4th Igenomix
APAC Symposium

Abstract

According to WHO 2020, there are about 48 million infertility couples in the world currently. In recent years, assisted reproductive technology has been developed strongly and achieved significant milestones. According to Koot 2012, however, there are still about 8-10% of couples with recurrent implantation failure (RIF). One of the reasons, even with the good quality embryo or an euploid embryo transfer, is the abnormal endometrium or related to the implantation window. Thus, it is necessary to use molecular diagnostic tests including ERA, EMMA and ALICE to provide information on the implantation window of the endometrium, microbiome profile and chronic endometritis. At the ART Center of Tam Anh General Hospital in Hanoi, Vietnam, we have applied this trio-tests to patients who have RIF. From March 2020 to February 2022, 17 patients with recurrent implant failures were concurrently tested for ERA, EMMA and ALICE. In 13 patients had embryo transfer after the test, 6 patients got pregnant, in which 1 patient had five previous failures. This is a promising result, opening up hope for patients with RIF. However, the advantage of these tests needs more evidence to confirm.

Biography

Graduating from Hanoi Medicine University in Obstetric Surgery in 1990, Assoc. Prof. Le Hoang worked at the National Hospital of Obstetrics and Gynecology (NHOG). In 1998, he was one of the first Northern doctors sent to Thailand to learn IVF techniques. He took a Gynecology and Obstetric intern course in France between 2001 and 2002. From 2011 to 2017, he was the Vice Director of the ART Center of NHOG and became the Vice Director of NHOG from 2013 to 2017.

He has been the Director of the ART Center, Tam Anh General Hospital, since 2017 until now. He is also the Vice President of Ha Noi ART Association, the honorary member of the French College of Obstetricians and Gynecologist (CNGOF), a member of the Executive Committee of Vietnam Association of Obstetricians and Gynecologist, Secretary of Vietnam Society for Reproductive Medicine, and the member of American Society of Reproductive Medicine.

Publications

1. First author: Pregnancy Outcomes Following the First Frozen Blastocyst Transfer Among Women Aged Less Than 35 Years Old: A Retrospective Cohort Study, Fertility & Reproduction. 2021; Vol. 03, No. 04, pp. 143-149
2. Co-author: Erectile Dysfunction and Infertility: A Pilot Study in Male Partners of Infertile Couples, Nephro-Urology Monthly. 2021; 13(3):e112638.
3. First author: Comparative Effectiveness of Mild or Conventional GnRH-Antagonist Protocols for Ovarian Stimulation in Poor Responders (Poseidon Group 4), Frontiers in Reproductive Health. 2020; doi: 10.3389/frph.2020.606036
4. Co-author: Preimplantation Genetic Testing of Aneuploidy by Next Generation Sequencing: Association of Maternal Age and Chromosomal Abnormalities of Blastocyst, Open Access Macedonian Journal of Medical Sciences. 2019; 7(24): 4427–4431.
5. Co-author: Short Tandem Repeats Used in Preimplantation Genetic Testing of Β-Thalassemia: Genetic Polymorphisms For 15 Linked Loci in the Vietnamese Population, Open Access Macedonian Journal of Medical Sciences. 2019; 7(24):4383-4388.

Abstract

Endometrial receptivity issues represent a potential source of implantation failure. The aim of this clinical study was to evaluate our experience with the endometrial receptivity array (ERA) among patients with a history of repetitive implantation failure.
In recent years, an efficacy of the ERA in Korea has been discussed and debated among physicians. So, I investigated whether the contribution of the endometrial factor could be identified with the ERA test and if actionable results can lead to improved outcomes such pregnancy rate increase.
Today, through a care review, we would like to discuss the practical application of ERA.

Biography

• ~2005: School of Medicine, Seoul National University
• ~2010: M.D., Department of Obstetrics / Gynecology, College of Medicine, Seoul National University
• 2013~Present: Physician, Chief of Fertility Preservation Center, Maria Fertility Hospital in Seoul
• Academic Committee in Korean Society for Reproductive Medicine (KSRM) / Korean Society for Assisted Reproduction (ASAR) / Korean Society for Fertility Preservation (KSFP)
• General Affairs Director, Korean Society for Reproductive Immunology

Awards

1. Best Poster Presentation award (2017) : KSFP (Korean Society for Fertility Preservation)

Publications

1. In vitro maturation: Clinical applications. Lim KS, Chae SJ, Choo CW, Ku YH, Lee HJ, Hur CY, Lim JH, Lee WD. Clin Exp Reprod Med. 2013 Dec;40(4):143-7. doi: 10.5653/cerm.2013.40.4.143. Epub 2013 Dec 31. PMID: 24505559
2. Intravenous immunoglobulin G in women with reproductive failure: The Korean Society for Reproductive Immunology practice guidelines. Sung N, Han AR, Park CW, Park DW, Park JC, Kim NY, Lim KS, Shin JE, Joo CW, Lee SE, Kim JW, Lee SK; IVIG Task Force, Korean Society for Reproductive Immunology.

Abstract

The difficult patients in ART include Poseidon group 4, RIF, POI, POR and AMA (advanced maternal age). AMA is a proverbial challenge that compromises the ART success rate. By using the ERA test, we discovered that displacement of WOI was greater than 50% in patients with AMA and RIF, and the receptive ERA decreased as the patient’s age increased. The pregnancy rate achieved 71% (37/52) following the readjustment of WOI after the ERA-FET. Ongoing pregnancy rate in the matched population of ERA-FET cycles vs. Non ERA-FET cycles was 52.2% vs.37.7% (p<0.001), respectively. The PGT-A is able to identify the euploid blastocyst for FET to reduce miscarriage rate. Some add on treatments such as Atosiban pre-treatment before FET may be beneficial in patients with AMA. Calcium ionophore can improve fertilization rate in severe male factor infertility. The extended culture of embryo from Day3 to Day5 followed by FET could optimize pregnancy outcomes. Adjuvant therapy with growth hormone (GH) may enhance pregnancy rate in poor responders. Early detection of chronic endometritis, endometrial polyps and sub-mucous fibroid by hysteroscopy is important before FET.

Biography

• 1969-1976 : M.D., School of Medicine, Taipei Medical University, Taiwan.
• 1980-1981 : Master of Public Health (MPH) in Maternal and Child Health, School of Public Health, Harvard University, Boston, MA, U.S.A.
• 1981-1983 : Research Fellow, Fertility and Endocrinology, Department of Obstetrics and Gynaecology, Brigham and Women’s Hospital, Harvard Medical School, Boston, U.S.A
• 1994-2017 : Chairman, Department of Obstetrics and Gynaecology, Taipei Medical University
• 1994-2019 : Director, Center for Reproductive Medicine, Taipei Medical University Hospital
• 1996-1998 : President, Taiwan Society for Reproductive Medicine (TSRM)
• 1993-2000 : Vice superintendent, Taipei Medical University Hospital, Taipei
• 2004-2013 : Dean, College of Medicine, Taipei Medical University
• 2008-2014 : President, Pacific Society for Reproductive Medicine(PSRM)
• 2013-2015 : President, Taiwan Society for Mitochondrial Research Medicine(TSMRM)
• 2016-2018 : President, Asia Pacific Initiative on Reproduction(ASPIRE)
• 2021-2025 : Secretary General, Asia Pacific Initiative on Reproductive (ASPIRE)

Awards

1. Lifetime achievement award of The Global Chinese Association for Reproductive Medicine (GCARM) (2012)
2. Prized Poster, European Society of Human Reproduction & Embryology (ESHRE) (2001, 2003, 2007)
3. Star Award, American Society for Reproductive Medicine (ASRM) (2010, 2014, 2015, 2017, 2018, 2021)

Publications

1. Yi-Xuan Lee, Chi-Huang Chen, Shyr-Yeu Lin, Yi-Hui Lin, Tzeng CR. Adjusted mitochondrial DNA quantification in human embryos may not applicable as a biomarker of implantation potential. Journal of Assisted Reproduction and Genetics. J Assist Reprod Genet, 36 (9), 1855-1865 Sep 2019
2. Yi-Xuan Lee, Meng-Shun Shen and Chii-Ruey Tzeng. Low Dose Growth Hormone Adjuvant Treatment With Ultra-Long Ovarian Stimulation Protocol in Poor Responders Showed Non-inferior Pregnancy Outcome Compared With Normal Responders. Front. Endocrinol. 10:892, 20 Dec 2019
3. Chou, Ya-Ching; Chen, Yu-Chun; Chen, Ming-Jer; Chang, Ching-Wen; Lai, Guan-Lin; Tzeng, Chii-Ruey. Exposure to Mono-n-Butyl Phthalate in Women with Endometriosis and Its Association with the Biological Effects on Human Granulosa Cells. Int J Mol Sci. 2020 Mar 5;21(5):1794.
4. Dilip Bhargava Sreerangaraja Urs, Wen-Han Wu, Katerina Komrskova, Pavla Postlerova, Yung-Feng Lin, Chii-Ruey Tzeng, Shu-Huei Kao. Mitochondrial Function in Modulating Human Granulosa Cell Steroidogenesis and Female Fertility. Int J Mol Sci. 2020 May 19;21(10):3592.
5. Ya-Ching Chou, Ming-Jer Chen, Pi-Hua Chen, Mu-Hsien Yu, Yi-Jen Chen, Eing-Mei Tsai, Shih-Feng Tsai, Wun-Syuan Kuo, Chii-Ruey Tzeng. Integration of genome-wide association study and expression quantitative trait locus mapping for identification of endometriosis-associated genes. Scientific Reports. 2021 Jan 12; 1(1):478.

Abstract

Efficacy of EndomeTRIO and reproductive outcome improvement of RIF patients with real cases and data.

Biography

• Member of Reproductive Health and Birth Defects Intervention Professional Committee of Chinese Association for Improving Birth Outcome and Child Development
• Member of Female Reproductive Society of China Sexology Association
• Young Member of Reproductive Care Professional Committee of China Maternal and Child Health Association
• Director Member of Reproductive Care Professional Committee of Hainan Provincial Maternal and Child Health Association
• Standing Member of Reproductive Medicine Professional Committee of Hainan Provincial Medical Association
• Member of Hainan Provincial Quality Control Center of Assisted Reproductive
• Standing Member of Reproductive Medicine Professional Committee of Hainan Provincial Association of Chinese Medicine
• Standing Member of Medical Genetics Professional Committee of Hainan Provincial Medical Association
• Director of Hainan Provincial Genetics Society
• Member of Fetal Medicine Professional Committee of Hainan Provincial Genetics Society
• As project leader, she has presided over 6 provincial and municipal scientific research projects related to reproduction and genetics.

Awards

1. The Young Talent of Hainan Provincial “Nanhai Famous Experts”

Publications

1. She has published more than 30 professional papers, including 6 SCI papers with the first authorship, edited 2 professional books, and obtained 1 software copyright.

Abstract

Assisted reproductive technology (ART) has evolved since 1978, and some new technologies pushed the technology up to new era. The biggest change in 2000s is brought by the clinical use of preimplantation genetic test (PGT). PGT increases clinical pregnancy rate and reduces spontaneous abortion per embryo transfer. Therefore, the relative importance of implantation failure has become greater. ERA test has been reported to be effective in case of implantation failure by many researchers. However, some researchers also reported the effectiveness as still sceptical. In this session, we want to confirm how effective is ERA test and how to use it in clinical management.

Biography

Dr Enatsu graduated from Kagoshima University and was awarded an MD in 2005. He completed his clinical training in urology in 2011 in Kameda Medical Center, and received a PhD in reproductive medicine from the Kobe University, school of medicine in 2015. He has been working for infertile couples (both men and women) at Hanabusa Women’s Clinic since 2018.

Awards

1. KOBE Biomedical Innovation Cluster, Grant/Award 2021: Kobe Medical Industry Development Project
2. Morimoto Yoshiharu Award, 2021 annual meeting of Japan IVF society.
3. Best presentation award, 2015 annual meeting of Japan society of reproductive medicine.

Publications

1. Enatsu N, Miyatsuka I, An LM, et al. A novel system based on artificial intelligence for predicting blastocyst viability and visualizing the explanation. Reproductive medicine and biology. 2022;21(1):e12443.
2. Enatsu N, Enatsu Y, Okada K, et al. Sperm retrieval from a male with the rare 47, XXYqs variant of Klinefelter syndrome for intracytoplasmic sperm injection: A case report. Andrologia. 2020;52(1):e13489.
3. Enatsu N, Chiba K, Sumii K, et al. Dutasteride‐mediated morphological changes in the genitourinary tract associated with altered expression patterns of the androgen and estrogen receptors in male rats. Andrology. 2017;5(2):347-353.
4. Enatsu N, Miyake H, Haraguchi T, Chiba K, Fujisawa M. Effects of dutasteride on serum free‐testosterone and clinical significance of testosterone changes. Andrologia. 2016;48(10):1195-1201.
5. Enatsu N, Miyake H, Chiba K, Okada K, Sumii K, Fujisawa M. Testicular Nephrin and Podocin Expression Patterns are Impaired in Infertile Men. BAOJ Urol Nephrol. 2016;1(003).
6. Enatsu N, Miyake H, Chiba K, Fujisawa M. Predictive factors of successful sperm retrieval on microdissection testicular sperm extraction in Japanese men. Reproductive medicine and biology. 2016;15(1):29-33.
7. Enatsu N, Chiba K, Fujisawa M. The development of surgical sperm extraction and new challenges to improve the outcome. Reproductive medicine and biology. 2016;15(3):137-144.
8. Enatsu N, Miyake H, Chiba K, Fujisawa M. Identification of spermatogenically active regions in rat testes by using narrow-band imaging system. Urology. 2015;86(5):929-935.
9. Enatsu N, Miyake H, Chiba K, Fujisawa M. Candesartan mediated amelioration of cisplatin-induced testicular damage is associated with alterations in expression patterns of nephrin and podocin. BioMed Research International. 2015;2015
10. Enatsu N, Yamaguchi K, Chiba K, Miyake H, Fujisawa M. Clinical outcome of microsurgical varicocelectomy in infertile men with severe oligozoospermia. Urology. 2014;83(5):1071-1074.

Abstract

Previous evidence indicates associations between the composition of the female reproductive tract microbiome and reproductive outcome in infertile patients undergoing assisted reproduction. We performed a multicentre prospective observational study using 16S rRNA gene sequencing to analyze endometrial fluid and biopsy samples before embryo transfer in a cohort of 342 infertile patients undergoing assisted reproductive treatments.

A dysbiotic endometrial microbiota profile composed of Atopobium, Bifidobacterium, Chryseobacterium, Gardnerella, Haemophilus, Klebsiella, Neisseria, Staphylococcus and Streptococcus was associated with unsuccessful outcomes (no pregnancy, biochemical pregnancy, and clinical miscarriage). In contrast, Lactobacillus was consistently enriched in patients with live birth outcomes. These findings indicate that endometrial microbiota composition before embryo transfer could be a useful biomarker to predict reproductive outcome, offering an opportunity to further improve diagnosis and treatment strategies.

Biography

Dr. Iolanda García Grau graduated in Biotechnology in 2014 and with a master’s degree in Biochemistry, Molecular Biology and Biomedicine. In 2016, she started in the field of Reproductive Medicine and received a University Teacher Training (FPU) grant from the Spain Ministry to perform a PhD in Biomedicine and Biotechnology at the University of Valencia and Igenomix Foundation, being part of the research group led by Dr. Carlos Simón Vallés and Dr. Inmaculada Moreno. Her thesis focused on the analysis of the endometrial microbiome and its impact on human reproduction.

Dr. Iolanda García Grau has participated in several scientific publications and has attended numerous national and international congresses. In 2020, she derived her professional career to clinical diagnosis as EndomeTRIO Specialist at Igenomix HQ, evaluating both endometrial receptivity and microbiome.

Publications

1. Moreno, I*., Cicinelli, E*., Garcia-Grau, I*., Gonzalez-Monfort, M., Bau, D., Vilella, F., De Ziegler, D., Resta, L., Valbuena, D., & Simon, C. (2018). The diagnosis of chronic endometritis in infertile asymptomatic women: a comparative study of histology, microbial cultures, hysteroscopy, and molecular microbiology. Am J Obstet Gynecol. 218(6). https://doi.org/10.1016/j.ajog.2018.02.012.
2. Chenoll, E., Moreno, I., Sánchez, M., Garcia-Grau, I., Silva, Á., González-Monfort, M., Genovés, S., Vilella, F., Seco-Durban, C., Simón, C., & Ramón, D. (2019). Selection of New Probiotics for Endometrial Health. Front Cell Infect Microbiol, 9, 114. https://doi.org/10.3389/fcimb.2019.00114.
3. Garcia-Grau, I., Perez-Villaroya, D., Bau, D., Gonzalez-Monfort, M., Vilella, F., Moreno, I., & Simon, C. (2019). Taxonomical and Functional Assessment of the Endometrial Microbiota in A Context of Recurrent Reproductive Failure: A Case Report. Pathogens, 8(4). https://doi.org/10.3390/pathogens8040205.
4. Moreno, I*., Garcia-Grau, I*., Bau, D., Perez-Villaroya, D., Gonzalez-Monfort, M., Vilella, F., Romero, R., & Simón, C. (2020). The first glimpse of the endometrial microbiota in early pregnancy. Am J Obstet Gynecol, 222(4), 296-305. https://doi.org/10.1016/j.ajog.2020.01.031.
5. Moreno, I*., Garcia-Grau, I*., Perez-Villaroya, D., Gonzalez-Monfort, M., Bahçeci, M., Barrionuevo, MJ., Taguchi, S., Puente, E., Dimattina, M., Colin Lee, S., Meneghini, G., Aubuchon, M., Leondires, M., Izquierdo, A., Kopcow, L., Chavez, A., Seethram, K., Bau, D., Gomez, C., Valbuena, D., Vilella, F., Simon, C. (2022). Endometrial microbiota composition is associated with reproductive outcome in infertile patients. Microbiome 10, 1. https://doi.org/10.1186/s40168-021-01184-w.

Reviews and book chapters

1. Moreno, I*., García-Grau, I*., & Simon, C. (2018). Microbiota and pathogen screening in the female reproductive tract. Encyclopedia of Reproduction, Second Edition. 10.1016/B978-0-12-801238-3.64730-X.
2. Garcia-Grau, I., Simon, C., & Moreno, I. (2019). Uterine microbiome-low biomass and high expectations. Biol Reprod, 101(6):1102-1114. https://doi.org/10.1093/biolre/ioy257
3. Critchley, H. O. D., Babayev, E., Bulun, S. E., Clark, S., Garcia-Grau, I., Gregersen, P. K., Kilcoyne, A., Kim, J. J., Lavender, M., Marsh, E. E., Matteson, K. A., Maybin, J. A., Metz, C. N., Moreno, I., Silk, K., Sommer, M., Simon, C., Tariyal, R., Taylor, H. S., Wagner, G. P., & Griffith, L. G. (2020). Menstruation: science and society. Am J Obstet Gynecol, 223(5), 624-664. https://doi.org/10.1016/j.ajog.2020.06.004.