Infertility and subfecundity in population-based samples from Denmark, Germany, Italy, Poland and Spain

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Ifertility ad subfecudity i populatio-based samples from Demark, Germay, Italy, Polad ad Spai W1LFR1ED KARMAUS, SVEND JUUL, ON BEHALF OF THE EUROPEAN INFERTILITY AND SUBFECUNDITY STUDY GROUP Backgroud: No uiform data which give basic Iformatio o the societal burde of ifertility ad subfecudity exists i Europe. Methods: I a populatio-based survey the prevalece of subfecudity was ascertaied by meas of a stadardized iterview with wome i Demark, Germay, Polad, Italy ad Spai. The time of uprotected itercourse (TUI) either leadig or ot leadig to pregacy was applied as a uiform measure of fecudity. Populatio-based samples of wome 25-44 years of age were recruited. Results: Altogether 6,630 wome participated i the study. With regard to the first pregacy, 19 of all couples had a TUI of more tha 12 moths, which is withi the rage of most previous fidigs. Regardig the most recet ad first TUI i idividual lives, if it had occurred withi previous 5 years, 23.4 overall did ot coceive withi 12 moths (i Polad 33.3, i orth Italy ad Germay 26.2, I Demark 23.3, i Spai 18.6 ad i south Italy 14.8). Secodary subfecudity was more prevalet i Polad. Whe stratifyig for plaig of a pregacy, the differeces betwee coutries dimiished, particularly for the most recet TUI. However, the patter of a higher prevalece of subfecudity i Polad, orth Italy, Demark ad Germay ad a lower prevalece (<20) i Spai ad south Italy remais. Coclusios: Importat differeces i the prevalece of subfecudity exist betwee the six Europea regios ivestigated. Comparisos should first cosider TUIs or plaed TUIs to reduce the impact of distortig factors, which are maily due to differig cultures of family plaig i Europe. Keywords: birth cotrol, ifertility, plaed pregacy, subfecudity, time to pregacy Several ivestigatios i Europe have provided a wide rage of estimates of the prevalece of ifertility (from 6 to 20). However, the methods applied varied ad the results are rarely comparable. With the exceptio of the USA o uiform demographic survey o family growth, which would give basic iformatio o the societal burde of ifertility or which could be used to idetify treds, exists. 12 ' 15 I order to fill this gap a Europea study group was established (Europea Studies of Ifertility ad Subfecudity, ESIS) with the purpose of studyig the occurrece of fertility problems ad related help-seekig behaviour i Europe. This report cocetrates o a populatio-based study of wome 25-44 years of age, comparig estimates of fecudity i Demark, Germay, Italy, Polad ad Spai. The purpose of this paper is to give a overview of material, methods ad mai fidigs. * W. Karmaus 1, S. Juul 2 1 Departmet of Epkfemiotogy, Michiga State Uiversity, USA 2 Departmet of Epidemiology ad Soaal Medicie, Aarhus Uiversity, Demark Europea Studies of Ifertility ad Subfecudity b a EC/COST Cocerted Actio Research Program. Correspodece: Wilfried Karmaus, MD, MPH, Departmet of Epidemiology, Michiga State Uiversity, 4660 S. Hagador Rd, Suite 600, East Lasig, Ml 48823, USA, e-mail: karmausomsu.edu METHODS Cocepts ad defiitios Ufortuately some cetral terms are used differetly by demographers, cliicias ad epidemiologists. We use the term 'fecudity' for biologic ability, 'subfecudity' for evidece of decreased fecudity ad 'sterility' for kow iability to coceive, e.g. due to hysterectomy or sterilizatio. For pregacies, fecudity ca be described by the 'time to pregacy' (TTP) the time spa or umber of mestrual cycles durig which the woma was exposed to uprotected itercourse util coceptio. 14 It is ecessary to determie the 'startig date', the 'date of coceptio' of a recogized pregacy ad/or the 'time period betwee these evets'. 15 While TTP ca be determied for pregacies, o similar term exists for periods of uprotected itercourse ot or ot yet leadig to pregacy (PUNP). We decided to use the term 'time of uprotected itercourse' (TUI) for all periods of uprotected itercourse, whether these lead to pregacy or ot. TUIs (TTPs ad PUNPs) describe actual behaviour ad a TUI ca be with or without itetio of achievig a pregacy. Questioaire ad iterview A questioaire desiged to be admiistered by iterviewers was developed by a collective process durig

EUROPEAN JOURNAL OF PUBLIC HEALTH VOL. 9 1999 NO. 3 Figure 1 Distributio of the first time of uprotected itercourse (TUI) startig withi 5 years before the iterview i differet Europea regios cotrollig for age at the start of the TUI; -932, x 2 = 13, df-5, p 0.05 several cycles of pilot testig i several coutries. It starts widi ascertaimet of demographic iformatio ad a overview ofreproductivehistory (pregacies, outcomes ad dates). Regardig TTP, plaig ad potetial risk factors for a delay (smokig, alcohol, workplace, etc.), data o each pregacy is ascertaied i deptii. Data o male ad female sterility is gadiered before iformatio o curret or previous periods of uprotected itercourse (PUNPs). Fially help seekig behaviour is ascertaied. Potetial iterviewees were cotacted before the iterview ad gave iformed coset accordig to atioal regulatios. Iterviews took 30-90 miutes. All iterviewers were female ad had received thorough istructio ad traiig. TUIs were recorded i weeks ad/or moths ad/or years. We did ot ask about umber of mestrual periods because pilotig experiece had show that wome recall log TUIs i caledar time, ot i mestrual cycles. No TTP iformatio was collected for iduced abortios. Study populatio The survey was coducted i five Europea coutries betwee August 1991 ad February 1993 ad we used wome as iformats of the couple's experiece. Populatio-based samples of wome 25 44 years old were determied by usig populatio registers, i accordace with what was techically ad legally possible i the various coutries. Statistical methods TTP distributios caot be directly traslated ito coceptio probabilities, as TUIs ot or ot yet resultig i a pregacy (PUNP) are ot icluded. Coceptio probabilities ad related estimates are calculated whe both pieces of iformatio are aalysed together. The most recet TUI might have eded with a pregacy (TTP) or be a PUNP. Data o PUNPs was oly collected for time periods which started o more tha 5 years before the iterview, as recall problems caused us ot to ask about earlier TUIs ot resultig i a pregacy. Whe aalysig all periods of a give time widow together - both PUNPs ad TTPs - ad ot excludig wome ad observatios without pregacies, it was ecessary to have the same restrictio o the time widow for both PUNPs ad TTPs (period which started 5 years before the iterview oly). For the combied aalysis of TTPs ad PUNPs we applied die Cox proportioal hazards model usig the 'proportioal hazards regressio model' (PHREG). 16 ' 17 TUIs without coceptio were treated as cesored data. The PHREG procedure estimates survival probabilities for ot coceivig ad the media time to coceptio. We cotrolled statistically for age at the start of the TUI. To accout for the occurrece of ties, exact maximum likelihood estimates were calculated. The estimated survival probabilities for ot coceivig are plotted agaist moths of observatio for the differet coutries separately (figure 1). Aalyses were first coducted for the most recet TUIs. The observatios icluded ulh- ad multigravide wome ad may have bee self-selected due to precedig experiece. This is the reaso why we additioally aalysed the sample of first reported TUI (either a TTP to the first pregacy or a PUNP). The iformatio from these two subsamples was additioally stratified for itetio of plaig a pregacy. RESULTS Altogether 6,630 wome participated i the study. The proportio of participatio differed betwee coutries (Demark 86.8 based o data from the populatio register, Germay 53.6 from the populatio register, Polad 88.4 from electoral rolls, orth Italy 74.4 from the cesus register, soudi Italy 78.7 from electoral rolls ad Spai 69.6 from a cesus). Due to differeces i populatio distributio ad participatio rates, there were relatively may youg wome i the samples from Demark ad south Italy ad relatively more older wome i the samples from Polad ad Spai (table 1). Reproductive history showed marked differeces betwee coutries, particularly i the youg age groups (table I). The proportio of youg wome who had bee pregat at ay time was high i die sample from Polad ad low i die sample from orth Italy, while differeces were smaller i the older age groups. The proportio of wome havig experieced oe or more miscarriages was radier uiform, at approximately 15 (table I). Cotrary to this, die proportio of wome

Sxibfecudity m Europe reportig oe or more iduced abortios varied cosiderably, from a high of 31 i Demark to a low of 2 i Spai. The prevalece of couples with kow sterility (volutary or ivolutary due to diseases ad operatios) varied, with high proportios i Germay, Spai ad Demark ad low proportios i Polad ad Italy. Volutary sterilizatios accouted for the major part of the variatio (table 1). A total of 338 wome (6) reported a disease or operatio leadig to male or female sterility that was uwated, i.e. the couple wished for more childre after the evet. A first pregacy, ot icludig those followed by iduced abortios, was reported by 73 of all wome (table 2). Of these pregacies 12 occurred i spite of cotraceptio. Two-thirds of the first pregacies were classified as plaed by the wome (table 2), while aother 6 could ot decide whether the pregacy was plaed or ot. For the last pregacy (ot icludig a first ad oly pregacy) the proportio of cotraceptive failures (a total of 23) was higher tha for the first pregacy i Polad, Italy ad Spai (table 2). The proportio of plaed pregacies was higher for the last tha for the first pregacy i Demark ad Germay, but lower i the other coutries. Most PUNPs were curret (table 2) ad the proportio of wome reportig a curret or recetly cesored TUI (PUNP) was much higher i Polad tha i other coutries. TUI iformatio was give for 98 of these couples. Plaig to become pregat was less frequet for PUNPs tha for TUIs resultig i pregacy. Survival aalyses with the TUIs as cotiuous variables ad cotrollig for the age of the wome at the startig time were coducted for the first ad the most recet TUI which may have eded i pregacy or ot (table 3, figure I). For the latter, however, TUIs were restricted to those with a startig date withi 5 years prior to the iterview. Statistically sigificat differeces i coditioal probabilities of coceivig i samples from the differet coutries for the most recet TUI ca be see i figure 1. A loger TUI showed up i the Polish, Germa ad orth Italia samples. I order to pi poit the probabilities for differet time periods we extracted ad tabulated period- Table 1 Age at iterview ad reproductive experiece Number of iterviews Age at iterview (mea) 25-29 years () 30-34 years () 35-39 years () Demark 1,028 33.5 31.9 25.6 Til Germay 1,531 34.6 22.7 28.7 253 Polad 442 35.4 19.2 23.1 30.1 North Italy 1,914 34.4 27.6 23.1 23.5 South Italy 815 33.7 29.7 27.1 22.8 Spai 9,00 35.1 21.8 27.4.3 Total 6,630 34.4 26.0 25.8.2 40-44 years () Proportio pregat at ay time () 25-29 years () 30-34 years () 35-39 years () 40-44 years () 20.3 76.5 51.8 84.8 86.8 933 23.2 81.5 65.1 81.3 89.4 89.3 27.6 88.9 78.8 91.2 90.2 92.6 25.9 66.4 30.4 70.1 82.2 873 20.4 81.2 62.8 83.7 9 94.0 26.3 78.1 53.8 76.8 87.6 91.1 23.9 76.4 51.1 79.2 87.0 90.2 Mea umber of live births 1.18 1.42 1.59 8 1.40 1.45 1.27 25-29 years (mea) 30 34 years (mea) 35 39 years (mea) 40-44 years (mea) Proportio at ay time experieced 0.43 1.18 1.53 1.96 0.84 1.39 1.73 1.69 1.11 1.54 1.77 1.78 030 9 1.26 1.42 0.86 1.46 1.58 1.92 0.57 1.25 1.76 2.12 0.58 1.25 1.56 1.74 Live birth () Miscarriage () Iduced abortio () Proportio of sterile wome O purpose () Other reasos ad o desire of a child () Other reasos ad desire of childre () 63.5 15.0 31.2 4.1 7.0 73.0 16.5 20.4 10.5 11.8 6.5 87.1 17.4 1 1.8 61.0 12.5 12.5 1.6 2.5 4.8 77.1 15.5 13.9 2.0 1.1 3.2 74.2 15.7 2.2 5.2 1.8 69.7 14.9 16.0 4.5 4.5 4.9 Proportio of sterile parters O purpose () Other reasos ad o desire of a child () Other reasos ad desire of childre () 7.9 2.5 4.4 2.2 1.6 0.0 0.0 0.5 0J 0.4 0.1 0.7 1.1 6.9 0.3 0.3 33 1.2 Proportio of sterile couples O purpose () Other reasos ad o desire of a child () Other reasos ad desire of childre () 11.5 3.6 9.3 13.8 13.6 7.5 23 1.8 5.5 2.1 1.7 4.0 12.0 2.0 3.2 7.4 5.2 5.9

EUROPEAN JOURNAL OF PUBLIC HEALTH VOL. 9 1999 NO. 3 ical (3, 12 ad moths) survival probabilities for coceivig from the survival aalyses for most recet TUIs ad the first TTPs. I additio, regardig the first 1 IF, the cumulative probabilities of coceivig differed (table 3). Polad, orth Italy ad Germay had the logest TTPs ad Souther Europe the shortest. TUIs ivolvig plaig were o average shorter tha other TUIs (table 3). Eve whe stratifyig for plaig to coceive the coutry patter stayed detectable (table 3). DISCUSSION Whe comparig the coutries, differeces i probabilities of coceivig were obvious (figure 1). The geeral tedecy was that fecudability i south Italy ad Spai was somewhat higher tha i Polad, orth Italy ad Germay (table 3). Regardig 'period prevalece' the proportio of couples i our study who had a TTP of more tha 12 moths was 13.8 overall for the first pregacy (more tha moths, 6.7). As to the first reported period of uprotected itercourse (TTP or PUNP) with a startig date less tha 5 years before the iterview, the respective cumulative probabilities were 23.3 ad 17.6 (table 3, right side). For the most recet TUI with a startig date of less tha 5 years before the iterview, 71.0 of the wome had a TUI of 12 moths or less ad 76.2 of moths or less. The cumulative probability for couples who plaed to coceive was higher: 81.3 for 12 moths or less for the first TUI ad 79.7 for the most recet TUI. Comparability of study populatios I each coutry oe or a small umber of areas were studied ad thus, the results are ot iteded to be represetative of the etire coutries. Participatio rates varied betwee cetres ad it is possible that oparticipats differed from participats with respect to reproductive experiece. The low participatio i Germay was probably due to the fact that the data protectio authorities required iformed coset by both the woma Table 2 Iformatio about TTP ad its coditios for the first ad last pregacy ad for PUNPs (absolute umber ad ) Number of iterviews Demark 1,028 Germay 1,531 Polad 442 North Italy 1,914 South Italy 815 Spai 900 Total 6,630 First pregacies" ( of all) Despite birth cotrol ( of first pregacies) Most commo methods ( of despite birth cotrol) Safe periods Iterrupted itercourse Codom Plaed pregacy ( of first pregacies) Mea age at startig date (years) 705 114 18 18 58 68.6 16.2 15.8 15.8 5 456 64.7 2: 1.7 1,176 163 79 20 28 76.8 13.9 48.5 12.3 17.2 643 54.7 23.0 392 62 44 37 19 88.7 15.8 71.0 59.7 30.6 191 48.7 22. A 1,218 114 47 49 63.6 9.4 41.2 43.0 21.1 833 68.4.6 653 86 31 68 7 80.1 13.2 36.0 79.1 8.1 513 78.6 23..2 691 51 15 21 9 76.9 7.2 29.4 41.2 17.6 551 79.6 23.9 4,835 589 234 213 145 7 12.2 39.7 36.1.6 3,187 65.9 111.6 Last pregacies amog multipara" (ofall) Despite birth cotrol ( of last pregacies amog multipara) Most commo methods ( of despite birth cotrol) Safe periods Iterrupted itercourse Codom Plaed pregacy ( of last pregacies amog multipara) Mea age at startig date (years) 502 75 10 10 30 48.8 14.9 133 133 40.0 370 73.7 28.4 864 144 70 18 29 56.4 16.7 48.6 12.5 20.1 541 62.6 27..8 268 78 55 49 21 60.6 29.1 70.5 62.8 26.9 100 373 27. 1 719 173 80 68 50 37.6.1 46.2 393 28.9 438 6 29.0 463 151 45 111 19 56.8 32.6 29.8 73.5 12.6 288 62.2 27.6 502 150 43 72 38 55.9 29.9 28.7 48.0 253 296 58.8 28.8 3318 771 311 328 187 50.1 233 403 42.5 3 2,033 613 28.2 Iformatio about PUNPs (ofall) Without previous pregacies ( of iformatio about PUNPs) Curret TUI ( of all) Plaig to become pregat ( of iformatio about PUNPs) Mea age at startig date (years) 151 49 111 14.7 32.5 10.8 92 6 30.4 196 59 128 12.8 30.1 8.4 95 48.5 30..1 98 14 78 22.2 143 17.6 16 163 29. 2 5 97 156 12.8 39.6 8.2 112 45.7 3 61 23 51 7.5 37.7 63 42 68.9 29.5 72 31 61 8.0 43.1 6.8 43 59.7 30.2 823 273 585 12.4 33.2 8.8 400 48.6 30.2 a: Iduced abortios excluded TTP: time to pregacy; PUNP: periods of uprotected itercourse ot or ot yet leadig to pregacy; TUI: time of uprotected itercourse

Subfecudity m Europe ad her parter. I additio, most households i Rostock (former GDR) were ot available by telephoe, makig pre-iterview cotact difficult. Regardig age, the samples from Polad ad Spai comprised more wome of 40 years of age ad older ad fewer youger oes (25-29 years). Curret family plaig methods varied betwee the seve regios, with the Polish ad south Italia samples havig frequet use of usafe methods. Reproductive experiece varied betwee coutries, particularly for youger wome, the extremes beig orth Italy with few ad Polad with may prior pregacies ad live births (table I). Quality of iformatio I our study, the media time that had elapsed sice the startig date for the first pregacy was 12 years ad was more tha 20 years for oly 15 of the iterviews. However, Joffe et al. 18 foud oly mior differeces betwee TTPs ascertaied several years ago (media 14 years) i compariso with iformatio gathered later ad cocluded that the retrospective iformatio could be cosidered valid. Regardig the recall of other reproductive evets, such as past pregacies ad miscarriages, excellet agreemet betwee questioaires ad medical record was reported by Tilley et al. Recall problems might differ betwee cultures. They ca, however, hardly explai the very marked differeces i fecudity estimates. Compariso of differet studies Methodological differeces exist betwee differet approaches. Firstly, the deomiator varies: all wome/ couples or wome/couples with uprotected itercourse. Secodly, the defiitio of the umerator varies i) with regard to how to ask for impaired fecudity (impossible to get pregat, waitig time to pregacy or cosultatio of medical services), ii) with regard to the outcome (coceptio or live birth), lii) with regard to the time period ( 12 moths, >12 moths, etc.), ad iv) with regard to itetio to coceive. However, comparisos ad future harmoizatio are ecessary to icrease the state of the art. We aalysed couples 'at risk' (uprotected itercourse) ad the time spa without observed coceptio. From the cotiuous distributio of this time spa we used iformatio for differet cut-off poits. Rachooti ad Olse" reported a prevalece of 16 for couples with a delay i coceptio of at least 1 year for the first pregacy i Demark. Thoeau et al. 6 estimated a cumulative icidece of ifertility (of at least 1 year duratio) of 141 for Frace. I Eglad, Vessey et al. 20 followed wome who stopped usig differet kids of cotraceptio. Usig failure to deliver a live child after moths as a proxy for failure to coceive after 12 moths, 13.7 of the wome had primary ad 5 secodary subfecudity. Page^ foud that 13.0 had bee o-users of birth cotrol for more tha 1 year without coceivig. Hull et al. 2 estimated a lifetime icidece of ifertility of 17. Accordig to Mosher ad Pratt 21 13.9 of all married couples i the USA reported ifertility problems. Cotrary to this, Marchbaks et al. 22 foud a prevalece of couples who had itercourse for 12 moths without coceptio of 32.6 ( moths 20.6) ad a prevalece of couples who defiitely tried to get pregat of 12.5. Altogether, the proportio of subfecudity i our study seems to be higher (most recet TUI withi i the previous 5 years ad >12 moths 29 ad 20.3 for plaed pregacies; table 3). Precedig reproductive experiece ad subfecudity The Polish sample differed i may respects from the other samples. O the oe had, Polish wome ted to start their reproductive career early, have more childre (table I), have shorter spacig betwee the first ad Table 3 Distributio of time of uprotected itercourse (TUI) startig withi 5 years before the iterview: cumulative coditioal probability of coceptio for the first ad the most recet observatio peod, widi ad without plaig of a pregacy cotrollig for age at start of the TUI (PHREG) 17 Demark Germay Polad North Italy South Italy Spam First TUI, cesored (PUNP) or edig with a pregacy All periods of uprotected itercourse (TUI), -932 181 193 30 286 116 126 Number of moths 3 12 50.3 77.7 47.6 73.8 41.1 66.7 47.5 73.8 60.1 85.2 55.5 81.4 82.6 80.0 73.2 79.9 89.9 81.4 TUIswith pregacy plaig!, -706 134 132 17 207 107 109 Number of moths 3 54.7 50.0 43.8 55.3 63.9 59.0 12 79.9 76.3 69.8 71.1 87.9 84.3-82.0 75.9 86.3 91.9 88.9 Most recet TUI, cesored (PUNP) or edig with a pregacy All periods of uprotected itercourse (TUI), -1788 341 441 87 480 222 217 Number of moths 3 47.7 49.8 26.0 43.9 60.0 55J 12 71.0 72.2 43.8 66.9 82.7 78.6 77.2 77J 48.9 82.4 87.0 83.4 TUIs with pregacy plaig, =1291 257 303 29 321 201 180 Number of moths 3 52.5 54.6 54.8 54.5 65.7 60J 12 76.1 78.1 68.2 78.0 87.2 83.1 81.4 83.2 73.9 83.1 91.1 87.6 Total 932 51.5 76.6 82.4 706 55.7 81.3 86.4 1788 48.3 71.0 76.2 1291 56.7 79.7 85.6 PUNP: periods of uprotected itercourse ot or ot yet leadig to pregacy; PHREG- proportioal hazards regressio model

EUROPEAN JOURNAL OF PUBLIC HEALTH VOL. 9 1999 NO. 3 secod pregacies below the age of 25 years (media 1.6 years ad =115 versus 2.1 years overall ad =l,189) ad a loger spacig betwee the first ad secod pregacy after the age of 30 years (media 5.2 years ad =52 versus 4.4 years overall ad =880). Fewer pregacies were plaed i Polad tha i other coutries. O the other had, the distributio of the most recet TUI (table 3) gave the impressio that impaired fecudity is much more frequet i Polad. However, whe distiguishig primary (o previous coceptio) ad secodary subfecudity (previous coceptio) withi the group of wome with a TUI >12 moths, oly 10.8 of the wome i the Polish sample were primarily subfecud versus 27.7 of the total study populatio (see also the proportio of PUNPs without previous pregacies i table 2). Plaig of pregacies ad subfecudity A high proportio of pregacies i Polad were uplaed ad may pregacies occurred despite cotraceptio. Plaig is oe strog predictor of TUI ad the lower proportio of coceptios i most recet observatio periods i the Polish sample ca also be partly explaied by this (table 3): Polish sample, all periods 43.8, ad with itetio to coceive 68.2. However, takig age at the 'startig time' ito cosideratio, lack of plaig is also related to youg age. I the samples from Germay ad Polad, 28 ad 23 respectively started their first TUI below the age of 20 years (overall 20) ad, i this age group had the highest proportio of uplaed pregacies (Germay 60, Polad 62 ad overall 48). Thus, alog with the exclusio of uplaed pregacies, a high proportio of youger couples were also excluded. Secod ad subsequet pregacies teded to be plaed more tha the first pregacy i Demark ad Germay ad less tha the first i Polad ad the souther coutries. These differeces might idicate a differet approach of couples towards family plaig oce a family is established or a differet approach after havig experieced their idividual fecudity. Fecudity is oly observable i couples who are regularly exposed to sexual itercourse without practisig ay kid of birth cotrol. Oly few adult populatios fulfil these criteria. I may surveys, the populatio at risk is restricted to either couples who pla a pregacy or couples who cohabit without usig ay cotraceptive methods. The choice betwee these two optios had a profoud impact o compariso of the frequecy of subfecudity betwee the differet coutries, as show i this paper (table 3). Family plaig i the populatio plays a importat role i the uderstadig of these differeces, sice couples usig usafe cotraceptive methods may by experiece have a idea of their fecudity ad couples widi low fecudity may gradually stop usig ay cotraceptive methods widiout ay wish for a pregacy. Natios widi such a profile of cohabitatio will have a high frequecy of subfecudity, whe die aalysis is based upo die populatio at risk diat icludes all exposed. The Polish sample might be a example. Couples usig very safe cotraceptive metliods, such as oral cotraceptio, oly gai experiece of dieir fecudity whe tryig to become pregat (proportio of curret oral cotraceptive users: Demark 12.3, Germay.5, Polad 4.8, orth Italy 18.9, south Italy 1 ad Spai 11.7). Due to diis self-selective mechaism, populatios i which more couples use safe cotraceptive mediods will have lower subfecudity estimates whe diese are based upo a populatio at risk of all exposed. Curret use of usafe mediods ('safe periods' ad 'iterrupted itercourse') was most prevalet i Polad widi 71.2 of all wome usig cotraceptives ad least prevalet i Demark at 10.1 (Germay 14-8, orth Italy 35.2, south Italy 61.2 ad Spai 25.4 of all cotraceptive users). Thus, die compariso will be partly cofouded by 'selfidicatio for uprotected itercourse' due to differeces i past fecudity experiece. Additioally, i coutries widi frequet use of usafe methods, die most fecud have a high risk of becomig pregat i spite of usig cotraceptive methods ad such couples have o defied IIP (table 2). If couples who get pregat whe usig cotraceptive mediods are excluded from aalyses, coutries i which die populatio frequedy practices usafe cotraceptive mediods will experiece a bias towards icreased proportios of subfecudity (e.g. soudi Italy). Icludig diese couples i die aalyses widi a short waitig time (for example, less dia 3 modis) will, however, also bias die results, but i die opposite directio ad die true frequecy may be foud withi diese limits. I coclusio, after cosideratio of die biases, differeces i fecudability exist betwee five Europea regios ad diese eed further aalyses. Our study shows diat die ascertaimet of cotiuous data o TUI ad/or TTP for the populatio at risk seems to offer a stadardized ad uiform approach ad provides the opportuity of applyig differet cut-off poits for die sake of comparisos. Whe differet coutries are compared, we would advise harmoizig die collectio of iformatio, which ca be doe by basig it o questios from the questioaire from die ESIS Group. NOTE Europea Studies of Ifertility ad Subfecudity is a EC/COST Coceited Actio Research Program. Members of die project maagemet group were: S. Juul (project leader), W. Karmaus, J. Olse, T. Fletcher, F. Bolumar, I. FigS-Talamaca, P. Thoeau, S. Patelakis. Resposible for the collectio of the data were: S. Juul (Demark), W. Karmaus (Germay), L. Bisati ad A. Spielli (Italy), R. Biczysko (Polad), F. Bolumar (Spai). We thak Jor Olse for review ad helpful commets o earlier versios of this mauscript. 1 Greehall E, Veisey M. The prevalece of subfertility: a review of the curret cofusio ad a report of two ew studies, Fertil Steril 1990;54:978-83. 2 Hull MGR, Glazeer CMA, Kelly NJ et al. Populatio study

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