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1 대한생식의학회지 : 제 35 권제 3 호 2008 관동대학교의과대학제일병원산부인과불임및생식내분비분과 김혜옥 김민지 연명진 차선화 궁미경 송인옥 * Predictor of IVF Outcomes Following Single Embryo Transfer in Poor Responder Patients Hye Ok Kim, Min Ji Kim, Myeong Jin Yeon, Sun Wha Cha, Mi Kyoung Koong, In Ok Song * Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Kwandong University College of Medicine, Seoul, Korea Objective: To evaluate predictor of IVF outcomes following single embryo transfer in patients with decreased ovarian reserve. Methods: A retrospective review was performed in 919 IVF cycles with elevated basal serum FSH ( 12 miu/ml), the number of retrieved oocytes 4 and serum E 2 concentration on hcg day <500 pg/ml between Jan and Dec Two hundred thirty five IVF cycles following single embryo transfer were included. Pregnancy rates and live birth rates was evaluated according to maternal age, serum E 2 on hcg day, basal FSH level, the number of blastomere on day 3 ET, stimulation protocol, the number of cycles of ET. Statistical analysis was used SPSS 12.0 program. Results: OPU cancellation rates were 25.6% (235 cycles), OPU failure rates were 18.5% (170 cycles), embryo transfer cancellation rates were 14.0% (129 cycles). Pregnancy rates following single embryo transfer was 8.1% (19 cycles) and live birth rates was 4.7% (11 cycles). Pregnancy rates and live birth rates of women under 35 years old was statistically higher than those of women above 35 years old (20% vs. 3.5% (p<0.0001), 12.3% vs. 1.8%, (p=0.002)). There was no difference in basal FSH, serum E 2 on hcg day, and the number of blastomere on ET, and stimulation protocol. Cumulative pregnancy rates according to the number of cycles of ET were 1 st 8.1%, 2 nd 9.2%, 3 rd 9.7%, 4 th 9.0%, and 5 th 9.5%. Conclusion: Pregnancy rates and live birth rates of IVF-ET cycles following single embryo transfer in patients with decreased ovarian reserve are statistically increased in women under 35 yrs old. There is no difference in cumulative pregnancy rates. These data may be helpful for counseling women with decreased ovarian reserve in attempting IVF with their own eggs or when choosing donor oocytes. [Korean. J. Reprod. Med. 2008; 35(3): ] Key Words: Poor responder, Single embryo transfer, IVF 불임여성의성공적인체외수정 (IVF, In vitro fertilization) 을위해서는과배란유도 (COH, controlled hyperstimulation) 로적정수의난자를획득하고, 이를통해양질의배아를선별하여자궁내이식함으로써높은임신율을기대할수있다. 주관책임자 : 송인옥, 우 ) 서울특별시중구묵정동 1-19, 관동대학교의과대학제일병원의학연구소산부인과 Tel: (02) , Fax: (02) Inok2@unitel.co.kr 체외수정시난자와배아의배양조건이향상되고미세조작술, 포배기배아이식등의방법을통해임신율이향상되고있지만, 과배란유도시적은수의난자가채취되는저반응군 (Poor responder) 불임여성에서의시험관아기의임신성공률이낮다. 1,2 특히, 과거에난소수술을받았거나여성의연령이높아져 Ovarian reserve가감소된불임여성은얻어지는난자의수가적기때문에배아이식

2 대한생식의학회지 시에도 embryo selection을하지못하고, 체외수정시난자채취실패 (OPU fail) 와배아이식취소 (ET cancellation) 의가능성이높게된다. 3~5 이러한저반응군환자에게외국에서는난자공여 (ooctye donation) 를권유하고있지만, 6,7 우리나라에서는정서상난자공여를받아들이기가쉽지않고, 제도적으로도난자공여자를구하기가쉽지않은상황이다. 그리고, 불임치료의중단또는난자공여등의방법들을권유할때의기준이치료자에따라상당히다양하게제시되는경향이있어, 8 이러한저반응군여성이자신의난자로임신하기를원할때어느시점까지체외수정을통한임신시도가효과적인지불분명하다. 또한, 저반응군불임여성에서한개의배아만을이식할수밖에없는경우가빈번하고, 한개의배아만을이식한경우는직접적으로배아의상태와임신율과의관계를평가할수있다. 9 따라서, 저자들은난소기능이저하된저반응군불임여성에서, 특히한개의배아만을이식한경우에임신율에영향을주는요인에대해분석해보고자하였다. 연구대상및방법 1. 연구대상 1996년 4월부터 2006년 6월까지제일병원아이소망센타에서시험관시술을받은환자중, 1) 기저난포자극호르몬 (basal FSH) 이 12 miu/ml 이상또는 2) 획득된난자가 4개이하또는 3) hcg 투여일에혈청 E 2 가 500 pg/ml 미만인저반응군환자를대상으로총 919 주기를후향적으로분석하였다. 이중한개의배아만을이식한경우는 235주기였다. 남성요인중비폐색성무정자증 (non-obstructive azoospermia) 과난관요인중난관수종을가지고있는경우는제외하였다. 여성의연령, hcg 투여일에혈청 E 2, 기저난포자극호르몬, 3일째배아이식시할구 (blastomere) 수, 과배란유도방법, 이식횟수에따른임상적임신율 (clinical pregnancy rates) 과생존아출생률 (live birth rates) 을비교하였다. 2. 연구방법 1) 과배란유도체외수정을위한과배란유도는단기 (short) 또는장기 (long protocol) 요법, 초단기 (ultrashort protocol) 요법, GnRH antagonist 요법, 클로미펜단독또는성선자극호르몬병합요법을사용하였고, 일부에서는자연주기법을이용하였다. Pituitarydown regulation을위하여단기요법은 GnRH agonist (Bucerelin acetate, Suprefact, Hoechst, Germany) 를생리주기 2~3일부터, 장기요법은전생리주기에서배란을확인하고, 황체기중반부터 GnRH agonist 를투여하였고, 과배란유도 (ovulation induction) 는생리주기 3~5일부터 human recombinant FSH (Puregon, Organon, Netherlands; Gonal-F, Serono, Switzerland) 또는 hmg 제재 (Pergonal, Serono, Switzerland) 를이용하여매일투여하였다. 초단기요법은 GnRH agonist를생리주기 2~3일부터 3일간사용후중단하고, 과배란유도는생리 3~5일부터성선자극호르몬을이용하여매일투여하였다. GnRH antagonist 요법은생리주기 2~3 일부터과배란유도를위해성선자극호르몬을투여하여, 우성난포직경이 12~14 mm이거나혈중에스트라디올농도가 200~400 pg/ml 이상인날부터 GnRH antagonist 0.25 mg/day (Cetrorelix acetate, Cetrotide, Serono, Switzerland) 를매일투여하였다. 클로미펜 (Clomiphene citrate, Clomid ) 은생리주기 3일째부터 5일간 100 mg/day 투여하였으며, 단독요법시생리주기 7~8일째부터 2~3일간격으로질식초음파와혈청에스트라디올농도를측정하였고, 클로미펜병합요법시에는생리주기 7~8일째부터성선자극호르몬을투여하였다. 각프로토콜에따른과배란유도후성숙난포의직경이 17~ 18 mm에도달하였을때, hcg (Pregnyl, Organon, Netherlands) 10,000 IU를투여하고, 34~36시간이후

3 제 35 권제 3 호, 2008 김혜옥 김민지 연명진 차선화 궁미경외 1 인 난자채취를시도하였다. 체외수정은고식적체외수정시술 (conventional IVF) 또는세포질내정자주입술 (ICSI, intracytoplasmic sperm insemination) 의방법을이용하였고, 2개의극체와전핵 (pronucleus) 이관찰되면수정으로확인하였다. 배아이식은난자채취후 2~5일후에한개의배아를자궁강내에이식하였다. 배아의상태는 Veeck 17 의분류를기준으로할구 (blastomere) 의균등성과세포질파편 (cytoplasmic fragment), 세포질공포 (bleb) 등으로등급을 (embryo grading) 을 Grade I, Grade I-a, Grade II, Grade II-a, Grade III로판정하였다. 황체기보강을위해 progesterone in oil (Progest, 삼일제약 ) 을 2주간근주하였다. 2) 임신결과의판정임신의확인은난자채취후 12일째에혈중 β- hcg가 5 miu/ml 이상이고, 추적검사에서상승을보이며임신 5~6주사이에태낭 (Gestational sac) 이확인되면임상적임신으로판정하였고, 태낭이보이기전에혈중 β-hcg가감소되어조기임신이종료된경우는생화학적임신 (biochemical pregnancy) 으로판정하여임상적임신율에서제외하였다. 수정률 (fertilization rate) 은획득된성숙난자에대해생성된수정란 (2PN, pronucleus) 의비율로, 착상률 (Implantation rate) 은이식된배아수에대해확인된태낭수의비율로, 생존아출생률은 (live birth rate) 은배아이식주기당생존했던태아의비율로정의하였다. 3) 통계분석통계학적분석은 SPSS 12.0 program (SPSS Inc., Chicago, IL) 을이용하였고, 임상적데이터와체외수정의결과는평균값과표준편차 (mean ± SD), 범위 (range) 로나타내었고, 임상적임신율과생존아출생률은퍼센트 (%) 로나타내었다. 각그룹간의비율의분석은 Chi-square test를이용하여분석하였고, p-value가 0.05 미만인경우를통계학적으로유의한차이가있는것으로판정하였다. Table 1. Results of initiated IVF cycles in poor responder patients Initiated IVF cycles in Total 919 cycles poor responder OPU cancellation 235 cycles (25.6%) OPU fail 170 cycles (18.5%) ET cancellation 129 cycles (14.0%) Cycles of transferred embryo 385 cycles (41.9%) 결 과 1. 임상적특징과체외수정의결과 저반응군총 919주기 (cycles) 중난자채취취소율 (OPU cancellation rates) 은 25.6% (235주기), 난자채취실패율 (OPU fail) 은 18.5% (170 주기 ), 배아이식취소율 (ET cancellation rates) 은 14.0% (129주기) 였고, 41.9% (385주기) 만이배아이식을받았고, 그중한개의배아를이식한경우는전체이식주기중 61% (235주기) 에해당하였다 (Table 1). 한개의배아를이식한 235주기 (cycles) 의임상적특징을살펴보면, 불임여성의평균연령은 38.3±5.1세 (yrs) 였고, 불임기간은 67.9±63.8개월 (months), 과거체외수정은 3.4±2.6주기시행받았으며, 기저치난포자극호르몬은 18.9±7.2 (miu/ml) 였다. 체외수정의결과는 hcg 투여일에혈중에스트로겐은 280.5±107.7 (pg/ml), 회수된난자의수는 1.43±0.74개, 수정률은 82.8±26.8 (%), 착상률은 7.2±26.0 (%), 임신낭을확인할수있었던임상적임신율은 8.1% (19주기), 생존아출생률은 4.7% (11 주기 ) 였다 (Table 2). 2. 연령, hcg 투여일의 E 2, 기저치난포자극호르몬, 3일째배아이식시할구수, 과배란유도방법에따른임신율의차이 여성의연령을 35세이하, 35~39세, 40~44세, 45 세이상의 4 그룹으로분류하였을때, 각그룹은

4 대한생식의학회지 Table 2. Demographic characteristics and IVF outcomes following single embryo transfer in poor responder patients Single embryo transfer in poor responder Total 235 cycles Age (years) (Range) 38.3±5.1 (25~48) Duration of Infertility (months) (Range) 67.9±63.8 (2~291) Prior treated IVF cycles (Rage) 3.4±2.6 (1~14) Basal FSH (miu/ml) (Range) 18.9±7.2 (12~47) E 2 on hcg day (pg/ml) (Range) 280.5±107.7 (36~490) The number of retrieved oocytes (Range) 1.43±0.74 (1~4) Fertilization rates (%) 82.8±26.8 Implantation rates (%) 7.2±26.0 Pregnancy rates 8.1% (19 cycles) Live birth rates 4.7% (11 cycles) 65주기, 68주기, 74주기, 28주기였으며, 임상적임신율은 20%, 7.4%, 1.4%, 0% 였으며, 생존아출생률은각각 12.3%, 4.4%, 0%, 0% 였고, 35세미만의여성에서 35세이상의여성보다임신율과생존아출생률이통계적으로유의하게높았다 (20% vs. 3.5% p< , 12.3% vs. 1.8% p=0.002) (Figure 1). hcg 투여일에혈청 E 2 는범위가 36~490 pg/ml 로다양하였는데, 혈청 E 2 가 100 이하, 100~200, 201~300, 301~400, 401~500 (pg/ml) 의 5 그룹으로분류하였을때, 각그룹의임신율은 0%, 9.1%, 6.8%, 5.3%, 13.2% 이고 (p=0.642), 생존아출생률은각각 0%, 7.3%, 3.4%, 1.8%, 10.5% 로 (p=0.322), 각그룹간의통계적인차이는없었다 (Figure 1). 기저치난포자극호르몬의농도를 12~15, 16~ 20, 20~30, 31~40 (miu/ml) 로분류하여비교하였을때, 각각의임신율은 6.9%, 7.9%, 9.8%, 10% 이며 (p=0.922), 생존아출생률은각각 3.0%, 6.3%, 3.9%, 10% (p=0.496) 로각그룹간의통계적인차이를보이지않았다 (Figure 1). 전체 235주기중 198주기 (84%) 에서 3일째배아이식을시행받았으며, 3일째배아이식시할구 (blastomere) 의수에따라, 4개이하, 5개, 6개, 7개, 8개, 9개이상으로분류하였을때, 각각의임신율은 1.4%, 6.9%, 11.1%, 9.5%, 13.8%, 8.3% 였으며, 생존아출생률은각각 0%, 3.4%, 8.3%, 4.8%, 7.7%. 8.3% 이고, 그룹간의통계적인차이는없었다 (Figure 1). 과배란유도방법은클로미펜단독요법이 38.2% 로가장많이사용되었고, 클로미펜과성선자극호르몬병합요법이 18.1%, 단기요법이 24.6%, 자연주기법이 5.5%, GnRH antagonist 요법이 3.5% 를차지하였다. 각각의임신율은 6.6%, 2.8%, 12.2%, 0%, 28.6% 였으며, 생존아출생률은각각 5.3%, 2.8%, 2.0%, 0%, 28.6% 였고, 그룹간의통계적인차이는없었다 (Figure 1). 3. 이식횟수에따른누적임신율 (cumulative pregnancy rates) 체외수정횟수에따른누적임신율은각각 1회에 8.1%, 2회에 9.2%, 3회에 9.7%, 4회에 9.0%, 5회에 9.5% 로이식횟수가증가함에따라누적임신율의증가는관찰되지않았고, 6회에서 14회까지시행받은 46주기중한주기에서임신과출산을하였으며, 임신한여성의연령은 33세였다 (Figure 2). 또한, 35세미만의불임여성에서전체평균보다임신율이증가됨을알수있었으나, 이식횟수에따른누적임신율의증가는없었다 (Figure 2)

제 35 권제 3 호, 2008 김혜옥 김민지 연명진 차선화 궁미경외 1 인 A Pregnancy rates (%) Live birth rates (%) E Pregnancy rates Live birth rates (%) 25.0 20.0 15.0 10.0 5.0 0.

5 제 35 권제 3 호, 2008 김혜옥 김민지 연명진 차선화 궁미경외 1 인 A Pregnancy rates (%) Live birth rates (%) E Pregnancy rates Live birth rates (%) Age ( % ) Short Antagonist CC+hMG CC only Protocol B (%) Pregnancy rates Live birth rates < E2 on hcg day (pg/ml) Figure 1. Pregnancy rates and live birth rates according to (A) maternal age, (B) E 2 on hcg day, (C) basal FSH, (D) the number of blastomere on day 3 ET, (E) stimulation protocol in poor responder patients C Pregnancy rates Live birth rates (%) ~15 16~20 21~30 31~40 basal FSH (miu/ml) Figure 2. Cumulative pregnancy rates according to the number of IVF cycles 고 찰 D (%) Pregnancy rates Live birth rates the number of blastomere on day 3 ET 여성의사회활동의참여로결혼과출산연령이늦어지면서, 불임클리닉을찾는여성중 35세이상의고연령여성이많아지고, 원인불명의조기폐경또는난소수술과관련되어난소기능이저하된여성이증가하고있다. 3~5 또한, 과배란유도시특별한난소수술의병력없이도저반응 (poor response) 을보이는불임여성또한흔하게관찰된다. 저반응군에대한공통적인기준이마련되지않았지만, 일반적으로난소기능검사에서고성선자극호르몬을보이거나, 과배란시고농도의성선자극

6 대한생식의학회지 호르몬이필요하거나, 성장난포의수가적거나, 혈청에스트로겐농도가낮거나체외수정시적은수의난자가채취되는경우가해당된다. 10 체외수정시이러한저반응군은성선자극호르몬에대한반응이적어주기가취소 (cycle cancellation) 되거나이식할배아의수가적게얻어져낮은임신율을보이기때문에이러한저반응군환자에서더많은수의난자를획득하기위해고용량의성선자극호르몬을쓰거나, 황체기에스트로겐요법, microdose GnRH agonist 요법, GnRH antagonist 요법, letrozole, low dose aspirin, transdermal testosterone 요법등다양한여러가지방법을시도하는노력이있어왔으나, 10~18 뚜렷이검증된방법은현재없는실정이다. 또한, 이러한저반응군환자에게외국에서는난자공여 (ooctye donation) 를권유하고있지만, 6,7 우리나라에서는정서상난자공여를받아들이기가쉽지않고, 제도적으로도난자공여자를구하기가쉽지않은상황이다. 또한, 불임치료의중단또는이러한난자공여등의방법들을권유할때의기준이치료자에따라상당히다양하게제시되는경향이있고, 이러한저반응군여성에서자신의난자로임신하기를원하는경우, 임신율자체가아주낮아비용효과적인면에서계속적인체외수정을통한임신가능성을예측하기어렵기때문에어느시점까지체외수정을통한임신시도가효과적인지불분명하다. 하지만, Check 등 8,19~23 은임박한폐경 (imminent ovarian failure) 여성에서성공적인임신을보고하여이러한저반응군또는임박한폐경여성에서도비용효과적인측면에서경제적이지않지만, 적극적인체외수정의필요성을강조하였다. 본저자들이살펴본저반응군은체외수정을시작한총 919주기 (cycles) 중 41.9% (385주기) 만이배아이식까지가능하여높은체외수정취소율 (58.1%) 을보였고, 그중한개의배아만을이식할수밖에없는경우도전체이식주기중 61% (235 주기 ) 에해당하였다. 이러한저반응군의높은체외수정취소율에도불구하고, 지속적으로체외수정을 시도해볼수있는근거로서임신의가능성을예측하기위한지표들을비교하게되었는데, 임상적인지표로는불임여성의연령, hcg 투여일의에스트로겐농도, 기저치난포자극호르몬, 과배란유도방법등을이용하여임신율을비교해볼수있겠고, 체외수정결과의지표로서는배아의착상가능성 (implantation potential) 을예측할수있는전핵의형태 (pronuclear morphology), 분열속도 (cleavage speed), 배아의형태 (morphology on day 3) 등으로좋은배아의선별이중요한지표가될수있다. 24~26 특히배아의착상가능성을예측함에있어한개의배아를이식했을경우직접적인배아와임신율간의인과관계를예측할수있는장점이있어본저자들은한개의배아를이식한경우만을대상으로하여연구하게되었다. 모든연구에서공통적이지는않지만, 27,28 3일째배아의형태, 특히 6~8개의할구수를보이는배아를이식할때좋은임신율을보고하였고, 29~32 Check 등 9 은 ovarian reserve가감소된불임여성에서한개의배아를이식한경우, 3 일째배아의할구 (blastomere) 수가 6~8개인그룹에서 4~5개인그룹보다더높은임신율을보고하고 (40.4% vs. 6.6%), 따라서 6개이상의할구를보이는경우에좀더체외수정을시도해볼것을제시하고있다. 하지만, 본저자들은 3일째배아이식시할구수에따른임신율의차이를확인할수없었고, 임상적지표로서 hcg 투여일에혈청에스트로겐농도, 기저치난포자극호르몬의농도에따른임신율의차이도없었다. 또한과배란유도방법에따른임신율을비교하여보았을때, GnRH antagonist 요법에서임신율 (28.6%) 과생존아출생률 (28.6%) 이높았으나, 전체 235주기중 7주기로대상주기의수가매우적어전체적인결과로확대하는데제한점이있으므로, 앞으로대상주기를좀더늘려임신율을비교하는방법이필요하겠고, 그이외의다른요법들에따른임신율의차이는없었다. 그러나, 35세미만의여성에서한개의배아를이식할수밖에없는저반응군에서도 35세이상의

7 제 35 권제 3 호, 2008 김혜옥 김민지 연명진 차선화 궁미경외 1 인 여성보다높은임신율을보여, 여성의연령이임신율을예측하는중요한임상지표임을다시한번확인하였고, 35세미만의불임여성에서저반응군이라할지라도적극적인체외수정을권유할수있는근거가될수있겠다. 결론적으로, 저반응군의체외수정에서한개의배아를이식할때, 불임여성의연령이 35세미만에서임신율과생존아출생률이유의하게증가함을확인하였고, 이식횟수에따른누적임신율은차이가없었다. 이는체외수정을시도하려고하는난소기능저하의불임여성에서구체적인상담자료로유용하게이용될수있겠다. 참고문헌 1. Crosignani PG, Ragni G, Lombroso GC, Scarduelli C, de Lauretis L, Caccamo A, et al. IVF: induction of ovulation in poor responders. J Steroid Biochem 1989; 32: Loutradis D, Vomvolaki E, Drakakis P. Poor responder protocols for in-vitro fertilization: options and results. Curr Opin Obstet Gynecol 2008; 20(4): Ragni G, Somigliana E, Benedetti F, Paffoni A, Vegetti W, Restelli L, et al. Damage to ovarian reserve associated with laparoscopic excision of endometriomas: a quantitative rather than a qualitative injury. Am J Obstet Gynecol 2005; 193(6): Somigliana E, Ragni G, Benedetti F, Borroni R, Vegetti W, Crosignani PG. Does laparoscopic excision of endometriotic ovarian cysts significantly affect ovarian reserve? Insights from IVF cycles. Hum Reprod 2003; 18(11): Ho HY, Lee RK, Hwu YM, Lin MH, Su JT, Tsai YC. Poor response of ovaries with endometrioma previously treated with cystectomy to controlled ovarian hyperstimulation. J Assist Reprod Genet 2002; 19(11): Moomjy M, Mangieri R, Beltramone F, Cholst I, Veeck L, Rosenwaks Z. Shared oocyte donation: society's benefits. Fertil Steril 2000; 73(6): Maxwell KN, Cholst IN, Rosenwaks Z. The incidence of both serious and minor complications in young women undergoing oocyte donation. Fertil Steril 2008 Feb 2. [Epub ahead of print]. 8. Check JH. In vitro fertilization is expensive: when should a couple be advised to stop trying with their own gametes and seek other options? Review of three cases. Clin Exp Obstet Gynecol 2008; 35(1): Check JH, Summers-Chase D, Yuan W, Horwath D, Wilson C. Effect of embryo quality on pregnancy outcome following single embryo transfer in women with a diminished egg reserve. Fertil Steril 2007; 87: Mahutte NG, Aydin Arici. Role of gonadotropin-releasing hormone antagonists in poor responders. Fertil Steril 2007; 87: Land JA, Yarmolinskaya MI, Dumoulin JC, Evers JL. Highdose human menopausal gonadotropin stimulation in poor responders does not improve in vitro fertilization outcome. Fertil Steril 1996; 65(5): Frattarelli JL, Hill MJ, McWilliams GD, Miller KA, Bergh PA, Scott RT. A luteal estradiol protocol for expected poorresponders improves embryo number and quality. Fertil Steril 2008; 89(5): Frattarelli JL, McWilliams GD, Hill MJ, Miller KA, Scott RT. Low-dose aspirin use does not improve in vitro fertilization outcomes in poor responders. Fertil Steril 2008; 89(5): Ubaldi F, Rienzi L, Baroni E, Ferrero S, Iacobelli M, Minasi MG, et al. Hopes and facts about mild ovarian stimulation. Reprod Biomed Online 2007; 14(6): Barrenetxea G, Agirregoikoa JA, Jiménez MR, de Larruzea AL, Ganzabal T, Carbonero K. Ovarian response and pregnancy outcome in poor-responder women: a randomized controlled trial on the effect of luteinizing hormone supplementation on in vitro fertilization cycles. Fertil Steril 2008; 89(3): Schoolcraft WB, Surrey ES, Minjarez DA, Stevens JM, Gardner DK. Management of poor responders: can outcomes be improved with a novel gonadotropin-releasing hormone antagonist/letrozole protocol? Fertil Steril 2008; 89(1): Frankfurter D, Dayal M, Dubey A, Peak D, Gindoff P. Novel follicular-phase gonadotropin-releasing hormone antagonist stimulation protocol for in vitro fertilization in the poor responder. Fertil Steril 2007; 88(5): Balasch J, Fábregues F, Peñarrubia J, Carmona F, Casamitjana R, Creus M, et al. Pretreatment with transdermal testosterone may improve ovarian response to gonadotrophins in poorresponder IVF patients with normal basal concentrations of FSH. Hum Reprod 2006; 21(7):

8 대한생식의학회지 19. Check JH. A 59-year-old woman gives birth to twins--when should a fertility specialist refuse treatment? Clin Exp Obstet Gynecol 2008; 35(2): Check JH, Katsoff B, Brasile D, Choe JK, Amui J. Pregnancy outcome following in vitro fertilization-embryo transfer (IVF-ET) in women of more advanced reproductive age with elevated serum follicle stimulating hormone (FSH) levels. Clin Exp Obstet Gynecol 2008; 35(1): Check ML, Check JH, Kaplan H. Pregnancy despite imminent ovarian failure and extremely high endogenous gonadotropins and therapeutic strategies: case report and review. Clin Exp Obstet Gynecol 2008; 35 (1): Katsoff B, Check JH. Successful pregnancy in a 45-year-old woman with elevated day 3 serum follicle stimulating hormone and a short follicular phase. Clin Exp Obstet Gynecol 2005; 32(2): Check JH. Live delivery following transfer of a single frozenthawed embryo derived from a 42-year-old woman with marked decreased oocyte reserve. Clin Exp Obstet Gynecol 2005; 32(1): Scott L, Alvero R, Leondires M, Miller B. The morphology of human pronuclear embryos is positively related to blastocyst development and implantation. Hum Reprod 2000; 15: Tesarik AM, Junca A, Hazout FX, Aubriot C, Nathan P, Cohen-Bacrie, et al. Embryos with high implantation potential after intracytoplasmic sperm injection can be recognized by a simple, non-invasive examination of pronuclear morphology. Hum Reprod 2000; 15: Shoukir Y, Campana A, Farley T, Sakkas D. Early cleavage of in vitro fertilized human embryos to the 2-cell stage: a novel indictor of embryo quality and viability. Hum Reprod 1997; 12: Ziebe S, Petersen K, Lindenberg S, Andersen AG, Garielsen A, Andersen AN. Embryo morphology or cleavage stage: how to select the best embryos for transfer after in-vitro fertilization. Hum Reprod 1997; 12: Alikani M, Calderon G, Tomkin G, Garrisi J, Kokot M, Cohen J. Cleavage anomalies in early human embryos and survival after prolonged culture in-vitro. Hum Reprod 2000; 15: Hoover L, Baker A, Check JH, Lurie D, O'Shaughnessy A. Evaluation of a new embryo-grading system to predict pregnancy rates following in vitro fertilization. Gynecol Obstet Invest 1995; 40: Check JH, Wilson C, Summers-Chase D, Choe JK, Nazari A, Lurie D. Pregnancy rates (PRs) according to embryo cell number at time of embryo transfer (ET). Clin Exp Obstet Gynecol 2001; 28: Fisch JD, Rodriguez H, Ross R, Overby G, Sher G. The graduated embryo score (GES) predicts blastocyst formation and pregnancy rate from cleavage-stage embryos. Hum Reprod 2001; 16: Fisch JD, Sher G, Adamowicz M, Keskintepe L. The graduated embryo score predicts the outcome of assisted reproductive technologies better than a single day 3 evaluation and achieves results associate with blastocyst transfer from day 3 embryo transfer. Fertil Steril 2003; 80:

9 제 35 권제 3 호, 2008 김혜옥 김민지 연명진 차선화 궁미경외 1 인 = 국문초록 = 목적 : 난소기능이저하된저반응군불임여성에서한개의배아를이식할때임신율에영향을주는요인에대해알아보고자한다. 연구방법 : 본원에서 1996년 6월부터 2006년 4월까지시험관시술을받은환자중, basal FSH가 12 miu/ml 이상, 획득된난자가 4개이하, hcg 투여일에혈청 E 2 가 500 pg/ml 미만인저반응군총 919주기에서한개의배아만을이식한 235주기를대상으로하였다. 여성의연령, hcg 투여일에혈청 E 2, basal FSH, 3일째배아이식시할구수, 과배란유도방법, 이식횟수에따른임신율과생존아출생률을비교하였으며, 통계학적인방법은 Chi-square를이용하여 p-value 0.05 이하인경우를유의하게평가하였다. 결과 : 총 919주기중난자채취취소율은 25.6% (235주기), 난자채취실패율은 18.5% (170주기), 배아이식취소율은 14.0% (129주기) 였다. 한개의배아를이식한군의전체임신율은 8.1% (19주기), 생존아출생률은 4.7% (11주기) 였고, 35세미만의여성에서 35세이상의여성보다임신율과생존아출생률이통계적으로유의하게높았다 (20% vs. 3.5% p<0.0001, 12.3% vs. 1.8%, p=0.002). hcg 투여일에혈청 E 2, basal FSH, 3일째배아이식시할구수, 과배란유도방법에따른임신율과생존아출생률은차이가없었다. 이식횟수에따른누적임신율은 1회에 8.1%, 2회에 9.2%, 3회에 9.7%, 4회에 9.0%, 5회에 9.5% 였다결론 : 저반응군의체외수정에서한개의배아를이식할때, 불임여성의연령이 35세미만에서임신율과생존아출생률이유의하게증가함을확인하였고, 이식횟수에따른누적임신율은차이가없었다. 이는체외수정을시도하려고하는난소기능저하의불임여성에서구체적인상담자료로사용할수있겠다. 중심단어 : 저반응군, 한개의배아이식, 시험관아기

Microsoft Word - 8-송인옥.DOC

Microsoft Word - 8-송인옥.DOC 대한생식의학회지 : 제 34 권제 2 호 2007 저반응군의체외수정시술을위한과배란유도에있어 GnRH Antagonist 요법과 GnRH Agonist Flare Up 요법의효용성에관한연구 관동대학교의과대학제일병원산부인과 안영선 연명진 조연진 김민지 강인수 궁미경 김진영양광문 박찬우 김혜옥 차선화 송인옥 GnRH Antagonist Versus Agonist