Postcoital Test

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    Human Reproduction vol.15 no.9 pp.19531957, 2000

    The prognostic power of the post-coital test for natural

    conception depends on duration of infertility

    Cathryn M.A.Glazener1,3, W.C.L.Ford2 and IntroductionMichael G.R.Hull2,* To manage infertile couples effectively, the clinician needs a

    realistic and practical prediction of their chance of conception1Health Services Research Unit, University of Aberdeen, Aberdeenwithout treatment. If this is poor, the couple should proceedand 2University of Bristol, Division of Obstetrics and Gynaecology,

    Bristol, UK to definitive treatment immediately, otherwise they can be

    advised to continue trying to achieve a natural conception.3To whom correspondence should be addressed at: Health ServicesThus, diagnostic investigations that refine the cliniciansResearch Unit, University of Aberdeen, Polwarth Building,

    Foresterhill, Aberdeen AB25 2ZD, UK. predictive power will promote appropriate and efficient use ofE-mail: [email protected] resources. Sperm dysfunction is the commonest defined cause

    of infertility (Hull et al., 1985; Cates et al., 1985), but*After a short illness, Michael Hull, Professor of ReproductiveMedicine and Surgery in the Division of Obstetrics and its diagnosis remains uncertain. Sperm concentration and

    Gynaecology, University of Bristol, died on 22 November, 1999, morphology, assessed according to World Health Organizationaged 60 years. He went to Bristol from London in 1976 as

    criteria (WHO, 1992), were related to the monthly chance ofConsultant Senior Lecturer in Obstetrics and Gynaecology with a

    conception in a group of Danish trade unionists attempting todeveloping reputation in clinical reproductive endocrinology frombecome pregnant (Bonde et al., 1998) but in infertility practicehis time in London and elsewhere. His contributions to knowledge

    and practice of reproductive medicine, particularly in all aspects of the conventional semen analysis is poorly predictive of outcomemale and female infertility, brought international renown to his unit. except when results are very poor (Glazener et al., 1987;He was appointed to a Personal Chair in 1989. He brought strong Polansky and Lamb, 1988; Tomlinson et al., 1999).ethical principles to his research and clinical practice and

    Sperm function tests might offer greater predictive powercampaigned locally and nationally for public understanding and

    but at present are recommended only for use in specializedfunding of infertility services.centres (Royal College of Obstetricians and Gynaecologists,

    Controversy about the value of the post-coital test (PCT) 1998). The post-coital test (PCT) requires no expensive equip-has prompted us to re-analyse data from 207 couples, ment and a negative PCT reduced the cumulative chance oforiginally studied between 1982 and 1983, with at least 12

    conception at 24 months after first attending an infertilitymonths infertility at presentation, complete diagnostic clinic almost four-fold (Glazeneret al., 1987). It could provideinformation and exclusion of female factors, to clarify a generally applicable test of sperm function. However itsthe effect of duration of infertility on the prediction of value is the subject of intense controversy and a recent trialconception. In couples with less than 3 years infertility and that compared outcomes in patients randomized to undergoa positive PCT, 68% conceived within 2 years compared PCT or not appeared to demonstrate that inclusion of the testwith 17% of those with a negative result. After 3 years, increased the number of investigations the couples werecorresponding rates were 14% and 11%. The relative risks subjected to but had no effect on outcome. The authorsof conception [95% confidence interval (CI)] calculated concluded that the test was of no value and indeed could beusing the Coxs proportional hazards model were 0.23 actually harmful (Oei et al., 1998). This study was heavily(0.120.43) for a negative PCT (reference positive PCT) criticized in subsequent correspondence to the British Medicaland 0.25 (0.130.51) for more than 36 months infertility Journal: Hull and Evers (1999) pointed out that a diagnostic(reference 1223 months). Semen analysis had no extra test can only affect outcome if treatment is modified in the

    predictive power given the duration of infertility and the light of the result. In Oeis study treatments were applied non-PCT. The PCT is an effective predictor of conception where specifically and inconsistently. Since the PCT result did notdefined female causes of infertility are absent and duration alter the management of the patients it is hardly surprisingof infertility is less than 3 years. Once infertility is prolonged that it had no effect on outcome. Oei also failed to give a(beyond 3 years) the conception rate is low even with a clear definition of a positive PCT result. The biased selection

    positive test because a large proportion of couples of references to substantiate the poor prognostic power of the

    remaining childless so long have true unexplained in- PCT and the ineffectiveness of intrauterine insemination (IUI)

    fertility. Use of the PCT will enable clinicians to allocate was also criticized (Cohlen et al., 1999). Attention was also

    scarce, expensive and invasive resources effectively. drawn to the value of the test in revealing antisperm antibodies

    Key words:cumulative conception rates/duration of infertility/ (Hendry, 1999). Therefore despite its powerful statistical

    post-coital test/semen analysis/sperm function design, the Oei study does not answer the question of the

    efficacy of the PCT and this deserves further analysis.

    European Society of Human Reproduction and Embryology 1953

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    Post-coital test and duration of infertility

    Table I. Univariate relationship between chance of conception and independent risk factors calculated usingthe Cox proportional hazards model

    Significance Number Relative risk 95% CI(P value)

    Age (years)22 (reference) 135 1

    3034 0.9028 59 0.9699 0.591.5835 0.9778 13 0.9857 0.362.73

    Duration infertility (months)1223 (reference) 102 12435 0.9437 44 0.9818 0.591.6436 0.0002 61 0.2736 0.140.54

    Post-coital testPositive (reference) 145 1Negative 0.001 62 0.25 0.130.47

    Semen analysis (MNSC 106/ml)01.99 0.0431 38 0.4737 0.230.9823.99 0.2453 33 0.6727 0.341.3147.99 0.7096 49 0.9029 0.531.558 (reference) 87 1

    CI confidence interval; MNSC motile normal sperm concentration.

    Table II. Multivariate relationships between chance of conception and riskfactors calculated using Cox proportional hazards model. Motile normalsperm concentration was also offered to the model but was not selected as asignificant predictor

    Independent risk factors Relative risk 95% CI

    Negative PCT (reference positive PCT) 0.233 0.120.43

    Duration of infertility2435 months 1.1088 0.661.8536 months (reference 1223 months) 0.2548 0.130.51

    Figure 1. Cumulative conception rates by duration of infertility atPCT

    post-coital test. presentation and post-coital test (PCT) result; a positive resultrequired the presence of at least one motile spermatozoon in most

    selected as predictive of fertility. No significant interactions high powerfields. Error bars shown at staggered 8 month intervalsrepresent 95% confidence intervals. 3y less than 3 yearswere identified. The relative chance of conception in couplesinfertility; 3y more than or equal to 3 years infertility;with a negative PCT was about a quarter of that when thepos positive PCT; neg negative PCT.

    PCT was positive [RR 0.23, 95% confidence interval (CI)

    0.120.43] (Table II). Taking the PCT result into account,

    couples were four times less likely to conceive when duration PCT were low, irrespective of the MNSC below or aboveof infertility exceeded 3 years (RR 0.25, 95% CI 0.130.51). 4106/ml (10 versus 23% respectively,P 0.064, Figure 3).

    Graphic depiction of these results by life table analysis

    shows that only couples with a positive PCT and a durationDiscussionof infertility 3 years at presentation had a good chance of

    conception within the next 2 years (68%). Couples with a In a population of infertile couples, with otherwise normal

    results after complete investigations, the chance of conceptionnegative PCT, more than 3 years infertility or both had a poor

    chance of success (17, 14 or 11% respectively, Figure 1). The was predicted by their duration of infertility atfirst presentation

    and the result of the PCT, but not by semen parameters or theeffect of the PCT was highly statistically significant (Wilcoxon)

    in couples with less than 3 years infertility (P 0.0001) but womans age. Regression analysis using Coxs proportional

    hazards method suggested that duration of infertility and PCTnot in couples with more than 3 years (P 0.682). By

    contrast, the semen analysis results as encapsulated in the had independent effects: each decreased the probability of

    conception by about 80%. Thus, the likelihood of conceptionMNSC had relatively little effect on the chance of conception

    given the duration of infertility (Figure 2), and no statistically given a negative PCT would be even less in couples

    infertile for more than 3 years, but because of small numberssignificant effect given the PCT result (Figure 3). Although

    the effect of MNSC was statistically significant in couples in this category (n 19), the statistical power to examine this

    interaction was low. We suspect that in some couples in thiswith 3 years infertility (56 compared with 38%, P 0.023,

    Figure 2), the conception rates in couples with a negative group poor sperm function is the sole cause of their infertility

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    C.M.A.Glazener, W.C.L.Ford and M.G.R.Hull

    infertility. If defined causes of female fertility had not been

    excluded, the conception rate in the positive PCT group would

    be lower and the apparent power of the test decreased.

    In a recent randomized controlled trial of post-coital testing

    as part of routine infertility investigations, it was found that

    the chance of conception amongst those who did and did not

    have a PCT was similar (Oeiet al., 1998). However, this study

    also reported that the pregnancy rate was the same whetherthe women had a positive (38%) or negative (34%) result. The

    low rate in the positive PCT group could be because of failure

    to exclude women with confounding causes of infertility but

    the rate in the negative group remains surprisingly high,

    possibly reflecting the success of treatments such as IUI andFigure 2. Cumulative conception rates by duration of infertility atpresentation and motile normal sperm concentration (MNSC) in-vitro fertilization (IVF).(sperm concentration 106/ml% progressively motile% The current study describes the natural conception ratesmorphologically normal/10 000). Error bars shown at staggered 8 without treatment in otherwise unexplained infertility, andmonth intervals represent 95% confidence intervals. 3y less

    describes practice before the advent of IVF and intracyto-than 3 years infertility; 3y more than or equal to 3 yearsplasmic sperm injection (ICSI). It would be difficult to repeatinfertility; MNSC motile normal sperm concentration

    (106/ml). these studies today because of the ethical problem of delaying

    effective treatment to achieve sufficient follow-up time. In-

    vitro testing of interaction between spermatozoa and mucushas since been shown to be correlated with in-vitro fertilizing

    ability of spermatozoa for assisted conception (Hull et al.,

    1986; Aitken et al., 1992; Berberoglugil et al., 1993; Biljan

    et al., 1994), further underlining the functional ability of the

    mucus to differentiate between fertile and infertile sper-

    matozoa.

    We believe that the PCT is a good test of sperm function

    when sufficient care is taken to eliminate negative results due

    to poor mucus quality. Conventional seminology offers much

    poorer discrimination, the chance of conception only decreas-

    ing significantly where the concentration of motile normalFigure 3. Cumulative conception rates by PCT (a positive result spermatozoa is very low.required the presence of at least one motile spermatozoon in most

    Once the woman has been proven to be normal, the PCThigh power fields) and MNSC (sperm concentration 106/ml%provides a rational basis for patient management. In couplesprogressively motile% morphologically normal/10 000). Error

    bars shown at staggered 8 month intervals represent 95% with less than 3 years infertility, those with a negative PCTconfidence intervals. pos positive PCT; neg negative PCT; can proceed at once to effective treatment such as IUI, IVFMNSC motile normal sperm concentration (106/ml). or ICSI whereas those with a positive result can be advised to

    continue to try for a natural conception with good chance of

    success, thus avoiding these complex and expensive treatments.and their chance of conception will not be affected by the

    duration of infertility. However others may have covert causes Couples with more than 3 years infertility should be offered

    assisted reproduction without further delay.in addition, the two factors both acting to decrease the chance

    of conception as predicted by the proportional hazards model.

    The strength of the current study lies in its thoroughAcknowledgementsexclusion ofnoisefrom confounding female infertility factorsThanks are due to Linda Hunt and Craig Ramsay for statistical advice.and their treatment, a problem highlighted in other studies

    (Oei et al., 1995). A strict definition of the PCT was used,

    including a new requirement for a poor-positive PCT to beReferences

    confirmed in a second cycle, and subsequent reclassificationAitken, R.J., Bowie, H., Buckingham, D. et al. (1992) Sperm penetration into

    of these couples into the negative PCT categoryas suggested a hyaluronic acid polymer as a means of monitoring functional competence.J. Androl., 13 , 4454.by more recent work (Oei et al., 1995). By focusing on

    Berberoglugil, P., Englert, Y., Van den Bergh, M. et al. (1993) Abnormalcouples where the woman was normally fertile (tubal patency,sperm-mucus penetration test predicts low in vitro fertilization ability of

    ovulation, coitus and normal cervical mucus production), theapparently normal semen. Fertil. Steril., 59 , 12281232.

    effect of variations in less well-defined factors could be Biljan, M.M., Taylor, C.T., Manasse, P.R.et al.(1994) Evaluation of differentsperm function tests as screening methods for male fertilization potential explored. Although these measures reduced the numbers avail-the value of the sperm migration test. Fertil. Steril., 62, 591598.able for analysis we can be confident that the women were

    Bonde, J.P., Ernst, E., Jensen, T.K. et al. (1998) Relation between semennormal so far as current diagnostic procedures allowed us to quality and fertility: a population-based study of 430 first-pregnancy

    planners (see comments). Lancet, 352 , 11721177.judge. This enabled us to focus on male and on unexplained

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