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1 대한생식의학회지 : 제 34 권제 4 호 2007 정상정자소견을나타내는불임부부에서일반적인체외수정과세포질내정자주입술을병행하는분할수정법의효용성 관동대학교의과대학제일병원생식생물학및불임연구실 1, 산부인과학교실 2 홍승범 1 박동욱 1 신미라 1 최수진 1 이선희 1 송인옥 2 전진현 1 * Efficacy of the Split Insemination Method Combining Conventional IVF and ICSI in Non-male Factor Infertile Couples with Normal Sperm Parameters Seung Bum Hong 1, Dong Wook Park 1, Mi Ra Shin 1, Su Jin Choi 1, Sun Hee Lee 1, In Ok Song 2, Jin Hyun Jun 1 * 1 Laboratory of Reproductive Biology and Infertility, 2 Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Kwandong University College of Medicine, Seoul, Korea Objective: To evaluate the efficacy of split insemination method in treatments for non-male factor infertility. Method: Laboratory and clinical data were collected from 505 cycles of split insemination during 2002~2005 in our center. The subjects were non-male factor infertility such as endometriosis, tubal, uterine, PCOS and idiopathic infertility without any sperm defects. Retrieved oocytes were randomly divided, and inseminated by conventional IVF or ICSI. Fertilized zygotes were cultured for 2~5 days to ET date, and surplus zygotes and embryos were frozen for subsequent frozen-thawed ET cycles. Clinical outcomes according to insemination method were compared by statistical analysis. Results: The overall fertilization per retrieved oocytes was significantly higher in ICSI than that of conventional IVF in sibling oocytes (62.5±22.3% vs 52.9±28.0%, p<0.01). Total fertilization failure occurred only in 2 of 505 cycles (0.4%) in split insemination cycles. Incidence of fertilization failure and poor fertilization rate less than 30% by ICSI were significantly lower than those of conventional IVF (1.1% and 7.5% vs 8.5% and 22.0%, p<0.01). Delivery rates after transfer of fresh and thawed embryos from split insemination cycles were 40.0% (185/462) and 35.0% (55/157), respectively. There was no significant difference in the implantation and delivery rates of ET with embryos from conventional IVF or ICSI. Conclusion: Taken together, the split insemination method improves poor fertilization rates resulting in successful clinical outcomes and thus could be used for non-male factor infertile couples in human ART program. [Korean. J. Reprod. Med. 2007; 34(4): ] Key Words: Split insemination, ICSI, Conventional IVF, Fertilization failure, Fertilization rate, Clinical outcomes 세포질내정자주입술 (intracytoplasmic sperm injection, ICSI) 은일반적인체외수정방법 (conventional IVF) 을통하여난자를수정시킬수없는남성요인 주관책임자 : 전진현, 우 ) 서울특별시중구묵정동 1-19, 관동대학교의과대학제일병원생식생물학및불임연구실 Tel: (02) , Fax: (02) junjh55@hanmail.net 불임 (male factor infertility) 을극복하는데효과적인보조생식술로알려져있다. 1~3 이러한세포질내정자주입술의적용으로폐쇄성또는비폐쇄성무정자증, 정자형태및운동성이상에의한남성불임에서의성공적인임상결과가많은연구자들에의해보고되고있다. 2,4~7 뿐만아니라정상정자소

2 일반적인체외수정과세포질내정자주입술을병행하는분할수정법의효용성 대한생식의학회지 견을나타내는비남성요인불임 (non-male factor infertility) 또는원인불명불임 (unexplained infertility) 으로진단된환자에있어서도 ICSI를시행한환자군이일반적체외수정을사용한군보다더높은수정률및낮은수정실패율을보이는것으로보고되었다. 8,9 일반적으로임상에서시행되는검사를통해모든불임환자의원인을명확하게밝히기는현실적으로한계가있으며, 전체불임환자의 10~20% 정도에서원인불명의불임으로진단된다. 더욱이이전의체외수정시술결과가없는경우정상적인정자소견을나타내는경우에도실제적인정자의수정능력을판정하기가쉽지않으며, 일반적으로비남성요인불임환자의체외수정에서 5~10% 의수정실패율이보고되고있다. 9 따라서, Hershlag 등은보조생식술의시도에서완전한수정실패를방지하기위해서원인불명불임환자에게서채취된동일한난자를일반적체외수정과 ICSI로각각나누어수정시키는분할수정법 (split insemination method) 을제안하였다. 2,4,8 이러한분할수정법은정상적인정자소견을나타내는원인불명불임환자와경증의자궁내막증환자에서도수정실패율을현저하게낮출수있었으며, 10 경계성정액인자 (borderline semen parameter) 를보인환자에게있어서는통계적으로유의한개선효과를나타냈다. 11,12 정상적인정자소견을보이는비남성요인불임환자의경우에도난구세포, 난자의투명대, 난자의세포질성숙등에이상이있는경우에는일반적인체외수정에서수정률이현저하게저하될수있으며, 완전한수정실패를나타내는경우가발생할수있다. 따라서이러한예기치못한수정실패를예방하기위해서일차적인수정방법으로세포질내정자주입술이제시되기도하였다. 2,4,8 본연구에서는정상적인정자소견을나타내는비남성요인불임부부에서일반적인체외수정과세포질내정자주입술을병행하는분할수정법의효용성을살펴보고자하였다. 연구대상및방법 1. 연구대상 2003년 1월부터 2005년 12월까지제일병원아이소망센터에서체외수정시술을받았던환자들에서분할수정법이시행된비남성요인불임환자의임상결과를후향적으로분석하였다. 이중자궁내막증이 120주기, 다낭성난소증후군이 45주기, 난관요인이 135주기, 원인불명이 102주기, 그외자궁, 복막, 고령원인등이 103주기였다. 또한같은시기에서분할수정법에의해수정된잉여배아의동결-융해이식을시행한 157주기의임상결과도분석하였다. 2. 연구방법 1) 과배란유도, 체외수정, 체외배양및배아이식과배란유도는 Gonadotrophin-releasing hormone (GnRH) agonist (Suprafact, Aventis, France, 또는 Leucrin, Abbott, France) 또는 GnRH antagonist와 recombinant FSH (Puregon, Organon, Netherland 또는 Gonal-F, Serono, Switzerland) 또는 highly purified FSH (Metrodin, Serono, Switzerland) 및 human menopausal gonadotropin (Pergonal, Serono, Switzerland) 을사용하였다. 초음파상에서난포의크기가 18 mm 이상의난포가 2개이상일때, hcg (Pregnyl, Serono, Switzerland) 10,000 IU를주사하였고, hcg 투여 35~36시간후에질식초음파를이용하여난자를채취하였다. 회수된난자는무작위로두군으로나누어 G-Fert TM (Vitrolife, Sweden) 배양액에서 4~6시간배양하였다. 체외수정시한환자에서회수된난자들 (sibling oocytes) 을무작위로두군으로나누어일반적인체외수정과세포질내정자주입술을병행하여분할수정법을시행하였다. 2 수정유도후 16~18시간에전핵형성유무를관찰하여수정을확인하였다. 수정된배아는 3~5일동안 GIII series (Vitrolife, Sweden) 의 G1, G2 배양액에서체외배양하여자궁

3 제 34 권제 4 호, 2007 홍승범 박동욱 신미라 최수진 이선희외 2 인 내이식을실시하였다. 2) 정자처리정액은 3일간의금욕후수음에의하여소독된용기에채취한후상온에서 30분간액화시켰다. WHO의기준에의해정액을평가한후 15 ml 원심분리관에정액을옮겨 90%, 70%, 40% 3층의 Sperm Grad (Vitrolife, Sweden) 에 1~1.5 ml의정자를올려놓은후 1460 rpm에 20분간원심분리하였다. 상층액을제거하고정자괴에다시 5% Human Serum Albumin (HSA) 가첨가된 5 ml의 G-Sperm 배양액 (Vitrolife, Sweden) 을첨가하여현탁액을만든후 1460 rpm에서 10분간다시원심분리하였다. 최종적으로정자의상태를확인한후 5% HSA가첨가된 G-Fert TM 배양액으로정자의농도를조정하여, 분할수정법에사용하였다. 3) 배아의동결보존및동결-융해배아이식수정확인후전핵단계의잉여배아나배양 3일째배아이식후양질의잉여배아를완만동결법으로동결보관하였다. 동결보관된배아는적절한시간에급속해동법으로융해한후이식전까지신선주기배아이식에서와동일한조건하에서체외배양하였다. 동결-융해배아이식을위한자궁내막준비는생리시작 1일이나 2일째부터 estradiol valerate (Progynova, Schering AG, Germany) 를일일용량 6 mg으로경구투여하였으며, 혈중농도가 100 pg/ml 미만이거나자궁내막두께가 7 mm 미만인경우용량을 8 mg으로증량하였다. 자궁내막의두께가 7 mm 이상으로두꺼워진경우분비기자궁내막으로의분화를유도하기위해프로게스테론을투여하였다. Table 1. Overall outcomes of split insemination cycles Oocytes pick-up cycles 505 Number (%) Mean ± SD Mean age (year) 32.7±3.5 Retrieved oocytes 9, ±9.8 Ooctyes for ICSI 4,973 (52.8) 9.8±5.8 Fertilized oocytes by ICSI 3,043 (61.2) a 62.5±22.3% b Oocytes for conventional IVF 4,447 (47.2) 8.8±4.8 Fertilized oocytes by conventional IVF 2,291 (51.5) a 52.9±28.0% b Complete fertilization failure 2 (0.4) Cryopreserved embryos 2,971 (55.8) Cryopreserved cycles 328 (65.0) Transferred embryos 1,622 (30.4) 3.5±0.7 Transferred cycles 462 (91.5) Clinical pregnancy cycles 208 (45.0) Gestational sacs 338 (20.8) Delivery cycles 185 (40.0) Values are number (percentage) or mean ± SD. a p<0.01, compared by Chi-square test. b p<0.01, compared by paired t-test. Fertilization rates were calculated by allocated number of oocytes for ICSI or IVF

4 일반적인체외수정과세포질내정자주입술을병행하는분할수정법의효용성 대한생식의학회지 Table 2. Incidence and distribution of fertilization rates in split insemination cycles Split insemination cycles (n=505) ICSI Insemination method Conventional IVF P-Value 0% of fertilization rate 5 (1.1%) 43 (8.5%) <0.01 0~30% of fertilization rate 38 (7.5%) 111 (22.0%) <0.01 0~50% of fertilization rate 125 (24.8%) 197 (39.0%) < % of fertilization rate 41 (8.1%) 35 (6.9%) NS NS, not significant. Fertilization rates were calculated by allocated number of oocytes for ICSI or IVF. 4) 임신및분만확인임신의확인은배아이식후 12일째혈중 β-hcg 가 5 miu/ml 이상이고, 추적검사에서지속적인상승을보이며, 임신 5~6주사이에태낭 (gestational sac) 이확인되면임상적임신 (clinical pregnancy) 으로판정하였다. 이식한배아수에대한태낭수의비율로착상율을계산하였다. 임신후추적조사를통해분만결과를확인하였다. 5) 통계처리결과에대한통계학적분석은통계프로그램으로 SPSS (ver. 10.0) 를이용하였으며, 비율비교시 Chi-square test를평균치비교에는 Student's t-test를시행하였다. 이때 p<0.05인경우를통계학적유의성이있는것으로간주하였다. 결과분할수정법을시행한 505주기에서회수된난자는 9,420개, 평균 18.7±9.8개였고, 대상환자의평균연령은 32.7±3.5세였다 (Table 1). 채취난자는무작위로나누어세포질내정자주입술과일반적인체외수정을통해수정을유도하였다. 그결과세포질내정자주입술에서 61.2% (3,043/4,973) 가수정되었고, 일반적인체외수정에서는 51.5% (2,291/4,447) 가수정되었다. 세포질내정자주입술에서일반적으로나타내는미성숙난자를제외한성숙난자당수정률은 77.0% (3,043/3,952) 였다. 환자들의평균수정률비교에서는세포질내정자주입술이 62.5± Figure 1. Frequency distribution of fertilization rates of ICSI and conventional IVF in split insemination cycles. 22.3% 의수정률로일반적인체외수정의수정률 52.9±28.0% 보다통계적으로유의하게높았다 (Table 1; p<0.01). 분할수정법을시행한주기에서수정에완전히실패한경우는 2주기 (0.4%) 였으며, 328주기 (65.0%) 에서 2,971개의잉여배아를동결하였다. 이식에사용된배아는 462주기에서 1,622개로주기당평균 3.5±0.7개의배아를이식하였다. 초음파소견에서태낭이확인된임상적임신률은배아이식당 45.0% (208/462) 였으며, 185주기 (40.0%) 에서분만에성공하였다. 분할수정법에서수정방법에따른수정률분포빈도는 Table 2에나타내었으며, 분포는 Figure 1에도식화하였다. 수정을시도한난자들에서전체적인수정실패는세포질내정자주입술에서 1.1% (5/505), 일반적인체외수정에서 8.5% (43/505) 로 ICSI에서

5 제 34 권제 4 호, 2007 홍승범 박동욱 신미라 최수진 이선희외 2 인 Table 3. Pregnancy outcomes with fresh or frozen-thawed embryos from ICSI and/or conventional IVF in split insemination cycles Transferred embryos from ICSI Conventional IVF Combined With fresh embryos No. of ET cycles Mean age (years) 32.7± ± ±3.7 Clinical pregnancy rate 32.1% (18/56) 44.5% (57/128) 47.8% (133/278) Implantation rate 16.3% (30/184) 20.9% (91/435) 21.6% (217/1,003) Delivery rate 28.6% (16/56) 38.3% (49/128) 43.2% (120/278) With frozen-thawed embryos No. of ET cycles Mean age (years) 32.8± ± ±3.6 Clinical pregnancy rate 43.8% (28/64) 54.5% (6/11) 40.2% (33/82) Implantation rate 16.1% (37/229) 15.0% (6/40) 12.8% (37/288) Delivery rate 39.1% (25/64) 36.3% (4/11) 31.7% (26/82) There was no significant difference. 통계적으로유의하게낮았다 (p<0.01). 저조한수정률인 0~30% 이하의수정률을나타내는빈도도세포질내정자주입술에서 7.5% (38/505), 일반적인체외수정에서 22.0% (111/505) 로 ICSI에서통계적으로유의하게낮았다 (p<0.01). 또한, 0~50% 이하의수정률을나타내는빈도도세포질내정자주입술에서 24.8% (125/505), 일반적인체외수정에서 39.0% (197/505) 로 ICSI에서통계적으로유의하게낮았다 (p<0.01). 수정을시도한난자가전부수정된빈도는세포질내정자주입술에서 8.1% (41/505), 일반적인체외수정에서 6.9% (35/505) 로두군간에유의적인차이가없었다. 전체적인수정률분포는세포질내정자주입술에서는정규분포에가까운분포를나타내었지만, 일반적인체외수정에서는수정실패와저조한수정률의빈도가상대적으로높게나타났다 (Figure 1). 분할수정법에서얻어진배아를수정방법에따라구분하여배아이식후임신율, 착상률, 분만율등을비교하였다 (Table 3). 신선주기배아이식에서 는세포질내정자주입술에서유래한배아만을이식하였을때임상결과가다소저조하였지만, 동결 -융해배아이식에서는세포질내정자주입술에서유래한배아에서가장높은착상률과분만율을나타내었다. 전체적으로세포질내정자주입술와일반적인체외수정에서유래한배아를이식한경우에각각 16.2% (67/413) 와 20.4% (97/475) 의착상률그리고 34.2% (41/120) 와 38.1% (53/139) 의배아이식당분만율을보여통계적으로유의한차이를나타내지않았다. 그리고시행한분할수정법중에서 43주기 (8.5%) 에서일반적인체외수정방법으로수정란을얻는데실패하였으나, 세포질내정자주입술로 41주기 (95.3%) 에서수정란을확보할수있었다. 이렇게일반적인체외수정방법으로수정에실패한경우에도세포질내정자주입술유래의배아를이식하여난자채취당 30.2% (13/43) 의분만율을얻을수있었다

6 일반적인체외수정과세포질내정자주입술을병행하는분할수정법의효용성 대한생식의학회지 고찰세포질내정자주입술은인간의보조생식술에서남성불임을극복하기위한방법으로사용되어왔다. 그러나정상정자소견을나타내는불임환자의경우에도일반적인체외수정을시행하였을때수정률이낮거나수정의실패가관찰된적이있는경우에는선택적으로세포질내정자주입술이적용되고있다. 5,7,13 또한, 원인불명불임환자의경우일반적인체외수정에서수정의실패를방지하기위해서동일한환자의해당주기에서채취한난자를일반적인체외수정과세포질내정자주입술을병행하는분할수정법을시행하여효과적인임상결과들이보고되고있다. 2,6,9 본연구에서는정상정자소견을보이지만일반적인체외수정방법으로는안정적인수정률을기대하기어려운장기간의원인불명의불임, 이전체외수정결과가없는경우, 자궁내막증과다낭성난소증후군과같이난자의상태에영향을미칠가능성이있는경우등에서분할수정법을시도하였다. 또한, 본연구실 10년이상의수정률통계에서비남성요인의일반적인체외수정에서의수정실패율은 5~7% 를나타내었으며, 이는많은문헌들에서의보고와유사하였다. 따라서, 비남성요인의불임에대한첫번째시험관아기시술에서채취된난자의수가 10개이상으로충분하고, 일반적인체외수정당시정자의운동성및상태가만족스럽지않은경우에도수정실패율을낮추기위해선택적으로분할수정법을실시하였다. 대상환자의평균나이는 32.7세였으며, 평균 18.7±9.8개의난자를채취하였다. 전체적인수정률은세포질내정자주입술에서일반적인체외수정에비해통계적으로유의하게높았으며 (Table 1), 세포질내정자주입술에서성숙난자당수정률은 77.0% (3,043/3,952) 로남성요인불임에서의일반적인수정률인 60~70% 에비해다소높았다. 2,5 이는정상적인형태와운동성을갖는정자를사용했기 때문으로생각된다. 일반적인체외수정을시도한경우 8.5% 에서수정란을얻을수없었다. 난자의세포질에정자를직접적으로주입하는세포질내정자주입술과는달리일반적인체외수정에서는정자의첨체반응, 정자와난구세포의상호작용, 정자의투명대부착및통과, 정자세포막과난자세포막의융합그리고난자의활성화등의일련의과정을통하여수정되는것으로알려져있다. 따라서, 이러한일련의과정에서의이상은수정실패로나타날수있다. 최근에는체외수정과정에서많은수의정자에의해생성되는 superoxide anion (O - 2) 과 hydrogen peroxide (H 2 O 2 ) 같은활성산소류 (reactive oxygen species, ROS) 가정상적수정기전을저해하는것으로보고되기도하였다. 14,15 수정방법에따른배아의발생능력을비교하기위해이식된배아를수정방법에따라구분하여착상률과분만율을비교하였으나, 세포질내정자주입술과일반적인체외수정에서유사한임상결과를확인하였다. 이러한결과는일반적으로제시되고있는세포질내정자주입술에서발생할수있는난자세포질의손상에의한배아의발생능력저하가능성과는상반된결과로, 숙달된시술자에의한미세조작술의시행이관련이있을것으로생각된다. 또한, 원인불명과비남성요인에의한불임인경우일반적인체외수정과세포질내정자주입술을시행하였을때임신율에차이가없다는결과들이최근까지보고되고있다. 16,17 잉여수정란을이용한동결-융해배아이식에서도신선주기배아이식과차이가없는임상결과를얻을수있어, 높은수정률로많은수의수정란을확보하고잉여수정란을동결보관할수있는가능성이높은세포질내정자주입술이임상적으로는선호되는경향이있다. 그러나아직까지세포질내정자주입술의안전성에대한논란이있기때문에, 18~21 이를고려한세포질내정자주입술의선별적인적용이필수적이다. 그리고분할수정법에따라세포질내정자주입술을병행하여일반적인체외수정의수정실패를

7 제 34 권제 4 호, 2007 홍승범 박동욱 신미라 최수진 이선희외 2 인 95% 이상극복할수있었으며, 이러한배아를이용하여 30% 이상의만족스러운분만율을얻을수있었다. 본연구에서도많은논문들에서주장하고있는분할수정법의수정실패방지효과와안정적인수정률확보에대한효용성을확인할수있었다. 결론적으로정상정자소견을나타내는비남성요인불임에서일반적인체외수정에비하여세포질내정자주입술의수정률이높을뿐만아니라수정에실패할확률이낮음을알수있었으며, 배아의발생능력은체외수정방법뿐만아니라동결- 융해배아이식에서도차이가없음을확인하였다. 따라서, 시험관아기시술에서일반적인체외수정결과에대한확신이부족한경우에는일차적으로분할수정법을적용하여그수정결과를토대로향후체외수정방법을결정하는것이효과적일것으로사료된다. 참고문헌 1. Devroey P, Van Steirteghem A. A review of ten years experience of ICSI. Hum Reprod Update 2004; 10: Hershlag A, Paine T, Kvapil G, Feng H, Napolitano B. In vitro fertilization-intracytoplasmic sperm injection split: an insemination method to prevent fertilization failure. Fertil Steril 2002; 77: Palermo G, Joris H, Devroey P, Van Steirteghem AC. Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte. Lancet 1992; 340: Bungum L, Bungum M, Humaidan P, Andersen C. A strategy for treatment of couples with unexplained infertility who failed to conceive after intrauterine insemination. Reprod Biomed Online 2004; 8: Fishel S, Aslam I, Lisi F, Rinaldi L, Timson J, Jacobson M, et al. Should ICSI be the treatment of choice for all cases of in-vitro conception? Hum Reprod 2000; 15: Hwang JL, Seow KM, Lin YH, Hsieh BC, Huang LW, Chen HJ, et al. IVF versus ICSI in sibling oocytes from patients with polycystic ovarian syndrome: a randomized controlled trial. Hum Reprod 2005; 20: Nagy Z, Liu J, Cecile J, Silber S, Devroey P, Van Steirteghem A. Using ejaculated, fresh, and frozen-thawed epididymal and testicular spermatozoa gives rise to comparable results after intracytoplasmic sperm injection. Fertil Steril 1995; 63: Li Z, Lin H, Xiao W, Wang Y. Fertilization of IVF/ICSI using sibling oocytes from couples with subfertile male or unexplained infertility. J Huazhong Univ Sci Technol Med Sci 2004; 24: Mahutte NG, Arici A. Failed fertilization: is it predictable? Curr Opin Obstet Gynecol 2003; 15: Ruiz A, Remohi J, Minguez Y, Guanes PP, Simon C, Pellicer A. The role of in vitro fertilization and intracytoplasmic sperm injection in couples with unexplained infertility after failed intrauterine insemination. Fertil Steril 1997; 68: Aboulghar MA, Mansour RT, Serour GI, Sattar MA, Amin YM. Intracytoplasmic sperm injection and conventional in vitro fertilization for sibling oocytes in cases of unexplained infertility and borderline semen. J Assist Reprod Genet 1996; 13: Van der Westerlaken L, Naaktgeboren N, Verburg H, Dieben S, Helmerhorst FM. Conventional in vitro fertilization versus intracytoplasmic sperm injection in patients with borderline semen: a randomized study using sibling oocytes. Fertil Steril 2006; 85: Van Steirteghem A, Nagy Z, Joris H, Liu J, Staessen C, Smitz J, et al. High fertilization and implantation rates after intracytoplasmic sperm injection. Hum Reprod 1993; 8: Alvarez JG, Touchstone JC, Blasco L, Storey BT. Spontaneous lipid peroxidation and production of hydrogen peroxide and superoxide in human spermatozoa: superoxide dismustase as a major enzyme protectant against oxygen toxicity. J Androl 1987; 8: Aitken RJ, Clarkson JS. Cellular basis of defective sperm function and its association with the genesis of reactive oxygen species by human spermatozoa. J Reprod Fertil 1987; 81: Aboulghar MA, Mansour RT, Serour GI, Amin YM, Kamal A. Prospective controlled randomized study of in vitro fertilization versus intracytoplasmic sperm injection in the treatment of tubal factor infertility with normal semen parameters. Fertil Steril 1996; 66:

8 일반적인체외수정과세포질내정자주입술을병행하는분할수정법의효용성 대한생식의학회지 17. Kim HH, Bundorf MK, Behr B, McCallum SW. Use and outcomes of intracytoplasmic sperm injection for non-male factor infertility. Fertil Steril 2007; 88: Bonduelle M, Legein J, Buysse A, Van Assche E, Wisanto A, Devroey P, et al. Prospective follow-up study of 423 children born after intracytoplasmic sperm injection. Hum Reprod 1996; 11: Bonduelle M, Liebaers I, Deketelaere V, Derde MP, Camus M, Devroey P, et al. Neonatal data on a cohort of 2889 infants born after ICSI ( ) and of 2995 infants born after IVF ( ). Hum Reprod 2002; 17: Macas E, Imthurn B, Keller PJ. Increased incidence of numerical chromosome abnormalities in spermatozoa injected into human oocytes by ICSI. Hum Reprod 2001; 16: Wennerholm UB, Bergh C, Hamberger L, Lundin K, Nilsson L, Wikland M, et al. Incidence of congenital malformations in children born after ICSI. Hum Reprod 2000; 15: = 국문초록 = 목적 : 본연구에서는일반적인체외수정과세포질내정자주입술을병행하여시행하는분할수정법의효용성을정상적인정자소견을나타내는비남성요인불임환자의체외수정및배아이식술에서살펴보고자하였다. 연구방법 : 제일병원아이소망센터에서정자소견상결함이없는비남성요인불임환자에게분할수정법을이용한 505주기의임상결과를후향적으로분석하였다. 획득된난자는무작위로나누어일반적인체외수정이나세포질내정자주입술을이용하여수정을시켰다. 수정란은이식할때까지 2~5일간배양하였고, 잉여의수정란과배아는동결보관하여동결-융해이식에사용하였다. 수정방법에따른임상결과를통계학적인방법으로비교하였다. 결과 : 획득된난자의수정율은분할수정법을시행하였을때일반적인체외수정보다세포질내정자주입술에서통계적으로유의하게높게나타났다 (52.9±28.0% vs 62.5±22.3%, p<0.01). 전체적인수정의실패는분할수정법을시행한 505주기중에서단지 2주기에서만 (0.4%) 나타났으며, 수정실패와 0~30% 이하의수정률을나타내는빈도는세포질내정자주입술에서일반적인체외수정보다통계적으로유의하게낮았다 (1.1% and 7.5% vs 8.5% and 22.0%, p<0.01). 분할수정주기에서의신선배아와동결-융해배아이식후분만율은각각 40.0% (185/462) 와 35.0% (55/157) 였으며, 일반적인체외수정이나세포질내정자주입술로얻어진배아의착상률과분만율은유의적인차이가나타나지않았다. 결론 : 결론적으로비남성요인불임환자의보조생식술에서분할수정법이수정실패와낮은수정율을방지하고성공적인임상결과를제공할수있는효과적인방법으로사료된다. 중심단어 : 분할수정법, 세포질내정자주입술, 일반적인체외수정, 수정실패, 수정률, 임상결과

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歯 PDF * * The Effects of Oocyte Oocytes Intracytoplasmic ICSI) Kee TaekHoo Hai * SikChun Department of Obstetrics and Gynecology, School of Medicine, Kyungpook Taegu, *Department of Animal Science, Taegu Kyungbuk,