체외수정시술시 배아의 보조부화술을 이용한 임신율 향상에 관한 연구

김석현,김광례,채희동,이재훈,김희선,류범용,오선경,서창석,최영민,김정구,문신용,이진용,Kim, Seok-Hyun,Kim, Kwang-Rye,Chae, Hee-Dong,Lee, Jae-Hoon,Kim, Hee-Sun,Ryu, Buom-Yong,Oh, Sun-Kyung,Suh, Chang-Suk,Choi, Young-Min,Kim, Jung-Gu,Moon, S 대한생식의학회 1997 Clinical and Experimental Reproductive Medicine Vol.24 No.1

In spite of much progress in vitro fertilization and embryo transfer (IVF-ET) program, the pregnancy rate remains at 20-30%, and the endometrial implantation rate per embryo transferred at 10-15%. As a result, about 90% of embryos may fail to implant to the endometrium, and many attempts such as optimization of follicular development, improvement of in vitro culture system including coculture, and micromanipulation of zona pellucida have been made to improve embryonic implantation after IVF-ET. Recently, several procedures of assisted hatching (AH) using micromanipulation have been introduced, and pregnancies and births have been obtained after AH. To develop and establish AH as an effective procedure to improve embryonic implantation, AH with partial zona dissection (PZD) was performed in 116 cycles of 89 infertile couples who had previous repeated failures of standard IVF-ET more than two times (Group I: 71 cycles in 54 patients), or who had implantation failure of embryos with good quality (Group II: 15 cycles in 13), or who had undergone AH without specific indication (Group III: 30 cycles in 22) from January, 1995 to Februry, 1996, and the outcomes of AH were analyzed according to pregnancy rate. The number of oocytes retrieved after controlled ovarian hyperstimulation (COH) was $9.9{\pm}7.1$ in Group I, $11.5{\pm}4.5$ in Group II, and $7.9{\pm}6.4$ in Group III. The number of embryos transferred after AH was $4.7{\pm}1.8$ in Group I, $5.3{\pm}1.3$ in Group II, and $3.5{\pm}2.4$ in Group III. The mean cumulative embryo score (CES) was $56.8{\pm}30.0$ in Group I, $76.1{\pm}35.9$ in Group II, and $38.5{\pm}29.9$ in Group III. The overall clinical pregnancy rate per cycle and per patient was 12.7% (9/71) and 16.7% (9/54) in Group I, 33.3% (5/15) and 38.5% (5/13) in Group II, and 6.7% (2/30) and 9.1% (2/22) in Group III, respectively. There were significant differences in the numbers of oocytes retrieved and embryos transferred, CES, and the clinical pregnancy rate per cycle among three groups. There was a significant inverse correlation between basal serum FSH level and CES, and no pregnancy occurred in patients with CES less than 20. In conclusion, AH of human embryos with PZD prior to ET has improved the implantation and pregnancy rates in IVF-ET patients with the past history of repeated failures, especially in spite of transfer of embryos with good quality, and AH will provide a range of novel techniques which may contribute much to effective management of infertile couples.

착상 전 유전진단 기술 개발의 동물실험 모델로서 할구 생검된 생쥐 배아에서 동결보존 융해 후 배아 발생 양상과 공배양 효과에 관한 연구

김석현,김희선,류범용,최성미,방명걸,오선경,지병철,서창석,최영민,김정구,문신용,이진용,채희동,김정훈,Kim, Seok-Hyun,Kim, Hee-Sun,Ryu, Buom-Yong,Choi, Sung-Mi,Pang, Myung-Geol,Oh, Sun-Kyung,Jee, Byung-Chul,Suh, Chang-Suk,Choi, Young-Min,Kim, Jung 대한생식의학회 2000 Clinical and Experimental Reproductive Medicine Vol.27 No.1

Objective: The effects of cryopreservation with or without coculture on the in vitro development of blastomere-biopsied 8-cell mouse embryos were investigated. This experimental study was originally designed for the setup of a preclinical mouse model for the preimplantation genetic diagnosis (PGD) in human. Methods: Eight-cell embryos were obtained after in vitro fertilization (IVF) from F1 hybrid mice (C57BL(표현불가)/CBA(표현불가)). Using micromanipulation, one to four blastomeres were aspirated through a hole made in the zona pellucida by zona drilling (ZD) with acid Tyrode's solution (ATS). A slow-freezing and rapid-thawing protocol with 1.5M dimethyl sulfoxide (DMSO) and 0.1M sucrose as cryoprotectant was used for the cryopreservation of blastomere- biopsied 8-cell mouse embryos. After thawing, embryos were cultured for 110 hours in Ham's F-10 supplemented with 0.4% bovine serum albumin (BSA). In the coculture group, embryos were cultured for 110 hours on the monolayer of Vero cells in the same medium. The blastocyst formation was recorded, and the embryos developed beyond blastocyst stage were stained with 10% Giemsa to count the total number of nuclei in each embryo. Results: The survival rate of embryos after cryopreservation was significantly lower in the blastomere-biopsied (7/8, 6/8, 5/8, and 4/8 embryos) groups than in the non-biopsied, zona intact (ZI) group. Without the coculture, the blastocyst formation rate of embryos after cryopreservation was not significantly different among ZI, the zona drilling only (ZD), and the balstomere-biopsied groups, but it was significantly lower than in the non-cryopreserved control group. The mean number of cells in embryos beyond blastocyst stage was significantly higher in the control group ($50.2{\pm}14.0$) than in 6/8 ($26.5{\pm}6.2$), 5/8 ($25.0{\pm}5.5$), and 4/8 ($17.8{\pm}7.8$) groups. With the coculture using Vero cells, the blastocyst formation rate of embryos after cryopreservation was significantly lower in 5/8 and 4/8 groups, compared with the control, 7/8, and 6/8 groups. The mean number of cells in embryos beyond blastocyst stage was also significantly lower in 4/8 group ($25.9{\pm}10.2$), compared with the control ($50.2{\pm}14.0$), 7/8 ($56.0{\pm}22.2$), and 6/8 ($55.3{\pm}25.5$) groups. Conclusion: After cryopreservation, blastomere-biopsied mouse embryos have a significantly impaired developmental competence in vitro, but this detrimental effect might be prevented by the coculture with Vero cells in 8-cell mouse embryos biopsied one or two blastomeres. Biopsy of mouse embryos after ZD with ATS is a safe and highly efficient preclinical model for PGD of human embryos.

미세수술적 난관복원술 후 임신에 실패한 환자에서의 체외수정시술 결과

김석현,홍준석,구승엽,서창석,최영민,김정구,문신용,이진용,Kim, Seok-Hyun,Hong, Joon-Seok,Ku, Seung-Yup,Suh, Chang-Suk,Choi, Young-Min,Kim, Jung-Gu,Moon, Shin-Yong,Lee, Jin-Yong 대한생식의학회 2001 Clinical and Experimental Reproductive Medicine Vol.28 No.4

Objective: To evaluate the clinical outcomes and influencing factors of in vitro fertilization and embryo transfer (IVF-ET) in patients with failed pregnancy after microsurgical reversal of tubal sterilization. Materials and Methods : From January, 1997 to December, 2000, IVF-ET was performed in two groups; the study TR (tubal reanastomosis) group consisted of 147 cycles in 66 patients with failed microsurgical reversal of tubal sterilization, and the control group of 115 cycles in 67 patients with bilateral tubal occlusion (BTO). The two groups were evaluated and compared for clinical characteristics, clinical pregnancy rates, and factors influencing the outcomes of IVF-ET. Results: Compared with the control BTO group, age and the previous parity were significantly higher ($36.3{\pm}2.7$ vs. $33.6{\pm}2.0$ years, p<0.05; $1.6{\pm}0.7$ vs. $0.2{\pm}0.4$, p<0.05), and the clinical pregnancy rate per cycle was significantly lower (23.8% (35/147) vs. 29.3% (34/115), p<0.05) in the TR group. Difference in the clinical pregnancy rates was age-related, since there was no significant difference between the two groups, except for the previous parity ($1.6{\pm}0.7$ vs. $0.1{\pm}0.3$, p<0.05), when the patients aged 37 years or older were excluded. No difference was found in terms of the following: the proportion of controlled ovarian hyperstimulation (COH) cycles with GnRH agonist ultrashort protocol, the duration of COH, the dosage of gonadotropins used, and the numbers of oocytes retrieved and of embryos transferred, irrespective of age correction. Conclusions: The outcomes of IVF-ET following the failed microsurgical reversal of tubal sterilization depend upon patient age. The previous fertility of patients does not seem to be a factor of better IVF-ET prognosis.

고효율 직접교환기(Direct Contact Exchanger)의 특성과 응용

김석현,Kim, Suk-Hyun 대한설비공학회 1986 설비저널 Vol.15 No.2

체외수정시술 후 임신된 환자에서 혈중 ${\beta}-hCG$ 측정에 의한 임신 결과 예측에 관한 연구

김석현,서창석,최두석,최영민,신창재,김정구,문신용,이진용,장윤석,Kim, Seok-Hyun,Suh, Chang-Suk,Choi, Doo-Seok,Choi, Young-Min,Shin, Chang-Jae,Kim, Jung-Gu,Moon, Shin-Yong,Lee, Jin-Yong,Chang, Yoon-Seok 대한생식의학회 1992 Clinical and Experimental Reproductive Medicine Vol.19 No.1

Serum level of ${\beta}$ subunit of human chorionic gonadotropin (${\beta}-hCG$) was studied to evaluate its predictability of pregnancy outcome in 98 in vitro fertilization and embryo transfer(IVF-ET) patients using gonadotropin-releasing hormone(GnRH) agonist. Serial serum ${\beta}-hCG$ levels were established for 42 singleton pregnancies, 20 normal multiple pregnancies, 18 preclinical abortions, 14 clinical abortions and 4 ectopic pregnancies. In comparison to normal singleton pregnancies, multiple pregnancies showed significantly higher ${\beta}-hCG$ levels on the post-ET day 10 to 13 and day 24 to 25. Clinical abortions did not show significantly lower ${\beta}-hCG$ levels in early pregnancy except the post-ET day 16-17, but showed significantly lower ${\beta}-hCG$ levels from the post-ET day 22, compared with singleton pregnancies. Preclinical abortions showed significantly lower ${\beta}-hCG$ levels than those of singleton pregnancies. Ectopic pregnancies showed lower ${\beta}-hCG$ levels than those of singleton pregnancies without statistical significance. In conclusion, determination of serum ${\beta}-hCG$ level in early pregnancy is a useful tool for the prediction of preclinical abortions and multiple pregnancies and serial measurement of serum ${\beta}-hCG$ levels will be helpful in predicting clinical abortion.

난자 세포질내 정자 주입술을 이용한 체외수정시술시 누적임신율에 관한 연구

김석현(Seok Hyun Kim),심순섭(Soon Sup Shim),지병철(Byung Chul Jee),최성미(Sung Mi Choi),김희선(Hee Sun Kim),류범용(Buom Yong Ryu),오선경(Sun Kyung Oh),서창석(Chang Suk Suh),최영민(Young Min Choi),배광범(Kwang Bum Bai),김정구(Jung Gu 대한산부인과학회 2001 Obstetrics & Gynecology Science Vol.44 No.3

N/A Objective : To evaluate the cumulative pregnancy rate(CPR) of in vitro fertilization and embryo transfer(IVF-ET) with intracytoplasmic sperm injection(ICSI). Methods : Medical records of 260 infertile patients undergoing 519 cycles of IVF-ET with ICSI from January, 1994 to December, 1999 were retrospectively reviewed. The CPR beyond 12 weeks of gestation was estimated by Kaplan-Meier method. The CPRs were compared by log-rank test between groups divided by age of patients, indication of ICSI, and method of sperm retrieval for ICSI. Results : As 70 patients achieved an on-going pregnancy after IVF-ET with ICSI, the PR was 26.9% per patient and 13.5% per cycle. The overall CPR was 54.9% after 6 cycles of IVF-ET with ICSI. As expected, age had a significant strong effect on the CPR; CPRs afer 4 cycles of ICSI were 61.8% in the age group of 30 years(n=81), 43.7% in 31-35 years(n=106), and 15.3% in 36 years(n=73). There was no significant difference in the CPR between abnormal semen analysis group(n=184) and prior low fertilization rate group(n=66). In abnormal semen analysis group, the CPR of surgically retrieved sperm subgroup(n=60) was not significantly different from that of ejaculated sperm subgroup(n=124). Conclusions : The CPR of IVF-ET with ICSI was presented, and it could be of much help in the clinical counseling of IVF-ET patients. ICSI technique could be used successfully for IVF-ET in infertile couples who had the male factor infertility or the past history of low fertilization rate in the previous cycles.

[회원기고] 색연필 과학만화

김석현(Suk Hyun KIm) 한국진공학회 2018 진공 이야기 Vol.5 No.3

생쥐 난자의 동결보존 후 세포질내 방추사의 손상에 관한 연구

김석현(Seok Hyun Kim),최성미(Sung Mi Choi),지병철(Byung Chul Jee),김희선(Hee Sun Kim),오선경(Sun Kyung Oh),서창석(Chang Suk Suh),최영민(Young Min Choi),김정구(Jung Gu Kim),이진용(Jin Yong Lee),문신용(Shin Yong Moon) 대한산부인과학회 2001 Obstetrics & Gynecology Science Vol.44 No.9

N/A Objective : To investigate the extent of meiotic spindle damages in cryopreserved-thawed mouse mature oocytes. Methods : After slow freezing and ultra-rapid thawing using 1.5M dimethylsulfoxide(DMSO), mouse mature oocytes were stained by anti-α tubulin monoclonal antibody. The meiotic spindle and chromosomes configuration were assessed using confocal microscope. The influence of time to post-hCG oocytes retrieval (i.e. 12 hrs vs 17 hrs) was also evaluated. Results : The normal meiotic spindles were observed in 89.8% of post-hCG 12 hrs group, and 80.1% of post-hCG 17 hrs group, and these were significantly lower than that of each unfreezed control. Post-hCG 12 hrs group showed a significantly higher incidence of normal meiotic spindles, compared with post-hCG 17 hrs group. Conclusion : The extent of meiotic spindle damages was significantly increased after cryopreservation in mouse mature oocytes. We proposed that 12 hrs interval of post-hCG oocytes retrieval may be more beneficial.

신부전이 없는 환자에서 발생한 Cefepime에 의한 뇌병증 1예

김석현 ( Suk Hyun Kim ),남영희 ( Young Hee Nam ),전동섭 ( Dong Sub Jeon ),이혜원 ( Hye Won Lee ),남희주 ( Hee Joo Nam ),이수걸 ( Soo Keol Lee ) 대한천식알레르기학회 2014 Allergy Asthma & Respiratory Disease Vol.2 No.3

Cefepime is an extended-spectrum, fourth-generation cephalosporin that has been widely used for approved indications such as febrile neutropenia. Common adverse events of cefepime include headache, skin rash, gastrointestinal problems, and fever. However, encephalopathathy caused by cefepime has been sporadically reported worldwide over the last decade. We experienced a rare case of cefepime-induced encephalopathy. A 75-year-old man with a 30-year history of chronic obstructive pulmonary disease was admitted to the medical intensive care unit under a diagnosis of pneumonia. Initial antibiotic therapy was started with piperacillin/sulbactam and ciprofloxacin. His condition was improved with this treatment. About 2 months later, his condition was aggravated again, with mild fever and purulent sputum. Intravenous cefepime was selected on the basis of antibiotic susceptibility to Pseudomonas aeruginosa isolated from his sputum. However, his mentality became drowsy 48 hours after cefepime adminstration. He showed tremors and right facial paralysis. Neurologic examination for motor power and sensory function revealed normal findings. Laboratory tests, including serum electrolytes, glucose, osmolality, and ammonia, gave normal results. Brain magnetic resonance imaging showed chronic ischemic and atropic changes, and an electroencephalography revealed triphasic waves. The administration of cefepime was stopped, and his symptoms started to improve within 48 hours. Electroencephalography results became normalized, and he completely recovered within 48 hours after discontinuation of cefepime.

호르몬 대체요법을 받고 있는 폐경여성에서 혈청 인슐린유사 성장인자의 변화양상과 골밀도의 변화양상사이의 연관성

김석현(Seok Hyun Kim),최영민(Young Min Choi),서창석(Chang Suk Suh),김정구(Jung Gu Kim),신찬수(Chan Soo Shin) 대한산부인과학회 2000 Obstetrics & Gynecology Science Vol.43 No.1

목적: 폐경여성 여성에서 호르몬 대체요법이 혈청 IGF에 미치는 영향과 치료후 혈청 IGF의 변화양상이 골밀도 변화를 반영할 수 있는지를 알아보고자 한다. 연구 방법: Premarin 단독요법, 또는 premarin-MPA 병합요법을 시행받고 있는 폐경 여성에서 치료전, 치료후 3, 6, 12개월에 방사면역법으로 혈청 IGF-I, IGF-II 농도를 측정하고 요추, 대퇴 근위부의 골밀도를 치료전, 치료후 12개월에 이중 에너지 방사선 흡수계측기(DEXA)로 측정하여 혈청 IGF-I, IGF-II 농도의 변화양상과 치료후 1년에서의 골밀도 변화양상을 분석하고 이들사이의 상관성을 분석하였다. Paired t-test, student's t-test, repeated measures ANOVA test, Pearson's coefficient를 통계분석에 사용하였다. 결과: 호르몬대체요법을 시행한 후 요추 및 대퇴 근위부에서 골밀도 증가가 있었으나 투여방법에 따른 차이가 없었다. Premarin-MPA 투여군에서만 치료후 3, 6, 12개월에 혈청 IGF-I 농도의 유의한 감소를 보였으며 혈청 IGF-II 농도의 경우에는 premarin 단독투여군, premarin-MPA 투여군 모두에서 치료후 6, 12개월에 유의하게 증가하였다. 혈청 IGF의 변화율은 호르몬 반응성 여부 에 따른 유의한 차이가 없었다. 치료전 및 치료후 혈청 IGF-II의 변화양상과 치료후 1년간 골밀도 변화양상사이에 연관성이 없었으나 치료후 제 6개월에서는 혈청 IGF-I의 변화양상과 Ward's triangle에서의 골밀도 변화양상사이에서 유의한 음성 상관관계가 있었다. 결론: 호르몬대체요법은 혈청 IGF에 영향을 미치며 혈청 IGF-I의 변화양상으로 Ward's triangle에서의 골밀도 변화양상을 예측할 가능성이 있다. Purposes: To evaluate the effect of hormone replacement therapy(HRT) on serum insulin-like growth factors(IGFs) levels and to investigate if changes in serum IGFs reflect changes in BMD after HRT in postmenopausal women. Material & methods: IGF-I and IGF-II were measured by radioimmunoassay after Bio-spin P-10 seperation in sera obtained every 3 months from postmenopausal women who was taking premarin alone (premarin group; n=17) or premarin-medroxyprogesterone acetate(MPA group; n=42) for 1 year. Also, bone mineral density(BMD) were determined before and 1 year after HRT by dual energy X-ray absorptiometry(DEXA). All statistics were performed by Paired t-test, student's t-test, repeated measures ANOVA test, Pearson's coefficient. Results: HRT increased BMD of the lumbar spine and proximal femur in both premarin group and MPA group, but any difference in degreee of increase in BMD was not noted between premarin group and MPA group. Compared with pretreatment levels, serum IGF-I levels decreased at 3, 6 and 12 months after therapy only in latter group whereas serum IGF-II levels increased at 6 and 12 months after HRT in both groups. Changes in serum IGF-I and IGF-II levels during therapy did not show any difference by the bone response to HRT. Changes in serum IGF-II levels after HRT did not correlated with the 1 year changes in BMD at any skeletal sites studied, but changes in serum IGF-I levels from pretreatment to 6 months after HRT was negatively correlated with change in BMD of Ward's triangle. Conclusion: HRT influences serum IGF levels in postmenopausal women and changes in serum IGF-I levels may predict the changes in BMD of Ward's triangle after HRT.