체외수정 과배란 유도에서 hCG 주사 당일의 혈청 Progesterone과 Estradiol 농도가 수정율 및 임신율에 미치는 영향에 관한 연구

이은숙,이상훈,배도환,Lee, Eun-Sook,Lee, Sang-Hoon,Bae, Do-Hwan 대한생식의학회 1996 Clinical and Experimental Reproductive Medicine Vol.23 No.1

체외수정 시술을 위해 중앙대학교부속병원 산부인과학 교실 불임크리닉을 방문한 환자중 1993년 3월부터 1994년 8월까지 난관폐쇄로 인하여 불임이 된 환자 113명(119주기)을 대상으로 GnRH-a 병합요법 중 Short protocol 방법으로 과배란시 임신된 45명(47주기)과 임신이 되지 않은 68명(72주기)에서 hCG 투여 당일 혈청내 E2 및 P4 수치를 측정하여 임신의 결과를 비교하였다. 1. 환자의 평균 연령 및 불임기간은 임신군에서 $33.2{\pm}14.8$세 및 $4.2{\pm}3.4$년이었으며 비 임신군에서는 $34.5{\pm}21.7$세 및 $3.9{\pm}2.8$년으로 연령 및 불임기간의 차이는 없었다. 2. hGC 투여 당일 측정한 혈중 E2치는 임신군에서는 $1643{\pm}987.9$ pg/ml, 비임신군에서는 $1367{\pm}875.8$ pg/ml로 임신군에서 유의하게 높았다(P<0.01). 또한 혈중 LH치는 인신군 에서는 $16.7{\pm}10.4$ ng/ml, 비임신군에서는 $18.3{\pm}8.3$ ng/ml로 임신군에서 유의하게 낮았다 (P<0.01). 혈중 P4치는 임신군에서는 $1.0{\pm}0.7$ ng/ml이었고 비임신군에 서는 $2.1{\pm}1.4$ ng/ml로서 임신군에서 유의하게 낮았다(P<0.001). 3. hCG 투여당일 E2/P4 비는 임신군에서 $1865.6{\pm}318.1$, 비임신군에서는 $1324{\pm}377.7$ 로서 유의한 차이가 있었다(P<0.01)(Table 3). 4. 주기당 수정율은 임신군에서 $61.3{\pm}21.3%$, 비임신군에서는 $41.1{\pm}20.3%$로 임신군에서 의미있게 높았고(P<0.01) 이식된 배아의 수는 임신군 47주기에서 $4.2{\pm}2.2$개, 비임신군 72주기에서는 $2.3{\pm}1.2$개로 두 군간의 차이는 없었다(Table 4). 이상에서 임신이 된 군은 임신이 안된 군보다 혈중 progesterone 치가 의미있게 낮았고 혈중 estradiol 치는 의미있게 높았음을 알 수 있었다. 혈중 progesterone 및 estradiol치는 과배란 유도 후 체외수정시술에 있어서 수정율 및 임신율에 영향을 줄 수 있다고 생각되며 이는 체외수정시술시 과배란후 임신의 예후판정에 효용성이 있을것으로 사료된다. Controlled Ovarian hyperstimulation(COH) is generally used to obtain synchronous high quality oocytes in in vitro fertilization-embryo transfer(IVF-ET). Many investigators have studied the relationship between serum hormone levels and outcomes of IVF-ET because there is no accurate estimation method of oocyte quality. Early premature luteinization of follicles before oocyte retrieval is the most troublesome problem in COH for IVF-ET. Gonadotropin-releasing hormone agonists(GnRH-a) are used as adjuncts with gonadotropins for COH in patients undergoing in IVF. The possible benefits of GnRH-a pretreatment include improving oocyte quality, allowing a more synchronous cohort of follicles to be recruited, and preventing premature lueinization hormone surges. In COH of IVF cycles, we investigated whether an elevated progesterone(P4) level on the day of human chorionic gonadotropin(hCG) administration indicates premature luteinization and is associated with a lower fertilization rate. Many investigators have studied that the lower fertilization rates seen in patients with elevated P4 levels might result from an adverse effect of P4 on the oocytes. We hypothesizes that serum P4 levels around the day of hCG may be helpful prediction of out come in IVF-ET cycles. Success rates after COH of IVF-ET cycles are dependent upon many variable factors. Follicular factors including the number of follicles, follicular diameters and especially serum estradiol(E2) levels as an indirect measurement of follicular function and guality have been thought to influence the outcomes of IVF-ET. To assess whether serum P4 and E2 levels affect the fertilization and pregnancy rate, we reviewed the stimulation cycles of 113 patients (119 cycles) undergoing IVF-ET with short protocol with GnRH-a, from March 1993 to August 1994 retrospectively. The serum P4 and E2 levels were compared on the day of hCG in the pregnant group, 45 patients(47 cycles) and in the non-pregnant group, 68 patients (72 cycles) respectively. The serum E2 level in non-pregnant group was $1367{\pm}875.8$ pg/ml which was significantly lower than that of pregnant group, $1643{\pm}987.9$ pg/ml( p< 0.01 ). And the serum P4 level in non-pregnant group was $2.1{\pm}1.4$ ng/ml which was significantly higher than that of pregnant group, $1.0{\pm}0.7$ ng/ml( p< 0.001 ). The fertilization rate was $61.3{\pm}21.3%$ in pregnant group which was higher than that of non-pregnant group, $41.1{\pm}20.2%$ (p< 0.01). We suggest that the serum levels of P4 and E2 on the day of hCG administration are additional parameters that predict the outcomes of IVF-ET cycles.

미수정 및 저수정율의 기왕력을 지닌 체외수정시술 환자에서의 난자 세포질내 정자 주입술을 이용한 미세보조 수정술에 관한 연구

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

Although IVF-ET is widely applied in the treatment of couples with male factor infertility, it may fail in many infertile couples with normal semen parameters, and certain couples cannot be accepted for standard IVF-ET due to unfertilization or extremely low fertilization rate of oocytes. Recently, several procedures of microassisted fertilization (MAF) using micromanipulation have been introduced, and pregnancies and births have been obtained after partial zona dissection (PZD), subzonal insertion (SUZI), and intracytoplasmic sperm injection (ICSI). This clinical study was performed to develop and establish ICSI as an effective procedure of MAF in infertile couples who could not undergo standard IVF-ET repetitively because of failure in fertilization or extremely low fertilization rate of oocytes with the conventional fertilization technique in the previous IVF-ET cycles. From March, 1995 to May, 1996, 27 cycles of IVF-ET with ICSI in 19 infertile patients were included in study group, and the outcomes of ICSI were analyzed according to fertilization rate, cumulative embryo score (CES), and pregnancy rate. The number of oocytes retrieved after controlled ovarian hyperstimulation (COH) was $10.50{\pm}6.13$ in 30 previous cycles, and $10.57{\pm}5.53$ in 27 ICSI cycles. In ICSI cycles, the number of oocytes optimal for ICSI procedure was $7.89{\pm}4.30$, and the fertilization rate of $67.9{\pm}20.2%$ could be obtained after ICSI. The number of embryos transferred was $1.43{\pm}2.40$ in previous cycles, and $4.36{\pm}1.77$ with the mean CES of $41.8{\pm}27.4$ in ICSI cycles. In ICSI cycles, the overall pregnancy rate was 29.6% (8/27) per cycle and 42.1% (8/19) per patient with the clinical pregnancy rate of 22.2% (6/27) per cycle and 31.6% (6/19) per patient. In conclusion, MAF of human oocytes with ICSI is a promising fertilization method for IVF-ET patients, especially with the past history of failure in fertilization or low fertilization rate of oocytes in the previous IVF-ET cycles, and ICSI using micromanipulation procedures applied to human oocytes will provide a range of novel techniques which may dramatically improve the pregnancy rate in IVF-ET program and contribute much to effective management of infertile couples.

체외수정시술시 5 일간의 체외배양을 이용한 포배기 배아 이식술에 관한 연구

김석현(Seok Hyun Kim),구승엽(Seung Yup Ku),지병철(Byung Chul Jee),김은경(Eun Kyung Kim),천은경(Eun Kyung Chun),김희선(Hee Sun Kim),오선경(Sun Kyung Oh),서창석(Chang Suk Suh),최영민(Young Min Choi),김정구(Jung Gu Kim),문신용(Shin Yong 대한산부인과학회 2001 Obstetrics & Gynecology Science Vol.44 No.11

N/A Objective : To evaluate the clinical efficacy of human blastocyst transfer following in vitro culture for five days in vitro fertilization and embryo transfer (IVF-ET), and to compare the efficiency of P1-BL and G1-G2 media in the culture of human blastocyst. Methods : Seventy-two infertile patients undergoing blastocyst transfer in IVF-ET were classified into the conventional IVF (n=52) and ICSI (n=20) groups, and P1-BL (n=37) and G1-G2 (n=35) groups. The outcomes of blastocyst transfer cycles were evaluated and compared, respectively. Results : There were no significant differences in the outcomes of controlled ovarian hyperstimulation (COH) and IVF-ET, such as duration of COH, total dosage of gonadotropins used, serum estradiol (E2) level on hCG day, numbers of oocytes retrieved and fertilized, and number of blastocysts transferred between the conventional IVF and ICSI groups, and between P1-BL and G1-G2 groups, respectively. Total blastulation rate was significantly higher in IVF group than ICSI group (53.6% vs. 37.3%, p<0.05). Implantation, clinical pregnancy, and multiple pregnancy rates were significantly higher in IVF group than ICSI group (15.1% vs. 4.1%, p<0.05; 36.5% vs. 15.0%, p<0.05; 36.8% vs. 0%, p<0.01). There were no significant differences in total blastulation, implantation, and clinical pregnancy rates between P1-BL and G1-G2 groups. However, multiple pregnancy rate was significantly higher in G1-G2 group than P1-BL group (60.0% vs. 8.3%, p<0.05). Conclusions : In human blastocyst transfer following in vitro culture for five days in IVF-ET, conventional IVF showed better outcomes of embryo development and pregnancy than ICSI. The efficiency of P1-BL media in the culture of human blastocyst was comparable to that of G1-G2 media. Further investigation will be necessary to compare the efficiency of various media in the blastocyst culture and to confirm the risk of multiple pregnancy in cases using G1-G2 media.

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.

체외수정시술의 결과를 예측할 수 있는 인자로서 난구세포의 활용에 관한 연구

김광대,김기형,나용진,이규섭,Kim, Kwang-Dae,Kim, Ki-Hyung,Na, Yong-Jin,Lee, Kyu-Sup 대한생식의학회 1999 Clinical and Experimental Reproductive Medicine Vol.26 No.3

Objective: To establish the evaluation system of the quality of oocytes on the basis of the incidence of cumulus cells apoptosis, to investigate the relationships beween the incidence of cumulus cells and the outcomes of IVF-ET. Method: Thirth-four cycles undergoing controlled ovarian hyperstimulation for IVF-ET with tubal infertility (23 cycles) or unexplained infertility (11 cycles) were included in this study. Cumulus cell masses surrounding mature oocyte and co-culture of embryos with autologous cumulus cells during IVF-ET process. The incidence of apoptosis in cumulus cells was assessed by apoptosis detection kit fluorescein. The effect of co-culture using cumulus cells and the incidence of cumulus cells apoptosis. Results: The results were as follows: 1. The incidence of apoptosis in cumulus cells markedly increased in patients aged 40 or over, while the fertilization rate was greatly decreased in those age group. 2. Apoptosis in cumulus cells was found in both the fertilized oocytes and unfertilized oocytes, but the incidence of apoptosis was higher in unfertilized oocytes. 3. There is no clear correlation between apoptosis in cumulus cells and the number of oocytes retrieved. However, the incidence of apoptosis was increased when the number of oocytes retrieved was 5 and fewer in comparison with $6{\sim}10$. 4. Embryo grade was significantly affected by the incidence of apoptosis in cumulus cells. 5. Pregnancy rate of IVF-ET per cycle was 29.4%, and the pregnant group had the higher fertilization rate and a significantly lower incidence of apoptosis in cumulus cells compared with the nonpregnant group. 6. When cumulus cells were used as helper cells in the co-culture of the embryo, in vitro activity of cumulus cells based on morphological change and proliferation did not influence the quality of embryo, but was closely associated with the implantation rate and pregnancy rate, which was enhanced when morphological changes and proliferation of cumulus cells was more active. 7. This difference in the outcome of IVF-ET according to in vitro activity of cumulus cells used for co-cultue was not associated with the incidence of apoptosis in cumulus cells; but rather had likely relations with the different secretion pattern of protein, which may be an embryo trophic factor by cumulus cells. Conclusion: These results suggest that the incidence of apoptosis in cumulus cells can be used in predicting oocyte qualities and the outcomes of IVF-ET. And the effect of co-culture largely depends on the in vitro activity of cumulus cells as well.

골반결핵으로 인한 불임 환자에서 체외수정 시술의 결과

김진영,강인수,Kim, Jin-Yeong,Kang, Inn-Soo 대한생식의학회 2002 Clinical and Experimental Reproductive Medicine Vol.29 No.4

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.

체외수정.배이식 불성공후의 자연주기에 임신이 성립된 5예

배병주,Bai, Byoung-Choo 대한생식의학회 2000 Clinical and Experimental Reproductive Medicine Vol.27 No.1

IVF-ET therapy was originally developed as a method for treating patients with absolute mechanical infertility for whom spontaneous conception is almost impossible. Objective: To report that the recent IVF-ET is now applied to couples not only untreatable tubal infertility but also peritubal periovarial adhesions, endometriosis, male-related or unexplained infertility. Material and Method: Case report. Result: We experienced 5 Pregnancies after unsuccessful IVF-ET attempt with additional non IVF-ET therapy or without therapy. Conclusions: The follicular puncture and ovarian enlargement may result in restoration of pituitary-ovarian axis and peritoneal environment in infertility patients.

체외수정 및 배아이식 후의 일란성 쌍태임신 3례

최성연,정병준,최형민,강영제,이응수,송현진,Choi, Sung-Yun,Jung, Byeong-Jun,Choi, Hyung-Min,Kang, Young-Jae,Lee, Eung-Soo,Song, Hyun-Jin 대한생식의학회 2000 Clinical and Experimental Reproductive Medicine Vol.27 No.3

Objective: To report three cases of monozygotic twinning after IVF-ET transfer. Methods: Private practice in two different assisted reproductive technology clinics. Results: Three intrauterine monozygotic twin pregnancies occurred after IVF-ET. One of them was complicated by cord entanglement, another is progressing normal pregnancy without complication and the other was had a normal pregnancy without complication and delivered twin by cesarean section. Conclusion: The reported prevalence of multiple gestations in IVF-ET is a approximately 30%, and it is only 2.7% to be monozygotic twinning in IVF-ET. We report three cases of monozygotic twining after IVF-ET.

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.

정상 갑상선기능을 가진 여성에서 항갑상선항체가 체외수정시술결과에 미치는 영향

김정훈,Kim, Chung-Hoon 대한생식의학회 1997 Clinical and Experimental Reproductive Medicine Vol.24 No.1

The present study was designed to investigate if antithyroid antibodies (ATA) could affect the pregnancy outcome in euthyroid women undergoing in vitro fertilization and embryo transfer (IVF-ET). From October 1995 to September 1996, 28 euthyroid women with ATA who underwent IVF-ET were studied. Fifty-one euthyroid women without ATA who underwent IVF-ET served as control. Thyroid peroxidase antibody (TPOA) and thyroglobulin antibody (TGA) were assayed using radio ligand assay kits as ATA. All patients included in study and control groups had only tubal factor in infertility. Long protocol of gonadotropin-releasing hormone agonist (GnRH-a) was used for controlled ovarian hyperstimulation (COH) in all patients. There were no significant differences between study and control groups in patient characteristics such as age, infertility duration and hormonal profile. There were also no significant differences between two groups with respect to the clinical response to COH and IVF results such as number of retrieved oocytes, fertilization rate, number of embryos frozen and number of embryos transfered. There were no correlations between ATA (TPOA and TGA) titers and fertilization rate. The clinical pregnancy rate per cycle seemed to be lower in the study group than in the control group (26.3% vs 39.3%), but the difference was not statistically significant. The biochemical pregnancy rate per cycle and miscarriage rate were significantly higher in the study group at 18.4% (7/38) and 40.0% (4/10) compared with 5.6% (5/89) and 11.4% (4/35) in the control group. In the study group, both TPOA and TGA titers were significantly higher in the biochemical pregnancy group than in the clinical pregnancy group or non-pregnancy group. In 10 women with ATA who achieved pregnancy following IVF-ET, both TPOA and TGA titers were significantly higher in the miscarriage group than in the ongoing or delivery group. In conclusion, euthyroid women with ATA appear to represent a less favorable subset within other tubal factor patients when treated with IVF-ET.