• Clinical and Experimental Reproductive Medicine
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• 제22권2호
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• pp.123-130
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• 1995

Many types of medication regimens have been used for controlled ovarian hyperstimulation for assisted reproductive technique(ART). Questions are now being raised regarding how to lower the escalating costs of assisted reproduction and decrease the extent of patient discomfort and disruption of life style without sacrificing success rates. In this investigation, from January 1994 through August 1994 patients presenting to the Chung-Ang university hospital, infertility clinic were offered the option of the clomiphene citrate (CC)/single Human Menopausal Gonadotropin(HMG) combination and conventional GnRH-agonist combination method. 60 patients (78 cycles) were given CC/single HMG combination as a study group, and 78 patients (102 cycles) were given conventional GnRH-a combined ultrashort protocol as a control group for IVF-ET program and the resulting number of oocyte retrieved, embryo produced, and pregnancy initiated were compared. There were no differences between the two groups in mean age, serum $E_2$, LH and FSH level on menstrual cycle day 2. HMG requirement was 2 ampules in study group and $24.2{\pm}6.8$ ampules in control group. On the day of HCG injection, serum LH and FSH levels were not significantly different, but serum $E_2$, was significantly higher in control group(p<0.001). There was relatively well endometrial quality in control group but not significant compare to study group. In control group, numbers of retrieved oocyte and transferred embryo were significantly more than study group(p<0.001). Fertilization rate was not significantly different in the two groups and pregnancy rates were 20.2% in study group 28.4% in control group(p<0.001). CC/single HMG protocol for IVF-ET is less expensive than GnRH-a combined ultrashort protocol and minimizes patients discomfort. In addition, CC/single HMG protocol produces acceptable pregnancy rate and represents an attractive alternative to select patients undergoing IVF-ET.

• Clinical and Experimental Reproductive Medicine
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• 제21권3호
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• pp.241-245
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• 1994

Despite increasing success rate of IVF, poor response to ovarian stimulation remains a problem. So, attempts to improve ovarian responses, for example, by using combined gonadotropin-releasing hormone analogue(GnRH-a) and human menopausal gonadotropin(hMG) have shown limited success. It is reported that response of granulosa cells in vitro to FSH is stimulated by co-incubation with IGF-l, and IGF-l production can be increased by growth hormone. This suggest that combination regimen of G.H. and hMG may augment follicle recruitment. In fifteen patients who had previous history of poor ovarian response to gonadotropin stimulation after pituitary suppression with mid -luteal GnRH-a, the effectiveness of cotreatment with G.H. in IVF program was evaluated using a combination regimen of G.R. and hMG at Korea University Hospital IVF Clinic. Ovarian responses to gonadotropin stimulation in control and GH-treated cycles assessed by total dose and duration of hMG treatment, follicular development and peak $E_2$ level, number of eggs retrieved, and fertilization rates were also assessed. In each group, serum and follicular fluid IGF-1 concentrations on day of egg collection were measured by RIA after acidification and extraction by reveresed phase chromatography. Patients receiving G.H. required fewer days and ampules of gonadotropins, developed more oocytes, and more embryos transferred. But, the differences were not statistically significant, except the duration of hMG treatment. Our data showed a significantly higher concentration of IGF-l in the serum, not in the follicular fluid, of patients treated with G.H. compared with control group. These data suggest that growth hormone treatment does not improve the ovarian response in women with limited ovarian reserve to gonadotropin stimulation for IVF.

• Clinical and Experimental Reproductive Medicine
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• 제30권1호
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• pp.95-103
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• 2003

Objective : To assess and compare the clinical outcomes between GnRH agonist long protocol and GnRH antagonist short protocol in oocyte donation program. Materials and Methods: Of total 18 oocyte donation cycles, controlled ovarian hyperstimulation (COH) were performed with GnRH agonist long protocol and GnRH antagonist short protocol in initial 9 cycles and later 9 cycles, respectively. Oral estradiol valerate and progesterone in oil we re administrated to all recipients for endometrial preparation. Oral estradiol administration was started from donor cycle day 1 after full shut down of gonadal axis with GnRH agonist in patients with ovarian function. Progesterone was injected from oocyte retrieval day of donor initially, then continuously till pregnancy 12 weeks if pregnancy was ongoing. We compared the parameters of clinical outcomes, such as number of the retrieved oocytes, fertilization rate, high grade embryo production rate, clinical pregnancy rate, implantation rate, ongoing pregnancy rate, COH duration, total gonadotropin dose for COH between GnRH agonist long protocol group and GnRH antagonist group. Statistical analysis was performed using Mann-Whitney test, p<0.05 was considered as statistically significant. Results: The number of retrieved oocytes, fertilization rate, high grade embryo production rate, clinical pregnancy rate, implantation rate, ongoing pregnancy rate were $14.89{\pm}7.83$, 81%, 64%, 78%, 31%, 78%, respectively in GnRHa long protocol group and $11.22{\pm}8.50$, 79%, 64%, 67%, 34%, 56%, respectively in GnRH antagonist group. There was no significant differences in parameters of clinical outcomes between 2 groups (all p value >0.05). Duration and total gonadotropin dose for COH were $10.94{\pm}1.70$ days and $43.78{\pm}6.8$ vials in 18 cycles, $12.00{\pm}1.73$ days and $48.00{\pm}6.93$ vials in agonist group, $9.88{\pm}0.78$ days and $39.55{\pm}3.13$ vials in antagonist group, respectively. In GnRH agonist long protocol group, significantly longer duration and higher gonadotropin dose for COH were needed (p=0.012). Conclusion: In oocyte donation program, clinical outcomes from controlled ovarian hyperstimulation with GnRH antagonist were comparable to those from GnRH agonist long protocol group, so controlled ovarian hyperstimulation with GnRH antagonist may be effective as GnRH agonist long protocol. At least there may not be harmful effects of GnRH antagonist on oocyte development and quality.

• Clinical and Experimental Reproductive Medicine
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• 제28권2호
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• pp.161-167
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• 2001

Objective: Granulocyte-macrophage colony stimulating factors known to be secreted in murine and human reproductive tract. The development of human, bovine and murine embryos could be promoted by addition of GM-CSF in culture medium. However, the pregnancy and implantation rate of embryos cultured in GM-CSF have not been evaluated. The aim of this study was to assess the effect of GM-CSF in embryo development, pregnancy and implantation rate. Methods: A total of 191 IVF cycles were divided into control and GM-CSF supplement group (control=96, GM-CSF=95). The embryos were cultured for three day with or without 2 ng/ml of recombinant human GM-CSF. The quality of embryo, developmental velocity, pregnancy and implantation rates were compared. Results: There was no difference in age, number of gonadotropin ampules used, number of oocytes and fertilization. The number of ICSI cycle was higher in GM-CSF group. In GM-CSF group, G-1 grade embryos were the highest in proportion (56.4%), while G-2 grade embryos were highest (44.3%) in control group. The developmental velocity of embryos were not different between GM-CSF and control group. The pregnancy and implantation rates were significantly higher in GM-CSF group than control (47.4% vs. 33.3%, 17.0% vs. 11.1% respectively). Conclusion: By adding GM-CSF in culture medium, the quality of embryo, pregnancy and implantation rate could be improved.

• 한국발생생물학회지:발생과생식
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• 제5권2호
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• pp.123-129
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• 2001

포유동물의 난포내 난자의 성숙 시에는 난자를 둘러싸고 있는 난구세포의 확장 현상이 일어나는데 이 현상에는 hyaluronic acid 뿐만 아니라 다른 성분도 관여하는 것으로 알려져 있다. 본 연구는 조직 재구성 과정에서 중요한 역할을 하는 matrix metalloproteinase(MMP)가 사람의 성숙한 난자-난구 복합체의 extracellular matrix(ECM)에 존재하는지의 여부를 알아보고자 하였다. 체외수정 시술 시에 얻어지는 사람의 난자-난구 복합체를 재료로 zymography와 western blotting 방법으로 조사한 결과 난자-난구 복합체의 ECM에는 300kDa, 240kDa, 200kDa, 180kDa, 116kDa, 97kDa, 그리고 84kDa의 분자량을 갖는 적어도 7종류의 gelatinase들이 존재하는 것이 관찰되었다. 이들 gelatinase가 MMP인지를 확인하기 위해 zymography 동안에 ethylenediaminetetraacetic acid 혹은 phenanthroline 등의 MMP 억제제를 처리한 결과 7종류 모두의 gelatinase 효소활성이 사라졌다. 또한 MMP의 활성제인 aminophenylmercuric acetate를 zymography를 시행하기 전에 ECM에 처리한 결과 200kDa, 180kDa, 97kDa, 84kDa의 gelatinase활성이 사라지고, 대신에 80kDa, 65kDa, 60kDa의 분자량을 갖는 새로운 gelatinase 단백질의 효소활성이 나타났다. 이로 미루어 사람 난자-난구 복합체의 ECM에는 여러 종류의 gelatinase들이 있으며 이들 중 일부는 MMP-2와 MMP-9의 동위효소들인 것으로 여겨진다.

• Clinical and Experimental Reproductive Medicine
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• 제29권4호
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• pp.287-294
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• 2002

Objectives: Pelvic tuberculosis (TB) causes infertility despite of anti-TB chemotherapy and IVF-ET is effective treatment to achieve pregnancy. The aim of this study is to assess the outcomes of IVF-ET in pelvic TB, especially according to main Tb lesion, and to investigate the factors affecting the successful outcome. Methods: A total of 135 IVF-ET cycles were performed in 54 patients with pelvic TB and the outcome was compared with that of control group with tubal factor not associated with TB in 301 cycles, 227 patients. Anti-TB chemotherapy was performed in the patients with pelvic TB. Pregnancy rate was compared according to main TB lesion as salpingitis, peritonitis, and endometritis. In the patients with endometrial TB, when complicated with uterine synechia, hysteroscopic lysis was done before IVF-ET and pregnancy rate was compared according to the presence of uterine synechia. Results: There was no significant difference in peak E2 ($2,790{\pm}280.1$ vs $2,554{\pm}101.2$, p>0.05), the number of retrieved oocytes ($13.5{\pm}0.7$ vs $12.5{\pm}0.4$, p>0.05) and fertilized oocytes ($7.7{\pm}0.5$ vs $7.8{\pm}0.3$, p>0.05) between patient and control group. Clinical pregnancy rate per transfer in pelvic TB group was 22.9% and showed no difference from that of control group (24.3%, p>0.05). Although it was not statistically significant, pregnancy rate in the endometrial Tb (18%) was lower than that in the salpingitis (28.5%) or peritonitis (26.5%) (p>0.05). In the endometrial TB with uterine synechia, pregnancy rate was significantly lower than that of the patients without synechia even after hysteroscopic lysis (9.7% vs 31.6%, p<0.05). Conclusion: IVF-ET after anti-TB chemotherapy is the most effective treatment to achieve pregnancy in infertile patients with pelvic TB. Because the presence of endometrial TB and resulting uterine synechia affects the outcome of IVF-ET, thorough evaluation for endometrium with endometrial biopsy and hysteroscopy is important to predict the prognosis of IVF-ET treatment.

• Clinical and Experimental Reproductive Medicine
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• 제21권3호
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• pp.233-240
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• 1994

This study was conducted to compare the endocrine milieu, and pregnancy rates in In Vitro Fertilization and Embryo Transfer(IVF-ET) program employing combined with gonadotropin releasing hormone agonist(GnRH-a) and pergonal(LH 75lU+FSH 75lU) when either human chorionic gonadotropin(HCG) or progesterone were used for luteal phase support. A total number of 40 IVF-ET treatment cycles were prospectively studied. Ovarian hyperstimulation method was modified ultrashort protocol using GnRH-a. All patients started Decapeptyl at menstrual cycle day # 2, and HMG was started at # 3 days. When leading follicle was ${\geqq}$18mm or at least two follicles were ${\geqq}$14mm in diameter, HCG 10000lU intramuscularly was injected. After 36 hours HCG administration, oocytes were retrieved as usual guided by transvaginal ultrasound. Embryo were transfered 36-48 hours later. The patient's cycles were prospectively randomized to receive HCG(20cycles) or Progesterone (20cycles) for luteal support. The progesterone group received 25mg 1M starting from the day of ET. The HCG group received 1500IU 1M. on days 0, +2, +5 after ET. Estadiol($E_2$) and Progesterone($P_4$) were measured on the day of oocyte aspiration, ET day, and every 6 days thereafter. Results were follows as; 1. Estradiol, progesterone and LH levels on the day of HCG trigger, retrieved oocytes and number of transfered embryo were not significantly different in both groups. 2. On the day of aspiration and embryo transfered day, $E_2$, $P_4$ level were significantly higher in progesterone group than HCG group(p<0.01). 3. $E_2$, $P_4$ level on 6 days after ET were significantly higher in progesterone group than HCG group(p<0.01). But, $P_4/E_2$ ratio was not different in both groups. 4. $E_2$, $P_4$ level 12 days after ET were decreased abruptly in both groups and higher hormonal level appeared in HCG group(P<0.01). 5. The total pregnancy rate in the HCG group was 40% (8/20) and in the progesterone group 15%(3/20). 6. Comparing the pregnant and nonpregnant cases progesterone group was not different the hormonal status. In HCG group, pregnant cases appeared in higher $P_4$, $P_4/E_2$ ratio than nonpregnanct cases(P<0.01).

• 한국수정란이식학회지
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• 제19권2호
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• pp.155-163
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• 2004

본 연구는 도축돈의 난소로부터 난자를 채취하여 체외배양시킨 후 세포 안정제와 원심분리 그리고 OPS를 이용한 유리화동결 하였다. 동결 융해한 수정란을 경산돈에 외과적 또는 비외과적으로 이식하여 자돈을 생산하는 것을 목적으로 수행하였다. ${\cdot}$ 도축돈 난소로부터 채란되어진 돼지 미성숙난은 Funahashi 등(1994) 방법에 따라 체외 성숙-수정-배양하였다. 체외배양액은 glucose-free NCSU 23을 이용하였으며, 5일째에 10% Fatal bovine serum (FBS)을 첨가 배반포로 발달을 유도하였다. ${\cdot}$ 체외배양된 수정란은 7.5${\mu}$g.mL cytochalasin B에 30분 처리 후 13,000 rpm에 13분간 원심 분리하였고, ethylene glycol(EG) 동결액으로 처리한 뒤 OPS를 이용하여 동결${\cdot}$융해하였다. ${\cdot}$ 동결수정란과 비동결수정란을 plastic straw에 loading 한 후 3두에는 경산돈에 외과적 방법으로 각각 100개, 100개의 동결수정란과 대조군으로 34개의 비동결수정란을 이식하였고 다른 3두에는 비외과적 방법으로 각각 150개, 150개의 동결수정란과 대조군으로 100개의 비동결수정란을 각각 이식하였다. 외과적이식돈의 대조군에 사용한 신선수정란은 비경산돈 3두에서 채란하였다. ${\cdot}$이식 결과 6두 모두 지연성 발정을 보였으며 이중 동결수정란 이식돈은 임상적으로 정상이였으나 비동결수정란은 이식한 경우는 자궁내막염과 복강탈장이 관찰되었다. 주요 원인은 시술시 기술의 미숙과 야외수술에 의한 감염, 난자의 이동과 수송에 의한 영향 그리고 주입 미숙 등이 주요 원인인 것으로 생각되며 융해 후 생존효율이 높은 수정란의 준비, 이식 기술의 개선과 자궁상태가 청결한 비경산돈의 이식으로 임신율을 높일 수 있을 것으로 기대된다.

• Clinical and Experimental Reproductive Medicine
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• 제37권3호
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• pp.253-259
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• 2010

목 적: 과배란유도 환자에서의 우성난포의 성장속도와 임상인자들과의 연관성을 평가하고자 하였다. 연구방법: 체외수정시술을 위한 과배란유도 313주기를 대상으로 혈중 호르몬 농도를 측정하고 과배란유도 주기 중 난포 직경의 변화를 초음파를 이용하여 연속적으로 측정하였다. 우성난포의 성장 속도를 계산하고, 임상지표와의 연관성을 분석하였다. 결 과: Gonadotropin releasing hormone 작용제와 길항제 주기 사이에 우성난포의 성장속도의 유의한 차이는 관찰되지 아니하였다. 우성난포의 성장속도와 환자의 연령, 체질량 지수, 생리 시작 3일의 follicle stimulating hormone, luteinizing hormone, 에스트라디올, 획득 난자의 수, 수정률 등의 임상지표는 유의한 연관성이 없었다. 결 론: 본 연구 결과는 우성난포의 성장속도는 난소 반응을 포함한 임상지표와 연관성이 없는 독립적인 변수임을 시사한다.

• Clinical and Experimental Reproductive Medicine
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• 제19권1호
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• pp.41-48
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• 1992

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.