Gynecology-endocrinology

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1 Gyneclgy-endcrinlgy FERTILITY AND STERILITY Cpyright 1994 The American Fertility Sciety Vl. 61, N. I, January 1994 Printed n acid-free paper in U. S. A. The predictin f the chance t cnceive in subfertile cuples* J. Marietta Eimers, M.Sc.t Egbert R. te Velde, M.D., Ph.D.:!: Rene Gerritse, M.D.:!: Elly T. Vgelzang, M.D.:!: Caspar W. N. Lman, M.Sc.t J. Dik F. Habbema, Ph.D.t Erasmus University Rtterdam, Rtterdam, and University Hspital Utrecht, Utrecht, The Netherlands Objective: T develp a mdel that can predict the chance t cnceive spntaneusly in subfertile cuples. Design: In a chrt study, a cnsecutive series f patients cnsulting infertility was fllwed up. We related infrmatin frm previus histry, physical examinatin, pstcital tests (PCT), semen analyses, and sperma penetratin meter tests with the ccurrence f a spntaneus pregnancy. Setting: Fertility center in a university hspital. Patients: Nine hundred ninety-six cuples cnsulting fr infertility due t cervical hstility, male subfertility, r unexplained infertility. Interventins: Nne. Main Outcme Measure(s): Time between intake and ccurrence f the first spntaneus pregnancy. Results: Infrmatin frm the previus histry (duratin f infertility, primary r secndary female infertility, age f the wman, fertility prblems in male's family), the percentage mtile sperm in the first semen analysis, and the result f the first PCT are sufficient t predict the chance t cnceive. A pcket chart is presented fr easy use f the mdel. Cnclusins: With a limited amunt f diagnstic infrmatin, the chance t cnceive spntaneusly can be predicted. Fertil Steril 1994;61:44-52 Key Wrds: Male infertility, female infertility, pregnancy rate, pstcital test, semen analysis, previus histry In mst clinics that treat subfertile cuples, a previus histry is btained, and a physical examinatin f bth partners is perfrmed. Mrever, varius diagnstic tests are perfrmed n bth the wman and the man. One f the bjectives f this fertility wrk-up is t btain sme idea abut the chance t cnceive spntaneusly. Mst dctrs are prbably nt cnscius f their prgnstic esti- Received February 16, 1993; revised and accepted September 15, * Supprted by grant OG8966 f the Dutch Sickness Fund Cuncil, Amstelveen, Hlland. t Department f Public Health, Erasmus University. :j: Department f Obstetrics and Gynaeclgy, University Hspital. Reprint requests: Egbert R. te Velde, M.D., Ph.D., Department f Obstetrics and Gynaeclgy, University Hspital, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. mates, but in the prcess f cunseling these estimates implicitly play an imprtant rle. Fr example, a yung cuple with a shrt duratin f infertility and n explanatin whatsever fr the absence f cnceiving might be advised t be patient and keep trying. On the ther hand, in the case f very pr sperm qualities in which the chances t cnceive spntaneusly are almst zer, the cuple shuld be advised accrdingly. Prgnstic infrmatin is essential fr the cuple t decide what actin t take in their individual and unique situatin. Their decisin may vary frm starting t accept a childless life t treatment with IVF r dnr inseminatin. Can a mre bjective and precise predictr f the chances t cnceive be cnstructed fr an individual cuple using all available prgnstic infrmatin? In develping such a prgnstic "mdel," it 44 Eimers et al. Predictins f cnceiving

2 shuld be realized that much f the diagnstic infrmatin is likely t be redundant because f strng crrelatins between tests that, therefre, give mre r less the same infrmatin. Existing mdels either d nt take this redundancy int accunt (1) r als include treatment-dependent pregnancies (2-4). In the present study, we shall cnstruct a mdel taking int accunt length f fllw-up and crrelatins between tests, including nly treatment-independent pregnancies and using infrmatin f bth the male and female partner. Patients MATERIALS AND METHODS Frm 1974 t 1984, apprximately 300 infertile cuples registered yearly at the Infertility Centre f Utrecht University Hspital, Utrecht, The Netherlands. After registratin, demgraphic and clinical data n bth partners were cllected, and a physical examinatin was perfrmed. The perid f diagnstic fertility wrk-up was apprximately 6 mnths, during which the wman had t measure her BBT. During the first cycle, a semen analysis and an in vitr sperm penetratin meter test were perfrmed. In the secnd cycle, a pstcital test (PCT) was cnducted 9 t 12 hurs after intercurse, and a secnd semen specimen was investigated. In the third cycle, a PCT was cnducted 2 t 4 hurs after intercurse. During the furth cycle, the wman received 50 mg ethinyl E2 tw times per day frm days 2 t 15, after which a prgestagen was given until day 22. In this artificial cycle a third PCT, a sperma penetratin meter test, and a semen analysis were planned between days 8 and 15 f the cycle. In the fifth cycle, a hystersalpinggram (HSG) was perfrmed, unless this recently had been dne elsewhere and was judged t be nrmal. Finally, in the 6th mnth a cncluding reprt was prepared and discussed with the cuple. If n pregnancy ensued within 9 t 12 mnths, a laparscpy was perfrmed. This standardized diagnstic scheme and the labratry cnditins did nt change until Bth were supervised by the same physician. All dctrs wrked accrding t the prtcl and had t fill in the data n a standard histry and physical frm. Inclusin criteria fr the present study are as fllws: [1] duratin f infertility f> 12 mnths; [2] a cycle f 23 t 35 days and a biphasic BBT during the diagnstic phase; [3] n abnrmalities explain- ing the infertility detected by HSG r laparscpy (unless a pregnancy ccurred befre HSG r laparscpy was perfrmed); and [4] at least ne fthe semen samples cntains at least ne spermatzn. Between 1974 and 1984, a cnsecutive series f996 cuples met these criteria and was included in this study. The mean age f the wmen was 29 years (range, 19 t 45 years). The median duratin f infertility was 3 years (range, 1 t 18 years). Infertility was primary in 83 % f the wmen and secndary in 17%. Fllw-up After the diagnstic data were cmpleted, the 996 cuples were fllwed up. With a standard frm, infrmatin was cllected n ccurrence and date f the first pregnancy after registratin and the kind and date f treatment. Fllw-up data were cllected independently frm diagnstic data. The registratin date was taken as the start f the fllw-up. Of the 397 cuples wh became spntaneusly pregnant (215 during the 1st year, 182 thereafter) the date f the last menstruatin plus 2 weeks was taken as the end f the fllw-up perid. Because treatment mdalities were limited at that time, nly 202 patients (23%) received therapy during fllw-up: artificial inseminatin husband (n = 160), artificial inseminatin dnr (n = 23), vaginal irrigatin (n = 15), and IVF (n = 4). Unless a cervical factr was diagnsed r the duratin f infertility had been lng, cuples were advised t await the pssible therapeutic effect f HSG fr at least 9 mnths until treatment was cnsidered. The limited number f patients treated during the 1st year (n = 83) therefre either had a cervical factr r a lng duratin f infertility. The fllw-up f all patients wh received therapy was cnsidered t end at the start f the first treatment. In ur analysis, therefre, nne f these patients became spntaneusly pregnant. Fr 887 cuples the fllw-up infrmatin was cmplete until 1 year after intake. Fr the remaining 109 cuples, we did nt knw whether a pregnancy had ccurred r whether treatment was given during the fllw-up. They were cnsidered t be fllwed until the day fhsg, except fr 36 cuples wh had had an HSG elsewhere befre intake. These 36 cuples had t be excluded frm the prgnstic analysis. Previus Histry The previus histry f the wman included the fllwing: age, duratin f infertility, primary r Vl. 61, N.1, January 1994 Eimers et a1. Predictins f cnceiving 45

3 secndary infertility (ever pregnant), fertility-reducing factrs (abrtus prvcatus, ectpic pregnancy, gnrrhea, salpingitis, curettage, abdminal surgery, use f diethylstilbestrl [DES] by the mther), fertility prblems in the first-degree family (males and females), smking habits, alchl cnsumptin, age at menarche, length f cycle, and frequency f intercurse. The previus histry f the man included the fllwing: fertility-reducing factrs (gnrrhea, partitis after puberty, intrascrtal inflammatin, hernitmy, retenti testis, radiatin, and drugs), fertility prblems in the firstdegree family (males and females), primary r secndary infertility (ever impregnated a wman), smking habits, alchl cnsumptin, DES use by mther, pubertal develpment, sexual disturbances, and frequency f intercurse. Physical Examinatin A rutine gyneclgical examinatin f the wman was perfrmed. The physical examinatin f the man included the fllwing: examinatin f the secndary sex characteristics, penis, testis vlume and turgr, epididymides, and vasa deferentia. Special attentin was paid t the presence f a variccele r hydrcele. Semen Analysis Semen analyses were perfrmed accrding t the recmmendatins f the Wrld Health Organizatin (WHO) (5). The quality f the mtility f the spermatza was graded accrding t Tinga et al. (6). Semen analyses included the fllwing: perid f abstinence, vlume (ml), ph, appearance, cnsistency, density (106/mL), mtility (%), quality f mtility, agglutinatin, cellular elements ther than spermatza, nrmal mrphlgy (%), amrphus heads (%), abnrmal acrsmes (%), pirifrm heads (%), tapering heads (%), small val heads (%), large val heads (%), duble heads (%), pin heads (%), cytplasmic drplets (%), defective midpieces, shrt tails, duble tails, headless tails, spermatcytes, spermatids, leukcytes, epithelial cells, ther cells, bacteria, and the indirect mixed antiglbulin reactin test t test sperm antibdies. Pstcital Test Pstcital tests were perfrmed accrding t the recmmendatins f the WHO (5). Mst cuples had three PCTs: PCT1 after 9 t 12 hurs (evening citus), PCT2 after 2 t 4 hurs (mrning citus), and PCT3 during an artificial cycle. During the natural cycles, PCTs were planned during the prevulatry phase based n the result f previc'us cycle lengths and previus BBT(s). If n ptimal mucus was present, the patient was asked t cme back n ne f the next days. If again the result was nt ptimal, she came back again until a clear rise in BBT was present. Only the best PCT frm each cycle was reprted. In additin t the result f the actual PCT (negative: n spermatza visible; nnprgressive: nly immtile r lcally mtile spermatza present; r prgressive: ne r mre frwardly mving spermatza detected), the qualities f the cervical mucus (CM) were scred: clarity, cnsistency, spinnbarkeit, ferning, sum scre, and ph (5). Sperm a Penetratin Meter Test Sperma penetratin meter tests were perfrmed accrding t the recmmendatins f the WHO (5). Mst cuples had five sperma penetratin meter tests: in the mucus f the female partner, in dnr mucus, in mucus f the female partner during an artificial cycle, in serum f the female partner, and in AB-serum. Each sperma penetratin meter test cnsisted f the fllwing items: migratin distance, penetratin density at 1, 3, and 4.5 cm and duratin f the prgressive mvements. Frm these results, a sum scre was cnstructed accrding t Kremer (7). Statistical Analysis Statistical analyses were dne using Statistical Package fr Scial Sciences PC (SPSS Inc., Chicag, IL) and Epidemilgical Graphics, Estimatin, and Testing Package (EGRET; Statistics and Epidemilgy Research Crpratin, Seattle, WA). Crrelatins between diagnstic tests were calculated by Pearsn's crrelatin cefficient. The relatin between diagnstic tests and cumulative spntaneus pregnancy rates (PRs) was tested by Cx regressin (8). Cx regressin cmpares the mnthly PR (r fecundity rate) f tw r mre subgrups by calculating the rati f the PR f the favrable grup(s) and the unfavrable grup. We shall refer t this rati as the fecundity rati (equivalent t the hazard rati used in survival analysis). Diagnstic tests with a significant univariate relatin with the spntaneus PR were used fr the frward stepwise Cx regressin. Frward stepwise Cx regressin first selects the diagnstic test mst strngly related t the spntaneus PR, and then 46 Eimers et al. Predictins f cnceiving

4 ne by ne adds t the mdel the tests that cntribute mst t the prgnstic infrmatin already btained. The "adjusted" fecundity ratis calculated by this methd take int accunt interrelatins with the fecundity ratis f ther imprtant factrs. Fecundity ratis were calculated and cmpared fr tw perids: until 1 year after intake and thereafter. Because the ratis becme less significant after 1 year and because mst cuples are especially interested in their chances f becming pregnant within the 1st year, nly the fllw-up during the 1st year is used fr the mdel. During the 1st year, 215 pregnancies ccurred. The gdness-f-fit f the Cx regressin mdel was tested by adding interactins and quadratic frms in the mdel. N imprvement culd be btained. The validity f the mdel was tested by the split-half methd; t avid verptimizing, the ppulatin was randmly divided int tw equal parts. A mdel was built based n ne part, whereas the ther half that was nt used in mdel cnstructins was used t cmpare the bserved and predicted number f pregnancies. RESULTS Table 1 presents the diagnstic parameters that are significantly related t the chance t cnceive. Previus histry results in six variables related t the chance t cnceive: tw female characteristics (age and primary r secndary female infertility), tw male characteristics (primary r secndary male infertility and fertility prblems in the male's family), and tw characteristics fthe cuple (duratin f infertility and frequency f intercurse). N variables f the physical examinatin related t the spntaneus chance t cnceive. It shuld be nted that mst abnrmalities are very rare, s unlikely t relate significantly t the spntaneus chance t cnceive. We therefre cmbined them t a male fertility-reducing factr and a female fertility-reducing factr (see Materials and Methds). These tw factrs als did nt relate t the chance t cncelve. Several semen parameters crrelate strngly t the chance t cnceive. Their mutual crrelatin is mderate t high (median, r = 0.38; range, 0.03 t 0.95). The results f all three PCTs (negative, nnprgressive, r prgressive) als have a relatin with the spntaneus chance t cnceive. The quality f the CM des nt have prgnstic value, whereas its ph has nly sme prgnstic value after recent intercurse. Almst all sperm a penetratin meter test parameters are related t the chance t Table 1 Parameters Frm Previus Histry, Physical Examinatin, Sperm Analysis, PCT, and Sperma Penetratin Meter Test That Were Significantly Related t the Chance t Cnceive* Previus histry Duratin f infertilityt Female infertilityt Male infertilityt Age f the wmant Frequency f intercurse Fertility prblems in male's family Physical examinatin in male and female Nne Semen analysis Percent mtilityt Densityt mtile densityt N. f mtile spermt N. f spermt Percent nrmal mrphlgyt Percent teratfrmt Mtility (quality) PCT Result after evening intercurset Result after mrning intercurset Result in artificial cyelet ph after mrning intercuset Sperma penetratin meter test Serum AB: Migratin distance, penetratin density at 1, 3, and 4.5 cm, vitality after 6, 24, and 48 hurs, sum scre Serum f female: Migratin distance, penetratin density at 1, 3, and 4.5 cm; vitality after 6, 24, and 48 hurs, sum scre Hmlgus: Migratin distance, penetratin density at 1, 3, and 4.5 cm; vitality after 6 and 24 hurs, sum scre Heterlgus: Migratin distance, penetratin density at 1, 3, and 4.5 cm; vitality after 6 hurs, sum scre Artificial: Migratin distance, penetratin density at 1 and 3 cm; vitality after 6 hurs, sum scre * Univariate Cx regressin relating diagnstic parameter with chance t cnceive within 1 year. t P < 0.00l. :j: P < P < cnceive. They are, hwever, all crrelated with each ther (median, r = 0.41; range, 0.10 t 0.92) and with the sperm parameters (median, r = 0.35; range, 0.06 t 0.80). Frward stepwise Cx regressin was first applied t the parameters frm the previus histry (presented in Table 1). Fur f the six variables with a significant univariate relatin t the chance t cnceive were selected: age f the wman, duratin f infertility, primary r secndary female infertility, and fertility prblems in the male's family. All labratry tests were subsequently added t this prgnstic mdel, but nly the result f the first Vl. 61, N.1, January 1994 Eimers et al. Predictins f cnceiving 47

5 Table 2 Distributin f the Number f Pregnancies in Varius Subgrups f the Selected Parameters N. f N. f Selected parameter cuples pregnancies Duratin f infertility (y) (30)* (28) 3 t (25) 5 t (17) :?: (11) Female infertility Primary (20) Secndary (38) Age f the wman (y) 21 t (27) 26 t (24) 31 t (22) 36 t (20) 41 t (0) Fertility prblems in male's family N (24) Yes (18) PCT Negative (8) Nnprgressive (19) Prgressive (37) Mtility (%) t (11) 20 t (24) 40 t (29) :?: (35) Ttal (24) * Values in parentheses are percents. pet and the mtility in the first semen analysis added prgnstic infrmatin. All ther labratry tests were either crrelated t the pet r t the semen analysis and were, therefre, nt selected. Althugh the age f the wman and fertility prblems in the male's family were statistically significant, adding the pet result and sperm mtility t the mdel decreases the imprtance f these variables. The distributin in varius subgrups f the six selected parameters and the number f pregnancies are shwn in Table 2. Table 3 presents the adjusted fecundity ratis f the six selected parameters. A parameter with a fecundity rati > 1 has a favrable effect n the fecundity and a negative effect if the rati is <1. The age f the wman has an adverse effect n fecundity, althugh the effect is rather small: 1 year increase f age decreases the chance t cnceive by 3 %. Duratin f infertility als has a negative effect n fecundity. Having been infertile fr 1 year lnger decreases the chance t cnceive by 11 %. A 6-year difference in infertility duratin halves the chance t cnceive ( = 0.5); thus, a wman wh has nt cnceived fr 7 years has half the chance f ding s f a wman with 1 year f infertility. Secndary female infertility increases the chance t cnceive by 74%, whereas fertility prblems in the male's family decreases the chance t cnceive by 31 %. As expected, a gd pet and a gd semen analysis have a psitive effect n the fecundity rate. A wman with a nnprgressive pet has 110% mre chance t cnceive cmpared with a negative result, whereas ne with a prgressive pet has 330% mre chance. Mtility increases the chance by 1.3% fr each percentage increase. S a difference f 10% mtility increases the chance t cnceive by 12% ( ). Fr a "rugh and ready" estimatin f the chance t cnceive, we have develped a pcket chart (see Table 4). T use this chart, circle the infertility scre fr each f the six variables that represents the actual situatin f the cuple. Scre 0 means n fertility endangering factr, whereas every increase by 10 halves the chance t cnceive each mnth. After adding the scres t the fertility index, the chance t cnceive within 1 year can be read in Figure 1. This chance t cnceive was calculated fr each cuple in ur ppulatin. Figure 2 presents the distributin f this chance: apprximately 9% f the cuples have a chance < 50% and 43% have a chance f <20%. DISCUSSION In this study, we have develped a mdel t predict the spntaneus chance t cnceive fr an indi- Table 3 Fecundity Ratis With 95% Cnfidence Interval fr the Six Parameters That Were Selected by Multivariate Cx Regressin Adjusted 95% fecundity cnfidence Selected parameter ratis interval Duratin f infertility (per y) t 0.96t Female infertility Primary 1 Secndary t 2.36* Age f the wman (per y) t 1.01 Fertility prblems in male's family N 1 Yes t 1.09 PCT Negative 1 Nnprgressive t 3.70t Prgressive t 7.41* Mtility (per %) t 1.021* * P < t P < Eimers et al. Predictins f cnceiving

6 Table 4 Pcket Chart fr Calculating PR Within 1 Year and the Mnthly Fecundity Rate Parameter Age f female 21 t 25 years 26 t 30 years 31 t 35 years 36 t 40 years 41 t 45 years Duratin f infertility 1 year 2 years 3 t 4 years 5 t 6 years "2:.7 years Female infertility Secndary Primary Fertility prblems in male's family N Yes PCT Prgressive N nprgressive Negative Mtility "2:.60% 40%-60% 20%-40% 0%-20% Prgnstic index Infertility scre* * Circle the infertility scres fr each f the parameters and add them t the prgnstic index. Use the curve in Figure 1 t estimate the PR within 1 year. vidual cuple with a fertility prblem that is nt due t tubal disease r cycle disturbances. Existing mdels had several drawbacks. Althugh they are suggested t measure the spntaneus chance t cnceive, sme mdels, in fact, d nt distinguish between treatment-dependent and treatment-independent pregnancies (2-4). Therefre, they are likely t verestimate the chance t cnceive spntaneusly. Other mdels d nt take int accunt the length f the fllw-up perid. It is bvius that mdels based n a shrt fllw-up perid will result in a lwer chance t cnceive spntaneusly than mdels with a lng fllw-up perid. Furthermre, sme mdels include nly infrmatin n ne f the partners (9, 10). Because bth partners cntribute t the chance t cnceive, including nly ne will never result in an ptimal mdel (11). Finally, sme mdels d nt take crrelatins between diagnstic tests int accunt (1). We fund that nly six parameters frm the previus histry relate t the chance t cnceive during the 1st year (Table 1). The wman's age had a univariate fecundity rati f 0.94 during the 1st year. pregnancy rate 100% 80% 60% 40% 20% 0% Figure 1 Relatin between prgnstic index (see Table 4) and PR within 1 year. Dunphy et al. (12) fund an even greater effect f age (fecundity rati = 0.92). Duratin f infertility (2, 4, 9, 12, 13) is caused by the selectin effect f trying time. Nrmal fertile cuples may still be present amng cuples cnsulting fr infertility until 2 years f trying t becme pregnant. Between 3 and 5 years, the prprtin f mild r mderately subfertile cuples will decrease. After 5 years, nearly nly severely sub fertile cuples r infertile cuples are left (1). Primary r secndary female and male infertility are als related t the chance t cnceive (2, 9, 12, 14). Surprisingly, that is, because this has never been mentined in ther studies, infertility in the male's family was significantly related t the PR and even mre t semen quality (median mtility is 30% in the grup with fertility prblems and percentage f cuples 30%r--...".,. 25%.. 20% 15% 10% 5% 0% 0-10% 10-20% 20-30% 30-40% 40-50% 50-60% 60-70% >70% predicted pregnancy rate within ne year Figure 2 Distributin f the predicted PR within 1 year accrding t the prgnstic mdel (n = 949). Vl. 61, N.1, January 1994 Eimers et al. Predictins f cnceiving 49

7 .. 40% in the nrmal grup). We assume that hereditary prperties f the semen are behind this family effect. Inquiring abut infertility in the first-degree family shuld therefre becme cmmn practice. Finally, frequency f intercurse seems t have prgnstic value. Three r mre times a week clearly enhances the chance t cnceive. Hwever, because f crrelatin with age and duratin f infertility, frequency f intercurse has n additinal statistically significant effect and is therefre nt included in the final mdel. N variable frm the physical examinatin, either f the man r the wman, is related t the chance t cnceive. Lack f effect f variccele and epidydimis pathlgy was als fund by Dunphy et al. (15), whereas Duct et al. (2) fund n effect f urgenital infectin, hypgnadism, variccele, and cryptrchidism. Unlike Abramssn and Duchek (9), we culd nt find a relatin between testicular vlume and the chance t cnceive. It shuld be nted, hwever, that Abramssn and Duchek (9) als included azspermic males in his study. Our results f the prgnstic value n sperm parameters are similar t thse f thers. Dunphy et al. (16) and Glazener et al. (17) als fund that sperm density, nrmal mrphlgy, mtility, ttal number f sperm, and mtile sperm density have an impact n PRs. Cnfirming Glazener et al. (17) and Hull et al. (18), we fund a strng relatin between PCT and the chance t cnceive. Our data indicate that the PCT after intercurse in the evening seems t be the best single predictr f future pregnancy. There is minimal published research n the prgnstic value f the sperma penetratin meter test. Only Eggert-Kruse et al. (19) prved prgnstic value f the sperma penetratin meter test in an artificial cycle. We fund prgnstic values in all kinds f medium fr the sperma penetratin meter test (CM, dnr CM, artificial stimulated CM, dnr AB-serum, serum), but because f strng relatins between sperma penetratin meter test and semen analysis and PCT, the sperma penetratin meter test did nt cntribute t the final mdel. The final mdel includes nly six parameters. Althugh a great number f parameters were statistically significant in the univariate analysis, their additinal value t the mdel with the six selected variables is nt significant. This is due t strng interrelatins amng diagnstic variables. These strng interrelatins als cause anther phenmenn: fecundity ratis f the multivariate Cx regressin are mstly clser t 1 than the univariate fecundity ratis. Fr instance, duratin f infertility has a univariate fecundity rati f 0.86, whereas the multivariate fecundity rati is nly Adding new diagnstic parameters t the mdel can cause lss f statistical significance fthse already in the mdel. This happened t the parameter wmen's age and fertility prblems in the male's family. Adding the PCT and the percentage mtility t the mdel caused a lss f statistical significance f these tw parameters frm previus histry. Hwever, because f their significance in a mdel with nly parameters frm previus histry, we chse t retain them in the final mdel. The mdel nly applies t PRs during the 1st year after intake. After 1 year, three prcesses ccur: the baseline mnthly fecundity rate slwly diminishes, the effect f the wman's age grws while the effect f PCT and semen diminishes (results nt shwn). Each prcess has its wn pssible explanatin: a diminishing baseline fecundity rate can be caused by a selectin effect, that is, cuples with the same prgnstic index d differ in fecundity. The nrmal fertile and mildly subfertile cuples will achieve pregnancy, whereas the mderately and severely subfertile cuples need n average mre time, s after 1 year the baseline will be lwer. The increasing effect f wman's age is explained by the increasing lss f fertility as wmen grw lder. This means that when the ppulatin grws lder, differences between age grups becme mre prnunced. The decreasing effect f PCT and semen can be caused by tw phenmena. First, the diagnstic tests are perfrmed shrtly after intake. Because all bilgical parameters are subject t variatin' repeating the tests after a few years will give a different result (sme cuples will have a better result, sme a wrse ne). Therefre, it is expected that the initial PCT and semen analysis will diminish in prgnstic value. Secnd, there will be sme kind f selectin effect. Cuples with a nrmal PCT and n ther abnrmalities will becme pregnant, whereas thse with a nrmal PCT and ther (unstated) abnrmalities will remain infertile. The latter d nt differ n PR frm cuples with an abnrmal PCT. S the prgnstic value f the PCT will diminish after a while. Weare aware that the mdel nly applies t wmen withut vulatry prblems r tubal disease. This means diagnstic wrkup must include tests t evaluate these pssible causes. An HSG and eventually a laparscpy have t be perfrmed t exclude tubal pathlgy, whereas hrmnal wrkup and cycle analysis are necessary in wmen with 50 Eimers et al. Predictins f cnceiving

8 cycle disturbances. Hwever, if tubal pathlgy is present, usually a clear therapeutic apprach is bvius. Likewise, in cuples with cycle disturbances vulatin inductin is mst likely t be applied. Withut the bvius therapeutic appraches, bth cnditins usually have a pr pregnancy prgnsis; thus, frm the cunseling pint f view, bth cnditins are straightfrward. In cntrast, in the hetergeneus ppulatin f cuples withut tubal pathlgy r cycle disturbances (the ppulatin this study fcuses n), there is much mre need f a prgnstic mdel that enables the physician t cunsel the cuple. Sme patients with regular cycles and BBTs might have had subtle vulatin disrders. At that time, the perfrmance f varian functin tests was unusual and inadequate. Even nw it is debatable what the value is f an vulatin disrder btained in ne cycle in wmen with therwise regular cycles and biphasic BBTs. We knw fr example that luteinized unruptured fllicle cycles quite ften are nly ccasinally present. We cnclude frm this that if it wuld have been pssible t detect thse patients with subtle vulatin disrders wh then wuld have been excluded frm analysis, ur predicted PRs wuld have been slightly higher. Hw shuld we use the prgnstic infrmatin? Figure 2 presents the predicted prgnsis f the cuples in ur data set. Apprximately 10% had a rather gd chance t cnceive (>50% within 1 year). Further diagnsis and therapy may be a bit verdne fr these cuples, but pstpning therapy fr 1 r 2 years will select cuples with a real fertility prblem. Frty-eight percent had a mderate chance t cnceive (20% t 50%) and culd be advised t pstpne therapy fr 1 year. Only thse cuples with a pr chance (0% t 20%) are withut dubt suitable fr further diagnstic wrk-up and, if apprpriate, immediate therapy. Using the pcket chart f Table 4 is a quick way t infrm cuples abut their chance t cnceive after a minimum f diagnstic tests. The prgnstic index can als be used by cmparing it with the PR during therapy. The mnthly fecundity rate can be cmpared with the success rate during therapy. If the success rate ftherapy is significantly better than this baseline fecundity rate, effectiveness f the therapy may be suspected. Only a blind randmized trial can give real prf f effectiveness. It is cmmn fr wmen t becme pregnant 1 r 2 mnths after their initial evaluatin fr infertility. At that time the HSG r laparscpy are nt yet perfrmed, s we d nt knw whether a tubal factr is present r nt. Hwever, because a pregnancy ccurred spntaneusly, a (serius) tubal factr seems unlikely. Because the number f pregnant wmen with a tubal factr will be very small in cmparisn with the number f pregnant wmen withut a tubal factr, we included this grup f early spntaneus pregnancies, as did Cllins et al. (20) in a similar study. We validated the mdel by the split-half methd. The initial data set (n = 914) was split randmly in tw equal parts. A prgnstic mdel was develped n ne half. Parameters were similar t the nes in the mdel based n the whle ppulatin. The mdel develped n ne half was applied n the ther half. The predicted number f pregnancies (114) des nt differ significantly frm the bserved number f pregnancies (100) (X 2 = 1.72, P > 0.05). Applying the mdel t an external ppulatin will increase the validity f the mdel. We shall reprt n this in a future paper. We cnclude that in cuples in whm the wman has neither cycle disturbances nr tubal pathlgy, fur variables frm the previus histry, the result f the first PCT, and the sperm mtility result f the first semen analysis are sufficient t predict the spntaneus chance t cnceive. Other diagnstic infrmatin btained frm the previus histry, by physical examinatin, r by labratry tests seems t be redundant fr prgnstic purpses. REFERENCES 1. Cmhaire FH. Simple mdel and empirical methd fr the estimatin f spntaneus pregnancies in cuples cnsulting fr infertility. Int J AndrI1987;10: Duct B, Spira A, Feneux D, Juannet P. Male factrs and the likelihd f pregnancy in infertile cuples. II. Study f clinical characteristics, practical cnsequences. Int J Andrl 1988;11: Juannet P, Duct B, Feneux D, Spira A. Male factrs and the likelihd f pregnancy in infertile cuples. I. Study f sperm characteristics. Int J Andrl 1988;11: Hargreave TB, Eltn RA. Fecundability rates frm an infertile male ppulatin. Br J UrI1986;58: Wrld Health Organizatin. Labratry manual fr the examinatin f human semen and semen-cervical mucus interactin. In: Belsey MA, Eliassn R, Gallegs AJ, Mghissi KS, Paulsn CA, Prasad MRN, editrs. Singapre: Press Cncern, Tinga DJ, Jager S, Bruijnen CLAH, Kremer J, Mensink HJ. Factrs related t semen imprvement and fertility after variccele peratin. Fertil Steril1984;41: Kremer J. The in vitr spermatzal penetratin test in fertility investigatins. [thesis). Grningen, The Netherlands: Vl. 61, N.1, January 1994 Eimers et al. Predictins f cnceiving 51

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