Long-term ongoing pregnancy rate and mode of conception after a positive and negative post-coital test

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1 A C TA Obstetricia et Gynecologica AOGS MAIN RESEARCH ARTICLE Long-term ongoing pregnancy rate and mode of conception after a positive and negative post-coital test MARLOES HESSEL 1,2, MONIQUE BRANDES 1,2, JAN PETER DE BRUIN 1, ROB S.G.M. BOTS 3, JAN A.M. KREMER 2, WILLIANNE L.D.M. NELEN 2 & CARL J.C.M. HAMILTON 1 1 Department of Obstetrics and Gynecology, Jeroen Bosch Hospital, s-hertogenbosch, 2 Department of Obstetrics and Gynecology, Radboud University Medical Center, Nijmegen, and 3 Department of Obstetrics and Gynecology, St. Elisabeth Hospital, Tilburg, the Netherlands Key words Infertility, post-coital test, spontaneous pregnancy, intrauterine insemination, IVF, ongoing pregnancy rate Correspondence Marloes Hessel, Radboud University Medical Center, Department of Obstetrics & Gynecology, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands. marloes.hessel@radboudumc.nl Conflict of interest The authors have stated explicitly that there are no conflicts of interest in connection with this article. Please cite this article as: Hessel M, Brandes M, de Bruin JP, Bots RSGM, Kremer JAM, Nelen WLDM, et al. Long-term ongoing pregnancy rate and mode of conception after a positive and negative post-coital test. Acta Obstet Gynecol Scand 2014; 93: Received: 20 November 2013 Accepted: 8 June 2014 DOI: /aogs Abstract Objective. Many fertility clinics have decided to abolish the post-coital test. Yet, it is a significant factor in prognostic models that predict the spontaneous pregnancy rate within one year. The aim of this study was to evaluate (1) the long-term outcome of infertile couples with a positive or a negative post-coital test during their fertility work-up and (2) the contribution of the different modes of conception. Design. Retrospective cohort study. Setting. Three fertility clinics in the Netherlands, of which two are secondary care training hospitals and is a one tertiary care academic training hospital. Population newly referred infertile couples, where a post-coital test was performed in 1624 couples. Methods. After basic fertility work-up, couples were treated according to the national treatment protocols. Main outcome measures. Spontaneous and overall ongoing pregnancy rate. Results. The spontaneous and overall ongoing pregnancy rates after three years were 37.7 and 77.5% after a positive post-coital test compared with 26.9 and 68.8% after a negative test (p < 0.001). Even in couples with severe male factor infertility (total motile sperm count <3) (p = 0.005) and mild male factor infertility (total motile sperm count 3 20) (p < 0.001), there was a significantly higher spontaneous ongoing pregnancy rate, justifying expectant management. Conclusion. After a follow-up of three years a positive post-coital test is still associated with a higher spontaneous and a higher overall ongoing pregnancy rate, even in couples with severe male factor infertility. Abbreviations: ART, assisted reproductive technology; CI, confidence interval; hpf, high power (microscope) field; ICSI, intracytoplasmic sperm injection; IUI, intrauterine insemination; IVF, in vitro fertilization; OPR, ongoing pregnancy rate; OR, odds ratio; PCT, post-coital test; TMSC, total motile sperm count. Introduction In an era where the emphasis is increasingly placed on efficient use of available financial resources, it is even more important to identify those infertile couples who have a favorable prognosis when it comes to their chances Key Message The post-coital test plays a significant role in prognostic models for prediction of spontaneous pregnancy in couples with, until then, unexplained infertility. In addition, the post-coital test is particularly useful in male factor infertility, where a positive test was associated with a higher spontaneous pregnancy rate. ª 2014 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica 93 (2014)

2 PCT in relation to pregnancy rate M. Hessel et al. of spontaneous pregnancy. These couples benefit from a certain period of expectant management before fertility treatment is started. Different prognostic models exist, some with and some without the post-coital test (PCT) (1). The usefulness of the PCT as a predictor for treatmentindependent pregnancy is still heavily debated in the literature. According to Oei et al. (2), the PCT has no correlation with the eventual conception rates, but it does increase the number of diagnostic tests and interventions. Other authors state that the PCT is expensive (over 50 million dollars per year in the USA only), can lead to sexual dysfunction and is emotionally straining (3 5). On the other hand, in larger studies the PCT was found to be a significant factor in prognostic models that predict spontaneous pregnancy within 1 year (6 9). Eimers et al. (6) even stated that the PCT is the best single predictor for future conception. Glazener et al. (10) found that the predictive value was highest in couples with infertility of less than three years. Besides its prognostic value, the PCT is also of diagnostic importance because it can discriminate between cervical and unexplained infertility (11). The cumulative ongoing pregnancy curves of couples with unexplained infertility differ from those of couples with cervical infertility, indicating that cervical infertility is a separate entity (12). Without the PCT, this diagnosis cannot be revealed. In 2004, van der Steeg et al. (13) published a model, based on semen analysis and obstetric history, which predicts the outcome of the PCT in 50% of infertile couples. However, this reflects only couples at both extremes, i.e. with a low or high chance of an abnormal PCT. Nonetheless, the PCT still could have clinical relevance in other cases. The role of the PCT has almost exclusively been investigated in relation to short-term pregnancy rates. Information on the long-term outcomes is lacking. Also, the need for treatments such as intrauterine insemination (IUI) and in vitro fertilization (IVF), and the contribution of these treatments to the overall pregnancy rate, have not been investigated. Therefore, the aim of this study was to evaluate the long-term outcome of infertile couples with a positive or negative PCT during their fertility work-up and the contribution of the different modes of conception. A sub-analysis was performed using the same exclusion criteria as applied for prognostic models. Finally, the results in the different groups of sperm quality were analyzed. Material and methods Between January 2002 and December 2006 a retrospective cohort study was performed in three fertility clinics in the Netherlands: Jeroen Bosch Hospital, s-hertogenbosch, St. Elisabeth Hospital, Tilburg (secondary care training hospitals) and Radboud University Medical Center (tertiary care academic training hospital). All couples (n = 2476) newly referred by their general practitioner because of infertility were included. Some data from this cohort, in particular about couples with unexplained infertility and male factor infertility, were published earlier (12,14). Infertility was defined as at least one year of unwanted non-conception. An exception was made for women with oligo-amenorrhea and women aged 37 years or more, who were referred earlier. Primary infertility was defined as a delay in conception for a couple where conception had never occurred, whereas in secondary infertility, couples had previously achieved a pregnancy, including miscarriage or ectopic pregnancy. The duration of infertility was defined as the period between the start of unwanted non-conception or the date of an earlier pregnancy loss, and the date of the first visit at our fertility clinic in months. We verified for each couple whether an ongoing pregnancy was attained, either spontaneously or after treatment. An ongoing pregnancy was defined as the presence of at least one intrauterine fetus with a positive heartbeat at 12 weeks gestation. The Dutch healthcare insurance system reimburses ovulation induction, intrauterine insemination (IUI) and three cycles of IVF/intracytoplasmic sperm injection (ICSI). For retrospective studies of this type, permission is not required by Dutch law, but with permission from the hospital s Medical Ethics Committee (approval August 2007) we contacted couples by phone if no pregnancy was documented, to collect follow-up data on any pregnancy or fertility treatments in other centers. These data were included in the analysis. In all couples the fertility work-up was performed according to the guidelines of the Dutch Society of Obstetrics and Gynecology (15). This work-up consists of a full history of both partners, evaluation of ovulation by vaginal ultrasound, an ultrasound timed PCT, midluteal serum progesterone, semen analysis, serum screening of CA-125 and Chlamydia antibody titer, and testing of tubal patency by hysterosalpingography or laparoscopy combined with dye test. After the fertility work-up, a single or combination diagnosis was determined. If fertility work-up was incomplete or if a couple withdrew after the first visit, couples were labeled as no diagnosis. Timing and standardization of PCT The PCT was performed in a standardized way (Table 1) and its timing was monitored by ultrasound. The first follicle measurement was performed two to four days prior to the expected ovulation. On the day of the PCT, 914 ª 2014 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica 93 (2014)

3 M. Hessel et al. PCT in relation to pregnancy rate Table 1. The protocol for ultrasound timing of the post-coital test (PCT). Situation Action Menstrual cycle duration Time of first ultrasound Cycle <25 days Cycle day 8 10 Cycle days Cycle day Cycle >30 days Cycle day Ultrasound result Ultrasound to be repeated Follicular diameter < 12 mm After 3 days Follicular diameter mm After 2 days Follicular diameter 15 mm After 2 days, plus PCT Follicular diameter 16 mm or more After 1 day, plus PCT PCT result Further management Positive Ultrasound within 1 3 days to confirm ovulation Negative, in the presence of Repeat PCT in 1 and 3 days a follicle of mm Negative, in the presence of Repeat PCT in 2 days a follicle >20 mm follicular diameter and endometrial thickness were recorded. In case of a negative PCT result, the test was repeated. Finally, a new ultrasound appointment was scheduled one to three days after the PCT to confirm follicle rupture. Patients were advised to have intercourse the evening before the test and its timing was checked before performing the PCT. After a non-moistened speculum was introduced, the cervix was cleaned of ectocervical mucus or discharge. A 1-mL plastic syringe was used to collect the mucus sample from the endocervical canal. After measuring the ph by dipstick, the mucus characteristics were scored. The cervical mucus was scored by evaluating amount, clarity, and spinnbarkeit (0 3 points per item). Mucus was considered poor if the total score was 3, moderate if the score was 4 or 5, and good if the score was 6 9. A mucus ph <6.8 was considered abnormal. In those cases, patients were advised to wash the vagina with sodium bicarbonate one hour prior to intercourse and to repeat the PCT. The mucus sample was then transferred to a microscope slide, covered by a glass slide, and examined by high power (9400) magnification. The number of spermatozoa per high power microscope field (hpf), and movement characteristics were recorded, after examining at least five hpfs. The PCT was considered positive if one or more progressive forward-moving spermatozoa per hpf were seen. The test was considered negative if no spermatozoa were seen at all, if only non-progressive spermatozoa were seen (e.g. death, shaking or circulating) or if less than one progressive forward-moving spermatozoon was present per hpf. Only the best PCT result or the most correctly timed result was used (closest to ovulation based on follicular diameter and date of ovulation). Outcome measures Infertile couples were treated according to the guidelines of the Dutch Society of Obstetrics and Gynecology (15). The main outcome measure was the ongoing pregnancy rate (OPR) after a follow-up period of three years. The overall OPR as well as the spontaneous OPR and OPR after fertility treatment were calculated. OPRs were measured for couples with a positive and negative PCT, separately (n = 1624). Secondary outcome measures were the need for IUI or assisted reproductive technology (ART) such as IVF/ICSI, related to the result of the PCT. To allow comparison with the studies that constructed prognostic models to predict spontaneous pregnancy in infertile couples (8,9), a subgroup analysis was performed after exclusion of the same diagnoses as were excluded for the prognostic models, i.e. tubal or uterine pathology, moderate to severe endometriosis (16), anovulation, inability to have intercourse, azoospermia or severe male factor infertility defined as a total motile sperm count (TMSC, the product of volume, concentration and motility) <3 (subgroup 1; n = 854). We also related the occurrence of spontaneous pregnancy to the result of the PCT for the different diagnostic groups (data not shown). Because of the significantly higher spontaneous OPR in couples with male factor infertility after a positive PCT, a separate analysis was done to evaluate the ongoing pregnancy rates per TMSC class. Therefore an additional subgroup analysis was performed in couples that met the above Hunault criteria (8,9), but with inclusion of all couples with male infertility, even the most severe male infertility (TMSC <1 and TMSC 1 3). Couples with azoospermia (n = 12) and couples in whom the result of the semen analysis was not available (n = 56) were excluded, resulting in a total of 871 couples in this additional subgroup (subgroup 2). Normally, in couples with severe male factor infertility a PCT is not performed anymore. However, when the result of the semen analysis was not available at the time of the PCT, the test was performed. Statistical analysis To describe clinical features we used median and range or number and percentage for most parameters. To compare groups for statistical differences we used the Mann Whitney U-test for continuous variables and Fisher s exact or chi-squared test for proportions or dichotomous variables. Logistic regression analysis was used to determine whether the ongoing spontaneous pregnancy rate was associated with the result of the PCT in male factor infertility. Cumulative ongoing pregnancy curves were constructed using the real data. As the follow-up of all ª 2014 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica 93 (2014)

4 PCT in relation to pregnancy rate M. Hessel et al. couples was known, the curves were not just approximations calculated with Kaplan Meier. The prognostic value of the PCT is expressed as sensitivity, specificity, positive and negative predictive value. In all analyses, a p-value of 0.05 was used to indicate statistical significance. Calculations were performed with SPSS version 20.0 (IBM Corp., Armonk, NY, USA) and EXCEL Microsoft Office 2007 (Microsoft Corp., Redmond, WA, USA). Results In 550 of 1624 couples (33.9%) in whom a PCT was performed, spontaneous ongoing pregnancy within the follow-up period of three years was reported. The spontaneous OPR after 3, 6 and 12 months were 15.9, 21.1 and 25.9%, respectively. In 852 (34.4%) couples a PCT was not performed. Upon analysis of this group we found several reasons for not performing the PCT. The major reasons were severe male infertility (TMSC <3) (n = 236) or spontaneous conception soon after the first visit (n = 178). Minor reasons were clear underlying pathology (n = 87) such as tubal or uterine factor infertility and endometriosis, which was recognized early in the work-up, or the inability to have sexual intercourse, so that the PCT had no additional value. Furthermore, some couples withdrew from the fertility work-up before the PCT was done (n = 51). The composition of the cohort and the reasons for not performing a PCT are shown in Figure 1. The characteristics of the couples in whom a PCT was performed are shown in Table 2, related to the result of the PCT. Couples with a negative PCT were more frequently diagnosed with primary infertility and had significantly lower TMSCs compared with couples with a positive PCT (p < 0.001). The overall ongoing pregnancy rate after three years was 77.5% after a positive PCT, compared with 68.8% after a negative PCT (p < 0.001) (Figure 2). Couples with a positive PCT more often conceived spontaneously or after ovulation induction. In contrast, more pregnancies occurred after IUI and ART if the PCT was negative, despite the fact that IUI and ART were more frequently performed in couples with a negative PCT. Table 2 shows the modes of conception and corresponding pregnancy rates for subgroup 1. After a positive PCT, 50.4% of the couples conceived spontaneously, compared with 31.6% after a negative PCT (p < 0.001). When fertility treatment was included this difference was reduced, with an overall OPR of 77.6% after a positive PCT compared with 73.2% after a negative PCT (non significant, NS).There was a significant difference between the two groups in the need for IUI (p < 0.001) and ART (p < 0.001). The OPR per couple after IUI was 28% in No PCT n = 852 Pregnant n = 178 TMSC <3 n = 236 Withdrawn n = 51 Pathology n = 87 Unknown n = 300 Excluded by diagnosis n = 770 Cycle n = 375 Endometriosis n = 60 TMSC <3 n = 85 Sexual disorder n = 4 Tubal pathology n = 86 Uterine n = 13 Other n = 106 Withdrawn n = 41 Positive PCT n = 1044 (64%) Positive PCT n = 544 (64%) Total cohort n = 2476 PCT performed n = 1624 Subgroup n = 854 Negative PCT n = 580 (36%) Negative PCT n = 310 (36%) Figure 1. Composition of the cohort (n = 2476). PCT, post-coital test; TMSC, total motile sperm count. couples with a positive PCT and 39.5% in couples with a negative PCT (p = 0.02). The OPR after ART was 56.5 and 61.9%, respectively (NS). The corresponding cumulative ongoing pregnancy curves are shown in Figure 3. Figure 4 shows the spontaneous OPR per TMSC class for subgroup 2. A significant difference in spontaneous ongoing pregnancy rates was found between positive and negative PCT groups for couples with severe male factor infertility defined as a TMSC <3 [odds ratio (OR) 5.1, 95% confidence interval (CI) ; p = 0.005], mild male factor infertility defined as a TMSC between 3 and 20 (OR 2.8, 95% CI ; p < 0.001) and no male factor infertility defined as a TMSC >20 (OR 1.6, 95% CI ; p = 0.015) in favor of a positive PCT. The prognostic value of the PCT for couples with severe, mild or no male factor infertility deteriorated when semen quality improved. For couples with a TMSC <3 we observed a sensitivity of 45.8% (95% CI %), a specificity of 85.7% (95% CI %), a positive predictive value of 61.1% (95% CI %) 916 ª 2014 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica 93 (2014)

5 M. Hessel et al. PCT in relation to pregnancy rate Table 2. Clinical features of the included couples, related to the result of the post-coital test (PCT) and occurrence of pregnancy with a followup period of three years (n = 2476). Subgroup analysis was performed for couples with unexplained, cervical factor and/or mild male factor infertility, therefore excluding couples with tubal or uterine pathology, endometriosis, ovulation disorders and severe male factor infertility (azoospermia and total motile sperm count (TMSC) <3 (subgroup 1; n = 854). PCT positive PCT negative p-value Total cohort (n = 2476) 1044 (64.3%) 580 (35.7%) Median age in years, range 31 (19 45) 31 (18 43) NS Median infertility duration in months, range 15 (0 168) 15 (0 115) NS Primary infertility 719 (68.9%) 483 (83.3%) <0.001 Semen analysis not available 103 (9.9%) 24 (4.1%) <0.001 Median TMSC + range 51 (0 999) (0 999) <0.001 Couples with TMSC < (19.8%) 269 (46.4%) <0.001 Treated with IUI 348 (33.3%) 263 (45.3%) <0.001 Treated with ART 230 (22.0%) 222 (38.3%) <0.001 Overall pregnancy rate 809 (77.5%) 399 (68.8%) <0.001 Spontaneous pregnancy rate 394 (37.7%) 156 (26.9%) <0.001 Pregnancy after OI 181 (17.3%) 30 (5.2%) <0.001 Pregnancy after IUI 101 (29.0%) 92 (35.0%) NS Pregnancy after ART 133 (57.8%) 121 (54.5%) NS Subgroup 1 (n = 1095) 544 (63.7%) 310 (36.3%) Treated with IUI 211 (38.8%) 162 (52.3%) <0.001 Treated with ART 115 (21.1%) 97 (31.3%) <0.001 Overall pregnancy rate 422 (77.6%) 227 (73.2%) NS Spontaneous pregnancy rate 274 (50.4%) 98 (31.6%) <0.001 Pregnancy after OI 24 (4.4%) 5 (1.6%) 0.03 Pregnancy after IUI 59 (28.0%) 64 (39.5%) 0.02 Pregnancy after ART 65 (56.5%) 60 (61.9%) NS ART, assisted reproductive technology; IUI, intrauterine insemination; OI, ovulation induction. 100% 90% 80% % % 50% 40% 30% No pregnancy * ART* IUI* OI * Spontaneous * 20% 10% % Negative PCT n = 580 Positive PCT n = 1044 Figure 2. Overall pregnancy rate and mode of conception related to the result of the post-coital test (PCT) (n = 1624). *p < (Pearson s chi-squared test) between positive and negative PCT groups. ART, assisted reproductive technology; IUI, intrauterine insemination; OI, ovulation induction. and a negative predictive value of 76.4% (95% CI %). For couples with a TMSC between 3 and 20 we observed a sensitivity of 64.0% (95% CI %), a specificity of 61.2% (95% CI %), a positive predictive value of 46.2% (95% CI %) and a negative predictive value of 76.5% (95% CI %). ª 2014 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica 93 (2014)

6 PCT in relation to pregnancy rate M. Hessel et al Overall OPR; PCT pos Overall OPR; PCT neg Spontaneous OPR; PCT pos Spontaneous OPR; PCT neg Figure 3. Overall and spontaneous cumulative ongoing pregnancy rates (OPR) for subgroup 1 (n = 854) in relation to post-coital test (PCT) result. The y-axis represents percentages and the x-axis months. The subgroup consists of couples with cervical factor infertility, mild male factor infertility and/or unexplained infertility. Overall OPR: ongoing pregnancy after spontaneous conception, ovulation induction, intrauterine insemination and/or assisted reproductive technology. Spontaneous OPR: ongoing pregnancy after spontaneous conception only. Spontaneous OPR 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% For couples with a TMSC >20 we observed a sensitivity of 49.7% (95% CI %), a specificity of 61.4% (95% CI %), a positive predictive value of 68.7% (95% CI %) and a negative predictive value of 35.7% (95% CI %). Discussion Positive PCT Negative PCT <3* 3 20** >20*** TMSC Figure 4. Spontaneous ongoing pregnancy rates after a follow-up of three years per total motile sperm count class in relation to post-coital test result (subgroup 2; n = 871). *OR 5.1, 95% CI ; p = **OR 2.8, 95% CI ; p < 0.001; ***OR 1.6, 95% CI ; p = Our study shows that the result of the PCT is correlated with the final chance of pregnancy. This difference is still visible after three years, and both the overall and the spontaneous OPR are significantly higher if the PCT is positive. Yet, in couples with a negative PCT, a higher percentage of pregnancies resulted from IUI and ART. Our findings are in accordance with Glazener et al. (10) and many other studies that showed a significant difference in pregnancy rate after a positive PCT compared with a negative test. They demonstrated that the PCT is particularly useful if the duration of infertility is less than three years, i.e. in newly referred couples. The relevance of the PCT was further substantiated by the PCT being an independent predictor in a number of prognostic models (6 9). If we focus on the same subgroup for which the prognostic models are constructed, the difference in spontaneous OPR is even more evident. The PCT helps to identify the group of patients that can be offered expectant management. A negative PCT justifies treatment without delay. The percentage of positive PCTs in the present study (64%) was consistent with percentages reported by others (60 68%) (9,13,17). We confirmed the finding of van der Steeg et al. (13) that couples with a negative PCT are diagnosed more frequently with primary infertility and have significantly lower TMSCs. Those authors found that semen analysis and obstetric history could predict the outcome of the PCT in 50% of infertile couples. Our study, however, shows that even in the case of severe male factor infertility there was a good chance of spontaneous conception if the result of the PCT is positive. Obviously the proportion of PCTs that yielded a positive result increase with a rising TMSC. 918 ª 2014 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica 93 (2014)

7 M. Hessel et al. PCT in relation to pregnancy rate Implementation of our results could be cost-effective, as fewer fertility treatments are necessary for couples with a positive PCT. This must be balanced against the direct and indirect or non-medical costs of performing a PCT. To confirm our results, a randomized controlled trial (RCT) is recommended in which, for 6 12 months, expectant management is compared with treatment in the case of a positive PCT in (severe) male factor infertility. At present, couples with severe male factor infertility are almost exclusively offered ICSI. Spontaneous conception while on the waiting list for ICSI is not uncommon, with a reported cumulative pregnancy rate of 6.6% after 12 months, without a plateau (18). This supports our finding that couples with male factor infertility and a positive PCT result have a better prognosis regarding (spontaneous) pregnancy. The role of the PCT as part of the infertility work-up is heavily debated. Although correct timing of the PCT is crucial for its prognostic value (19), the Dutch national guideline lacks a specified protocol. Importantly, an optimally timed positive PCT resulting in expectant management might be detrimental to couples with a very short window of fertility ( 1 day), as their 12-month spontaneous cumulative pregnancy rate was only 3.6% (20). Details about the method of timing, however, are rarely provided. In 1998, Oei et al. published the results of a trial that randomized couples to an infertility investigation with and without the PCT. The authors concluded that the PCT leads to more tests and treatments, without resulting in a higher pregnancy rate (2). Although for many clinicians this study provided the final proof that the PCT needs to be abolished, it has a number of serious drawbacks. Being an RCT, it is not surprising that the pregnancy rate in both groups was comparable, as the composition of both groups is likely to be the same. Moreover, Hull and Evers (21) suggested that Oei et al. applied inappropriate trial methods to a diagnostic procedure. They state that a diagnostic procedure can only influence outcomes by influencing the choice of treatment. This was not taken into account. The article of Oei et al. is the only one of its kind regarding the PCT but in our view it does not provide evidence necessary to abandon the test completely. Recently, the additional value of the PCT was investigated in a multicenter study. Prediction of pregnancy before and after including the PCT in the model was tested (17). Although a significant difference was found, the authors concluded that the additional value was so limited that a model without the PCT was sufficient. A strong point of our study was that we longitudinally collected data of an unselected cohort of infertile couples who were referred for the first time by their general practitioner to a gynecologist. The study cohort is representative for the Dutch situation and is representative for other countries as long as only newly referred couples are concerned. The data are not applicable to populations in tertiary care facilities. A weak point was that we mainly evaluated the data in a univariate way. However, besides the percentage of couples with primary infertility, there were no differences in the main predictors for pregnancy described by Hunault (8,9). In a future study we will try to validate the prediction model of Hunault with our data, including the result of the PCT. Although our study is an observational study and not an RCT, we believe that this study design corresponds well with the aim of our research. Understandably, the result of the PCT affects the choice of treatment, which therefore might bias the results. We followed the national fertility guideline to decide on the type of treatment. Couples with a positive PCT needed less IUI and ART. Yet, the pregnancy rate per couple was not significantly different, which substantiates that the guideline is correctly edited and ensures cost-effective care. The PCT is crucial for the diagnosis of cervical infertility. If PCT are no longer performed, couples belonging to this category will be restricted from using a proven therapy (11). Conversely, they will, eventually, be exposed to treatment with controlled ovarian stimulation (with IUI) when a period of expectant management turns out to be unsuccessful. In conclusion, we showed that the PCT is a valuable test in daily practice, as a negative outcome is associated with a lower OPR and a higher need of IUI and ART. Moreover, the PCT proved to be particularly useful in couples with male factor infertility, where a positive PCT results in a high spontaneous OPR. Therefore, a positive PCT could, in selected patients, reasonably support a recommendation for expectant management, irrespective of semen quality. Funding No financial or material support was obtained for this research. References 1. Leushuis E, van der Steeg JW, Steures P, Bossuyt PMM, Eijkemans MJC, van der Veen F, et al. Prediction models in reproductive medicine: a critical appraisal. Hum Reprod Update. 2009;15: Oei SG, Helmerhorst FM, Bloemenkamp KWM, Hollants FAM, Meerpoel DEM, Keirse MJNC. Effectiveness of the postcoital test: randomised controlled trial. BMJ. 1998;317: Griffith CS, Grimes DA. The validity of the postcoital test. Am J Obstet Gynecol. 1990;162: ª 2014 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica 93 (2014)

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