An elevated basal FSH re ects a quantitative rather than qualitative decline of the ovarian reserve

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1 Humn Reproduction Vol.19, No.4 pp. 893±898, 2004 Advnce Access publiction Mrch 11, 2004 DOI: /humrep/deh141 An elevted bsl FSH re ects quntittive rther thn qulittive decline of the ovrin reserve H.Abdll 1,2 nd M.Y.Thum 1 1 Lister Fertility Clinic, Lister Hospitl, Chelse Bridge Rod, London SW1W 8RH, UK 2 To whom correspondence should be ddressed. E-mil: sm@esynet.co.uk BACKGROUND: Mny cycling women with elevted bsl FSH level hve been discourged from undergoing IVF tretment. This is becuse elevted bsl FSH is ssocited with poorer ssisted reproduction tretment outcome. It hs been rgued tht high FSH re ects not only reduced ovrin reserve but lso poor oocyte qulity. The im of this study is to ssess the vlue of treting cycling women who hve elevted bsl FSH nd to ssess the resons for the reduction in both pregnncy rte (PR) nd live birth rte (LBR). METHODS: Between Jnury 1997 nd December 2001, 2057 ptients underwent 3401 consecutive IVF/ICSI cycles in which the bsl level of FSH (dys 2± 4) ws determined t n erlier cycle. Anlysis, however, ws only performed for single cycle per ptient. All cses were divided into four cohorts ccording to FSH levels: group A, FSH <10 IU/ml; group B, 10.1±15 IU/ml; group C, 15.1±20 IU/ml; nd group D, FSH >20 IU/ml. Ech group ws strti ed further into subgroups ccording to ge, <38 nd >38 yers. RESULTS: Both PR (A, 32.3%; B, 19.8%; C, 17.5%; nd D, 3%) nd LBR (A, 24.7%; B, 13.2%; C, 13.8%; nd D, 3%) were signi cntly reduced in the higher FSH level groups. LBR ws signi cntly higher in the younger subgroups (A, 32.2%; B, 21.8%; C, 20%; nd D, 16.7%) s compred with the older subgroups (A, 12.1%; B, 8.3%; C, 10.5%; nd D, 0%). Higher levels of FSH were signi cntly ssocited with more cycle cncelltion, lrger mount of gondotrophin required to chieve folliculr mturity, nd lower number of eggs collected, embryos vilble nd embryos trnsferred. In ll cses, however, there ws no signi cnt correltion between FSH levels nd fertiliztion rte or miscrrige rte. Younger cycling women with elevted FSH hd signi cntly higher LBR compred with older women with norml FSH (21.2% versus 12.1%). Furthermore, the cumultive LBR fter three cycles in these younger ptients with elevted FSH levels ws 49.3%. CONCLUSION: Although there is reduction in both PR nd LBR ssocited with higher levels of bsl FSH, it is cler tht in cycling women, high bsl FSH is not contrindiction to IVF tretment, nd respectble PR nd LBR cn be chieved especilly in young women. The reduction in PR nd LBR is due to reduced reserve rther thn poor oocyte qulity. Clinics refusing to tret cycling women with elevted bsl FSH levels my be denying these women resonble, lbeit low, chnce of chieving birth with their own genetic mteril. Clinicins should use bsl FSH levels s guide to dvise ptients bout their chnces of chieving live birth, not to exclude ptients with predicted lower success rte from tretment progrmme. Key words: bsl stimulting hormone/fsh/ivf/ivf outcome/pregnncy rte Introduction Determintion of ovrin reserve by mesuring dy 3 bsl FSH in norml cycling women is often used in mny IVF units prior to ssisted conception tretment to choose ptients eligible for strting ssisted reproduction technique (ART) cycles. Mny cycling women with borderline elevted bsl FSH hve been discourged from undertking ART tretment becuse the chnce of success is thought to be low, nd hve been directed to other modlities such s oocyte dontion or doption. The cycle dy 3 FSH level is one of the most commonly used tests for predicting success in IVF tretment. This ws rst described by Musher et l. (1988). Lenton et l. (1988) demonstrted tht women with n elevted cycle dy 3 FSH hd reduced ovrin reserve. Since then, severl studies hve shown tht women with n elevted FSH level, independent of ge, hve poor response to ovrin stimultion, leding to lower pregnncy rte with ART (Scott et l., 1989; Mrtin et l., 1996; Shrif et l., 1998; El-Toukhy et l., 2002). Recently, however, El-Toukhy et l. (2002) rgued tht young ge does not protect ginst the dverse effects of reduced ovrin reserve, suggesting tht n elevted dy 3 bsl FSH level is ssocited not only with low response, but lso with poor qulity oocytes leding not only to reduction in pregnncy rte but lso to rise in miscrrige rtes. Humn Reproduction vol. 19 no. 4 ã Europen Society of Humn Reproduction nd Embryology 2004; ll rights reserved 893

2 H.Abdll nd M.Y.Thum Tble I. Stimultion chrcteristics nd cycle outcome Group A (FSH <10.1 IU/l) Group B (FSH 10.1±15 IU/l) Group C (FSH 15.1±20 IU/l) Group D (FSH >20 IU/l) No. of ptients Men ge 6 SD b Durtion of infertility (men 6 SD) b Cncelltion rte (%) Dys of tking gondotrophins (men 6 SD) b No of mpoules c consumed (men 6 SD) d Estrdiol (IU) per follicle on HCG dy e Averge no. of oocytes collected d Fertiliztion rte (%) e,f 59.5% 58.3% 60.9% 62.0% Averge no of vilble embryos for trnsfer d Averge no of embryos trnsferred d Pregnncy rte per strted cycle in % (n) b 32.3 (554/1721) 19.8 (48/245) 17.5 (10/58) 3.0 (1/33) LBR per strted cycle in % (n) b 24.7 (425/1721) 13.2 (32/245) 13.8 (8/58) 3.0 (1/33) Pregnncy rte per egg collection in % (n) b 34.3 (554/1615) 23.0 (48/209) 25.6 (10/39) 5.3 (1/19) LBR per egg collection in % (n) b 26.3 (425/1615) 15.3 (32/209) 20.5 (8/39) 5.3 (1/19) Miscrrige rte in % (n) e 23.3 (129/554) 33.3 (16/48) 20.0 (2/10) 0 (0/1) LBR when 1±4 eggs collected in % (n) e 10.5 (26/248) 8.5 (7/82) 19.0 (4/17) 9.1 (1/11) Cumultive LBR fter three cycles 51.2% 38.9% 36.1% 19.2% Signi cnt sttisticl comprison using c 2 cross-tbultion test with P < b Vlues re not sttisticlly signi cnt. c Number of mpoules = in cses of pure FSH (75 IU FSH) nd in cses of HMG (75 IU FSH nd 75 IU LH). d Signi cnt sttisticl comprison using ANOVA test with P < e Not sttisticlly signi cnt. f Men no. of fertilized oocytes/men no. of oocytes collected g Men of verge mount of gondotrophin used for stimultion. Recently some studies hve shown tht women with elevted bsl FSH levels cn still chieve resonble pregnncy rtes with ART (Levi et l., 2001; Esposito et l., 2002; vn Rooij et l., 2003), especilly in younger women. Those cycling women who re discourged from undertking tretment my, therefore, be denied resonble chnce of chieving pregnncy with their own genetic child. In our deprtment, we operted on the principle tht if the womn ws cycling regulrly, then we should offer ART regrdless of the bsl level of FSH. The purpose of this study is to ssess the vlue of treting cycling women who hve n elevted bsl FSH nd to evlute the hypothesis tht the lower pregnncy rte in cycling women with elevted bsl FSH levels is due to reduced ovrin reserve (re ected by cncelltion rte, dose of gondotrophins used to stimulte the ovries nd number of eggs collected) rther thn poor oocyte qulity (re ected by fertiliztion nd miscrrige rtes). This would help the ptient understnd tht if they mnged to get to the stge of egg collection nd eggs were obtined, then their chnce of hving these eggs fertilized normlly would be similr to tht of ny other couple nd tht their chnce of becoming pregnnt ws similr to tht of women of their own ge with similr number of embryos generted. Moreover, should their cycle result in pregnncy, it would not be t higher risk of miscrrige. Mterils nd methods Dt of ptients undergoing IVF/ICSI tretment in our unit re routinely collected prospectively nd stored in system for IVF (MediclSys, London, UK). 894 Study popultion Between Jnury 1997 nd December 2001, ll ptients underwent IVF/ICSI tretment. The most recent bsl FSH level (dys 2±4 of the menstrul cycle) ws determined in cycle prior to the strt of IVF/ ICSI tretment. There ws no ttempt to check the level of FSH in the tretment cycle itself. Ptients were treted with either long or short protocol. All ptients, regrdless of ge or FSH levels, underwent ovrin stimultion. Serum FSH level test Serum FSH concentrtion ws mesured using two-step chemiluminescent microprticle immunossy (CMIA) nd nlysed by Abbott Architect Ô System (Abbott Lbortories, IL). The nlyticl sensitivity of the ssy ws clculted to be better thn 0.05 miu/ml (n = 36 runs). Anlyticl sensitivity is de ned s the concentrtion t 2 SDs from the ARCHITECT FSH MsterCheck Ô Level 0 (0.00 miu/ ml), nd represents the lowest mesurble concentrtion of FSH tht cn be distinguished from zero. The speci city of the ssy ws determined by studying the cross-rectivity of LH, thyroid-stimulting hormone (TSH) nd HCG. The percentge cross-rectivity ws clculted nd ws shown to be 0.002% for LH, 0.043% for TSH nd 0.001% for HCG. The inter- nd intr-ssy coef cients of vrition were 2.9 nd 3.8%, respectively. Tretment protocol Ovrin stimultion ws crried out with either recombinnt FSH, HMG or urinry FSH. A trnsvginl scn ws performed prior to ovrin stimultion to ensure the ovries were quiescent. For the long protocol, ptients were downregulted with either Nfrelin or Buserelin t mid-lutel phse. For the Cetrotide protocol, GnRH hormone ntgonist ws commenced when the leding follicle reched 12 mm. When follicles reched pre-ovultory size (18± 22 mm), IU (for ptients tking HMG) or IU (for

3 Elevted bsl FSH nd ART outcome ptients tking FSH) of HCG were dministrted. Oocytes were spirted using trnsvginl ultrsound guidnce 34±36 h fter HCG dministrtion. Embryo trnsfer ws performed on dy 2 or dy 3 using soft ctheter with trnsbdominl ultrsound guidnce. All ptients received progesterone 400 mg pessries s supplement throughout the lutel phse. A pregnncy test ws performed 2 weeks fter trnsfer of embryos. De nition of outcome A mture follicle ws de ned s follicle >17 mm on trnsvginl ultrsound scn. A miscrrige or spontneous bortion ws de ned s pregnncy lost before 24 weeks of gesttion. A pregnncy ws de ned s positive serum or urine HCG test nd sc seen on ultrsound scn, or n ectopic pregnncy. A live birth ws de ned s pregnncy resulting in delivery of vible infnt. Twins nd triplets were counted s one live birth. Fertiliztion rte ws de ned s number of two pronucler (2 PN) embryos per number of oocytes collected for ech tretment cycle including ICSI cycles. Cncelltion ws de ned s cycle strted but no egg collection performed. Tretment cycles which proceeded to egg collection but with no eggs retrieved were included s norml cycles. Dt nlysis Dt were collected in the Medicl System for IVF (MediclSys, London, UK) nd nlysed with the Sttistics Pckge for Socil Sciences (SPSS, Surrey, UK). Descriptive sttisticl nlysis ws performed initilly to exmine the normlity distribution of ll continuous vrinces for prmetric sttisticl tests. Associtions between FSH vlues nd pregnncy rtes, miscrrige rtes nd live birth rtes (LBRs) were exmined with c 2 cross-tbultion test strti ed by ge. Anlysis of vrince (ANOVA) ws then conducted to ssess the reltionships between FSH levels nd durtion nd mount of gondotrophin required to chieve folliculr mturity, number of mture follicles, number of vilble embryos for trnsfer, number of oocytes collected nd fertiliztion rte. Sttisticl signi cnce ws set t P < Results Between Jnury 1997 nd December 2001, 2057 ptients underwent 3401 consecutive IVF/ICSI cycles. Anlysis, however, ws only performed. Anlyses, however, ws only performed on the rst tretment cycle of ech ptient. Thus only 2057 cycles re studied. We hve nlysed the dt in reltion to different levels of FSH nd found no difference in pregnncy rte nd LBR or other outcome prmeters in ptients with FSH <5 IU/l, those between 5 nd 8 IU/l nd those between 8 nd 10 IU/l. We did, however, observe signi cnt chnges if the vlue of FSH ws >10 IU/l. All ptients with FSH <10 IU/l were therefore united in one group. For the purpose of nlysis, the cohort ws therefter divided into four groups s follows: group A, FSH <10 IU/l; group B, FSH 10.1±15 IU/l; group C, FSH 15.1±20 IU/l; nd group D, FSH >20 IU/l. Tble I shows the ptients' demogrphics, stimultion chrcteristics nd tretment outcome in ll four cohorts. Women's men ge ws slightly higher in the higher FSH groups but the difference ws not sttisticlly signi cnt. The pregnncy rte nd LBR per strted cycle nd per egg collection were signi cntly lower (P < 0.001) in the higher FSH groups. There were no signi cnt differences between the four groups with regrd to durtion of infertility, miscrrige rte, fertiliztion rte, serum estrdiol per follicle, durtion of stimultion nd verge number of embryos trnsferred. Furthermore, the men estrdiol level ws not different between study groups. However, the mount of gondotrophin required to chieve folliculr mturity nd the verge dily dose of gondotrophin used for stimultion were higher in the elevted FSH groups. The verge number of oocytes collected nd verge number of vilble embryos for trnsfer were signi cntly reduced (P < 0.001) in the elevted FSH groups. The cncelltion rte ws signi cntly higher (P < 0.001) in the elevted FSH groups. The highest FSH level mesured in ptient chieving live birth ws 32.8 IU/l. A singleton ws delivered t 39 weeks. We further nlysed the cumultive LBR fter three cycles for ech study group. This showed the sme pttern, with reduction in cumultive LBR s the level of FSH is elevted (group A = 51.2%, group B = 38.9%, group C = 36.1% nd group D = 19.2%). Tbles II nd III exmine the reltionship between ge nd level of FSH. Tble II illustrtes the effect of the level of FSH in women below nd bove the ge of 38. In this context, the sme trend s shown in Tble I is pprent for the two ge groups; however, in those ptients ged <38, the pregnncy rte nd LBR were reduced, but not signi cntly, s FSH levels incresed. An LBR of t lest 20% ws lwys chieved in ptients with FSH between 10 nd 20 IU/l, nd 16.7% in ptients with FSH >20 IU/l. The miscrrige rte nd fertiliztion rte were not in uenced by the incresed FSH levels. For those ptients ged >38, the pregnncy rte nd LBR were signi cntly reduced s FSH levels incresed; however, the fertiliztion rte ws not in uenced by the incresed FSH levels. None of the ptients with FSH >20 IU/l chieved pregnncy in their rst cycle; however, 16.7% hd live birth in their second tretment cycle. Tble III exmines the sme dt but illustrtes the effect of ge within ech FSH group. As shown, ge is signi cnt fctor ffecting tretment outcome. For those ptients in the sme FSH group, there ws mrked nd signi cnt difference in the two ge groups, i.e <38 nd >38, whereby the younger ptients hd lower cncelltion rte, higher numbers of eggs collected, more embryos vilble for trnsfer, higher pregnncy rte, LBR nd lower miscrrige rte. It is noticeble, however, tht the fertiliztion rte ws not signi cntly different within ny of the ge subgroups. Tble IV compres the outcome for younger ptients with high FSH nd older ptients with norml FSH. As shown, ge ws the most signi cnt fctor in in uencing the outcome. Although younger ptients with high FSH ppered to hve lower number of oocytes collected nd lower number of vilble nd trnsferred embryos, their pregnncy rte nd LBR were both signi cntly higher thn those of older women with norml FSH. Discussion Most clinics use bsl dy 3 FSH level s screening tool to ssess the chnce of one prticulr ptient chieving pregnncy or live birth with IVF tretment. This prctice is bsed on erlier studies showing tht elevted dy 3 FSH levels 895

4 H.Abdll nd M.Y.Thum Tble II. Stimultion chrcteristics nd cycle outcome of ptients ged <38 nd >38 in ll four FSH groups Age <38 yers Age >38 yers FSH groups Group A Group B Group C Group D Group A Group B Group C Group D No. of ptients Cncelltion rte (%) Averge no. of oocytes collected b Fertiliztion rte (%) c,d No. of embryos vilble for trnsfer b Averge no of embryos trnsferred d Pregnncy rte per strted cycle in % (n) 40.3 d (434/1082) 29.9 d (26/87) (5/20) 18.8 (120/639) 14.1 (22/156) 13.1 (5/38) LBR per strted cycle in % (n) 32.2 d (348/1082) 21.8 d (19/87) 20.0 d (4/20) 12.1 (77/639) 8.3 (13/156) 10.5 (4/38) Pregnncy rte per egg collection in % (n) 41.5 c (434/1035) 33.8 d (26/77) 31.3 d (5/11) 20.8 (120/577) 16.7 (22/132) 21.7 (5/23) LBR per egg collection in % (n) 33.6 d (348/1035) 24.7 d (19/77) (4/16) 13.2 (77/577) 9.8 (13/132) 17.4 (4/23) Miscrrige rte (%) NA Cumultive LBR fter three cycles 62.1% 51.7% 37.8% 16.7% 33.1% 29.5% 32.9% 16.7% Signi cnt sttisticl comprison using c 2 cross-tbultion test with P < b Signi cnt sttisticl comprison using ANOVA test with P < c Men no. of fertilized oocytes/men no. of oocytes collected d Not sttisticlly signi cnt. Tble III. Stimultion chrcteristics nd cycle outcome of ptients <38 nd >38 yers in ll four FSH groups Group A (FSH <10.1 IU/l) Group B (FSH 10.1±15 IU/l Group C (FSH 15.1±20 IU/l) Group D (FSH >20 IU/ol) <38 >38 <38 >38 <38 >38 <38 >38 No. of ptients Cncelltion rte (%) Averge no. of oocytes collected b Fertiliztion rte (%) c,d Avilble no of embryos for trnsfer b Averge no of embryos trnsferred d Pregnncy rte per strted cycle in % (n) 40.3 (434/1082) 18.8 (120/639) 29.9 d (26/87) 14.1 (22/156) (5/20) 13.1 (5/38) LBR per strted cycle in % (n) 32.2 (348/1082) 12.1 (77/639) 21.8 d (19/87) 8.3 (13/156) 20.0 d (4/20) 10.5 (4/38) Pregnncy rte per egg collection in % (n) 41.5 (434/1035) 20.8 (120/577) 33.8 d (26/77) 16.7 (22/132) 31.3 d (5/11) 21.7 (5/23) LBR per egg collection in % (n) 33.6 (348/1035) 13.2 (77/577) 24.7 d (19/77) 9.8 (13/132) (4/16) 17.4 (4/23) Miscrrige rte (%) NA Cumultive LBR fter three cycles 62.1% 33.1% % 37.8% 32.9% 16.7% 16.7% Signi cnt sttisticl comprison using c 2 cross-tbultion test with P < b Signi cnt sttisticl comprison using ANOVA test with P < c Men no. of fertilized oocytes/men no. of oocytes collected d Not sttisticlly signi cnt. re ssocited with reduced success rte of ART (Scott nd Hofmnn, 1995; Blsch et l., 1996; Brnhrt nd Osherof, 1998). However, there is no cler-cut division between norml nd n elevted FSH level (vn Montfrns et l., 2000; Esposito et l., 2002). It hs been suggested tht the reson tht clinics refuse to tret ptients with elevted bsl FSH is to mintin the clinic's overll success rte or to improve their position in the legue tbles (Shrif nd Afnn, 2003). Women with elevted FSH could be heterogeneous group. Some my hve true reduced ovrin reserve, other cses my be due to the presence of heterophylic ntibodies. Finlly, FSH 896 receptor polymorphism could lso result in n elevted vlue in ptients with otherwise norml ovries (Lmblk, 2003). In this study, however, we con rm tht elevted dy 3 FSH levels in previous cycle re ssocited with reduction in the overll LBR if compred with women with norml bsl FSH levels. Nevertheless, the LBR is resonble, especilly in cycling women under the ge of 38 with FSH between 10 nd 20 IU/l where the chnce of live birth is t lest 20%. This is comprble with the ntionl verge LBR in the UK (HFEA Ptient Guide, 2001) in ptients who re not considered by most ssessment to be verge. In fct, two ptients with FSH

5 Elevted bsl FSH nd ART outcome Tble IV. Stimultion chrcteristics nd cycle outcome of ptients <38 nd FSH >10 IU/l versus ptients >38 yers nd FSH <10 IU/l Age <38 nd FSH >10 IU/l Age >38 nd FSH <10 IU/l P-vlue No. of ptients) Men ge 6 SD Durtion of infertility (men 6 SD) NS Cncelltion rte (%) Dys of tking gondotrophins (men 6 SD) NS No of mpoules consumed (men 6 SD) NS Estrdiol (IU) per follicle on HCG dy Averge no. of oocytes collected (men 6 SD) Fertiliztion rte (%) c NS Averge no. of embryos vilble for trnsfer NS Averge no. of embryos trnsferred NS Pregnncy rte per strted cycle in % (n) 28.3 (32/113) 18.8 (120/639) LBR per strted cycle in % (n) 21.2 (24/113) 12.1 (77/639) Pregnncy rte per egg collection in % (n) 33.7 (32/95) 20.8 (120/577) LBR per egg collection in % (n) 25.3 (24/95) 13.2 (77/577) Miscrrige rte (%) Cumultive LBR fter three cycles 49.3% 33.1% Number of mpoules = in cses of pure FSH (75 IU FSH) nd in cses of HMG (75 IU FSH nd 75 IU LH). NS = difference not sttisticlly signi cnt (P > 0.05). >20 IU/l chieved live birth, one in her rst cycle nd the other in her second cycle, giving cumultive LBR of 19.2%. Indeed, in ptients of ll groups of elevted levels of FSH (>10 IU/l) where the ge ws <38, the LBR ws in excess of 20% per single cycle, with cumultive LBR fter three cycles of 49.3%. This, we believe, is fr better choice for signi cnt number of women thn the lterntives of oocyte dontion nd doption. In this study, there ws no ttempt to check the level of FSH in the tretment cycle itself. Previous studies (Scott et l., 1990; Mrtin et l., 1996) hve demonstrted tht inter-cycle vribility in bsl FSH vlues did not predict chnges in ovrin response to gondotrophin stimultion nd thus my not be used to select n optiml cycle in which to stimulte n individul ptient. These studies lso reported tht one previous elevted dy 3 FSH determintion drmticlly decresed the chnce of future IVF-ET pregnncy. El-Toukhy et l. (2002) rgued tht young ge does not protect ginst the dverse effects of reduced ovrin reserve, suggesting tht n elevted dy 3 bsl FSH level is not only ssocited with low response, but lso with poor qulity oocytes. They in fct rgued tht ptients with elevted dy 3 FSH perform s bdly s much older ptients with norml FSH. This ws not the cse in this study. We hve shown tht lthough younger cycling ptients with high FSH hd signi cntly lower number of oocytes collected nd lower number of vilble nd trnsferred embryos, their pregnncy rte nd LBR were signi cntly higher nd their miscrrige rte ws signi cntly lower thn older women with norml FSH. Their study ws, however, mixture of two groups, those with elevted dy 3 FSH nd lso those with previous poor response to stimultion nd, therefore, the conclusions cnnot be mde (nd should not hve been) speci c to ptients with high bsl FSH level. Furthermore, the men FSH vlue in ll three ge groups in their study ws <10 IU/l. Cycling women with elevted FSH required more mpoules for stimultion; this could be due to true poor response or possible bis due to knowledge in dvnce of bsl FSH vlue encourging the clinicin to prescribe higher dose of gondotrophins. The fct, however, is tht regrdless of the incresing dose of gondotrophins, there ws higher cncelltion rte nd the ultimte number of eggs collected ws progressively reduced in the elevted FSH groups. The fertiliztion rte, however, ws the sme in ll groups, indicting tht oocyte qulity is not ffected by the bsl FSH level. This nding is in keeping with the ndings of Shrif et l. (1998). Overll, however, the number of embryos vilble for trnsfer ws lower for those ptients with high bsl FSH, nd thus the number of embryos to choose from nd the number of embryos trnsferred were lower in tht group. This resulted in lower pregnncy rte. This implies tht elevted bsl FSH is ssocited with low ovrin reserve, but is not synonymous with poor oocyte qulity. This nding is illustrted in severl other studies (Check et l., 2002; Esposito et l., 2002; vn Rooij et l., 2003). It is of interest to note tht the fertiliztion rte ws ffected neither by the level of FSH nor the ge of the women. The miscrrige rte, however, ws ffected by ge but not by the FSH level. Within the sme ge group, it ws shown tht the miscrrige rte does not increse with n increse in bsl FSH level; however, the miscrrige rte does signi cntly increse with incresed ge. The incresed miscrrige rte is therefore ssocited with ge-relted chnges in the structure of the chromosomes of the oocytes. Furthermore, high FSH therefore does not re ect geing oocytes, it is just tht fewer re produced. This nding contrdicts tht of El-Toukhy et l. (2002) who showed tht poor responders hve high miscrrige rte regrdless of ge. However, they did not compre the miscrrige rte with norml control group. In ddition, s mentioned bove, their popultion ws mixture of ptients 897

6 H.Abdll nd M.Y.Thum with high FSH s well s poor responders with norml FSH. Nsseri et l. (1999) found n incresed incidence of bnorml kryotype in the bortuses of ptients with elevted FSH nd/or estrdiol. We hve no dt regrding the kryotype of the bortuses, but the miscrrige rte ws no different between the different levels of FSH within the sme ge group. Furthermore, they did not nd signi cnt difference in the incidence of bnorml kryotype in women ged <35 yers. From the dt in this study, we cn conclude tht n elevted bsl FSH level does not indicte deteriortion of oocyte nd embryo qulity. The fertiliztion rte does not decrese nd the miscrrige rte is not incresed. Our nding implies tht the reduction in pregnncy rte is result of reduced number of oocytes collected nd subsequently the limited choice of embryos vilble to be trnsferred. This ws clerly demonstrted in cycles in which only 1±4 eggs were collected. In those ptients, there ws no signi cnt difference in the LBR between ll FSH groups. This further con rms tht the observed reduction in LBR in the overll dt ws due to lower quntity of eggs rther thn poor qulity of these eggs. In other words, ptients ssume n LBR relted to their ge nd the number of eggs they produce rther thn the level of FSH. Clinicins should therefore dvise ptients with high bsl FSH level to expect lower pregnncy rte, due to the fewer eggs they will produce, s compred with their counterprts of similr ge who produce higher number of eggs. Clinicins nd ptients like should therefore ccept tht ptients with high FSH level will hve poorer ovrin response nd be prepred to go hed nd undergo egg collection when smll number of follicles hs developed. In summry, cycling women with high bsl dy 3 FSH will hve lower chnce of chieving live birth, but there is still resonble chnce of success even with FSH levels up to 20 IU/ l. In the current system, mny women with elevted FSH re led to believe tht they re unsuitble for IVF tretment nd would hve no chnce of successful outcome. Therefore, these women re forced to consider other tretment options to provide them with the chnce of motherhood, lthough not with their own genetic child. For these women, chnce, lthough reduced one of chieving pregnncy with their own genetic child is precious nd importnt opportunity for them to consider. Some womn my feel tht lower chnce is better thn no chnce t ll. The level of bsl FSH should not be used s screening tool to select ptients for tretment; insted it should be used s dditionl informtion to counsel ptients ppropritely regrding the relistic chnce of conception s well s iding the clinicin in determining the pproprite dose of gondotrophins. 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