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.Glazener
1,3
, W.C.L.Ford
2
and Introduction
Michael G.R.Hull
2,*
To manage infertile couples effectively, the clinician needs a
realistic and practical prediction of their chance of conception 1
Health Services Research Unit, University of Aberdeen, Aberdeen
without treatment. If this is poor, the couple should proceed
and
2
University of Bristol, Division of Obstetrics and Gynaecology,
Bristol, UK to denitive treatment immediately, otherwise they can be
advised to continue trying to achieve a natural conception. 3
To whom correspondence should be addressed at: Health Services
Thus, diagnostic investigations that rene the clinicians Research Unit, University of Aberdeen, Polwarth Building,
Foresterhill, Aberdeen AB25 2ZD, UK. predictive power will promote appropriate and efcient use of
E-mail: c.glazener@abdn.ac.uk
resources. Sperm dysfunction is the commonest dened cause
of infertility (Hull et al., 1985; Cates et al., 1985), but *After a short illness, Michael Hull, Professor of Reproductive
Medicine 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 Organization
aged 60 years. He went to Bristol from London in 1976 as
criteria (WHO, 1992), were related to the monthly chance of
Consultant Senior Lecturer in Obstetrics and Gynaecology with a
conception in a group of Danish trade unionists attempting to
developing reputation in clinical reproductive endocrinology from
become pregnant (Bonde et al., 1998) but in infertility practice
his 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 outcome
male 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 power
campaigned locally and nationally for public understanding and
but at present are recommended only for use in specialized
funding 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 of
originally studied between 1982 and 1983, with at least 12
conception at 24 months after rst attending an infertility
months infertility at presentation, complete diagnostic
clinic almost four-fold (Glazener et al., 1987). It could provide
information and exclusion of female factors, to clarify
a generally applicable test of sperm function. However its
the effect of duration of infertility on the prediction of
value is the subject of intense controversy and a recent trial
conception. In couples with less than 3 years infertility and
that compared outcomes in patients randomized to undergo
a positive PCT, 68% conceived within 2 years compared
PCT or not appeared to demonstrate that inclusion of the test
with 17% of those with a negative result. After 3 years,
increased the number of investigations the couples were
corresponding rates were 14% and 11%. The relative risks
subjected to but had no effect on outcome. The authors
of conception [95% condence interval (CI)] calculated
concluded that the test was of no value and indeed could be
using 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 Medical
and 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 modied 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
specically and inconsistently. Since the PCT result did not
dened female causes of infertility are absent and duration
alter the management of the patients it is hardly surprising
of 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 denition 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
efcacy of the PCT and this deserves further analysis.
European Society of Human Reproduction and Embryology 1953
C.M.A.Glazener, W.C.L.Ford and M.G.R.Hull
needle, after introducing the neck of the syringe up to its shoulder In judging the value of any test of sperm function a number
into the cervical canal. Suction was maintained as the syringe
of points must be borne in mind. First, infertility has a range
was withdrawn to avoid loss of content and to assess ductility
of discrete causes and any test of a single component (e.g.
(spinnbarkeit). The volume of mucus was noted before its transfer to
sperm function) can only effectively predict a successful
a glass microscope slide, where its clarity or turbidity was observed.
outcome once other causes have been eliminated. To take an
It was covered with a glass slip and examined at low (100) and
extreme example, even a couple with perfect sperm function
high (400) magnication. Fully developed mucus (at least 0.3 ml
cannot achieve a pregnancy if the womans tubes are blocked.
with stretch to 10 cm, and mostly clear to the naked eye) was required
Second, incidental factors like age (Schwartz and Mayaux,
to dene a negative result, which also required conrmation in a
1982) and duration of infertility (Hull et al., 1985; Eimers
second cycle.
et al., 1994) can be critical and must be controlled for. In accordance with evidence presented in a recent review (Oei
et al., 1995), a negative PCT result was more strictly dened in the Furthermore, in the case of the PCT, correlated functions such
current re-analysis as the absence of at least one progressively motile as sperm production, mucus secretion and coital competence
spermatozoon in most high power microscope elds (hpf) of the
must be accounted for.
mucus. The PCT was classied as follows: positive: at least one
A key element in the recent debate has been the effect of
forward-progressing spermatozoon per eld in most (at least ve)
duration of infertility on the predictive power of the PCT (Hull
hpf; negative: less than one forward-progressing spermatozoon in
and Evers, 1999; Oei et al., 1999). Our basic hypothesis is
most (at least ve) hpf.
that although these factors may be inter-related, duration of
Cox proportional hazards regression analysis was used to estimate
infertility is likely to affect prognosis only when a cause for
the relative predictive power for conception of duration of infertility,
infertility cannot be dened. Couples with a dened cause will
age, the PCT result and semen analysis parameters. Coxs regression
always be unlikely to conceive. Those without a dened cause
allows the effects of multiple factors to be compared in the same
will include fertile couples who have failed to conceive through model. It was designed to handle censored data. The coefcients
represent the change in the logarithm of the baseline survival function chance. As time progresses these will achieve pregnancy,
produced by a unit change in the parameter, in this case the extent leaving those with an unknown but real cause for their infertility
to which a change in the parameter alters the probability of pregnancy
who will not conceive even if the dened tests are normal.
in a given time. The relative risk (RR) was calculated as the natural
Consequently, any test of sperm function will be most effective
anti-logarithm of the coefcient. The method assumes that the effect
in changing the predicted chance of a couple conceiving when
of the parameters remains constant with time. Here this was conrmed
the duration of infertility is short.
by parallel log-minus-log plots (Norusis, 1993). Univariate relation-
In this study, we present the effect of duration of infertility
ships were investigated rst, after which all parameters were offered
by re-analysing data from a previous study that investigated
together with their interactions.
the power of the PCT and semen analysis to predict natural
Outcomes were graphically presented by time-specic cumulative
conception in otherwise normal couples, after complete
conception rates to rst pregnancy using life-table methods and
investigations and control for age (Glazener et al., 1987). This compared between groups using the Wilcoxon (Gehan) statistic.
paper addresses the question whether the PCT can rene the
ability of the clinician to predict the chance of conception
Results
in practice.
When the analysis was restricted to those couples for whom
complete data were available (duration of infertility, age,
Materials and methods
PCT result and MNSC), 207 couples were available for study.
We re-analysed previously published data on couples fully investigated
Their median duration of infertility prior to rst attendance
as described to conrm ovulatory cycles, normal pelvis (by laparos-
was 24 months (range 12144) and median age of the women
copy), normal uterus, normal cervical mucus secretion and normal
was 28 years (1842). Although 33% of the women were
coital performance and frequency (Glazener et al., 1987). In the
parous, this did not necessarily relate to their current partner,
present study, couples were included only if they had at least 1 year
and therefore was not taken into account.
of infertility at rst presentation and a complete set of data for
The womans age had no effect on the chance of conception
analysis. Duration of infertility before presentation and time to
(Table I) possibly because few older women were included
conception or loss to follow-up subsequently were based on the date
in the study group, and this parameter was omitted from of rst presentation at the clinic.
Based on standard semen microscopy, semen quality was classed subsequent analyses. Compared to couples with 12 years
by an overall estimate of motile, normally developed spermatozoa. infertility, the chance of conception was signicantly lower
This was derived as a composite score by multiplication of the
(P 0.0002) if the duration was over 3 years but not if
sperm concentration, the percentage motile and the percentage
duration was between 2 and 3 years (Table I). A negative PCT
morphologically normal, assessed according to WHO criteria (WHO,
was also signicantly associated with a reduced chance of
1980), giving the motile normal sperm concentration (MNSC).
conception (Table I). However, conventional semen parameters
Previous work showed that it had a better ability to predict natural
summarized in the MNSC had no signicant effect until the
conception than any other semen analysis parameter or combination
MNSCfell below210
6
/ml and then were only just statistically
thereof (Glazener et al., 1987). The cut-off value which best
signicant (Table I).
discriminated for fertility was 410
6
/ml.
When all the parameters were offered to regression
A pre-ovulatory phase PCT was done 618 h after coitus as
analysis using the Cox proportional hazards method, duration previously described (Hull et al., 1982). Mucus was extracted with a
standard narrow 1 ml, 10 cm long disposable plastic syringe, without of infertility and the PCT result were the only variables
1954
Post-coital test and duration of infertility
Table I. Univariate relationship between chance of conception and independent risk factors calculated using
the Cox proportional hazards model
Signicance Number Relative risk 95% CI
(P value)
Age (years)
22 (reference) 135 1
3034 0.9028 59 0.9699 0.591.58
35 0.9778 13 0.9857 0.362.73
Duration infertility (months)
1223 (reference) 102 1
2435 0.9437 44 0.9818 0.591.64
36 0.0002 61 0.2736 0.140.54
Post-coital test
Positive (reference) 145 1
Negative 0.001 62 0.25 0.130.47
Semen analysis (MNSC 10
6
/ml)
01.99 0.0431 38 0.4737 0.230.98
23.99 0.2453 33 0.6727 0.341.31
47.99 0.7096 49 0.9029 0.531.55
8 (reference) 87 1
CI condence interval; MNSC motile normal sperm concentration.
Table II. Multivariate relationships between chance of conception and risk
factors calculated using Cox proportional hazards model. Motile normal
sperm concentration was also offered to the model but was not selected as a
signicant predictor
Independent risk factors Relative risk 95% CI
Negative PCT (reference positive PCT) 0.233 0.120.43
Duration of infertility
2435 months 1.1088 0.661.85
36 months (reference 1223 months) 0.2548 0.130.51
Figure 1. Cumulative conception rates by duration of infertility at
PCT post-coital test.
presentation and post-coital test (PCT) result; a positive result
required the presence of at least one motile spermatozoon in most
selected as predictive of fertility. No signicant interactions high power elds. Error bars shown at staggered 8 month intervals
represent 95% condence intervals. 3y less than 3 years
were identied. The relative chance of conception in couples
infertility; 3y more than or equal to 3 years infertility;
with a negative PCT was about a quarter of that when the
pos positive PCT; neg negative PCT.
PCT was positive [RR 0.23, 95% condence 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 above
of infertility exceeded 3 years (RR 0.25, 95% CI 0.130.51).
410
6
/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 duration
Discussion
of 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 conception negative 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 at rst presentation
and the result of the PCT, but not by semen parameters or the effect of the PCT was highly statistically signicant (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 PCT not 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 conception MNSC 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 numbers signicant effect given the PCT result (Figure 3). Although
the effect of MNSC was statistically signicant in couples in this category (n 19), the statistical power to examine this
interaction was low. We suspect that in some couples in this with 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
1955
C.M.A.Glazener, W.C.L.Ford and M.G.R.Hull
infertility. If dened 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 (Oei et al., 1998). However, this study
also reported that the pregnancy rate was the same whether
the 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 reecting the success of treatments such as IUI and
Figure 2. Cumulative conception rates by duration of infertility at
presentation and motile normal sperm concentration (MNSC) in-vitro fertilization (IVF).
(sperm concentration 10
6
/ml% progressively motile%
The current study describes the natural conception rates
morphologically normal/10 000). Error bars shown at staggered 8
without treatment in otherwise unexplained infertility, and
month intervals represent 95% condence intervals. 3y less
describes practice before the advent of IVF and intracyto-
than 3 years infertility; 3y more than or equal to 3 years
plasmic sperm injection (ICSI). It would be difcult to repeat
infertility; MNSC motile normal sperm concentration
(10
6
/ml). these studies today because of the ethical problem of delaying
effective treatment to achieve sufcient follow-up time. In-
vitro testing of interaction between spermatozoa and mucus
has 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 sufcient 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 signicantly where the concentration of motile normal
Figure 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 PCT
high power elds) and MNSC (sperm concentration 10
6
/ml%
provides a rational basis for patient management. In couples
progressively 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 PCT
condence intervals. pos positive PCT; neg negative PCT;
can proceed at once to effective treatment such as IUI, IVF
MNSC motile normal sperm concentration (10
6
/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 thorough
Acknowledgements
exclusion of noise from confounding female infertility factors
Thanks 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 denition of the PCT was used,
including a new requirement for a poor-positive PCT to be
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