The better prognosis in secondary infertility is associated with a higher proportion of ovulation disorders*

Transcription

1 FERTILITY AND STERlLITY Copyright c 986 The America Fertility Society Prited i U.8A. The better progosis i secodary ifertility is associated with a higher proportio of ovulatio disorders* Joh A Collis, M.D. t:j: Carol A. Rad, B.Sc. Elaie H. Wilso, R.N.II William Wrixo, M.D.II RobertF. Casper, M.D.~ McMaster Uiversity ad the Grace Materity Hospital, Halifax, Nova Scotia, Caada To determie the reaso for the higher pregacy rate i couples with secodary ifertility, the authors compared 237 ifertile couples who had a previous pregacy i the curret partership (secodary ifertility) with 35 ifertile couples i whom the woma had bee pregat oly i a previous partership ad 925 couples with primary ifertility. Couples with secodary ifertility had the highest proportio of ovulatio disorders (36); these couples with secodary ifertility ad aovulatio disorder had the shortest duratio of ifertility (26 moths). Cumulative pregacy rates at 36 moths were 56 i secodary fertility, 44 i primary ifertility, ad 42 i pregacy i a previous partership (P = 0.00). I this study, the better progosis i secodary ifertility maybe related to the higher proportio of couples with ovulatio disorders, who had a.shorter duratio of ifertility. Abortio rates i the earlier pregacies with curret or previous parters were 37 ad 30, respectively; after the period of ifertility, the abortio rates were 4 ad 2, respectively. Fertil Steril45:6, 986 Although secodary ifertility log has bee associated with a better progosis for ifertile couples,, 2 reasos for this icreased likelihood of pregacy have otbee foud. Secodary ifer- Received August 9, 985; revised ad accepted Jauary 4, 986 *Supported by grat from the Natioal Health Research Developmet Program, Natioal Departmet of Health ad Welfare, ad the H.-B. Atlee Research Fud. tdepartmet of Obstetrics ad Gyaecology, McMaster Uiversity freprit requests: Dr. Joh A. Collis, Room 4D9, 200 Mai Street West, Hamilto, Otario, Caada L8N 3Z5. Departmet of Cliical Epidemiology ad Biostatistics, McMaster Uiversity. IIGrace Materity Hospital. ~Preset address: Departmet of Obstetrics ad Gyecology, Uiversity Hospital, Lodo, Otario, Caada. tility may occur amog all kids of ifertile couples, ad.a differet progosis i this group may cofoud the evaluatio ad. compariso of results. Thus it is importat to examie the 'associatio betwee secodary ifertility ad higher pregacy rates. Secodary ifertility should be defied strictly as the history of a pregacy i the curret partership. This history would rule out some of the kow ad as-yet-udiscovered ifertility factors for the curret partership. However, the defiitios available are less specific. For example, "there have bee oe or more pregacies prior to the preset coditio of ifertility." 3 As a result, wome with a past obstetric history (either with the curret parter or with a previous parter) may have bee assiged to the secodary ifertility group.2,4 The ma's history of parethood Collis et ai. Progosis i secodary ifertility 6

2 r geerally has ot bee cosidered for the purpose of classificatio. Amog reports with sample sizes of200 or more ifertile couples, the proportio with secodary ifertility varies from 32 to 55., 2, 5, 9 I four of these reports,, 2, 6, 8 the simple pregacy rates for couples with primary ifertility raged from 47 to 50, compared with 49 to 57 for those with secodary ifertility. These differeces may be cliically importat i the maagemet of ifertility ad should be cosidered i the desig ad evaluatio of cliical trials i ifertility. To determie the reasos for higher pregacy rates amog couples with secodary ifertility, we compared ifertile couples with differet pregacy histories: o previous pregacy (primary ifertility); previous pregacy i the curi."et partership (secodary ifertility); ad pregacy (for the woma) with a previous parter oly. MATERIALS AND METHODS From Jauary, 975 to Jue 30, 980, 375 couples registered at the Dalhousie Uiversity Ifertility Ceter with ifertility of at least 2 moths' duratio. We excluded 78 couples because the woma was pregat at the first visit ad followed the remaiig 297 couples util Jue 30, 983. A follow-up program by mail ad telephoe was istituted for couples who did ot retur to the cliic. Details of the cliical record, icludig diagostic, treatmet, ad follow-up data, were recorded for aalysis. Couples with a history of pregacy i the curret partership were distiguished from those couples i whom the woma gave a. history of pregacy oly with a previous parter. Details of the umber ad outcome of all previous pregacies were obtaied from both groups of wome. Previous pregacy outcomes were ot ascertaied by chart review. The iformatio we obtaied from me regardig previous parethood was reviewed ad evaluated as ureliable. The diagostic evaluatio icluded basal temperatures, edometrial biopsy, specime study, hysterosalpigography, postcoital tests, ad seme aalysis. I patiets with abormal fidigs o iitial pelvic examiatio or durig hysterosalpigogram, laparoscopy ad testig of tubal patecy with methylee blue were doe. Laparoscopy was also performed if pregacy did ot occur withi year after registratio. The primary 62 Collis et al. Progosis i secodary ifertility cliical diagosis was established by the attedig physicia after the completio of the diagostic ivestigatio. A cliical diagosis of tubal defect or edometriosis required laparoscopic cofirmatio. I all, 540 (42) of the wome were laparoscoped. Semial deficiecy was defied as a sperm desity of < 20 X 06/ml or sperm motility of < 40. Couples with o abormalities revealed by these covetioal tests were classed as havig idiopathic ifertility. Pregacies were cofirmed by delivery or pathology reports. We compared the previous pregacy groups with the use of stadard procedures for rates ad proportios. Aalysis of variace was used for the compariso of groups with cotiuous data. Pregacy rates durig the follow-up period were aalyzed with the use of life tables ad are represeted by cumulative pregacy rates at 36 moths with stadard errors (SE). These rates were compared with the use of log rak aalysis. IO The date of the termial evet for couples who experieced pregacy was defied as the date of the last ormal mestrual period. RESULTS The female parters i 372 (29) of the 297 ifertile couples gave a history of a previous pregacy. There were 237 wome (8 of the total) who had coceived with their curret parter, 7 of whom also had coceived with a previous parter; 35 wome (0) had coceived oly i a previous partership. The first group of 237 wome had 295 previous pregacies, ad the secod group of 35 wome had 94 previous pregacies. The total of 489 earlier pregacies resulted i 279 (57) term deliveries, 25 (5) premature deliveries, 69 (35) abortios, ad 6 (3) ectopic pregacies. The rates for these pregacy outcomes were similar for pregacies with curret ad previous parters (X 2, 3 df = 8.65, P = 0.34). Patiets i the previous pregacy group were similar with respect to several progostic factors, icludig age of the wome, age of the me, ad duratio of ifertility. Wome with primary ifertility were youger (P = 0.0) ad their duratio of ifertility loger (P = 0.03) (Table ), but these differeces were too small to be useful cliically. The distributio of the primary cliical diagoses amog the groups of couples with differet pregacy histories is show i Table 2. Wome previously pregat with the curret Fertility ad Sterility

3 Table. Age of Parters, Duratio of Ifertility, ad Pregacy History Amog Ifertile Couples a Age of parter Duratio of Male Female ifertility mea SE mea SE mea SE Primary ifertility a d 0. Secodary ifertility b ge 0.2 Pregacy with previ c ' 0.2 ous parter af".b,c (2 df) = 3.49, P = 0.03; Fe,{ ( df) =.74, P = 0.9; Fd,e'{ (2 df) = 25.2, P = 0.00; Fb,c ( df) =.65, P = parter were more likely to have a ovulatio disorder, ad wome pregat oly with a previous parter were more likely to have tubal disease. Couples with ovulatio disorders had a shorter duratio of ifertility tha other couples. I the secodary ifertility group, this differece was 2.9 moths (Table 3). We coducted a two-way aalysis of variace to evaluate simultaeously the effects of a cliical diagosis of ovulatio disorder ad pregacy history o the duratio of ifertility. The variace ratios (F) for pregacy history ad cliical diagosis are show i Table 3. The mai effects were sigificat (P = 0.00), ad the iteractios term was ot sigificat at the 5 level (P = 0.9). These results imply that the tedecy to earlier referral for ovulatio disorders is sigificatly greater for couples with secodary ifertility. We the compared the two groups with a pregacy history with respect to the outcome of the earlier pregacies (abortio, ectopic pregacy, stillbirth, or livebirth). Usuccessful outcome of the previous pregacy was ot associated with the' type of diagosis assiged after ivestigatio durig the period of ifertility (X 2, 3 df =.32, P = 0.72). Thus previous pregacy experiece does ot appear to accout for the differet proportios of ovulatio ad tubal disorders observed i the two partership groups. Cumulative pregacy rates at 36 moths were 55.8 ± 3.7 (SE) for secodary ifertility, 44.3 ±.9 i primary ifertility, ad 4.8 ± 5. for wome with pregacy oly i a previous partership (P = 0.00) (Fig. ). Pregacy rates were also compared withi major diagostic categories (Fig. 2). Withi the ovulatio deficiecy category, couples who had a previous pregacy with the curret parter had a sigificatly higher pregacy rate tha couples with primary ifertility or pregacy with a previous parter. Amog 39 couples with edometriosis ot show i Figure, there were six. pregacies, all i the group with primary ifertility. Table 2. Primary Cliical Diagosis Amog Ifertile Couples Primary ifertility Previous pregacy i Curret partership Previous partership Row total Ovulatio defects Oligoovulatio Ameorrhea Ameorrheal galactorrhea Luteal phase defect Semial defects d Tubal defects Obstructio Adhesios o7 Other disorders Idiopathic ifertility Cervical factor Fibroid uterus Uterie aomaly Edometriosis d 280a e b 68 5 o f c 6 6 o 4 5 g o Total a,b,cx2 (2 df) = 4.7, P = ; e,f,gx2 (2 df) = 49.8, P < 0-6. dnot sigificat. a,bx2 ( df) = 2.49, P = 0.5; b,cx2 ( df) = 3.9, P = e,{x2 ( df) = 4.0, P = 0.043; f,gx2 ( df) = 4.9, P = e,gx2 ( df) = 48.4, P < 0-6. Collis et ai. Progosis i secodary ifertility 63

4 r Table 3. Duratio of Ifertility Amog Couples with Secodary Ifertility ad Ovulatio Disorders a Duratio of ifertility (mos) mea SE Secodary ifertility Ovulatio deficiecy Other diagoses Primary ifertility Ovulatio deficiecy Other diagoses Pregacy with previous parter Ovulatio deficiecy Other diagoses a Aalysis of variace: pregacy history: F (2 df) = 4.3, P = Diagostic groups: F ( df) = 7.4, P = Pregacies occurrig after the period of ifertility had similar outcomes amog the pregacy history groups (Table 4). However, of the ectopic pregacies, 4 occurred i the relatively small group of wome who had a pregacy with a previous parter. Amog the wome with previous pregacies, the abortio rate was less tha oe half that reported i the previous pregacies (X2, df = 2.2, P = 0.00). Couples who had a previous abortio were o less likely to coceive (X2, df = 0.990, P = 0.325)ad o more likely to have a subsequet abortio (X2, df, = 0.480, P = 0.489). DISCUSSION Of the 297 ifertile couples i our study, 237 of the wome (8) gave a history of a previous pregacy with the curret parter (secodary ifertility). Couples with a previous pregacy i their partership had a better progosis; that group icluded a larger proportio of wome with ovulatio disorders, the most favorable diagosis. The higher pregacy rate was associated with a relatively short duratio of ifertility amog couples with secodary ifertility ad a ovulatio disorder. Although it seems self-evidet that wome with a ovulatio disorder would register earlier for ifertility, the earlier referral is more remarkable amog wome with secodary ifertility. Earlier registratio would ted to lead to a disproportioate excess of the early group i a ifertility sample. This arises because some couples who would have bee classified i other diagostic categories coceive before registerig ad others are excluded because the woma is pregat at the first visit. Also, earlier registratio durig a period of ifertility would lead to a better progosis i the earlier group for two reasos. First, pregacy rates are higher for couples with a shorter duratio of ifertility.3, 8, Secod, effective therapy ca be provided earlier.2 Thus, i our study, the better progosis for secodary ifertility seems to follow aturally from the early referral of the subgroup of couples with ovulatio ueficiecy. I this study, the icidece of previous pregacy i the curret partership is 8, which is less tha the reported rage of 32 to 55 for secodary ifertility., 2, 5-9 This differece appears to be a problem associated with the defiitio of secodary ifertility. Some authors may have classed as secodary ifertility oly those cases occurrig after a pregacy i the ifertile partership, but it is ot clear whether the strict defiitio has bee applied widely. Ideed, the issue of previous pregacy sometimes is igored i reportig ifertility outcomes.3-6 Also, at least two published data collectio forms2, 4 do ot distiguish the partership withi which the woma's past obstetric history occurred. The exclusioof couples with pregacy i a previous partership reduces the apparet proportio of couples with secodary ifertility ad may explai the lower proportio foud i our study, compared with other reports. It is importat to distiguish partership ad pregacy history, because couples with a previous pregacy i the curret partership have a superior outcome, ad the differece is large ~ z w (.)40 ffi Q '"""""' OVULATION TUBAL SEMINAL DEFICIENCY DEFECT DEFICIENCY Figure Cumulative pregacy rates for ifertile couples: primary ifertilitya, = 925, (.. 'l; prior pregacy with curret parter b, =.237, (-J; ad pregacy oly with previous parterc; = 35, (-- -J. Log rak X 2 were: a,b,cx2 (2 df) = 3.8, (P = 0.00); a,bx2 = 2.4 ( do (P = ; b,cx2 ( df) = 6.95 (P = 0.008J; a,cx2 ( df) = 0.26 (P = 0.6J. 64 Collis et ai. Progosis i secodary ifertility Fertility ad Sterility

5 i 60 I- z 50 c( z CJ 40 w a: Q. 30 I- Z w 20 0 a: w 0 Q. 00..,.,/ y.', /.' /~.., ".. - /... ~.... :;:.::.:,: :.::::.::.':.'::~. :,:::;':'; ~ I I I I I I ME AFTER REGISTRATION (Moths) Figure 2 Cumulative pregacy rates 36 moths after registratio ad cliical diagoses amog ifertile couples. Clear bars, prior pregacy with curret parter; hatched bars, pregacy oly with previous parter; solid bars, primary ifertility. Results oflog rak tests comparig the groups withi each diagostic category were: ovulatory deficiecy, P = 0.004; tubal defect, P = 0.293; semial defieicey, P = 0.569; ad other couples, P = eough to be of cliical importace. The cumulative pregacy rate i our study for couples with a history of pregacy i the curret partership was 56, compared with 44 for those with primary ifertility ad 42 for those i which the woma was pregat i a previous partership. The differece i pregacy rates for primary ad secodary ifertility (2) compares with a rage from 2 to 9 i previous reports., 2, 5, 6, 8 Whatever the explaatio for this better progosis, a clear statemet of pregacy history by partership should be a compoet of studies amog ifertile couples. We suggest that secodary ifertility be defied as follows: ifertility i which oe or more pregacies have occurred i the ifertile partership before the preset coditio of ifertility. Eve whe the outcome of the previous pregacy was usuccessful, this group had a better-tha-average progosis. Higher abortio rat~s before ifertility, compared with lower rates after ifertility, have bee observed., 8,7-9 I two reports icludig virtually o couples with edometriosis, the abortio rates before (ad after) the period of ifertility were 52 (3) ad 29 (2).8 These compare with our rates of 37 (4) i couples with secodary ifertility ad 30 (2) i couples i whom the woma had a previous pregacy with aother parter. Amog the couples i our study, the high abortio rate i pregacies before ifertility occurs amog all diagostic groups, i pregacies with the curret parter or aother parter, ad the history of abortio does ot ifluece the succeedig pregacy. I three reports o couples with edometriosis ad secodary ifertility, the rates before (ad after) ifertility were 46 (8),7 34 (9),8 ad 52 (9).9 Amog wome with edometriosis, the pheomeo has bee attributed to icreased prostagladi levels,7 icreased self-referral to fertility specialists after spotaeous abortio,8 ad possible associatios betwee edometriosis ad either corpus luteum dysfuctio or autoimmuity.9 A history of high abortio rates amog ifertile couples could reflect some widespread biologic disorder that is removed by effective treatmet. Ideed, the before ad after differeces are larger i the edometriosis studies amog couples who share some pathologic features. However, this observatio could be a artifact associated with observatioal studies. Because wome with ifertility are more likely to recall uusual past reproductive evets, they also may be likely to label those evets as abortios. Reportig bias of this kid would lead to a falsely high estimate of previous abortio rates ad is compatible with the observatio that the spotaeous abortio rate is higher i more recet pregacies before the period of ifertilityy Higher abortio rates i the immediately precedig years are recorded because recet evets, correctly or icorrectly idetified, are more likely to be give i a history. To determie whether the high abortio rates reported i the previous pregacies of ifertile couples arise from biologic disorders or from biased reportig will require a study i which the pregacy outcomes before ad after ifertility are ascertaied. Table 4. Outcome of Pregacy Occurrig After a Period of Ifertility Amog Ifertile Couples with Various Previous Pregacy Experieces Livebirths Stillbirths Abortios Ectopic pregacies Primary ifertility Previous pregacy i Curret Previous partership partership Collis et a. Progosis i secodary ifertility 65

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