An experience of preimplantation genetic diagnosis for Fabry disease

( Chung-hoon Kim ),( Yijo Jeung ),( Ilkyung Jeon ),( Jae-min Kim ),( Gu-hwan Kim ),( Han-wook Yoo ) 대한산부인과학회 2016 대한산부인과학회 학술대회 Vol.102 No.-

Fabry disease is an X-linked, lysosomal storage disorder caused by a mutation in the GLA gene leading to a deficiency in alpha-galactosidase A enzyme( a-Gal A) activity, which in turn results in accumulation of globotriaosylceramide in the vascular endothelium and smooths muscle cells of different organs, including kidney and heart, finally leading to impairment or failure of organ function. A-34 year old Korean woman suffered from Fabry disease came to our Reproductive Medicine and Infertility Clinic to have a healthy baby who is not affected with Fabry disease. She carries heterozygous c.386T>C(p.Leu129Pro) mutation on exon 1. She has experienced a missed abortion once before, her father died of a Fabry disease and two sisters carry Fabry disease. To carry out PGD for detection of mutation carried by a couple, primers for microsatellite marker (DXS8096 and DXS1225) and mutation detection were designed. 5 oocytes were retrieved and 3 out of 5 were cryopreserved following controlled ovarian stimulation (COS) using GnRH antagonist protocol on the first time. We obtained 16 oocytes in its second attempt, 8 oocytes were fertilized. We performed blastomere biopsy in day 3 embryos of 8 fresh embryos and 2 frozen thawed (FT) embryos. Microsatellite test and sequencing were performed in biopsied cells. Three of fresh embryos were affected with mutation. One of FT embryos was patient and the other one was either carrier or patient. Two unaffected blastocyst was transferred and this resulted in a clinical pregnancy. Chorionic villous sampling was performed when she was in the 12 weeks of pregnancy. The result shows normal DNA and currently she maintains pregnancy. PGD for Fabry disease can provides the hopeful chance to have normal unaffected baby to the Fabry disease patient who have GLA gene mutation.

Effect of metformin treatment on intrafollicular cytokines, ovarian response to gonadotropin and in vitro fertilization outcome in patients with polycystic ovary syndrome

( Chung-hoon Kim ),( Yijo Jeung ),( Joo-hee Lee ),( Jei-won Moon ),( Sung-hoon Kim ),( Hee-dong Chae ),( Byung-moon Kang ) 대한산부인과학회 2016 대한산부인과학회 학술대회 Vol.102 No.-

목적: This study was performed to investigate the effects of metformin on controlled ovarian stimulation (COS), in vitro fertilization (IVF) outcomes, and follicular fluid (FF) adiponectin, tumor necrosis factor-α(TNF-α) and interlekin-6 (IL-6)concentrations in patients with polycystic ovary syndrome (PCOS) undergoing IVF. 방법: A total of 24 infertile patients with PCOS were participated in this study. All patients were pretreated for 3 weeks with monophasic oral contraceptive (OC) before COS. We start COS using GnRH antagonist protocol to all patients after 5 days OC discontinuation .Patients were randomly allocated into the metformin or control groups. In the metformin group, we gave 500 mg of metformin twice a day from the day started from OC to the end of oocyte pick-up (OPU). During the same period, we gave one placebo tablet twice a day to the placebo group. Blood samples from all patients were collected for assays on the day of OC commencement and OPU. 결과: There were no significant differences in patient’s characteristics between the metformin and control groups. The numbers of oocytes retrieved, mature oocytes and fertilized oocytes were comparable between the two groups. However, the number of Grade Ⅰ and Ⅱ embryos in the metformin group was considerably greater than the placebo group (p=0.002). In addition, the metformin group shows the higher concentration of FF adiponectin levels whereas the lower concentrations of FF TNF-α and FF IL-6 compared to the placebo group. Serum levels of cytokines were comparable between the two groups. The rates of clinical pregnancy and embryo implantation were significantly higher in the metformin group than those of the placebo group. 결론: Metformin supplementation during the COS period increases FF adiponectin concentrations and reduces FF TNF-α and IL-6concentrations, and also improves the embryo quality and increase the clinical pregnancy and embryo implantation rates in infertile patients with PCOS undergoing IVF.

Effect of granulocyte colony-stimulating factor on pregnancy outcome following IVF/ICSI in patients with repeated implantation failure

( Chung-hoon Kim ),( Yijo Jeung ),( Soo-yeon Kim ),( Jun-woo Ahn ),( Sung-hoon Kim ),( Hee-dong Chae ),( Byung-moon Kang ) 대한산부인과학회 2016 대한산부인과학회 학술대회 Vol.102 No.-

목적: This study was performed to evaluate the effect of granulocyte colony-stimulating factor (G-CSF) on pregnancy outcome following IVF/ICSI in patients with repeated implantation failure (RIF). 방법: In this retrospective cohort study, we analyzed the clinical outcome of a total of 172 consecutive IVF/ICSI cycles in that recombinant human G-CSF (rhG-CSF) at a dose of 100 mcg was administered on the day of ET and the 3rd or 4th day after ET (study group, n=92) or rhG-CSF was not administered (control group, n=80) in 172 infertile patients with RIF between January 2009 and August 2015. RIF was defined as the failure of good quality embryos (grade I or II) to implant after at least 3 cycles of IVF/ICSI in infertile women without thrombophila and anatomic abnormalities of uterine cavity. 결과: There were no significant differences between the study group and control groups in terms of the age of patients, body mass index (BMI), infertility duration, endocrine profile and indications for IVF/ICSI. COS and IVF results were also comparable between the two groups. The rates of clinical pregnancy and embryo implantation were significantly higher in the study group than those in the control group (p<.01, p<.001, respectively). In singleton pregnant women following IVF/ICSI, serum β-hCG level on the eleventh day after ET was significantly higher in the study group of 195.4 ± 50.3 mIU/ml compared with 105.1 ± 43.7 mIU/ml in control group (p<0.001). 결론: The treatment of G-CSF can improve not only the pregnancy outcomes of IVF/ICSI in patients with RIF but also enhance the development of trophoblast.

The effect of follicle flushing during oocyte retrieval in monofollicular in vitro fertilization in poor responders

( Soo-youn Kim ),( Chung-hoon Kim ),( Yijo Jeung ),( Jei-won Moon ),( Sung-hoon Kim ),( Hee-dong Chae ),( Byung-moon Kang ) 대한산부인과학회 2016 대한산부인과학회 학술대회 Vol.102 No.-

목적: Recently, natural or minimal stimulation IVF have received much attention as a cost-effective alternative for poor responders and the way of successful oocyte retrieval become important subjects. This study was performed to investigate whether follicle flushing during oocyte retrieval in natural or minimal stimulation IVF cycles improves the IVF outcomes in poor responders. 방법: A total of 144 poor responders underwent 717 monofollicular oocyte retrievals in minimal stimulation or natural IVF cycles. Oocyte aspiration was performed using a aspiration needle with double lumen under TV-USG guidance. When metaphase II oocyte is fertilized with sperm, embryo freezing was performed. The oocyte yield rate, the proportion of mature oocytes, the fertilization rate were analyzed in each aspiration steps. 결과: The total 557 oocytes were obtained during 717 oocyte retrievals. Oocyte obtaining rate per aspiration was 13.5%(97/717) without flushing and 30.3%(217/717) with the 1st flushing and 16.7%(120/717) with the 2nd flushing. The oocyte obtaining rate was 6.8%(49/717) with the 3rd flushing and 10.3%(74/717) with more than the 4th flushing. The ratio of the number of oocytes obtained to the total number of oocytes was 13.2% when the number of flushing attempts are more than 4. The ratio of metaphase II of aspirated oocytes was 74% in group without flushing and the other groups showed similar ratio(1st flushing; 94%, 2nd; 84%, 3rd; 76% more than 4; 78%). The proportion of fertilization rate in each group was also similar. (without flushing; 47%, 1st; 63%, 2nd; 63%, 3rd; 63%, 4th ; 33%, 5th ; 60%, 6th; 56%, 7th ; 55%, 8th ; 63%, 9th ; 50%, more than 10; 0%). There were no significant effects on more than 10 times flushing attempts. 결론: The results suggests that follicle flushing during oocyte retrieval significantly increase the oocyte yield and the fertilization rate of oocyte aspirated with flushing is similar to that of oocyte aspirated without flushing in monofollicular IVF for poor responders.

Promoting of early development and implantation competence by secretory leukocyte protease inhibitor in mouse embryos

( Yong-pil Cheon ),( Chung-hoon Kim ),( Yijo Jeung ),( Sung-hoon Kim ),( Hee-dong Chae ),( Byung-moon Kang ) 대한산부인과학회 2016 대한산부인과학회 학술대회 Vol.102 No.-

목적: Secretory leukocyte protease inhibitor (SLPI) has been known a uterine implantation factor and is expressed in reproductive tracts. We investigated on the expression of Slpi and its role in preimplantation embryos. 방법: CD1 female mice were superovulated with PMSG and hCG, and their embryos were collected 46 hours after hCG administration. Two-cell stage embryos more than 80 per each group were cultured with or without recombinant SLPI. The expression of Slpi were analysed with RT-PCR. At 96 hours of hCG, the embryos were transferred to the pseudopregnant surrogate mother. Slpi mRNA specific antisense oligodeoxynucleotide (ODN) were used to knockdown Slpi expression. 결과: Slpi mRNA was detected in all cleavage stages except the morula stage. However, SLPI was localized in all examined stages at the cytoplasm or membrane in a stage dependent manners. Without changing in the total number of cells or inner cells numbers of blastocyst, the treatment of SLPL protein speeded up cleavage. Silencing of Slpi expression delayed the embryo development after 8-cell stage without changes in the total cell number or inner cell numbers of blastocyst. Through the treatment of SLPI protein, a decrease of the development speed and the rate of implantation by Slpi silencing were recovered. Especially, the implantation rate was significantly increased by the SLPI treatment in both in vitro developed and Slpi silenced embryos. 결론: Therefore, we may expect to control the cleavage speed and implantation competence of the early-stage of embryos through SLPI.

Prevalence of type 2 diabetes mellitus and cardiovascular disease in parents of Korean Women with polycystic ovary syndrome

( Ji-yeong Choi ),( Chung-hoon Kim ),( Yijo Jeung ),( Sung-hoon Kim ),( Hee-dong Chae ),( Byung-moon Kang ) 대한산부인과학회 2016 대한산부인과학회 학술대회 Vol.102 No.-

목적: The aim of the present study was to investigate the prevalence of type 2 diabetes mellitus(T2DM), hypertension, coronary heart disease(CHD) and cerebrovascular accident(CVA) in parents of Korean women with PCOS compared to parents of non-PCOS women with WHO group Ⅱ amenorrhea. 방법: Ninety-two PCOS patients and 92 non-PCOS patients(control group) with WHO group Ⅱ amenorrhea were consecutively recruited from Korean patients attending a university-based infertility clinic at the Asan Medical Center between March 2012 and August 2013. They were questioned whether each parent ever had T2DM, hypertension, CHD or CVA. The PCOS diagnosis was based on the revised PCOS diagnostic criteria of the 2003 Rotterdam consensus. The mean value was expressed as the mean ± standard deviation(SD). A Student’s t-test was used to compare the mean values. Chi-square test and Fisher’s exact test were used for the comparisons of fraction. Statistical significance was defined as p<0.05. All analyses were performed using the SPSS statistical package for Windows, version 11.0(SPSS INc, Chicago, IL). 결과: There were no significant differences in PCOS patient’s parents age between the control group. The prevalence of T2DM was significantly higher in fathers of PCOS group of 29.35% compared with 4.35% in fathers of controls(p<0.001). The prevalence of hypertension was significantly higher in both fathers and mothers of PCOS group(p=0.001, p<0.001, respectively). CHD was also more frequently found in fathers of PCOS group than in those of controls(p=0.002). There were no statistically significant differences in a CVA between two groups. 결론: Our study demonstrated that parents of Korean PCOS patients had an increased prevalence of T2DM, hypertension and CHD when compared with parents of non-PCOS patients with WHO group Ⅱ amenorrhea.