ISIVF-JSAR Regional-Symposium
August 27, 2022 (Saturday)
Individualization in Infertility Treatment
Program
OpeningJST
10:50-

Yoshiharu Morimoto (President of ISIVF)

11:00

Akira Iwase (Chair of ISIVF-JSAR Regional Symposium)
Challenge to refractory conditions (Live and Video on

Omnibus Session

demand)Chairs:Keynote Lecture

Hidetaka Okada (Japan) and Robert Norman (Australia)
11:0011:50

Endometriosis and infertility
Chii-Ruey Tzeng (Taiwan)

Varinos-sponsored

11:50-

Lecture12:25

The effect of chronic endometritis on implantation
Fuminori Kimura (Japan)

Tsubaki WC-

12:25-

Immunological approach and its treatment for repeatedsponsored Lecture

13:00

implantation failures
Atsushi Fukui (Japan)

13:0013:40～Lunch Break🍽～Continue・・・
Register Here!

https://isivf.org/events/regional-symposium/Invited Lecture I(Live and Video on demand)

Chair

Miyuki Harada (Japan)

Ferring-sponsored

13:40-

Algorithm based controlled ovarian stimulation; a basis for

14:30

personalised/precision medicine
Robert Lahoud (Australia)

14:3014:40～Coffee Break☕～Invited Lecture II(Live and Video on demand)

Chair

Akira Iwase (Japan)

Beckman Coulter-

14:40-

sponsored

15:30

AMH: a biomarker with growing clinical applications
Antonio La Marca (Italy)

15:3015:40
Symposium (Merck-～Coffee Break☕～Update on COS (Controlled Ovarian Stimulation) (Live only)

sponsored)
Chairs:Masahide Shiotani (Japan) and Young Min Choi (Korea)
15:4016:05

Mild ovarian stimulation in IVF treatment
Keiji Kuroda (Japan)

16:05-

Various novel stimulation protocols for poor-responders:

16:30

Which protocol should we choose?
Jei-Won Moon (Korea)

16:30-

Efficient ovarian stimulation methods for improving

16:55

cumulative live birth rate
Yukiko Katagiri (Japan)

16:5517:10
Closing

17:1017:15

Discussion
Masahide Shiotani (JSAR President)

On-demand delivery will be available shortly after the live
webinar!

Keynote Lecture
Endometriosis and infertility

Chii-Ruey Tzeng
Founder & CEO, Taipei Fertility Center
Honorary Professor, Taipei Medical University
Founding President, Taiwan Endometriosis Society

Endometriosis is a chronic gynecological disease characterized by the growth of endometrial tissue
outside the uterine cavity. It is a frequently benign gynecological disorder that affects 6-10% of womenand causes infertility. Oxidative stress in endometriosis triggered by free Iron in peritoneal fluid (PF)leads to both oocyte and embryo DNA damage and lipid peroxidation. Biomarkers of inflammation,
angiogenesis, MMP, anti-apoptosis and adhesion molecules activated by estradiol can be abolished by
GnRHa pretreatment. Association studies shows serum lead (Pb) and declined detoxification of GSTs
gene polymorphism are risk factors of endometriosis, whereas zinc has protective effect. Urinary
phthalate metabolites also act as endocrine-disrupting chemicals (EDCs) may increase the risk ofendometriosis. Endometriosis impacts on oocyte quality by decreasing mitochondria number and
mtDNA copy number, alternation oocyte morphology and embryo morphokinetics. Endometriosis
affects ART outcomes by decreasing Egg number, compromising both clinical pregnancy rate (CPR)
and live birth rate (LBR) particularly in stage III-IV disease. GnRHa pretreatment induces apoptosis
and autophagy of endometriotic tissue, eliminate the iron-containing PF and restores the implantation
markers such as HOX10 etc. Translational medicine following IUI, IVF and surgery therapies
highlights the better Pregnancy outcomes by GnRHa pretreatment than antagonist protocol in womenwith endometriosis. Future genome-wide association study (GWAS) in endometriosis may elucidate
the possible endometriosis-associated SNP and relative mapped genes.

EDUCATION
1969-1976
1980-1981
1981-1983

M.D., School of Medicine, Taipei Medical University, Taiwan.
Master of Public Health (MPH) in Maternal and Child Health, School of Public
Health, Harvard University, Boston, MA, U.S.A
Research Fellow, Fertility and Endocrinology, Department of Obstetrics andGynecology, Brigham and Women’s Hospital, Harvard Medical School, Boston,
U.S.A.

CURRENT POSITION:
2021-Present
Secretary General, Asia Pacific Initiative on Reproductive (ASPIRE)
2019-Present
Founder & CEO, Taipei Fertility Center (TFC)
2017-Present
Honorary Professor, Taipei Medical University
2017-Present
Board member, World Endometriosis Society (WES)
2008-Present
Board member, International Society for Fertility Preservation(ISFP)PROFESSIONAL CAREER AND EXPERIENCE:
1993-2000
Vice Superintendent, Taipei Medical University Hospital, Taipei, Taiwan.
1994-2017
Chairman, Department of Obstetrics and Gynecology, Taipei Medical University,
Taiwan.
1994-2019
Director, Center for Reproductive Medicine & Science, Taipei Medical University
Hospital, Taiwan.
1996-1998
President, Taiwan Society for Reproductive Medicine (TSRM).
2004-2013
Dean, College of Medicine, Taipei Medical University, Taiwan
2008-2014
President, Pacific Society for Reproductive Medicine (PSRM)
2013-2015
President, Taiwan Society for Mitochondrial Research Medicine (TSMRM)
2015-2021
Founding President, Taiwan Endometriosis Society (TES)
2016-2018
President, Asia Pacific Initiative on Reproductive (ASPIRE)

Varinos-Sponsored Lecture
The effect of chronic endometritis on
implanation
Fuminori Kimura
Professor, Department of Obstetrics and Gynecology,
Nara Medical University

Recovery of endometrial receptivity is thought to bring a new treatment strategy to many patients withimplantation failure. We focused on chronic endometritis (CE) as the cause of implantation failure. In
the present study, the effects of CE on implantation and pregnancy outcomes, the effects of CE on
endometrial function, and the effects of progesterone as treatment for CE were examined.
It was found that the pregnancy rate and live birth rate were significantly lower in CE patients, and themiscarriage rate was significantly higher in CE patients in a prospective study. When patients werediagnosed with CE, even though in vitro fertilization was carried out for 1 year, not only were thepregnancy rate and live birth rate significantly lower, but the miscarriage rate and preterm birth rate
were high after conception.
In in vitro study, we revealed the secretions of TNFα, IL1β, and IL6 per cell were significantly higher
in CE. The rate of Th1 was greater and it of Th2 was significantly lower in CE, and those of Tregs andTh17 was not different. Both PRL and IGFBP1, decidualizing markers, showed significant decreases
in secretion with CE, and conversely, the number of cells was significantly higher in the CE group.
Based on the results of bench studies, we hypothesized that an altered administration route andincreased dosage of progestogen may improve clinical outcomes. The clinical outcomes of patients
who underwent single frozen-thawed blastocyst transfer were examined for each hormone replacement
therapy. It was found that using a progesterone vaginal suppository in combination with an oral
progestin for hormone replacement improved the pregnancy rate and live birth rate in CE patients
when compared with using an oral progestin alone.
CE can cause implantation failure and affect pregnancy outcomes. CE altered the subpopulation of
immune cells in the endometrium and caused decidualization disorders. Although the pregnancy rate
was improved when luteal support was devised, there was a high preterm birth rate. It has beensuggested that the treatment of CE by the administration of antibiotics may improve uterine receptivity,and further verification including investigating pregnancy outcomes is necessary.

MD, PhD, Professor of Department of Obstetrics and Gynecology, Nara Medical University【MEMO】

TSUBAKI Women’s Clinic-Sponsored Lecture
Immunological approach and its treatment
for repeated implantation failures
Atsushi Fukui, Kohei Nakagawa, Kazuya Takeda,
Hidetaka Kamei, Ryu Takeyama, Yu Wakimoto, Ayano
Yamaya, Hiroaki Shibahara
Associate Professor, Department of Obstetrics and Gynecology,
Hyogo Medical University Graduate School of Medicine
Repeated implantation failure (RIF) occurs when implantation does not occur despite multiple embryotransfers during IVF-ET. Repeated IF is often defined as the failure to achieve pregnancy even after
two to three embryo transfers using good quality embryo(s). Immune cells such as T cells and NK cells
are present in the peripheral blood and uterine endometrium and play an important role in theestablishment and maintenance of pregnancy.
During pregnancy, type 1 (inflammatory immune response by TNF-α, IFN-γ, etc.) and type 2 (antiinflammatory response by IL-4, IL-10 , etc.) immune responses occur. Helper T cells (Th cells) areclassified by the cytokines they produce into Th1 cells that produce TNF-α, IFN-γ, etc. and Th2 cells
that produce IL-4, IL-10, IL-13, etc. In normal pregnancy, the type 2 shift of Th cells, i.e., the Th1/Th2
ratio is decreased, while the Th1/Th2 ratio is high in RIF. Regulatory T cells, which are
immunoregulatory T cells characterized as CD4+/CD25bright/Foxp3+, are also involved in
immunomodulation and they are increased in normal pregnancies but absent in RIF. On the other hand,uterine NK (uNK) cells increase from the luteal phase to early pregnancy, accounting for about 70%
of intrauterine lymphocytes in early pregnancy. We have reported that increase of cytotoxic NK cells
during IVF-ET make it difficult to achieve pregnancy, and that NKp46 receptor expression, which is
involved in cytokine production and cytotoxicity expressed on the NK cell surface, is decreased in RIF.
Now, there are two causes of RIF: embryonic side and endometrial side. The embryonic side of the
problem may be better understood with PGT-A. One of the endometrial side of the problem may be
immune. Various immunological approaches are being used to treat the endometrial side of the problem.
Although there is still insufficient data to provide sufficient evidence, tacrolimus, hydroxychloroquine,
TNF-α inhibitors, and immunoglobulin have been reported to be effective in treating RIF with highTh1/Th2 ratios. Corticosteroids, vitamin D, immunoglobulin, and lipid emulsion (LE) may also be
effective for RIF in patients with NK cell abnormalities.
In my talk, I will discuss immunological issues related to RIF and its treatment.

1999-2006
2007-20112011-20132014-20162016
2016-20182018-present
2020-present【MEMO】

Instructor, Department of OB/GYN, Hirosaki University Hospital
Assistant Professor, Department of OB/GYN, Hirosaki University Hospital
Lecturer, Department of OB/GYN, Hirosaki University Hospital
Clinical Associate professor, Department of OB/GYN, Hirosaki University Hospital
Clinical Director, Sendai Assisted Reproductive Technology Clinic
Lecturer, Department of OB/GYN, Hyogo College of Medicine
Associate professor, Department of OB/GYN, Hyogo Medical Univerity, School of
Medicine
Specially appointed professor, Fukushima Medical University (Part time)Ferring-Sponsored Invited Lecture
Algorithm based controlled ovarian
stimulation; a basis for
personalised/precision medicine
Robert Lahoud
Clinical Director IVF Australia North Shore

Reproductive medicine has moved from case reports to large randomised control trials to find answers
to evaluating therapeutic options. These studies look at large trends but are not able to personalise
treatment to each individual.
Personalised medicine uses uniquely personal information about an individual, such as genetic
information, to help guide health-related decisions.
In reproductive medicine dosing algorithms for tailoring precise controlled ovarian stimulation, using
machine learning in embryo selection and evaluating big data to profile patients, form means ofdeveloping personalised treatment approaches for patients. Individualised gene profiling will aid in the
diagnosis and treatment of the infertile patient.
A personalised approach with tailored support, can make the treatment journey easier for the patient.
The aim of this lecture is to explore the application of personalised medicine in the field of reproductive
medicine.

I am a reproductive endocrinologist with over 20 years of experience in the field. I work as the clinicaldirector at one of Australia's busiest IVF units.
My interests include education and research. My special interests include PCOS and endometriosis.

【MEMO】

Beckman Coulter-Sponsored Invited Lecture
AMH: a biomarker with growing clinicalapplications
Antonio La Marca
Professor of Obstetrics and Gynecology
University of Modena and Reggio Emilia, Modena, Italy

Antonio La Marca is Associate Professor of Obstetrics and Gynecology at the Department of Medical
and Surgical Sciences of the Mother, Children and Adults of the University of Modena and Reggio
Emilia, Italy. He was awarded his MD in 1996 by the University of Siena, Italy, specialized in obstetrics
and gynecology in 2001, and gained a PhD in Biology of Germ Cells in 2004.
His clinical activity covers all fields of reproductive medicine, gynecology and obstetrics and he hastaken part in thousands of laparoscopic and hysteroscopic surgical procedures. He has taken part inmany advisory boards and national and international special interest groups for the elaboration ofclinical guidelines for the diagnostic work up of infertile couples as well as their treatment
Professor La Marca’s research interests include ovarian reserve and endocrinology, pharmacologicalmanipulation of ovarian activity, including the prediction of ovarian response in IVF, thepersonalization of ovarian stimulation protocols, the physiological significance of anti-Müllerian
hormone and antral follicle count (including their measurement and clinical utility), and conventional
and alternative strategies for ovarian stimulation. He has published extensively in these fields, being
recognized as author or co-author of more than 200 peer-reviewed articles (of note he is the first Author
in about 35% of the articles), and is currently principal investigator in several phase 3 and 4 trials andrecipient of several competitively assigned national and international grants; his current h -index is 48,
with more than 9,900 citations (Scopus). The preclinical and clinical research led to 6 patents ofwhich La Marca is the inventor (three patent applications and three already issued).
He is member of the Editorial Board of the journal Reproductive Biomedicine Online, Frontiers ofEndocrinology and Editor-in-Chief of Minerva Obstetrics and Gynecology
Prof La Marca is involved as Principal Investigator (PI) in ministerial research programs awarded
on a competitive basis and he is PI of several Investigator Initiated Studies (IISs). He participates or
has participated in numerous national or international multicenter research projects and there are atleast thirty different groups with whom he has collaborated or still collaborates. He has been called
to be part of several international commissions for the evaluation of research projects of European
countries and for the academic progression of university professors.
31 March 2022

Merck-Sponsored Symposium
Mild ovarian stimulation in IVF treatment
Keiji Kuroda
Division Manager, Sugiyama Clinic Shinjuku
Juntendo University Faculty of Medicine

Mild ovarian stimulation for IVF treatment has been accepted as a safer, more affordable and morepatient-friendly protocol compared with conventional stimulation. Mild stimulation protocols use alower dose of gonadotropin (<225IU) or have a shorter duration of gonadotropin administration, or
both, compared with conventional stimulation protocols.
In Japan, single embryo transfer was recommended in 2008 for the establishment of safe pregnancy
and live birth after assisted reproductive technology (ART) treatment. Thus, to improve the clinicalpregnancy rate with a single embryo, the clinical pregnancy rates in Japan have risen in recent decades.
In 2018, the clinical pregnancy rate of 30- and 35-year-old women was 44.5% and 40.4% per ET cycle,
leading to 37.0% and 32.3% live birth rates, respectively. When 30–35-year-old women aim for a
cumulative live birth rate of 80% or higher, 4–5 embryos are calculatedly as necessary. Mild ovarian
stimulation aimed at collecting 5–10 oocytes can be one of the optimal ovarian stimulation protocols
in patients with a good prognosis.
In poor responders with a diminished ovarian reserve, conventional stimulation with a high daily doseof gonadotropin is not superior, thus mild stimulation may be sufficient for maximumly extracting
their ovarian function.
Mild stimulation can reduce treatment burdens with daily gonadotropin injections and the related
complications, thus decreasing the rate of drop-out from ART treatment. Mild ovarian stimulation canbe one of alternative choice as an optimal ovarian stimulation protocol in patients with a good
prognosis and diminished ovarian reserve.

Dr. Keiji Kuroda is a gynecologist and specialist in reproductive medicine and endoscopic surgery. He
is a division manager of intractable infertility as well as endoscopy, Sugiyama Clinic Shinjuku, Tokyoand a part-time associate professor at Juntendo University, Tokyo. He had researched oocyte activation
at Tokyo Women’s Medical University, from 2004 to 2005 and the function of decidualization ofhuman endometrium in Imperial College London and University of Warwick, UK, from 2010 to 2012.
Therefore, his current research interests include endometrial function during implantation and earlypregnancy. He is also interested in shortening the time to pregnancy and livebirth with safe andeffective IVF treatment.
Dr. Kuroda is regularly invited as a guest speaker to international conferences. He has also received
various prizes including 11th World Congress of Endoscopic Surgery, The Best Poster of the Session
Prize Award in 2008, 38th Global Congress of Minimally Invasive Gynecology, Best Endometriosis
Paper in 2009, and Journal of Obstetrics and Gynaecology Research, Best Reviewer Award in 2018.

【MEMO】

Merck-Sponsored Symposium
Various novel stimulation protocols for poorresponders: Which protocol should wechoose?
Jei-Won Moon
Co-medical director of M Fertility Center, Seoul, Korea

The mean age of women giving birth to their first child in Asian countries is rising (OECD Family
Database, 2020). As a result, more women face subfertility due to diminished ovarian reserve (DOR)or poor ovarian responses (POR) who then seek medical help to become pregnant. IVF is now thetreatment of choice in older women and it is estimated that almost 40% of all IVF cycles are performedin older women (NICE guidelines, 2013).
Various stimulation protocols have been introduced to improve pregnancy outcomes in DOR or POR
patients. use of increased gonadotropin doses, estradiol priming antagonist, long luteal protocol,
Lupron stop protocol, double stimulation, DHEA adjuvant therapy, adding growth hormone, mild
ovarian stimulation with oral compounds such as clomiphene citrate or letrozole, and natural cycle
IVF.
However, the optimal stimulation protocols for POR patients are currently unknown. In addition, there
is insufficient evidence to support the use of specific interventions to improve IVF treatment outcomesin poor responders. The Cochrane review of poor responder interventions concluded that no particulartreatment offered clear benefit, or could be recommended. The management of poor responders,
therefore, remains a significant challenge in assisted reproduction. POR patients usually exhibit DOR
to standard gonadotropin stimulation, and the efficiency of a high dose of gonadotropin administration
for such patients has been questioned. Also, there is one study that in subsequent IVF cycles, repeating
the same conventional ovarian stimulation protocol, compared with a different protocol, can result inslightly improved laboratory outcomes.
So it is worth it that we should look over various novel stimulation protocols for poor responders. And
evaluate which protocol might be suitable for the patients.

Education
2000-2006
2008-2017

Dankook University, College of Medicine, Korea
Postgraduate School, University of Ulsan, College of Medicine, Seoul, Korea

Professional Experience
2006-2007
Internship, Asan Medical Center, Seoul, Korea
2007-2011
Residency in Obstetrics & Gynecology, Asan Medical Center, Seoul, Korea
2011-2012
Public health doctor, Ulleung-gun Health center and County Hospital, Korea
2012-2014
Public health doctor, Mok-Po City Hospital, Mok-Po, Korea
2014-2016
Clinical Fellowship at reproductive endocrinology division, Asan Medical Center,Seoul, Korea
2016-Present
Co-medical director of M Fertility Center, Seoul, Korea
2018-Present
Board member of Korean Association of Obstetricians and Gynecologist and Korean
Society for Assisted Reproduction.
2020-Present
Board member of International Society for In Vitro Fertilization (ISIVF)
Activities
2018/03
ASIAN Expert Meeting on ART Symposium at Tokyo: Invited speaker
2018/08
10th Korea-Japan ART Conference at KOBE: Invited speaker
2019/07
11th Korea-Japan ART Conference at Pyeongchang: invited speaker
2020/04
Expert Panel Discussion by Merck:
2020/05
10th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE) in Philippine:
invited speaker
2021/02
KSAR conference: invited speaker
2021/11APAC Luteal Phase Support Advisor Board Meeting: Advisor【MEMO】

Merck-Sponsored Symposium
Efficient ovarian stimulation methods for
improving the cumulative live birth rate

Yukiko Katagiri
Professor in Department of Obstetrics and Gynecology,
Faculty of Medicine, Toho University

The goal of fertility treatment is to obtain a live birth. To obtain a live birth, it is necessary to obtainan embryo for transfer, which requires the retrieval of the enough number of oocytes. For this reason,
it is extremely important that an appropriate ovarian stimulation method be selected.
Clinical outcomes of assisted reproductive technology are often expressed in terms of pregnancy rates
per embryo transfer. However, behind the situation, this is the existence of treatment cycles that did
not result in embryo transfer. According to assisted reproductive technology in Japan: A summary
report by the Ethics Committee of the Japan Society of Obstetrics and Gynecology, transferable
embryos were not obtained in approximately 30% of egg retrieval cycles, and it is important to work
to reduce this number of unsuccessful cycles.
It is not easy to obtain euploid embryos in aged patient populations, Therefore, it is necessary tochoose an ovarian stimulation method that maximizes ovarian reserve and achieves the required
number of eggs retrieved.
In this presentation, it will be discussed ovarian stimulation methods aimed at achieving live birth in
an initial egg retrieval cycle.

1992
1992
1996
2001~2003
2003~2005
2007
2010
2016

【MEMO】

Graduated from Toho University School of Medicine
Admission for Toho University Graduate School of Medicine
Graduated from Toho University Graduate School of Medicine
Research Fellow in Center for Reproductive Medicine and Infertility, Weil Medical
College, Cornell University
Research Associate in Center for Reproductive Medicine and Infertility, Weil
Medical College, Cornell University
Assistant Professor in Department of Obstetrics and Gynecology, Faculty of
Medicine, Toho University
Associate Professor in Department of Obstetrics and Gynecology, Faculty of
Medicine, Toho University
Professor in Department of Obstetrics and Gynecology, Faculty of Medicine, Toho
University