2012. THE KOREAN SOCIETY FOR REPRODUCTIVE MEDICINE

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1 ORIGINAL ARTICLE pissn eissn Clin Exp Reprod Med 2012;39(1):22-27 Effectiveness of multiple dose protocol pplied during erly nd lte folliculr phse compred with long protocol in non-obese nd obese ptients with polycystic ovry syndrome undergoing IVF/ICSI Chung-Hoon Kim 1, Jei-Won Moon 1, Hyuk-Je Kng 1, Jun-Woo Ahn 2, Sung-Hoon Kim 1, Hee-Dong Che 1, Byung-Moon Kng 1 1 Division of Reproductive Endocrinology nd Infertility, Deprtment of Obstetrics nd Gynecology, Asn Medicl Center, University of Ulsn College of Medicine, Seoul; 2 Division of Reproductive Endocrinology nd Infertility, Deprtment of Obstetrics nd Gynecology, Ulsn University Hospitl, University of Ulsn College of Medicine, Ulsn, Kore Objective: To evlute the effectiveness of multiple dose protocol pplied during erly nd lte folliculr phse () in comprison with stndrd lutel long protocol () in ech non-obese nd obese polycystic ovry syndrome (PCOS) women undergoing IVF. Methods: Two hundred eleven infertile women with PCOS were recruited nd rndomized to undergo either (ntgonist group) or stndrd lutel (gonist group). IVF cycle outcomes were compred between the two groups. Results: Totl dose nd dys of recombinnt humn follicle stimulting hormone (rhfsh) dministered were significntly fewer in the ntgonist group thn in the gonist group. Incidence of severe ovrin hyperstimultion syndrome ws significntly lower in the ntgonist group. However, IVF nd pregnncy outcomes were similr in the two groups. When ll subjects were divided into non-obese nd obese subgroups, in non-obese PCOS subgroup, IVF nd pregnncy outcomes were comprble in the ntgonist nd gonist groups but totl dose nd dys of rhfsh were lso significntly fewer in the ntgonist group. Similr findings were lso observed in obese PCOS subgroup. Conclusion: is t lest s effective s nd my be more ptient-friendly lterntive in controlled ovrin stimultion for PCOS ptients undergoing IVF, independent of body mss index. Keywords: Polycystic ovry syndrome; ; ; Body mss index; Controlled ovrin stimultion; In vitro fertiliztion Introduction Polycystic ovry syndrome (PCOS) is the most common cuse of Received: Mr 23, 2012 Revised: Mr 30, 2012 Accepted: Mr 30, 2012 Corresponding uthor: Chung-Hoon Kim Division of Reproductive Endocrinology nd Infertility, Deprtment of Obstetrics nd Gynecology, Asn Medicl Center, University of Ulsn College of Medicine, 88 Olympic-ro 43-gil, Songp-gu, Seoul , Kore Tel: Fx: E-mil: chnkim@mc.seoul.kr This is n Open Access rticle distributed under the terms of the Cretive Commons Attribution Non-Commercil License ( which permits unrestricted non-commercil use, distribution, nd reproduction in ny medium, provided the originl work is properly cited. novultory infertility, ffecting 5% to 10% of women of reproductive ge [1]. PCOS is ssocited with elevted ndrogen levels nd/or chronic novultion, ultimtely leding to menstrul disorders including menorrhe, oligomenorrhe, nd infertility [2]. Infertile ptients with PCOS women re frequently fced with difficult problems in ovultion induction (OI) or controlled ovrin stimultion (COS). Hypersecretion of LH nd hyperndrogenemi re thought to be ssocited with decresed oocyte qulity, lower fertiliztion, lower implnttion lower pregnncy, nd incresed miscrrige rtes [3]. Therefore, there is theoreticl benefit in the use of GnRH nlogues in COS cycles, especilly in ptients with PCOS. Actully, 22 Copyright THE KOREAN SOCIETY FOR REPRODUCTIVE MEDICINE

2 CH Kim et l. in PCOS women s dministrtion before nd during ovrin stimultion cuses significnt reduction in the incidence of premture LH surges nd the frequency of cycle cncelltion, thus incresing the success rte of IVF-ET [4,5]. Therefore, long protocol () hs been commonly used for IVF cycles in PCOS ptients. However, hs certin drwbcks, including the need to dminister the gents for more thn 2 weeks to induce pituitry desensitiztion, n unnecessry elevtion of gondotropin levels during erly dministrtion of s, nd high costs ttributble to the incresed totl dose nd higher number of dys of gondotropin dministrtion. Moreover, this protocol cnnot reduce the incidence of ovrin hyperstimultion syndrome (OHSS) in COS cycles. This shortcoming of my be more problemtic in PCOS ptients whose ovries re very sensitive to stimultion nd often develop excessive folliculr development in response to exogeneous gondotropin. s tht were recently introduced for COS hve severl dvntges over s. They bind competitively to the GnRH receptors in pituitry, nd produce n immedite nd rpid decrese in LH nd FSH levels without GnRH receptor desensitiztion s well s flre-up effect. COS protocols using s hve been shown to be effective in preventing premture LH surge [6,7]. Furthermore, met-nlyses in generl popultion demonstrted tht protocols reduce the incidence of OHSS s well s the mount of gondotropins used nd the durtion of stimultion s compred with protocols [8,9]. However, these met-nlyses showed n inconsistent results on pregnncy outcome. Moreover, there re very limited studies compring protocol nd in PCOS ptients [10-14] nd the optiml stimultion protocol for these ptients is still under debte. Therefore, this study ws performed to investigte the effectiveness of multiple dose protocol pplied during erly nd lte folliculr phse () compred with the stndrd GnRH gonist lutel in PCOS ptients undergoing IVF-ET. Methods 1. Ptient popultion Our prospective rndomized study ws performed t universitybsed infertility clinic t the Asn Medicl Center, Seoul, South Kore. The study popultion consisted of 211 infertile women with PCOS who hd undergone 211 IVF cycles between Jnury 2003 nd Mrch The Institutionl Review Bord of our center pproved the study nd ll ptients provided written informed consent. The subjects, ged 25 to 39 yers, were rndomized into either the (ntgonist group, n=106) or the (gonist group, n = 105) by the use of seled envelopes nd computergenerted list. The sequence of lloction to the two groups ws provided to the investigting physicins nd rndomiztion ws performed s plnned ccording to the rndomiztion list order. The PCOS dignosis ws bsed on the revised PCOS dignostic criteri of the 2003 Rotterdm consensus [15]. All ptients were in good helth with norml crdic, heptic nd renl functions, nd they hd experienced spontneous onset of puberty nd norml sexul development. None of subjects hd ever tken ny hormonl therpy within the preceding three months. 2. Ovrin stimultion protocols All ptients received orl contrceptive (OC, Dine35; Byer Schering Phrm, Berlin, Germny) pretretment for 21 dys in the cycle preceding ovrin stimultion. In the ntgonist group, 5 dys fter discontinution of OC, ovrin stimultion ws commenced using 50 to 150 IU of recombinnt humn FSH (rhfsh, Gonl-F; Merck Serono SA, Genev, Switzerlnd) fter estblishing ovrin nd uterine quiescence using vginl ultrsound. RhFSH ws dministered in stepup fshion nd the dose of rhfsh ws djusted every 3 to 4 dys ccording to ovrin response., cetrorelix (Cetrotide; Merck Serono SA) mg/dy ws dministered in the morning of stimultion dy 1 nd 2. When the men dimeter of led follicle reched 13 mm, cetrorelix t dose of 0.25 mg/dy ws strted gin nd continued dily up to the dy of recombinnt hcg (rhcg, Ovidrel; Merck Serono SA) injection. In the gonist group,, triptorelin (Decpeptyl; Ferring, Mlmo, Sweden) t dose of 0.1 mg/dy ws initited from dy 18 of OC pretretment cycle. All ptients hd withdrwl bleeding fter discontinution of OC. When pituitry desensitiztion ws chieved, ovrin stimultion ws strted nd the dose of triptorelin ws reduced to 0.05 mg dily nd continues up to dy of rhcg dministrtion. Ovrin stimultion ws performed in the sme mnner with the ntgonist group. In both ntgonist nd gonist groups, rhcg of 250 μg ws dministered subcutneously to induce folliculr mturtion when one or more follicles reched men dimeter of 17 mm. Trnsvginl ultrsound-guided oocyte retrievl ws performed 36 hours fter rhcg injection, nd one to four embryos, fter IVF or ICSI, were trnsferred into the uterus on the 3rd dy fter oocyte retrievl. Lutel support ws provided by dministering 90 mg of vginl progesterone gel (Crinone gel 8%; Merck Serono SA) once dily from the dy of oocyte retrievl. Pregnncies were confirmed by rising serum β-hcg concentrtions nd trnsvginl ultrsonogrphic evidence of gesttionl sc. The serum level of β-hcg ws mesured 11 dys fter embryo trnsfer (ET). Mesurement of β-hcg ws performed by rdioimmunossy using hcg MAIAclone kit (Serono Dignostics, Woking, Sur- 23

3 Clin Exp Reprod Med 2012;39(1):22-27 rey, UK). Inter- nd intr-ssy vrinces were not more thn 10% nd 5%, respectively. Mesurement of estrdiol nd progesterone ws performed by rdioimmunossy using Cot-A-Count Estrdiol kit (Siemens Medicl Solutions Dignostics, Los Angeles, CA, USA) nd Cot-A-Count Progesterone kit (Siemens Medicl Solutions Dignostics); interssy nd intrssy vrinces in mesuring estrdiol nd progesterone were less thn 10% nd 5%, respectively. 3. Outcome mesures Primry efficcy endpoint ws clinicl pregnncy rte per cycle. Secondry efficcy vribles included totl mount nd dys of rhfsh dministered, the numbers of retrieved, mture, fertilized oocytes nd good qulity embryos, embryo implnttion rte, miscrrige rte, nd the incidence of severe OHSS. OHSS ws dignosed nd clssified in ccordnce with the clssifiction system proposed by Goln et l. [16]. Clinicl pregnncy ws defined s the presence of gesttionl sc by ultrsonogrphy, while miscrrige rte per clinicl pregnncy ws defined s the proportion of ptients who filed to continue development before 24 weeks of gesttion in ll clinicl pregnncies. Preterm birth ws defined s the delivery t or before 34 weeks of gesttion. Live birth ws defined s the delivery of fetus with signs of life fter twenty completed weeks of gesttionl ge. 4. Sttisticl nlysis The men vlue ws expressed s the men ± SD. Sttisticl nlysis for the comprisons of men vlues ws performed using Student s t-test. Chi-squre test nd Fisher s exct test were used for the comprisons of frction. Sttisticl significnce ws defined s p < All nlyses were performed using the SPSS ver (SPSS Inc, Chicgo, IL, USA). Results The ntgonist group nd gonist group were comprble with respect to ptients chrcteristics such s the ge of ptients, infertility durtion, body mss index (BMI), the proportion of nullipr, ntrl follicle count, bsl endocrine profile nd 2-hour glucose level fter 75 g glucose lod (Tble 1). The ntgonist group consisted of 106 cycles initited corresponding to 106 ptients, nd the gonist group consisted of 105 cycles initited corresponding to 105 ptients. One cycle (0.9%) in the ntgonist group nd 2 cycles (1.9%) in the gonist group were cncelled fter oocyte retrievl due to high risk of OHSS. There ws no significnt difference in cycle cncelltion rte between the two groups. Tble 2 presents the comprison of COS results nd IVF outcomes between the ntgonist nd gonist groups. Totl dys nd dose of rhfsh required for COS were significntly fewer in the ntgonist Tble 1. Ptients chrcteristics No. of ptients Age of ptients (yr) 32.5 ± ± 4.2 NS Age of husbnds (yr) 36.4 ± ± 4.8 NS Infertility durtion (yr) 3.3 ± ± 1.3 NS BMI (kg/m 2 ) 22.9 ± ± 2.9 NS No. of nullipr 64 (60.4) 66 (62.9) NS b AFC 27.7 ± ± 3.9 NS Fsting glucose (mg/dl) 97.4 ± ± 18.4 NS Two-hour glucose fter 75 g ± ± 24.6 NS glucose lod (mg/dl) Endocrine profile Bsl FSH (IU/L) 4.2 ± ± 1.0 NS Bsl LH (IU/L) 7.5 ± ± 1.6 NS Bsl T (ng/ml) 1.2 ± ± 0.4 NS Bsl free T (pg/ml) 1.3 ± ± 0.6 NS DHEAS (ng/ml) 2,148.7± ,111.2±299.7 NS PRL (ng/ml) 16.5 ± ± 3.3 NS IGF-1 (ng/ml) ± ± 59.5 NS Vlues re presented s men±sd or number (%)., multiple-dose protocol during erly nd lte folliculr phse;, long protocol; NS, not significnt; BMI, body mss index; AFC, ntrl follicle count; IGF-1, Insulin like growth fctor -1. Student s t-test; b Chi-squre test. group thn in the gonist group (p<0.001 nd p=0.003, respectively) (Tble 2). There were no significnt differences between the two groups with respect to serum concentrtions of progesterone nd estrdiol on the dy of hcg injection, nd the numbers of oocytes retrieved, mture oocytes, fertilized oocytes, grde I or II embryos, embryos trnsferred nd embryos cryopreserved (Tble 2). The two groups were similr in the clinicl pregnncy rte per cycle initited nd per ET cycle, embryo implnttion rte, live birth rte per ET cycle nd multiple pregnncy rte (Tble 2). However, the incidence of severe OHSS ws significntly lower in the ntgonist group of 0.9% (1/106), compred with 7.6% (8/105) in the gonist group (p = 0.019) (Tble 2). Of ll ptients with severe OHSS, 1 in the ntgonist group nd 7 in the gonist group becme pregnnt. All of the ptients who suffered from severe OHSS were hospitlized nd dischrged without ny complictions. All subjects were divided into non-obese subgroup (BMI <23 kg/ m 2 ) nd obese subgroup (BMI 23 kg/m 2 ). In the non-obese subgroup, totl dys nd dose of rhfsh required were lso significntly fewer in the ntgonist group thn in the gonist group (p < nd p = 0.012, respectively) (Tble 3). IVF nd pregnncy outcomes were lso comprble in the two groups (Tble 3). The incidence of severe OHSS seemed to be lower in the ntgonist group, but the difference did not chieve sttisticl significnce (p=0.113) (Tble 3). Similr results were observed in the obese subgroup consisted of 24

4 CH Kim et l. in PCOS women Tble 2. Comprison of COS results nd IVF/ICSI outcome in ll subjects PCOS women with BMI 23 kg/m 2 (Tble 4). Discussion No. of cycles initited No. of ET cycles No. of cycles cncelled 1 (0.9) 2 (1.9) NS No. of cycles with ICSI 42 (39.6) 38 (36.2) NS Dys of rhfsh 10.8 ± ± 2.0 < Totl dose of rhfsh (IU) 1,423.4 ± ,670.8 ± On the dy of hcg injection Progesterone (ng/ml) 0.3 ± ± 0.2 NS Estrdiol (pg/ml) 2,175.1 ± ,255.4 ± NS Endometril thickness (mm) 10.3 ± ± 1.3 NS No. of oocytes retrieved 14.7 ± ± 5.8 NS No. of mture oocytes 12.5 ± ± 5.0 NS No. of fertilized oocytes 12.3 ± ± 4.9 NS No. of grde I, II embryos 4.0 ± ± 2.1 NS No. of embryos trnsferred 3.0 ± ± 0.6 NS No. of embryos cryopreserved 4.1 ± ± 4.5 NS Clinicl PR per cycle initited (%) 38.7 (41/106) 38.1 (40/105) NS b Clinicl PR per ET (%) 39.0 (41/105) 38.8 (40/103) NS b Multiple PR (%) 19.5 (8/41) 20.0 (8/40) NS b Miscrrige rte (%) 12.2 (5/41) 10.0 (4/40) NS b Embryo implnttion rte (%) 16.7 (52/311) 16.7 (50/299) NS b Live birth rte per ET (%) 34.3 (36/105) 35.0 (36/103) NS b Severe OHSS (%) 0.9 (1/106) 7.6 (8/105) b Vlues re presented s number (%), men±sd, or % (number/totl number). COS, controlled ovrin stimultion;, multiple-dose protocol during erly nd lte folliculr phse;, long protocol; ET, embryo trnsfer; NS, not significnt; rhfsh, recombinnt humn follicle stimulting hormone; PR, pregnncy rte; OHSS, ovrin hyperstimultion syndrome. Student s t-test; b Chi-squre test or Fisher s exct test. Tble 3. Comprison of COS results nd IVF/ICSI outcome in ptients with BMI < 23 kg/m 2 No. of cycles initited No. of ET cycles No. of cycles cncelled 1 (1.8) 2 (3.7) NS No. of cycles with ICSI 21 (38.2) 18 (33.3) NS Dys of rhfsh 9.7 ± ± 1.5 < Totl dose of rhfsh (IU) 1,077.9 ± ,241.3 ± On the dy of hcg injection Progesterone (ng/ml) 0.4 ± ± 0.2 NS Estrdiol (pg/ml) 2,217.3 ± ,295.0 ± NS Endometril thickness (mm) 10.3 ± ± 1.2 NS No. of oocytes retrieved 15.0 ± ± 5.2 NS No. of mture oocytes 13.3 ± ± 4.7 NS No. of fertilized oocytes 12.9 ± ± 4.8 NS No. of grde I, II embryos 4.1 ± ± 2.2 NS No. of embryos trnsferred 3.0 ± ± 0.6 NS No. of embryos cryopreserved 4.5 ± ± 4.7 NS Clinicl PR per cycle initited (%) 41.8 (23/55) 40.7 (22/54) NS b Clinicl PR per ET (%) 42.6 (23/54) 42.3 (22/52) NS b Multiple PR (%) 26.1 (6/23) 22.7 (5/22) NS b Miscrrige rte (%) 4.3 (1/23) 4.5 (1/22) NS b Embryo implnttion rte (%) 19.1 (31/162) 18.5 (28/151) NS b Live birth rte per ET (%) 40.7 (22/54) 40.4 (21/52) NS b Severe OHSS (%) 1.8 (1/55) 9.3 (5/54) NS b Vlues re presented s number (%), men±sd, or % (number/totl number). COS, controlled ovrin stimultion;, multiple-dose protocol during erly nd lte folliculr phse;, long protocol; ET, embryo trnsfer; NS, not significnt; rhfsh, recombinnt humn follicle stimulting hormone; PR, pregnncy rte; OHSS, ovrin hyperstimultion syndrome. Student s t-test; b Chi-squre test or Fisher s exct test. This study evluted the effectiveness of compred with the stndrd lutel in PCOS ptients undergoing IVF-ET. We used the to correct for hormonl bnormlities seen during the erly folliculr phse, rther thn employing the stndrd MDP during the lte folliculr phse. Our findings suggest tht the protocol for COS cn be pplied to PCOS ptients nd my be beneficil in reducing totl dys nd dose of rhfsh required nd the incidence of severe OHSS in PCOS ptients undergoing IVF-ET. Prticulr ttention should be pid during OI or COS in PCOS ptients, becuse ovries of PCOS ptients hve surplus number of smll ntrl follicles nd these ptients re exposed to the risks of OHSS. Despite specil ttention, complictions, such s OHSS, multiple pregnncy nd premture luteiniztion, re usully more frequent in women with PCOS [17]. Other chrcteristics of women with PCOS, including elevted bsl serum LH, hyperndrogenemi, nd incresed intrfolliculr ndrogen levels hve been shown to dversely ffect COS or IVF results by interrupting the development of norml follicles nd inducing degenertion of mture follicles. The miscrrige rte is therefore higher in PCOS thn in norml women [3]. To overcome these problems, ws introduced for COS in PCOS ptients nd its use effectively prevented premture luteiniztion, incresed pregnncy rte, nd decresed miscrrige frequency [4,5]. However, the use of cnnot reduce the incidence of OHSS in PCOS ptients undergoing COS. This is n importnt reson to seek new tretment option thn in PCOS ptients t high risk of OHSS. Recently, protocols hve been reported to reduce the incidence of OHSS s well s dys nd dose of gondotropins required when compred with protocols [8,9] nd therefore the use of s hs been proposed s new sfer 25

5 Clin Exp Reprod Med 2012;39(1):22-27 Tble 4. Comprison of COS results nd IVF/ICSI outcomes in ptients with BMI 23 kg/m 2 No. of cycles initited No. of ET cycles No. of cycles cncelled 0 0 NS No. of cycles with ICSI 21 (41.2) 20 (39.2) NS Dys of rhfsh 12.0 ± ± Totl dose of rhfsh (IU) 1,796.1 ± ,125.6 ± On the dy of hcg injection Progesterone (ng/ml) 0.3 ± ± 0.2 NS Estrdiol (pg/ml) 2,129.5 ± ,213.5 ± NS Endometril thickness (mm) 10.3 ± ± 1.4 NS No. of oocytes retrieved 14.4 ± ± 6.3 NS No. of mture oocytes 12.3 ± ± 5.2 NS No. of fertilized oocytes 11.8 ± ± 5.0 NS No. of grde I, II embryos 3.9 ± ± 2.0 NS No. of embryos trnsferred 3.0 ± ± 0.5 NS No. of embryos cryopreserved 3.6 ± ± 4.2 NS Clinicl PR per cycle initited (%) 35.3 (18/51) 35.3 (18/51) NS b Clinicl PR per ET (%) 35.3 (18/51) 35.3 (18/51) NS b Multiple PR (%) 11.1 (2/18) 16.7 (3/18) NS b Miscrrige rte (%) 22.2 (4/18) 16.7 (3/18) NS b Embryo implnttion rte (%) 13.7 (21/153) 14.9 (22/148) NS b Live birth rte per ET (%) 27.5 (14/51) 29.4 (15/51) NS b Severe OHSS (%) (3/51) NS b Vlues re presented s number (%), men±sd, or % (number/totl number). COS, controlled ovrin stimultion;, multiple-dose protocol during erly nd lte folliculr phse;, long protocol; ET, embryo trnsfer; NS, not significnt; rhfsh, recombinnt humn follicle stimulting hormone; PR, pregnncy rte; OHSS, ovrin hyperstimultion syndrome. Student s t-test; b Chi-squre test or Fisher s exct test. stimultion option for PCOS ptients. However, there is limited number of published studies on the use of s in COS for PCOS ptients, nd n optiml protocol for these ptients is still controversil. During COS using s in PCOS women, elevted LH nd estrdiol levels in the erly folliculr phse my dversely ffect oocyte or embryo qulity nd my decrese endometril cceptbility nd pregnncy rtes [15]. For this reson, it hs been recommended to use s in the erly folliculr phse of cycles in these ptients [11-13]. Elkind-Hirsch et l. [11] demonstrted the effectiveness nd sfety of concurrent gnirelix nd follitropin-bet therpy for COS in women with PCOS. In ddition, pregnncy outcomes in PCOS ptients pretreted with OC followed by concomitnt dministrtion of cetrorelix from the first dy of stimultion, were similr to those of PCOS ptients treted with [12]. In our preliminry study [13], two dditionl use of GnRH ntgonist in the erly folliculr phse of stndrd MDP cycle lso yielded comprble IVF results nd pregnncy outcome with fewer dose nd dys of rhfsh used when compred with those of. The present study corrobortes the findings of our preliminry study. Met-nlysis by Griesinger et l. [18] showed similr pregnncy outcomes when protocols nd were compred in PCOS ptients undergoing IVF-ET. In rndomized controlled tril (RCT) by Lins et l. [14], even stndrd MDP lso resulted in similr pregnncy rte nd lower incidence of severe OHSS, compred with GnRH gonist. So fr, there re limited dt on COS using in PCOS ptients nd furthermore, there re very few published studies supporting benefits of protocols in PCOS ptients. This study showed tht protocol reduces the incidence of severe OHSS in PCOS ptients s compred with. In RCT by Lins et l. [14], severe OHSS lso occurred less frequently in the ntgonist group thn in the gonist group, lthough sme dose of hcg ws dministered in both groups. The explntion for this finding is tht itself my hve slowing effect of excessive folliculr development, especilly in the secondry follicles. Compred with non-obese women with PCOS, obese women with PCOS hve vrious endocrine chnges. High BMI is ssocited with gondotropin resistnce nd poor IVF outcome [19,20]. In ddition, high BMI hs n inhibitory effect on LH [21]. Therefore, protocol in obese PCOS women is likely to work differently thn in non-obese PCOS women. For this reson, we divided ll subjects into non-obese nd obese subgroups, nd then evluted the effectiveness of in ech subgroups. In non-obese subgroup, IVF results nd pregnncy outcome were comprble but totl dose nd dys of rhfsh were significntly fewer in the ntgonist group thn in the gonist group. Similr results were lso observed in obese subgroup. Our results implies tht MDP- EL is effective not only in non-obese PCOS ptients with theoreticlly higher LH levels but lso in obese PCOS ptients. In conclusion, cn provide similr IVF outcome with fewer dose nd dys of rhfsh dministered in both nonobese nd obese PCOS ptients, compred with. Moreover, cn reduce the incidence of severe OHSS. These findings suggest tht the cn be more cost-effective, more ptient-friendly nd sfer thn GnRH gonist in PCOS ptients. Therefore, protocol my be the protocol of choice for COS in PCOS ptients undergoing IVF- ET, independent of BMI. Conflict of interest No potentil conflict of interest relevnt to this rticle ws reported. 26

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