FINAL PROGRAM

REGIONAL SCIENTIFIC UPDATE MEETING FEATURING HIGHLIGHTS FROM ESHRE 2016: ASIA PACIFIC

Saturday, Sep. 17 2016 | KUALA LUMPUR, MALAYSIA

GENERAL INFORMATION

VENUEALOFT KUALA LUMPUR SENTRALNo. 5 Jalan Stesen Sentral50470 Kuala Lumpur, Malaysia www.aloftkualalumpursentral.com

LANGUAGE The official language of the symposium will be English.

SCIENTIFIC & ORGANISING SECRETARIATTOPEC Global LLC (GmbH)Löwenstrasse 1CH-8001 Zürich, Switzerland

EXCEMED - Excellence in Medical EducationSalita di San Nicola da Tolentino, 1/b00187 Rome, Italy

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AIM OF PROGRAM

This live educational and scientific program will provide attendees with interactive education to improve patient outcomes by optimizing the patient journey. Discussions will include

perspectives from clinicians and embryologists with a specific focus on quality management and individualized controlled ovarian stimulation.

COURSE LEARNING OBJECTIVES• Discuss ongoing and emerging studies as presented at the ESHRE annual meeting 2016• Employ strategies that incorporate evidence-based recommendations for improving practice• Apply new strategies for enhancement of fertility and preservation of fertility

TARGET AUDIENCEThis program is designed to meet the Continuing Medical Education needs of practicing reproductiveendocrinologists, embryologists and fertility treatment specialists.

ACKNOWLEDGEMENT OF COMMERCIAL SUPPORTThis program is supported by independent educational grants received from Merck KGaA, Darmstadt, Germany and MVZ Fertility Center Hamburg GmbH.

INTERNATIONAL PROGRAM CHAIR

Professor PC WongHead & Senior Consultant, Division of Reproductive Endocrinology & InfertilityDepartment of Obstetrics & GynaecologyDirector of the Assisted Reproduction ProgrammeNational University of SingaporeSINGAPORE

FACULTY MEMBERS

Professor Shee-Uan ChenTAIPEI, TAIWAN

Dr. Rohit Gutgutia, MBBS, DGOKOLKATA, INDIA

Dr. Keiji KurodaTOKYO, JAPAN

Dr. Gavin SacksSYDNEY, AUSTRALIA

Dr. Xu YangBEIJING, CHINA

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www.GlobalFertilityAcademy.org/APAC

SCAN TO ACCESS OR DOWNLOAD THE PRESENTATION SLIDES:

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SCIENTIFIC PROGRAM*

08:00

08:30

08:45

09:05

09:25

09:50

10:30

10:45

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11:25

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13:30

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14:00

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Registration and Check-In

Welcome and Introductions

Individualising IVF: Introduction to the POSEIDON Concept Dr. Gavin Sacks | SYDNEY, AUSTRALIA

Emerging View to Managing the Poor-Responder Dr. Xu Yang | BEIJING, CHINA

Small Group Discussion

Faculty Panel Discussion

Break

Special Situations: PCOS and EndometriosisProf. PC Wong | SINGAPORE

Approaches to Hyper-responsiveness and OHSS Prof. Shee-Uan Chen | TAIPEI, TAIWAN

Small Group Discussion

Faculty Panel Discussion

Lunch

Review of Morning Session Educational Highlights

Luteal Phase Support Dr. Keiji Kuroda | TOKYO, JAPAN

AMH and Biomarkers of IVF Outcome: How Valuable? Dr. Rohit Gutgutia | KOLKATA, INDIA

Small Group Discussion

Faculty Panel Discussion

Summary of Afternoon Educational Highlight

Closing Remarks

*Subject to change

Professor PC Wong | SINGAPORE

PC Wong, MD was the Head of the Department of Obstetrics & Gynaecology, at the Yong Loo Lin School of Medicine, National University of Singapore; as well as the Chief of the Department of Obstetrics & Gynaecology at the National University Hospital (NUH) in 2001 - 2008. He is currently the Head & Senior Consultant, Division of Reproductive Endocrinology & Infertility, Department of Obstetrics & Gynaecology, NUH and the Director of the Assisted Reproduction Programme in the Hospital. He has a long-standing interest in the various aspects of infertility, especially assisted reproduction. He was a member of the Editorial Board of ‘Human Reproduction’. He has published more than 50 peer-reviewed and refereed papers and written several chapters in books and reviews. He is actively involved with postgraduate training and has been a member of the Specialist Training Committee as well as the Postgraduate Examination Committee. He was the First President of the Asia Pacific Initiative on Reproduction (ASPIRE) and the founding Director of the Centre for Reproductive Education & Specialist Training (CREST).

Professor Shee-Uan Chen | TAIPEI, TAIWAN

Dr. Shee-Uan Chen was a graduate of College of Medicine, National Taiwan University. He completed the residency training of Obstetrics and Gynecology and research fellow of reproductive medicine in National Taiwan University Hospital. His major research interests include clinical and basic reproductive medicine, cryopreservation of oocytes, embryos and ovarian tissue and preimplantation genetic diagnosis. He has many research papers in reproductive medicine in JCEM, Hum Reprod, Fertility and Sterility, etc. and gets lots of research awards. Now he is professor and Director of Division of Reproductive Endocrinology and Infertility of Department of Obstetrics and Gynecology of National Taiwan University Hospital. And he is the president of Taiwanese Society of Reproductive Medicine.

INTERNATIONAL PROGRAM CHAIR

BIOGRAPHIES

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FACULTY MEMBERS

Dr. Rohit Gutgutia | KOLKATA, INDIA

Dr. Rohit has been a dedicated reproductive medicine practitioner since last 12 years after getting trained in Reproductive Medicine in Israel under Professor Amit Ami. During this time, he has helped in setting up numerous IUI and IVF facilities across most of Eastern India and Bangladesh. He has worked tirelessly to make fertility management easy and accessible for large sections of the local population. One of the more popular faces on national fertility scene, he has authored chapters in FOGSI publications and books, published papers in indexed journals and been an invited faculty member in numerous state and national meets.

Dr. Keiji Kuroda | TOKYO, JAPAN

Dr. Keiji Kuroda is currently an Associate Professor Department of Obstetrics and Gynecology at Juntendo University Hospital in Tokyo. He has been involved with the Juntendo University Hospital in Tokyo since 2001 as a clinical trainer and assistant professor before earning the position of Associate Professor. He also served as a research associate in the Department of Physiology at the Tokyo Women’s Medical University from 2004 to 2005. From 2010 to 2012, Dr. Kuroda spent time in the UK as a Postdoc researcher for the Division of Reproductive Health at the University of Warwick as well as the Institute of Reproductive and Developmental Biology at the Imperial College London Hammersmith Campus. He has earned the qualification of Medical Specialist in Obstetrics and Gynecology, Gynecologic and Obstetrics Endoscopy, Endoscopic Surgery, and Reproductive Medicine. Dr. Kuroda has an extensive list of honors and awards, including earning various research grants and subsidies through his work. At the 38th Global Congress of Minimally Invasive Gynecology, he won the Carlo Romanini Award for Best Endometriosis Paper. In 2013, he won the Clinical Award at the 34th Japan Society of Endometriosis. He also won the Juntendo University Young Investigator Award in that same year. His most recent award came in 2015 when he received the Medical Research Encouragement Prize of the Japan Medical Association.

Dr. Gavin Sacks | SYDNEY, AUSTRALIA

Dr. Gavin Sacks is a Fertility Specialist and Clinical Director at IVFAustalia. He strives to offer world-class fertility treatment and advanced science for addressing infertility, access to the very latest assisted reproduction technology and techniques, and the highest standard of care. He has a rare mix of skills; he is highly qualified, and extremely determined to help his patients succeed. He is one of the few IVF specialists to guide his patients all the way through their pregnancies and deliver their babies as well. Dr. Sacks is known for his persistence and dedication as he will never send a patient away after three failed attempts at IVF. His internationally recognized research into miscarriages and immunology, in particular ‘natural killer cells,’ has led to innovative treatments such as the Bondi protocol, whereby the patient is given prednisolone and blood thinners. Dr. Sacks is highly renowned for his flexibility as well has his systematic and rigorous approach to his research and testing.

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DR. XU YANG | BEIJING, CHINA

Dr. Xu Yang a chief physician and master tutor is the deputy director of OB/GYN and head of reproductive and genetic center at the Peking University first hospital. She is on the standing committee of the reproductive medicine branch of China Association of Chinese Medicine, Women’s and Children’s Health Research Institute of reproductive endocrine professionals, and the Sexual Medicine Professional Committee of China. Dr. Yang also serves as the reproductive group deputy team leader for the Sexual Medicine Professional Committee of China in addition to being on the standing committee. She is a member of the reproductive medicine branch of Chinese Medical Association, the National Assisted Reproductive Technology Expert Panel, and the Global Chinese Assisted Reproductive Medicine Association (GCARM). She is on the editorial board of International Journal of Reproductive Health and Family Planning, the Journal of Reproductive Medicine, and the Chinese Journal of Reproductive Health. Dr. Yang serves as the deputy editor of the Reproductive Endocrine Disease Diagnosis and Treatment. She also studied IVF reproductive endocrinology and assisted reproductive technology at Freiburg University in 2003.

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Primary Professional Affiliation: Fertility Center, CHA bundang Medical Center, CHA UniversityAddress: Seongnam-si, Korea, Republic ofCity/State/Zip/Country: Seongnam-si, Gyeonggi-do Korea, Republic ofPhone: 8210-3480-4732Email: eunak1@chamc.co.kr

TITLE: Comparison of pregnancy rates between UTM and EG (embryo glue) medium on day 3

SUBMITTER NAME: Dong-Hee Choi, Eun-Kyung Kim, Eun-Ah Kim, Eun-Ha Kim Ah leum, Lee, MI RAN, Lee, Ji-Eun Shin, Da- Young No, Hwang Kwon

ABSTRACT

INTRODUCTION: Hyaluronan(HA) is one of the components of the follicular fluid, cumulus cells, as well as the human female reproductive tract. And also it is known for improving development, implantation rates of human embryo. UTM and EG were developed for this goal. The objective of this study was to find the optimal supporting media of embryo development and implantation.

DESIGN: Retrospective analysis

MATERIALS AND METHODS: Between Jul.2013 and Mar.2014, 84 cycles (63 cycles: UTM; origio; 21cycles: EG(embryo Glue; Vitrolife)) undergoing IVF/ICSI cycles were divided into two groups using these media. Oocytes and embryos were cultured in P-1 medium supplemented with SSS (synthetic serum substitute). Embryos of two each groups were cultured for 3 days. Prior to transfer embryos selected were isolated and placed in either UTM media or EG for 20 minutes. Embryos were then loaded with UTM or EG and then transferred.

Statistical evaluation was performed using student’s t-test.

RESULTS: Clinical outcomes were compared two different HA containing ET medium. Although not statistically different, pregnancy rates of UTM medium groups (20/63(31.7%)) were slightly higher then EG groups (6/21(28.65)).

CONCLUSIONS: In this study, UTM seems to be slightly better than EG in terms of quality in IVF/ICSI program. Further studies will be proceeded to find optimal supporting media for development and implantation of oocyte.

ACCEPTED ABSTRACTS

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Does progesterone administration improve obstetric outcomes in patients with threatened abortion?Doa Kim1, Min Jung Kim1, Eung Gi Min1, Hye Ok Kim1, Kwang Moon Yang1, Il Pyo Son1

1 Division of Reproductive Endocrinology and Infertility, Department Obstetrics and Gynecology, Cheil General Hospital and Women’s Healthcare Center, Dankook University College of Medicine, South Korea

OBJECTIVE: To evaluate whether progesterone administration, especially high dose, can be helpful for improvement of obstetric outcomes in threatened abortion patients who needed hospitalization.

MATERIALS AND METHODS: Threatened abortion patients who had vaginal bleeding in 1st trimester of pregnancy and needed hospitalization were included. Among them, multiple pregnancies, patients with having severe uterine factors such as adenomyosis and uterine anomalies, history of recurrent miscarriage (>2) and cases which revealed fetal karyotyping abnormalities as a cause of abortion in this study period were excluded. As study population, total 150 patients were selected. Study populations were grouped into 3, non-progesterone used group who did not receive any medication (n= 38), low dose progesterone used group who were given 50 to 100mg of intramuscular progesterone injection daily (n=89) and high dose progesterone used group who were given 200 mg of intramuscular progesterone daily (n=23). The outcomes such as duration of hospitalization, the rate of pregnancy sustained up to 12 weeks and viable pregnancy rates which was defined as pregnancies sustained up to 25 weeks gestation were compared between groups. Qualitative and quantitative variables were analyzed statistically by Chi-Square test and One way ANOVA, Nonparametric test. The p-values of less than 0.05 were considered significant.

RESULT(S): Pregnancy rates which were successfully sustained up to 12 and 25 gestational weeks in non-progesterone used group (89.5% and 87.9%), low dose progesterone used group (88.8% and 82.1%) and high dose progesterone used group (91.3% and 83.3%) had no statistically significant differences between groups (p value ≥ 0.05). Also, duration of hospitalization was similar between groups.

CONCLUSION(S): According to our result, the progesterone administration seems to have no benefit in improving obstetric outcomes in patients with threatened abortion. But, more large scaled study is needed.

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Effect of human endometriotic cyst fluids on mouse in vitro folliculogenesis and oocyte acquisitionDa Yong Lee1, Byung Chul Jee1, Ki Chul Kim2, Won Young Paik3, Seok Hyun Kim4

1 Department of OBGY, Seoul National University Bundang Hospital, Seongnam,2 Hamchoon Women’s Clinic, Seoul,3 Gyeongsang National University Hospital, Jinju,4 Seoul National University Hospital, Seoul, Republic of Korea

STUDY QUESTION: Does the supplementation of human endometriotic cyst fluids (EMF) have a detrimental effect on in vitro follicle growth and oocyte acquisition in a mouse model.

SUMMARY ANSWER: Supplementation of human EMF negatively affects in vitro follicle growth, hormonal production and oocyte acquisition.

WHAT IS KNOWN ALREADY: An ovarian endometrioma contains free iron, reactive oxygen species, proteolytic enzymes and inflammatory molecules in concentrations from tens to hundreds of times higher than those present in peripheral blood or other types of benign cysts. The endometrioma is not surrounded by a true capsule, thus contents of endometrioma appear to across the lining cyst wall. It was postulated that the presence of an endometrioma per se may cause direct damage to the surrounding otherwise healthy ovarian tissues.

STUDY DESIGN, SIZE, DURATION: Prospective experimental animal study. Supernatants of human EMF were added to the growth and maturation medium containing preantral follicles obtained from 7- to 8-week-old BDF1 mice. A total of 409 preantral follicles were randomly divided into four groups according to the final concentrations of human EMF; 0%, 2.5%, 5%, and 10%.

PARTICIPANTS/MATERIALS, SETTING, METHODS: After in vitro growth and maturation of mouse preantral follicles for 12 days, survival rate of follicles, oocyte acquisition, meiotic spindle integrity of MII oocytes and hormonal levels of 17β-estradiol and anti-Müllerian hormone (AMH) in the final spent media were assessed.

MAIN RESULTS AND THE ROLE OF CHANCE: The survival rates of follicles at day 10 were significantly lower in three EMF-treated groups (56.1%, 30.6%, and 6.2%, respectively, p<0.05 for each when compared with 83.6% in 0%EMF group). The acquired total oocytes (34.7%, 18.4% and 4.1%) or MII oocytes (10.2%, 3.1%, and 1%) per initiated follicle were also significantly lower in three EMF-treated groups (p<0.05 for each when compared with 68.1% and 21.6% in 0%EMF group). Meiotic spindle was severely damaged in almost all of MII oocytes acquired from three EMF-treated groups. The level of 17β-estradiol was significantly lower in the 10%EMF-treated group and the levels of AMH were significantly lower in three EMF-treated groups when compared with those in 0%EMF group.LIMITATIONS, REASONS FOR CAUTION: We used a mouse model to demonstrate a detrimental effect of human EMF on in vitro folliculogenesis.

WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that contents of ovarian endometrioma could affect directly folliculogenesis in the adjacent ovarian tissues. Our results can greatly contribute to understand the mechanism of endometrioma-induced ovarian damage.

STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grant no. A120043 from the Korea Health Care Technology R&D Project, Ministry of Health and Welfare, Republic of Korea.

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Effect of regular exercise on reproductive function of aged female mice.Jung Bin Son1, Jong Kil Joo2, Kyu Sup Lee2

1 Department of Obstetrics and Gynecology, MIRAERO WOMEN’s HOSPITAL, Busan, Korea2 Department of Obstetrics and Gynecology, Pusan National University school of medicine, Busan, Korea

AIMS: This study was aimed to examine whether regular exercise can improve the expression of ovarian anigogenic factors, oocyte quality and fertility potential in aged female mice. MATERIALS AND METHODS: Firstly, 40 C57BL female mice of 30-32 weeks were divided into the two groups. One group (n=20) were regularly exercised (physical activity) by illuminating incandescent lights (60 Watts, 220V), placed on the top of the cage, for 30 minutes daily. The other group (n=20) were served as control without exercise. After 4 weeks, the female mice were mated with the same strained individual male mice of 12 weeks during 2 weeks maintaining the exercise protocol. Then pregnancy was observed for subsequent 2 weeks (1st observation). Mice that were not pregnant were re-mated during further 2 weeks and re-examined the pregnancy outcome for the following 2 weeks (2nd observation). Secondly, female mice of two age groups (6-8 weeks and 30-32 weeks) were treated with exercise protocol for 6 weeks, and then superovulated with pregnant mare serum gonadotrophin, followed by human chorionic gonadotrophin injection 48 hours later. Then they were mated with individual males. After 18 hours, zygotes were flushed and cultured to blastocyst. Just after zygote retrieval, both ovaries were collected and ovarian vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) expression was examined using western blot and immunohistochemistry, and ovarian apoptosis was assessed by TUNEL method.

RESULTS: The total number of pregnant mice was 15 (75%) in the exercise group, which was significantly higher than 5 (25%) in the control group (P<.05). The mean number of offspring was also significantly higher in the exercise group (9.2) than the control group (6.3) (P <.05). The mean number of one-cell embryos retrieved and blastocyst formation rate were 12.6 and 43.8% in the exercise group and 10.8 and 8.1% in the control group with a significant difference (P<.05). Ovarian VEGF and eNOS expression was increased, but ovarian apoptosis was decreased in the exercise group.

CONCLUSIONS: This study demonstrates that regular exercise induced by illumination with incandescent lights in aged mice improves their reproductive outcomes by improving ovarian function and oocytes quality. The beneficial effect of an optimal exercise on fertility may be associated with the activation of ovarian angiogenesis by increasing ovarian eNOS and VEGF expression.

We do not have any financial support received and/or any potential conflict of interest

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Estradiol Valerate Pretreatment in GnRH Antagonist Cycles for IVF Cycle Programming in women with various serum anti-mullerian hormone level.

Eun Bee Noe, Myung Hee Kim, Hyeon Jeong Jeong, Mi Kyung Chung, Hee Sun Lee

Seoul Rachel Fertility Center, Seoul, Republic of Korea

OBJECTIVE: To compare the use of Estradiol valerate pretreatment in GnRH antagonist cycles for IVF Cycle programming in women with various serum anti-mullerian hormone level.

DESIGN: Retrospective cohort study in in outpatient fertility clinic setting

MATERIALS AND METHODS: From December 2011 to April 2014, a total of 1762 infertility patients were enrolled in this study. The patients included in the trial were women ≤40 years of age, with a normal ultrasound scan. In the control group, a standard GnRH antagonist protocol was performed. And the pretreatment group underwent IVF cycle using a modified treatment protocol with Estradiol Valerate administration from cycle day 21 onwards prior to the start of gonadotrophin stimulation. We divided the patient group according to serum anti-mullerian hormone level (AMH<1.0ng/ml, 1.0ng/ml≤ AMH<5.0ng/ml, AMH≥5.0ng/ml).

RESULT: Mean age was 34.6±2.9 (control group) and 34.4±2.8 (E2 pretreatment group). In AMH AMH<1.0ng/ml group, number of picked oocyte was significant greater in women with estradiol valerate pretreatment (2.7±2.4 vs. 4.9±3.7, P value<0.001). But, clinical pregnancy rate was not statistically significant (31.4% vs. 41.9%, P value=0.07). In 1.0ng/ml≤ AMH<5.0ng/ml group, number of obtained oocyte was 9.2±5.6 (control group), 10.0±5.3 (E2 pretreatment group) and statistical significance was not noted. In AMH≥5.0ng/ml group, number of retrieved oocyte and clinical pregnancy rate showed no significant difference (14.5±7.6 vs. 15.1±7.3, P value=0.38) (46.5% vs. 55.9%, P value=0.10).

CONCLUSION: Cycle scheduling can be used to avoid weekend retrievals and quite convenient to patient. Scheduling GnRH antagonist cycle with estradiol pretreatment not seems to lead to deleterious impact on the IVF outcomes. And, especially in women with serum AMH level was less than 5.0ng/ml, Estradiol valerate pretreatment may increase number of retrieved oocyte.

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Müllerian Inhibiting Substance and Calcitriol induce growth inhibition and apoptosis in human endometrial stromal cells in endometriosis.

Dawn Chung1, Jieun Kang1, Ji Sun Park1, Hyuck Dong Han1, Yeon Soo Jung1

Department of obstetrics and gynecology, Wonju Severance Christian Hospital, Yonsei University College of Medicine, Wonju, Korea

INTRODUCTION: Endometriosis is a frequent gynecological disorder that occurs in 6–10% of the general female population and is more frequent in infertile women, where it occurs in 25–50%. Müllerian inhibiting substance (MIS) is produced in Sertoli cells of fetal testis and causes regression of Müllerian ducts in male embryos. MIS also can induce the cell cycle arrest and apoptosis in Müllerian duct-derived tumors in vivo and in vitro. Calcitriol (1, 25 – dihydroxycholecalciferol), the hormonally active form of Vitamin D, has long been known as an important regulator of calcium homeostasis and bone metabolism. It has recently been suggested that MIS constitutes a novel target regulated by calcitriol, and that induction of MIS expression may play an important role in the anti-tumor activity of calcitriol. Growing evidence suggesting that MIS and calcitriol can act synergistically to inhibit the growth of tumor cells prompted us to examine the effects of MIS in combination with calcitriol on endometriosis, which is derived from coelomic epithelial origin.

AIMS: This study aimed to investigate whether MIS in combination with calcitriol modulates proliferation and apoptosis of human endometrial stromal cells in endometriosis and to identify the signaling pathway by which MIS mediates apoptosis.MATERIALS AND METHODS: Endometrial stromal cells in endometriosis were treated with MIS in the absence or presence of calcitriol. Cell viability and proliferation were evaluated using the Cell Counting Kit-8 assay and apoptosis was evaluated by DNA fragmentation assay. Western blot and enzyme-linked immunosorbent assay were used to determine the signaling pathway.

RESULTS: The cells showed specific staining for the MIS type II receptor. Treatment of endometrial stromal cells with MIS and calcitriol led to dose- and time- dependent inhibition of cell growth and survival. The combination treatment significantly suppressed cell growth, down-regulating the expression of B-cell lymphoma 2 (Bcl-2); and up-regulating the expression of Bcl-2 associated X protein, caspase-3, and caspase-9.

CONCLUSIONS: These results suggest a rationale for testing the therapeutic potential of MIS, alone or in combination with calcitriol, in the treatment of endometriosis.

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Peroxisome proliferator activated receptor gamma (PPAR-γ) and pro-inflammatory genes expression in granulosa cells from stimulated follicles in women with polycystic ovary syndrome.

Ki Chul Kim1, Joong Yeup Lee1, Jin Cheol Tae1, Chung Hyon Kim1, Bung Chul Jee2, Doyeong Hwang1, Seok Hyun Kim3

1 Hamchoon Women’s Clinic, Seoul; 2 Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam; 3 Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea.

ABSTRACT

OBJECTIVE: To identify the difference in PPAR-γ and proinflammatory genes expression of the granulosa cells from polycystic ovarian syndrome patients and controls undergoing controlled ovarian stimulation in IVF

METHODS: Nine patients with PCOS and 6 controls were enrolled between November 2010 and May 2012. On the day of oocyte retrieval, granulosa cells were collected from pooled follicular fluid. Total RNAs were extracted from granulosa cells. Reverse transcription was performed and quantification of gene expression levels was achieved by real-time quantitative PCR.

RESULTS: There were no significant differences in age, body mass index, and total dose of gonadotropin except for LH/FSH ratio between PCOS and control group. PPAR-γ and COX-2 mRNA were significantly down-regulated in the granulosa cells of PCOS women compared with controls (p=0.034, 0.018 , respectively), but IL-6 and TNF-α did not show significant differences. No genes correlated with clinical characteristics and oocyte developmental quality including fertilization rate and rate of good embryo. A high correlations were found among PPAR-γ, COX-2, IL-6 and TNF-α expression.

CONCLUSION: Resulting data may provide novel clues for ovarian granulosa dysfunction in PCOS and indirectly provide evidence that the effect of PPAR-γ agonist in PCOS may come from altered ovarian follicular environment. Further studies are warranted.

The clinical courses of pregnancies which showed extremely low serum β-human chorionic gonadotropin level at initial pregnancy test.

Ji Hyun Jeon1, Min Jung Kim1, Sun Hwa Cha1, In Ok Song1, Kwang Moon Yang1, Hye Ok Kim1

1 Division of Reproductive Endocrinology and Infertility, Department of Obstetrics & Gynecology, Cheil general hospital and women s healthcare center, Dankook university College of medicine, South Korea

OBJECTIVE: To evaluate the clinical courses of pregnancies which showed extremely low β-human chorionic gonadotropin (β-hCG) levels at initial pregnancy test and to investigate the predictive indices in serial serum β-hCG which can distinguish the variable clinical courses of these pregnancy such as ectopic, biochemical, ongoing and spontaneous abortion.DESIGN: Retrospective analysis

MATERIALS AND METHODS: IVF cycles which were diagnosed as initial serum β-hCG on 12 days after oocyte retrieval and serially checked on 14, 16 days after oocyte retrieval were included. Among them, 108 cycles which resulted extremely low levels like as 5≤ β-hCG ≤10 mIU/mL on 12 days after ovum retrieval were selected as study population. They were divided into biochemical pregnancy(BP), ectopic pregnancy(EP) or spontaneous abortion(SA) and ongoing pregnancy(OP)(pregnancies sustained up to 25 weeks of gestation) group. The serum β-hCG levels and their serial changes were compared. And the cut-off levels of degree of serum β-hCG increase between 12 and 14 days, 12 and 16 days, 14 and 16 days after ovum retrieval were determined.

RESULTS: The clinical courses of study populations were resulted to BP(n= 85), EP or SA(n=15) and OP(n= 8). Notably, 8 cases(7.4%) among 108 goes to OP. Mean β-hCG on 14, 16 days in each groups showed meaningful result(BP-18.80 mIU/mL, EP or SA-28.57 mIU/mL, OP-28.57 mIU/mL, p-value=0.00 on 14 days and BP-31.44 mIU/mL, EP or SA-95.43 mIU/mL, OP-154.82 mIU/mL, p-value=0.00 on 16 days). Also, the increased rate of serum β-hCG of had meaningful differences. In EP or SA, the serum β-hCG increase rates between 12 and 14 days, 12 and 16 days, 14 and 16 days were 2.99(sensitivity 87.0%, specificity 71.8%), 8.12 (sensitivity 82.6%, specificity 83.5%), 2.21(sensitivity 91.3%, specificity 76.5%) and those in OP were 4.54(sensitivity 87.5%, specificity 90%), 13.19(sensitivity 75.0%, specificity 85.0%), 2.74(sensitivity 87.5%, specificity 83.0%) each.Conclusions: Although the incidence was low, the clinical courses of pregnancies which showed extremely low serum β-hCG level at initial pregnancy test can be resulted to ongoing pregnancy. Hence, serial checking of serum β-hCG seems to be reliable before determine the final clinical courses.

KEY WORDS: low β-hCG, ectopic pregnancy, spontaneous abortion, oocyte retrieval

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Time-lapse system Assessment of Phase-1 and Phase-2 Early cleavage on 3-day embryo quality

Jang E.J. a, Lee J.H. a, Kang Y.J. a Hyun C.S., Kim K.H. c

a Reproductive endocrinology, Maria Fertility Hospital, Pyungchon , Koreab Embryology, Maria Fertility Hospital, Seoul, Koreac Reproductive endocrinology, Maria Fertility Hospital, Bucheon , Korea

ABSTRACT

INTRODUCTION: In order to reduce the multiple birth rates without decreasing birth rate overall, it is important to increase the capability of selecting the most optimal embryos for transfer. Improvement of the results obtained with elective single embryo transfer(eSET) can be achieved by better selection of the most viable embryo. This study investigated the predictive value of phase 1 and phase 2 early cleavage(EC) as an additional parameter for selecting the embryo.

AIM: To compare 3-day embryo quality between phase-1 early cleavage embryos, and phase-2 early cleavage embryos using time-lapse system.

MATERIALS AND METHODS: 959 embryos from 109 patients were analyzed for 3-day embryo quality using time-lapse system. Phase-1 early cleavage embryos were defined as embryos reaching 2-cell stage before 23 hours after intracytoplasmic insemination (ICSI), or before 25 hours in case of conventional insemination. Phase-2 early cleavage embryos were defined as embryos reaching 2-cell stage within 23 to 25 hours after ICSI, or within 25 to 27 hours in case of conventional insemination. 2-cell cleavage time after insemination was observed, and recorded by embryoscope™ (Unisense Fertilitech). 3-day embryo quality was evaluated at 63-65 hours after IVF or ICSI, and was graded based on morphology, and number of blastomeres, and the percentage of fragmentation. Each embryos were classified into four categories (A, B, C, D), where category A being the best quality, and D being the worst according to 2011 Istanbul consensus workshop on embryo assessment.

RESULTS: Total number of embryos analyzed was 959. Of the 959 embryos 140(14.6%) embryos were classified as phase-1 early cleavage, 180(18.8%) embryos were classified as phase-2, and 639(66.6%) embryos as non-early cleavage embryos. On 3-day embryo transfer, 64(45.7%) phase-1 early cleavage embryos were classified as category A, 53(37.9%) were classified as category B, 18(12.9%) were classified as category C, and 5(3.5%) were classified as category D. Among phase-2 early cleavage embryos 67(37.2%) were classified as category A, 73(40.6%) were classified as category B, 27(15%) were classified as category C, and 13(7.2%) were classified as category D. (P<0.3480)

CONCLUSION: Phase-1 early cleavage embryos showed better embryo quality compare to phase-2 early cleavage embryos. We believe detailed evaluation of early cleavage embryos may be critical in selection of good quality embryos. Also breaking down early cleavage into 2 phases will help differentiate good quality embryos among early cleavage ones. Further study on implantation rate, clinical pregnancy rate, and live birth rate with these embryos is expected in near future.

KEY WORDS: time-lapse, early cleavage, embryo quality

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