16 post-retrieval. Thirty out of 57 (52.6%) women became pregnant. Multiple pregnancy rate was 4 out of 30 (13.3%) and comprised only of twins, and no ectopic pregnancy was found. In conclusion, a newly developed instrument and embryo transfer procedure by mechanical implantation of the embryo was achieved. By implanting the embryos, we have reduced the number of embryos that are transfered, minimized the chances of ‘losing’ embryos, and eliminated ectopic pregnancies.
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Rodrigo, Lorena, Emilia Mateu, Amparo Mercader, Ana Cristina Cobo, Vanessa Peinado, Miguel Milán, Nasser Al-Asmar, et al. "New Tools for Embryo Selection: Comprehensive Chromosome Screening by Array Comparative Genomic Hybridization." BioMed Research International 2014 (2014): 1–9. http://dx.doi.org/10.1155/2014/517125.
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The objective of this study was to evaluate the usefulness of comprehensive chromosome screening (CCS) using array comparative genomic hybridization (aCGH). The study included 1420 CCS cycles for recurrent miscarriage (n=203); repetitive implantation failure (n=188); severe male factor (n=116); previous trisomic pregnancy (n=33); and advanced maternal age (n=880). CCS was performed in cycles with fresh oocytes and embryos (n=774); mixed cycles with fresh and vitrified oocytes (n=320); mixed cycles with fresh and vitrified day-2 embryos (n=235); and mixed cycles with fresh and vitrified day-3 embryos (n=91). Day-3 embryo biopsy was performed and analyzed by aCGH followed by day-5 embryo transfer. Consistent implantation (range: 40.5–54.2%) and pregnancy rates per transfer (range: 46.0–62.9%) were obtained for all the indications and independently of the origin of the oocytes or embryos. However, a lower delivery rate per cycle was achieved in women aged over 40 years (18.1%) due to the higher percentage of aneuploid embryos (85.3%) and lower number of cycles with at least one euploid embryo available per transfer (40.3%). We concluded that aneuploidy is one of the major factors which affect embryo implantation.
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Hernández-Vargas, Purificación, Manuel Muñoz, and Francisco Domínguez. "Identifying biomarkers for predicting successful embryo implantation: applying single to multi-OMICs to improve reproductive outcomes." Human Reproduction Update 26, no. 2 (February 25, 2020): 264–301. http://dx.doi.org/10.1093/humupd/dmz042.
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Abstract BACKGROUND Successful embryo implantation is a complex process that requires the coordination of a series of events, involving both the embryo and the maternal endometrium. Key to this process is the intricate cascade of molecular mechanisms regulated by endocrine, paracrine and autocrine modulators of embryonic and maternal origin. Despite significant progress in ART, implantation failure still affects numerous infertile couples worldwide and fewer than 10% of embryos successfully implant. Improved selection of both the viable embryos and the optimal endometrial phenotype for transfer remains crucial to enhancing implantation chances. However, both classical morphological embryo selection and new strategies incorporated into clinical practice, such as embryonic genetic analysis, morphokinetics or ultrasound endometrial dating, remain insufficient to predict successful implantation. Additionally, no techniques are widely applied to analyse molecular signals involved in the embryo–uterine interaction. More reliable biological markers to predict embryo and uterine reproductive competence are needed to improve pregnancy outcomes. Recent years have seen a trend towards ‘omics’ methods, which enable the assessment of complete endometrial and embryonic molecular profiles during implantation. Omics have advanced our knowledge of the implantation process, identifying potential but rarely implemented biomarkers of successful implantation. OBJECTIVE AND RATIONALE Differences between the findings of published omics studies, and perhaps because embryonic and endometrial molecular signatures were often not investigated jointly, have prevented firm conclusions being reached. A timely review summarizing omics studies on the molecular determinants of human implantation in both the embryo and the endometrium will help facilitate integrative and reliable omics approaches to enhance ART outcomes. SEARCH METHODS In order to provide a comprehensive review of the literature published up to September 2019, Medline databases were searched using keywords pertaining to omics, including ‘transcriptome’, ‘proteome’, ‘secretome’, ‘metabolome’ and ‘expression profiles’, combined with terms related to implantation, such as ‘endometrial receptivity’, ‘embryo viability’ and ‘embryo implantation’. No language restrictions were imposed. References from articles were also used for additional literature. OUTCOMES Here we provide a complete summary of the major achievements in human implantation research supplied by omics approaches, highlighting their potential to improve reproductive outcomes while fully elucidating the implantation mechanism. The review highlights the existence of discrepancies among the postulated biomarkers from studies on embryo viability or endometrial receptivity, even using the same omic analysis. WIDER IMPLICATIONS Despite the huge amount of biomarker information provided by omics, we still do not have enough evidence to link data from all omics with an implantation outcome. However, in the foreseeable future, application of minimally or non-invasive omics tools, together with a more integrative interpretation of uniformly collected data, will help to overcome the difficulties for clinical implementation of omics tools. Omics assays of the embryo and endometrium are being proposed or already being used as diagnostic tools for personalised single-embryo transfer in the most favourable endometrial environment, avoiding the risk of multiple pregnancies and ensuring better pregnancy rates.
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Hardy, K., and S. Spanos. "Growth factor expression and function in the human and mouse preimplantation embryo." Journal of Endocrinology 172, no. 2 (February 1, 2002): 221–36. http://dx.doi.org/10.1677/joe.0.1720221.
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There is increasing evidence that even before implantation, human development is regulated by embryonically and maternally derived growth factors. Studies in other mammalian species have shown that growth factors and their receptors are expressed by the preimplantation embryo and the reproductive tract. Furthermore, a number of growth factors have been shown to affect rate of embryo development, the proportion of embryos developing to the blastocyst stage, blastocyst cell number, metabolism and apoptosis. Growth factor ligands and receptors are also expressed in human embryos and the maternal reproductive tract, and supplementation of culture medium with exogenous growth factors affects cell fate, development and metabolism of human embryos in vitro. Autocrine, paracrine and endocrine pathways that may operate within the embryo and between the embryo and the reproductive tract before implantation are proposed.
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Sevar, Raymond. "Chocolate and Embryo Implantation." Homoeopathic Links 28, no. 04 (December 16, 2015): 249–51. http://dx.doi.org/10.1055/s-0035-1566242.
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Wang, X. J., G. M. Warnes, R. J. Norman, C. A. Kirby, A. M. Clark, and C. D. Matthews. "Embryo viability and implantation." Human Reproduction 9, no. 2 (February 1994): 184–85. http://dx.doi.org/10.1093/oxfordjournals.humrep.a138475.
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Liu, Weimin, Ziru Niu, Qian Li, Ronald T. K. Pang, Philip C. N. Chiu, and William Shu-Biu Yeung. "MicroRNA and Embryo Implantation." American Journal of Reproductive Immunology 75, no. 3 (December 28, 2015): 263–71. http://dx.doi.org/10.1111/aji.12470.
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Simón, Carlos, Carlos Moreno, Jose Remohı́, and Antonio Pellicer. "Cytokines and embryo implantation." Journal of Reproductive Immunology 39, no. 1-2 (August 1998): 117–31. http://dx.doi.org/10.1016/s0165-0378(98)00017-5.
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Lefèvre, Pavine L. C., Marie-France Palin, Gary Chen, Gustavo Turecki, and Bruce D. Murphy. "Polyamines Are Implicated in the Emergence of the Embryo from Obligate Diapause." Endocrinology 152, no. 4 (February 8, 2011): 1627–39. http://dx.doi.org/10.1210/en.2010-0955.
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Abstract Embryonic diapause is a poorly understood phenomenon of reversible arrest of embryo development prior to implantation. In many carnivores, such as the mink (Neovison vison), obligate diapause characterizes each gestation. Embryo reactivation is controlled by the uterus by mechanisms that remain elusive. Because polyamines are essential regulators of cell proliferation and growth, it was hypothesized that they trigger embryo reactivation. To test this, mated mink females were treated with α-difluoromethylornithine, an inhibitor of ornithine decarboxylase 1, the rate-limiting enzyme in polyamine biosynthesis, or saline as a control during the first 5 d of reactivation. This treatment induced polyamine deprivation with the consequence of rearrest in embryo cell proliferation. A mink trophoblast cell line in vitro subjected to α-difluoromethylornithine treatment likewise displayed an arrest in cell proliferation, morphological changes, and intracellular translocation of ornithine decarboxylase 1 protein. The arrest in embryo development deferred implantation for a period consistent with the length of treatment. Successful implantation and parturition ensued. We conclude that polyamine deprivation brought about a reversible rearrest of embryo development, which returned the mink embryo to diapause and induced a second delay in embryo implantation. The results are the first demonstration of a factor essential to reactivation of embryos in obligate diapause.
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Li, Geng, Karam Khateeb, Erin Schaeffer, Bao Zhang, and Hasan Khatib. "Genes of the transforming growth factor-beta signalling pathway are associated with pre-implantation embryonic development in cattle." Journal of Dairy Research 79, no. 3 (June 12, 2012): 310–17. http://dx.doi.org/10.1017/s0022029912000210.
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One of the main factors affecting cattle fertility is pre-implantation development of the bovine embryo, which is a complex process regulated by various signal-transduction pathways. The transforming growth factor-β (TGF-β) signalling system, which is responsible for many biological processes including cell proliferation, differentiation and apoptosis, also is involved in embryo development. We hypothesized that altered expression of TGF-β genes in pre-implantation bovine embryos is associated with morphological abnormalities of these embryos. To test this hypothesis, we produced embryos in vitro and classified them at the blastocyst stage as either normally developed blastocysts or degenerates (growth-arrested embryos). The expression patterns of 25 genes from the TGF-β pathway were assessed using quantitative real time PCR. Ten genes showed differential expression between the two embryo groups, four genes displayed similar expressional profiles, and 11 genes had no detectable expression. An altered expression profile was statistically significant for 10 of the 14 expressed genes, and all were up-regulated in degenerate embryos vs. blastocysts. Furthermore, genomic association analysis of the cows from which embryos were produced revealed a significant association of ID3 and BMP4 polymorphisms—two of the most significant differentially expressed genes—with fertilization rate and blastocyst rate, respectively. Taken together, we conclude that TGF-β pathway genes, especially BMP4 and ID3 play a vital function in the regulation of pre-implantation embryo development at both embryo and maternal levels. Hence, these genes may be suitable as genetic markers for embryo development and fertility in cattle.
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Tsantsaridou, Angeliki, Olga Tsantsaridou, Maria Asprogianni, Spyros Potamianos, Kyriakos Spiliopoulos, Nikolaos Tsilimingas, Ioannis Skoularigis, Sophia Kalantaridou, and Georgios Valsamakis. "Nutritional Impact on Embryo Implantation. Review of the Literature." Journal of Nutritional Health & Food Science 8, no. 2 (October 23, 2020): 1–12. http://dx.doi.org/10.15226/jnhfs.2020.001178.
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The implantation procedure involves a “biofilmic” mechanism of organism protection against threat. Immune-inflammatory procedures expressed by nutritional, molecular and biochemical factors related to homeostasis ensure successful incorporation of blastocyst in the uterine ecology. The feeding chain of the host mother, the embryo and their microbiota modifies the human intrinsic environment, hormone levels, fetal characteristics and growth. This study was conducted to provide information about the effects of diet on implantation quality in an attempt to therapeutically synchronize the development of blastocyst within the nourishing mothers. The issue is generalized to all “windows of alien implantations”. The formation of life (: fertilization) and its development is a consequence of biochemical reactions (: mitochondrial cycle, replication, regeneration, oxidation, apoptosis, etc.). Homeostasis is called the body’s ability to keep its internal ecosystem stable despite exo orendogenous changes. The whole process involves energy consumption, operative coordination of various organs, especially between the nervous and endocrine systems. Instability of homeostasispredisposesto“miscarriages”. Key elements that enhance acid-base equilibrium, oxygen demands and indirectly implantation success are proteins, trace minerals, vitamins, omega-3 fatty acids, enzymes, fruit and vegetable phytonutrients, probiotics. Restriction of processed or foods polluted with endocrine disrupting chemicals and microbes, sugar, saturated and trans fatty acids prevents genetic deterioration, ageing and troublesome implantations. Balanced diet, digestion and hormone-dependent metabolism identifies the efficiency of our reproductive system and homeostatic implantation procedure. Key words: Implantation; Nutrition; Diet; Microbiota; Oxidative Stress; Inflammation;Immunity.
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Bueno, Aline, Yuri Karen Sinzato, Gustavo Tadeu Volpato, Franciane Quintanilha Gallego, Felipe Perecin, Tiago Rodrigues, and Débora Cristina Damasceno. "Severity of prepregnancy diabetes on the fetal malformations and viability associated with early embryos in rats†." Biology of Reproduction 103, no. 5 (September 1, 2020): 938–50. http://dx.doi.org/10.1093/biolre/ioaa151.
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Abstract Preexisting/pregestational diabetes enhances the risk of birth defects. Several factors have been involved during the implantation process, such as cytokines (granulocyte-macrophage–colony-stimulating factor [GM-CSF]). The objective was to evaluate the effects of two levels of diabetes on the redox status of preimplantation embryos during the implantation process to comprehend how both are involved in embryo and fetal viability against maternal diabetes. Female Sprague–Dawley rats received streptozotocin at birth (mild diabetes [MD]) or at adulthood (severe diabetes [SD]) to obtain two experimental diabetes intensities. After confirming the diabetic status, the nondiabetic and diabetic groups were mated around day 110 of life. At gestational day (GD) 21, fetuses were assessed for viability and malformations and ovaries for embryo loss before implantation. Other pregnant nondiabetic and diabetic rats were sacrificed at GD2–4 for maternal and preimplantation embryo oxidative stress markers, maternal serum insulin, uterine fluid GM-CSF, and preimplantation embryo morphological analysis. MD and SD caused abnormal redox levels, lower GM-CSF and insulin levels during the preimplantation period, and embryonic loss before implantation. SD caused lower fetal viability and higher fetal malformation percentages at GD21. The SD dam-derived preimplantation embryos presented lower glutathione levels and higher thiobarbituric acid reactive substances concentration at GD3 and an increased frequency of abnormal preimplantation embryos at GD4. In conclusion, preexisting diabetes leads to complications in the implantation process. Furthermore, maternal oxidative stress and other metabolic changes alter the redox state and morphological structure of preimplantation embryos, contributing to damaged growth and development in late pregnancy.
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Calderari, Sophie, Nathalie Daniel, Eve Mourier, Christophe Richard, Michele Dahirel, Franck Lager, Carmen Marchiol, et al. "Metabolomic differences in blastocoel and uterine fluids collected in vivo by ultrasound biomicroscopy on rabbit embryos†." Biology of Reproduction 104, no. 4 (January 18, 2021): 794–805. http://dx.doi.org/10.1093/biolre/ioab005.
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Abstract The success of embryo development and implantation depends in part on the environment in which the embryo evolves. However, the composition of the uterine fluid surrounding the embryo in the peri-implantation period remains poorly studied. In this work, we aimed to develop a new strategy to visualize, collect, and analyze both blastocoelic liquid and juxta-embryonic uterine fluid from in vivo peri-implantation rabbit embryos. Using high-resolution ultrasound biomicroscopy, embryos were observed as fluid-filled anechoic vesicles, some of which were surrounded by a thin layer of uterine fluid. Ultrasound-guided puncture and aspiration of both the blastocoelic fluid contained in the embryo and the uterine fluid in the vicinity of the embryo were performed. Using nuclear magnetic resonance spectroscopy, altogether 24 metabolites were identified and quantified, of which 21 were detected in both fluids with a higher concentration in the uterus compared to the blastocoel. In contrast, pyruvate was detected at a higher concentration in blastocoelic compared to uterine fluid. Two acidic amino acids, glutamate and aspartate, were not detected in uterine fluid in contrast to blastocoelic fluid, suggesting a local regulation of uterine fluid composition. To our knowledge, this is the first report of simultaneous analysis of blastocoelic and uterine fluids collected in vivo at the time of implantation in mammals, shedding new insight for understanding the relationship between the embryo and its local environment at this critical period of development.
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Bejarano, Ignacio, Mónica Dorado-Silva, Helia Sarmiento-Soto, Nuria Álvarez-Sánchez, Patricia Judith Lardone, Juan Miguel Guerrero, Pascual Sánchez-Martín, and Antonio Carrillo-Vico. "GPX3 Overexpression in Cumulus Cells Entails a Poor Prognosis for Uterine Implantation of Morphotype A Embryos." Biology 11, no. 9 (September 16, 2022): 1361. http://dx.doi.org/10.3390/biology11091361.
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Morphological embryo quality is an accurate prognostic tool for the success of assisted reproduction implantation, although complete certainty cannot be guaranteed. The transcriptome of the cumulus cells could be monitored as a faithful reflex of the physiological state of the oocytes, given the molecular crosstalk between both types of cells. Here, we compare the expression of specific genes related to oocyte competence, such as hyaluronic acid synthase 2 (HAS2), cell division control protein 42 (CDC42), connexin 43 (CX43), and glutathione peroxidase 3 (GPX3), in cumulus cells from implanted versus non-implanted embryos in 25 women, using RT-qPCR. After embryo transfer, two cohorts were differentiated: the pregnant group (women with the implantation of 100% of embryos transferred) versus the non-pregnant group (with an absence of embryo implantation), aiming to compare the possible differential expression of the selected genes in the cumulus cells of embryos from each group. HAS2, CDC42 and CX43 did not reveal differential expression between the two cohorts. However, GPX3 showed significantly reduced expression in the cumulus belonging to the pregnant group. Interestingly, even cumulus cells belonging only to morphotype A embryos showed a significantly lower expression of GPX3 in the pregnancy group. GPX3 overexpression in cumulus cells could be a poor prognostic indicator of implantation, discriminating beyond the capacity of the morphokinetic score. Unveiling the cumulus transcriptome could improve successful implantation in assisted reproduction treatments.
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Ding, Nai-Zheng, Cheng-Qiang He, and Zeng-Ming Yang. "Quantification of basigin mRNA in mouse oocytes and preimplantation embryos by competitive RT-PCR." Zygote 10, no. 3 (August 2002): 239–43. http://dx.doi.org/10.1017/s0967199402002319.
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Basigin is a member of the immunoglobulin superfamily and a key molecule related to mouse blastocyst implantation. Whether preimplantation mouse embryos express basigin mRNA is still unknown. The aim of this study was to use a quantitative competitive polymerase chain reaction to assess quantitatively the levels of basigin mRNA in mouse oocyte and preimplantation embryos. Basigin mRNA was detected in the oocyte and all the stages of preimplantation embryos. The levels of basigin mRNA were 0.0606 ± 0.0282 in the oocyte, 0.0102 ± 0.0036 in the zygote, 0.0007 ± 0.0003 in the 2-cell embryo, 0.0031 ± 0.0017 in the 4-cell embryo, 0.0084 ± 0.0024 in the 8-cell embryo, 0.0537 ± 0.0121 in the morula and 0.0392 ± 0.0161 attomoles in the blastocyst, respectively. The levels of basigin mRNA in the oocyte, morula and blastocyst were significantly higher than those in the zygote and embryos at the 2-cell, 4-cell and 8-cell stages. The high level of basigin expression in the blastocyst may play a role during embryo implantation.
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Gu, Shengchen, Xupeng Zang, Lei Jiang, Ting Gu, Fanming Meng, Sixiu Huang, Gengyuan Cai, Zicong Li, Zhenfang Wu, and Linjun Hong. "Differential MicroRNA Expression in Porcine Endometrium Related to Spontaneous Embryo Loss during Early Pregnancy." International Journal of Molecular Sciences 23, no. 15 (July 24, 2022): 8157. http://dx.doi.org/10.3390/ijms23158157.
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Litter size is an important indicator to measure the production capacity of commercial pigs. Spontaneous embryo loss is an essential factor in determining sow litter size. In early pregnancy, spontaneous embryo loss in porcine is as high as 20–30% during embryo implantation. However, the specific molecular mechanism underlying spontaneous embryo loss at the end of embryo implantation remains unknown. Therefore, we comprehensively used small RNA sequencing technology, bioinformatics analysis, and molecular experiments to determine the microRNA (miRNA) expression profile in the healthy and arresting embryo implantation site of porcine endometrium on day of gestation (DG) 28. A total of 464 miRNAs were identified in arresting endometrium (AE) and healthy endometrium (HE), and 139 differentially expressed miRNAs (DEMs) were screened. We combined the mRNA sequencing dataset from the SRA database to predict the target genes of these miRNAs. A quantitative real-time PCR assay identified the expression levels of miRNAs and mRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed on differentially expressed target genes of DEMs, mainly enriched in epithelial development and amino acids metabolism-related pathways. We performed fluorescence in situ hybridization (FISH) and the dual-luciferase report gene assay to confirm miRNA and predicted target gene binding. miR-205 may inhibit its expression by combining 3′-untranslated regions (3′ UTR) of tubulointerstitial nephritis antigen-like 1 (TINAGL1). The resulting inhibition of angiogenesis in the maternal endometrium ultimately leads to the formation of arresting embryos during the implantation period. This study provides a reference for the effect of miRNA on the successful implantation of pig embryos in early gestation.
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Parashchuk, V. Y., A. S. Lutsky, and N. G. Gryshchenko. "The effectiveness of different protocols of preparation of the endometrium when transferring vitrified/warmed embryos." HEALTH OF WOMAN, no. 2(118) (March 29, 2017): 30–32. http://dx.doi.org/10.15574/hw.2017.118.30.
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Currently, there is a tendency toward increasing usage of criocycles in programs of in vitro fertilization. This approach allows to achieve pregnancy as well as prevent the development of ovarian hyperstimulation syndrome and utilize the pre-implantation genetic diagnostics. The objective: to improve the efficiency of in vitro fertilization treatment cycles with transferring of cryopreserved/warmed embryos into the uterus. Patients and methods. The study of 824 treatment cycles (in natural menstrual cycle, in cycle with hormone replacement therapy, after egg donation, in natural cycle without embryo transfer in «fresh» cycle, in cycle with hormone replacement therapy without embryo transfer in «fresh» cycle). Vitrification and cryopreservation method. Results. The analysis of the study results has shown that the implantation rate of frozen embryos in the natural cycle is higher than in the cycle with hormone replacement therapy. The implantation rate of frozen embryos after the use of agonist gonadotropin-releasing hormone as a trigger of final maturation of the agonist is higher than that of human chorionic gonadotropin, which allows us to consider vitrification as an effective tool that provides great flexibility of conducting controlled ovarian stimulation cycles and prevention of ovarian hyperstimulation syndrome. Conclusion. The effectiveness of frozen embryo transfer protocols gives us grounds to assert that the optimum cycle for the transfer is a cycle without stimulation. Key words: in vitro fertilization, the endometrium, frozen embryo implantation.
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Govindasamy, Niraimathi, Binyamin Duethorn, Hatice O. Oezgueldez, Yung S. Kim, and Ivan Bedzhov. "Test-tube embryos - mouse and human development in vitro to blastocyst stage and beyond." International Journal of Developmental Biology 63, no. 3-4-5 (2019): 203–15. http://dx.doi.org/10.1387/ijdb.180379ib.
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Mammalian embryogenesis is intrauterine and depends on support from the maternal environment. Therefore, in order to directly study and manipulate early mouse and human embryos, fine-tuned culture conditions have to be provided to maintain embryo growth in vitro. Over time, the establishment and implementation of embryo culture methods have come a long way, initially enabling the development of few pre-implantation stages, expanding later to support in vitro embryogenesis from fertilization until blastocyst and even ex utero development beyond the implantation stages. Designing culture conditions that enable near physiological development of early embryos without maternal input, especially during the peri- and post-implantation stages, requires overcoming numerous experimental challenges, and it is still far from optimal. Nevertheless, embryo culture methods are an essential cornerstone of both assisted reproductive technologies and basic research, and these methods provide a platform to understand life’s greatest miracle – the development of a new organism.
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Maganha, Juliana, Evelise de Souza Rocha, Marcos Antônio Fernandes Brandão, Vera Maria Peters, and Martha de Oliveira Guerra. "Embryo development alteration in rats treated with lapachol." Brazilian Archives of Biology and Technology 49, no. 6 (November 2006): 927–34. http://dx.doi.org/10.1590/s1516-89132006000700010.
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Lapachol, a naphthoquinone extracted from plants of the genus Tabebuia (family Bignoneaceae), showed multiple therapeutic activities. Pregnant Wistar rats were treated with Lapachol from the 1st to the 4th (pre-implantation period) and from 5th to 7th (implantation period) post insemination day (PID). Mothers were sacrificed on the 5th or on the15th PID. Number of corpora lutea, preimplantation embryo, blastocysts, live and dead fetuses and resorptions were counted. There were no signs of maternal toxicity. The number and the morphology of embryos, during oviduct development (pre-implantation period), did not seem to be affected by this drug, but during the implantation period, lapachol was toxic causing the death of embryos and intrauterine growth retardation.
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Ridha, M. T., Fan Bigin, and W. R. Dukelow. "Implantation of double frozen hamster embryos following embryo transfer." Theriogenology 23, no. 1 (January 1985): 221. http://dx.doi.org/10.1016/0093-691x(85)90127-x.
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Imai, Hiroyuki, Tokuko Iwamori, Ken Takeshi Kusakabe, Yasuo Kiso, Etsuro Ono, and Kiyoshi Kano. "Hyper-polyploid embryos survive after implantation in mice." Zygote 28, no. 3 (March 10, 2020): 247–49. http://dx.doi.org/10.1017/s0967199420000064.
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SummaryPolyploids generated by natural whole genome duplication have served as a dynamic force in vertebrate evolution. As evidence for evolution, polyploid organisms exist generally, however there have been no reports of polyploid organisms in mammals. In mice, polyploid embryos under normal culture conditions normally develop to the blastocyst stage. Nevertheless, most tetraploid embryos degenerate after implantation, indicating that whole genome duplication produces harmful effects on normal development in mice. Most previous research on polyploidy has mainly focused on tetraploid embryos. Analysis of various ploidy outcomes is important to comprehend the effects of polyploidization on embryo development. The purpose of this present study was to discover the extent of the polyploidization effect on implantation and development in post-implantation embryos. This paper describes for the first time an octaploid embryo implanted in mice despite hyper-polyploidization, and indicates that these mammalian embryos have the ability to implant, and even develop, despite the harmfulness of extreme whole genome duplication.
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Yang, Yi, Jia-Peng He, and Ji-Long Liu. "Cell–Cell Communication at the Embryo Implantation Site of Mouse Uterus Revealed by Single-Cell Analysis." International Journal of Molecular Sciences 22, no. 10 (May 13, 2021): 5177. http://dx.doi.org/10.3390/ijms22105177.
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As a crucial step for human reproduction, embryo implantation is a low-efficiency process. Despite rapid advances in recent years, the molecular mechanism underlying embryo implantation remains poorly understood. Here, we used the mouse as an animal model and generated a single-cell transcriptomic atlas of embryo implantation sites. By analyzing inter-implantation sites of the uterus as control, we were able to identify global gene expression changes associated with embryo implantation in each cell type. Additionally, we predicted signaling interactions between uterine luminal epithelial cells and mural trophectoderm of blastocysts, which represent the key mechanism of embryo implantation. We also predicted signaling interactions between uterine epithelial-stromal crosstalk at implantation sites, which are crucial for post-implantation development. Our data provide a valuable resource for deciphering the molecular mechanism underlying embryo implantation.