Tubal subfertility and ectopic pregnancy. Evaluating the effectiveness of diagnostic tests Mol, B.W.J.

Transcription

1 UvA-DARE (Digital Academic Repsitry) Tubal subfertility and ectpic pregnancy. Evaluating the effectiveness f diagnstic tests Ml, B.W.J. Link t publicatin Citatin fr published versin (APA): Ml, B. W. J. (1999). Tubal subfertility and ectpic pregnancy. Evaluating the effectiveness f diagnstic tests General rights It is nt permitted t dwnlad r t frward/distribute the text r part f it withut the cnsent f the authr(s) and/r cpyright hlder(s), ther than fr strictly persnal, individual use, unless the wrk is under an pen cntent license (like Creative Cmmns). Disclaimer/Cmplaints regulatins If yu believe that digital publicatin f certain material infringes any f yur rights r (privacy) interests, please let the Library knw, stating yur reasns. In case f a legitimate cmplaint, the Library will make the material inaccessible and/r remve it frm the website. Please Ask the Library: r a letter t: Library f the University f Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. Yu will be cntacted as sn as pssible. UvA-DARE is a service prvided by the library f the University f Amsterdam ( Dwnlad date: 06 Dec 2017

2 6. Cmparisn f hystersalpinggraphy and laparscpy in predicting fertility utcme Ben W.J. Ml, Jhn A. Cllins, Elizabeth A. Burrws, Fulc Van der Veen, and Patrick MM. Bssuyt Human Reprductin In press. Abstract Objective: T cmpare the prgnstic significance f hystersalpinggrapy (HSG) and laparscpy fr fertility utcme. Methds: In a prspective chrt study in eleven clinics participating in the Canadian Infertility Treatment Evaluatin Study (CITES), cnsecutive cuples wh registered fr the evaluatin f subfertility and wh underwent HSG and laparscpy were included. Unilateral and bilateral tubal cclusin at HSG and laparscpy were related t treatmentindependent pregnancy. Cx regressin was used t calculate fecundity rate ratis (ERR) fr the ccurrence f nging pregnancy. Results: Of the 794 patients that were included, 114 (14%) shwed ne-sided tubal cclusin and 194 (24%) shwed tw-sided tubal cclusin n HSG. At laparscpy, 94 (12%) shwed ne-sided tubal cclusin and 96 (12%) shwed tw-sided tubal cclusin. Occlusin detected n HSG and laparscpy shwed a mderate agreement beynd chance (weighted kappa-value 0.42). Multivariate analysis shwed FRRs f 0.80 and 0.49 fr nesided and tw-sided tubal cclusin, respectively. Fr laparscpy, these FRRs were 0.51 and After a nrmal HSG r a HSG with ne-sided tubal cclusin, laparscpy shwed tw-sided cclusin in 5% f the patients, and fertility prspects in these patients were virtually zer. If tw-sided tubal cclusin was detected n HSG but nt during laparscpy, fertility prspects were slightly impaired. Fertility prspects after a tw-sided ccluded HSG were strngly impaired in case laparscpy shwed ne-sided and tw-sided cclusin, with FRRs f 0.38 and 0.19, respectively. Cnclusin: Althugh laparscpy perfrmed better than HSG as a predictr f future fertility, it shuld nt be cnsidered as the perfect test in die diagnsis f tubal pathlgy. Fr clinical practice, laparscpy can be delayed after nrmal HSG fr at least 10 mnths, since the prbability that laparscpy will shw tubal cclusin after a nrmal HSG is very lw. Reprinted by kind permissin frm Human Reprductin. 59

3 Chapter Intrductin Laparscpy is currently regarded as the mst reliable tl in the diagnsis f tubal causes f subfertüity. Since laparscpy visualizes mrphlgic abnrmalities f the fallpian tubes directly, it is generally accepted as the reference standard fr assessment f the perfrmance f ther diagnstic tls fr tubal pathlgy, such as hystersalpinggraphy (HSG) r Chlamydia Antibdy Testing (CAT). 13 In the pre-ivf era, surgical crrectin f tubal abnrmalities was the nly available treatment fr tubal subfertüity. Since then, in vitr fertilizatin and embry-transfer (TVF- ET) has gradually replaced tubal surgery as the treatment f chice fr tubal subfertüity in many cuntries. It has becme the treatment f last resrt fr persistent subfertüity due t any cause. In cntrast t tubal surgery, the chice fr IVF-ET des nt depend n die detectin f mrphlgic abnrmalities, but n fertility prgnsis. Therefre, the central issue in the wrk-up f subfertüity has changed frm a diagnstic questin int a prgnstic questin. Previus studies have shwn diät büateral tubal pathlgy diagnsed at HSG r laparscpy did affect fertility prspects strngly, whereas unüateral pathlgy affected future fertility less severely, as was shwn in chapter 5* 5 Althugh a substantial part f die ppulatin in these studies underwent HSG and laparscpy, a direct cmparisn n the prgnstic capacity between HSG and laparscpy has never been made. In a previus study in 11 Canadian infertility clinics addressing the prgnsis f live birth amng untreated subfertile cuples, presence f tubal pathlgy was shwn t reduce prspects fr treatment-independent pregnancy with 50%. 6 In that particular study, tubal pathlgy was detected with HSG and/r laparscpy. Cmparisn f HSG and laparscpy was beynd the scpe f that study. In the present study, the data f die Canadian study are reanalyzed fr this purpse. 6.2 Materials and Methds Patients We used data prspectively cllected in the Canadian Infertility Treatment Evaluatin Study (CITES). All cuples wh registered fr the first time in 11 Canadian academic infertility clinics between April 1, 1984 thrugh March 31, 1987, and wh had bth HSG and laparscpy dne were included. Patients with an abnrmal HSG usually underwent laparscpy withut delay, whereas in patients with a nrmal HSG, laparscpy was nly perfrmed in cases where subfertüity persisted fr a lnger perid f time. Findings at HSG were classified as n tubal cclusin, ne-sided tubal cclusin r twsided tubal cclusin (partial r ttal cclusin). Findings at laparscpy were classified as nrmal, ne-sided tubal cclusin r tw-sided tubal cclusin. Additinal tubal pathlgy bserved at laparscpy, i.e., phimsis r adhesins, was scred separately. Furthermre, endmetrisis detected at laparscpy was classified accrding t the classificatin f the American Fertility Sciety. 7 60

4 Cmparisn /HSG and lapamscpyfr fertility utcme The fllwing ptential prgnstic factrs were als used in the analysis: female age (per year lder than 30 years), duratin f subfertility at the time f laparscpy, type f subfertility (primary r secndary), vulatin factr, and sperm factr. Fllw up Fllw-up ended when treatment-independent pregnancy ccurred, r at the day at which fertility treatment started. Pregnancy was defined as an nging pregnancy at a gestatinal age f 12 weeks. When ectpic pregnancy r spntaneus abrtin ccurred, fllw-up ended n the estimated day f cnceptin. If a wman did nt becme pregnant and was nt treated, fllw-up ended n the day f last cntact. A wman was presumed t be 'at risk' fr treatment-independent cnceptin fr as lng as the cuple was in the study. Analysis Tubal cclusin detected at HSG was cmpared with cclusin detected at laparscpy in a three-by-three table. Sensitivity and specificity (with 95% cnfidence intervals [CI]) f HSG in the diagnsis f tubal cclusin were calculated, cnsidering laparscpy as the reference standard. Sensitivity and specificity were calculated twice, nce when tubal cclusin was defined as ne-sided r tw-sided cclusin, and nce when the definitin f tubal pathlgy was limited t tw-sided cclusin. Agreement beynd chance between HSG and laparscpy was expressed as a weighted kappa-statistic. Whereas an unweigthed kappa-statistic weights disagreement n ne tube equally wrse as disagreement n tw tubes in ne patient, a weighted kappa-statistic values cases in which HSG and laparscpy disagree n the status f ne tube, but agree n the status f the ther tube less severe than cases in which HSG and laparscpy disagree n bth tubes. Three-year cumulative pregnancy rates were calculated fr each categry f HSG and laparscpy findings, using Kaplan-Meier analysis. 8 Subsequently, fecundity rate ratis (FRR) and 95% cnfidence intervals (CI) fr the ccurrence f treatment-independent nging pregnancy were calculated fr HSG findings as well as fr findings at laparscpy thrugh Cx regressin mdeling. 9 Furthermre, the tubal status as assessed by a cmbinatin f HSG and laparscpy was related t treatment-independent pregnancy. In additin, we determined FRRs fr ther ptential prgnstic factrs. A FRR expresses the prbability f spntaneus intra-uterine pregnancy per time unit fr patients with a particular feature, relative t the prbability in thse withut that feature. T adjust the Table 1: Tubal status detected at HSG as cmpared t the tubal status deteded at laparscpy Laparscpy Tw-sided One-sided N HSG cclusin cclusin cclusin Tw-sided cclusin One-sided cclusin N cclusin Ttal Weighted kappa-value 0.42 (95% CI 0.37 t 0.48) Disease defined as any abnrmality: Sensitivity 0.81 (95% CI 0.76 t 0.87) Specificity 0.75 (95% CI 0.71 t 0.78) Disease defined as tw-sided abnrmality. Sensitivity 0.72 (95% CI 0.62 t 0.81) Specificity 0.82 (95% CI 0.79 t 0.85) 61

5 Chapter 6 FRRs f HSG and laparscpy findings fr these prgnstic factrs, multivariable analysis was perfrmed. Since the aim f the study was t cmpare the prgnstic significance f HSG and laparscpy, we perfrmed three separate multivariable analyses: ne in which the FRRs f HSG were crrected fr all ther prgnstic factrs but findings at laparscpy, ne in which the FRRs f laparscpy were crrected fr all ther prgnstic factrs but HSG findings, and ne in which the FRRs f cmbined results f HSG and laparscpy were crrected fr all ther prgnstic factrs. 6.3 Results Of the 2198 cuples that were included in CITES, 1357 had a HSG dne. Amng the 563 patients wh had a HSG but n laparscpy, 107 had a treatment-independent pregnancy. The 794 wh had a HSG and a laparscpy dne were included in the present study. Mean maternal age was 29.6 years (min 20 years - max 42 years) and mean duratin f subfertility was 41 mnths (min 12 mnths - max 153 mnths). The median time between HSG and laparscpy was 10 mnths when HSG was nrmal, 8.5 mnths when HSG was ne-sided abnrmal and 4.5 mnths when HSG was tw-sided abnrmal. Amng the 794 included wmen, 86 had a treatment independent pregnancy. Of these 86 cuples, 4 had an ectpic pregnancy, whereas 12 pregnancies resulted in miscarriage. Thus, 70 wmen had a treatment-independent nging pregnancy, f which 50 resulted in a live birth and three in a perinatal death. In 17 cuples pregnancy utcme was unknwn. Table 1 shws tubal status detected at HSG as cmpared t tubal status detected at laparscpy. At HSG, 114 patients (14%) shwed ne-sided tubal cclusin and 194 patients (24%) shwed tw-sided tubal cclusin. At laparscpy, 94 patients (12%) shwed ne-sided tubal cclusin and 96 (12%) shwed tw-sided tubal cclusin. Sensitivity f HSG was 0.81 (95% CI 0.76 t 0.81) and specificity f HSG was 0.75 (95% CI 0.71 t 0.78) when disease was defined as any frm f tubal cclusin detected at laparscpy, be it ne sided r tw-sided. Sensitivity and specificity f HSG were 0.72 (95% CI 0.62 t 0.81) and 0.82 (95% CI 0.79 t 0.85), respectively, when the définitin f disease Table 2: Tubal status deteded at HSG and laparscpy in relatin t the number f treatment-independent intra-uterine pregnancies and the tbree : year cumulative intra-uterine pregnancy rate. Tubal status at HSG and laparscpy Number Number Three-year cumulative f f nging intra-uterine patients IUPs* pregnancy rate HSG patent, laparscpy patent % HSG ne-sided ccluded, laparscpy patent % HSG tw-sided ccluded, laparscpy patent % HSG patent, laparscpy ne-sided ccluded % HSG ne-sided ccluded, laparscpy ne-sided ccluded % HSG tw-sided ccluded, laparscpy ne-sided ccluded % HSG patent, laparscpy tw-sided ccluded % HSG ne-sided ccluded, laparscpy tw-sided ccluded % HSG tw-sided ccluded, laparscpy tw-sided ccluded % 'IUP = intra-uterine pregnancy 62

6 Cmparisn fhsg and laparscpe fr fertility utcme S. U S 3 CL, c X >. 5 OH S^ i u CN (/5 v O >H ir.55 «2 «Pu M "^ CU D C u in O, X, -=> li 3 ff~ U ÜH c O ON T-4 ö S r- * CM ö ö Nct- CN CA NO NO OO ^H T-H T-H T-H g 1 H-J H-> CN CO en 00 T-H CA m O CD O OO O r c QO O NO NO CO CN T-H ^^ s s O ** c CN O O TH [Tl T-i O O ^ TH r- in T-i Ö T-* Tt- r- CN c ö ö NO OO CO lo r-h f- > ö CN O T-< i * T-l CO T-H ö ö in in r- * ö CN \0 CO LD T-H T-H T-H T-H T-H T-H 0 *H O 2 2 IT), c CN O 1 GO CO TJ- O O O O O CTN,_, c 00 vd r O O ^ ^_, O CN O CO LO T-( T-H T-H T-H H T-H 0 i s 2 2 +H 0O LO O CM O CN CN LO CO TTJö ö ö ö CN NO N-j- un p g NO un CN CN in c T-f ö ö ö ö CN NO CN T-H CN O 00 1^ Ö T-H Ö Ö O T-H r m NO Tt \ r- ^- ON CN LO CO THT ö ö ö ö ON CN r- q T-H >* * c T-H -^ T-. TH NO CN CN NO Nf t N O O O CN CN CO NO TH OO 4- t! T-H O CN) NO NO T-l (NTPóN <~s TH r -f î H - t H& c c S3' U c^ ^ ïï ' UJ S X. < i-«3 3. ^H = - ~.3 'S ^3 C u u ^ S!? 'S -a -a s t/j 3 <u «T3 V. T3 "O ^ U wi vj 3 CU P S ZOH P C J b-» 'A CU O 5^ PH CJ!» HC= "^ -Tl "3 -T-J "Ç g V CU «S ÇU al T3 cd - 3 O. 3 II J u O.. r. u. <-> -a "O -n NU cu 3 U-S "3 3 <2 a,^ rt rt u b2 - "> c OH U >,-TJ Cu <U -a O "O tu 3 "O -g J 2 s 8 à g-«s C «c! TÜ CM C 3 OH O <ti -SÙ D h «i C O C OOÜ <0 e? c C/N CNO cy^ s c e T) cm u i> 0-0T3 O T3 i-h \ A u ^ ^^ r ^ u "3 X) a-3 - h^r s T3 ^ CU CU d I-s twed c ed c >> 'S C/J OO c_ <u u p 0 E CU 'B '5 SBB RB p CU O "3 e e g, s, 0 CU - -a ÏTTCO OO rt rrj c c -KI ~x ZW«cp -si -si '7r> u -a -a E/3 CU "U P 0J O c/l u g CU >HT3 3 «-S-S 3 CJû Q ^ O * S n PH 3 «2 3 3 CU CL, II 63

7 Chapter 6 was limited t duble-sided tubal cclusin detected at laparscpe The weighted kappavalue expressing the agreement between HSG findings and laparscpy beynd chance was 0.42 (95% CI 0.37 t 0.48). Table 2 shws the distributin f HSG findings and laparscpy in relatin t the number f subsequent pregnancies and the 3-year cumulative nging pregnancy rate. Three-year cumulative nging pregnancy rates varied between 11% in case HSG and laparscpy were bth tw-sided patent r ne-sided ccluded and 0% in several categries. Table 3 shws the results f the univariable and multivariable Cx regressin analysis. In the multivariable analysis, ne-sided cclusin detected at HSG was fund t decrease fertility prspects slightly (FFR 0.80), whereas a tw-sided cclusin had a strnger impact n fertility prspects (FRR 0.49). Occlusin detected at laparscpy had a strnger impact n fertility prspects, with a FRR f 0.51 fr a ne-sided cclusin and 0.15 fr a twsided cclusin. Other tubal pathlgy at laparscpy, i.e., phimsis and/r adhesins, was assciated with a FRR f Endmetrisis grade I/II had a FRR f 0.52, whereas there were n pregnancies amng cuples with endmetrisis grade Ill/TV. If ne-sided cclusin at HSG was fllwed by nrmal laparscpy, fertility prspects were slightly impaired (FRR 0.81). If a nrmal HSG r a ne-sided ccluded HSG was fllwed by a laparscpy that shwed ne-sided cclusin, which ccurred in 8% f the patients (50/600) with such HSGs, fertility prspects were mderately decreased (FRR 0.58). When a nrmal HSG r a ne-sided ccluded HSG was fllwed by a laparscpy that shwed tw-sided abnrmalities, which ccurred in 5% f the patients (27/600) with such HSGs, n spntaneus pregnancies ccurred (FRR 0). When a tw-sided ccluded HSG was fllwed by a nrmal laparscpy, which ccurred in 42% f the patients (81/194) with such HSGs, fertility prspects were slightly impaired (FRR 0.70). When a tw-sided abnrmal HSG was fllwed by a laparscpy that shwed ne-sided r twsided abnrmalities, which ccurred in 23% (44/194) and 36% (69/194) f patients with such HSGs, respectively, fertility prspects were strngly impaired, with FRRs f 0.38 and 0.19, respectively. 6.4 Discussin Laparscpy is currently regarded as the best available methd t assess tubal cclusin. In this study, tubal cclusin was detected at 24% f the laparscpics. Twsided cclusin appeared t affect fertility prspects cnsiderably, whereas ne-sided cclusin affected fertility prspects less strngly. In the same sample f patients, HSG indicated tubal cclusin in 39%. The weighted kappa-value was 0.42 (95% CI 0.37 t 0.48), indicating mderate agreement beynd chance between HSG and laparscpy. Findings at laparscpy had a strnger impact n spntaneus fertility curse than results at HSG. After a cmpletely nrmal HSG r a HSG with a ne-sided abnrmality, a nesided ccluded laparscpy affected fertility prspects slightly, whereas n spntaneus pregnancies ccurred after duble-sided cclusin detected at laparscpy. After a HSG with tw-sided abnrmalities fertility prspects were nly slightly decreased in cases where 64

8 Cmparisn /HSG and laparscpy fr fertility utcme laparscpy shwed patent tubes. Hwever, in cases where laparscpy had ne-sided r tw-sided abnrmalities in these patients, fertility prspects were strngly decreased, with FRRs f 0.38 and 0.19 respectively. Laparscpy was perfrmed at the end f the wrk-up fr subfertility, after the perfrmance f HSG. Patients with an abnrmal HSG usually underwent laparscpy with a shrt delay, whereas in patients with a nrmal HSG laparscpy was withheld fr a lnger time. This selectin bias pssibly hampers the interpretatin f the findings in tw ways. Firstly, unexplained subfertility, that might be assciated with an unknwn fertility reducing factr, culd be verrepresented in patients with a nrmal HSG. If such a selectin bias were t play a rle in the present study, this bias might cause an underestimatin f the prgnstic capacity f HSG as detected in this study. Secndly, the delay f laparscpy amng patients with nrmal HSG results m an verestimatin f patients with abnrmal laparscpy amng all patients underging HSG. Many studies have assciated mrphlgic abnrmalities with fertility utcme in patients wh underwent micrsurgical crrectin fr tubal cclusin S far nly ne study has assessed the significance f findings at laparscpy in patients evaluated fr subfertility. Nrderskjöld et al. reprted n 433 subfertile wmen wh had laparscpy. 4 Presence f adhesins reduced fertility prspects in the same rder as unilateral tubal cclusin, with relative risks f 0.74 (95% CI 0.57 t 0.98) and 0.73 (95% CI 0.39 t 1.4), respectively. Nne f 10 patients widi a duble sided cclusin f die tube became pregnant. The fact that 101 (23%) f die patients had micrsurgery sme time after laparscpy was nt addressed in that study, thereby hampering interpretatin f the results. Furthermre, dichtmizing subfertile cuples int cuples wh cnceived and cuples wh did nt cnceive des nt address the true nature f (sub) fertility. Instead, analysis f time t pregnancy, as was dne in the present study, is mre apprpriate. In the meta-analysis cmparing results f HSG and laparscpy fr the diagnsis f tubal pathlgy that was discussed in chapter 3, HSG had a sensitivity f 65% fr the diagnsis f tubal cclusin, in case laparscpy was presumed t be the 'gld' standard. 1 This finding implicates that 35% f the tubes that were fund t be ccluded at laparscpy shwed patency at HSG. That particular finding made die chice f laparscpy as the 'gld' standard questinable, since patency at HSG in ur pinin prves that laparscpy was incrrect in diagnsing tubal cclusin in these patients. The results f the present study, hwever, seem t indicate that laparscpy is a better predictr fr infertility than HSG, be it nt a perfect ne. This cnclusin is hampered by the fact that the median interval t laparscpy after nrmal HSG was 10 mnths, cmpared t 4.5 mndis in cases where HSG was tw-sided abnrmal. Thus, the difference in prgnstic capacity between HSG and laparscpy is likely t be verestimated, nly prgnstic studies in which HSG and laparscpy are perfrmed at the same mment can vercme this issue. Despite the fact that laparscpy seems t be a better predictr fr subfertility than HSG, we think that HSG shuld keep its place in the diagnstic wrk-up fr subfertility. Nrmal HSG reduces the prbability that a tubal factr plays a rle in future fertility 65

9 Chapter 6 prspects. Only in 5% f the patients with nrmal HSG duble-sided tubal cclusin was detected at laparscpy. Althugh fertility prspects in these cuples were virtually zer, we think that a prbability f 1 in 20 t detect severe abnrmalities at laparscpy - that was bserved after a median time between HSG and laparscpy f 10 mnths - is s lw, that earlier laparscpy is nt justified. It shuld be kept in mind that the median delay f laparscpy f 10 mnths implicates that the fractin f abnrmal laparscpy amng all patients with a nrmal HSG is even lwer than 5%. When deciding abut a delay f laparscpy, ne shuld als take int accunt ther aspects f the prgnstic prfile f the cuple, female age being the mst imprtant. In case female age is exceeds 36 years, the success rates f IVF-ET are expected t decline strngly if this treatment is delayed. Expectant management is in that case nt justified. 13 u In cntrast, laparscpy perfrmed after a tw-sided abnrmal HSG shwed n abnrmalities in 42% f the patients. Since fertility prspects in these patients were nly slightly impaired, whereas patients with tw-sided ccluded HSG and a laparscpy shwing unlilateral r bilateral tubal cclusin had strngly impaired fertility prspects, a laparscpy perfrmed after a tw-sided abnrmal HSG culd be very useful, since it divides patients with such HSGs in a large grup in whm fertility prspects are slightly impaired and a large grup in which fertility prspects are strngly impaired. When cmparing HSG and laparscpy, we shuld keep in mind that bth prcedures prvide mre infrmatin than the cnditin f the fallpian tubes alne. Whereas HSG prvides infrmatin n the status f the intra-uterine cavity, laparscpy allws inspectin f the intra-abdminal cavity, fr instance t see if endmetrisis is present. The latter has becme especially imprtant, since it was recendy shwn that laparscpic treatment f endmetrisis imprves fertility prspects with 13%, crrespnding with a Numbers Needed t Treat f eight. 15 Thus, in the final decisin n the clinical value f HSG and laparscpy, ne shuld cnsider ther issues than slely tubal pathlgy. Such an analysis is beynd the scpe f this study. When fcusing n tubal pathlgy, it is cncluded diat laparscpy shuld nt be cnsidered as the perfect test in the diagnsis f tubal pathlgy In the next chapter several strategies cntaining HSG, laparscpy and/r CAT will be cmpared with respect t number f live births, time t pregnancy and csts. nts The authrs thank M. Y. Bngers MDJrm the department f Obstetrics and Gyneclgy, St. Jseph Hspital, Veldhven, The Netlierlandsfr critically reading the manuscript. 6.5 References 1. Swart P, Ml BWJ, Van der Veen F, Van Beurden M, Redekp WK, Bssuyt PMM. The accuracy f hystersalpinggraphy in the diagnsis f tubal pathlgy, a meta-analysis. Fertü Steril 1995;64: Ml BWJ, Dijkman AB, Wertheim P, Lijmer JG, Van der Veen F, Bssuyt PMM. Chlamydial antibdy titers in the diagnsis f tubal pathlgy; a meta-analysis. Fertil Steril 1997;67: Land JA, Evers JLH, Gssens VJ. Hw t use Chlamydia antibdy testing in subfertility patients? Hum Reprd 1998;13: Nrdenskjöld F, Ahlgren M. Laparscpy in female infertility. Acta Obstet Gynecl Scand 1983;62:

10 Cmparisn f HS G and lapamscpyfrfertiüty utcme 5. Ml BWJ, Swart P, Bssuyt PMM, Van der Veen F. Is hystersalpinggraphy an imprtant tl in predicting fertility utcme? Fertil Steril 1997;67: Cllins JA, Burrws EA, Willan AR. The prgnsis fr live birth amng untreated infertile cuples. Fertil Steril 1995;64: The American Fertility Sciety. Revised American Fertility Sciety classificatin f endmetrisis: Fertil Steril 1985;43: Cllett D. Mdeling survival data in medical research. Chapmann & Hall; 1994: Lndn. 9. Cx DR. Regressin mdels and life tables. J R Stat Sc : Caspi E, Halpenn Y, Bukvsky I. The imprtance f penadnexal adhesins in tubal recnstructive surgery fr infertility. Fertil Stenl 1979;31: Te Velde ER, Ber-Meisel ME, Meisner J, Schemaker J, Habbema JDF. The significance f preperative hystersalpinggraphy and laparscpy fr predicting the pregnancy utcme in patients with a bilateral hydrsalpinx. Eur J Obstet Gynecl Repr Bil 1989;31: Strandell A, Bryman I, Jansn P, Thrburn J. Backgrund factrs and scring systems in relatin t pregnancy utcme after fertility surgery. Acta Obstet Gynecl Scand 1995;74: Van Kij RJ, Lman OWN, Habbema JDF, Drland M Te Velde ER. Age-dependent decrease in embry implementatin rate after in vitr fertilizatin. Fertil Steril 1996;66: Templetn A, Mrris J PC, Parslw W. Factrs that affect utcme f in-vitr fertilisatin treatment. Lancet 1996;348: Marcux S, Maheux R, Bérubé S. Laparscpic surgery in infertile wmen with minimal r mild endmetrisis. N Engl J Med 1997;337:

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