Steures, P.

Chlamydia trachomatis IgG seropositivity is associated with lower natural conception rates in ovulatory subfertile women without visible tubal pathology (Article)

2011-11-01T00:00:00Z

Background The relation between Chlamydia trachomatis infection and subsequent tubal damage is widely recognized. As such, C. trachomatis antibody (CAT) testing can be used to triage women for immediate tubal testing with hysterosalpingography (HSG) or laparoscopy. However, once invasive tubal testing has ruled out tubal pathology, CAT serology status is ignored, as its clinical significance is currently unknown. This study aimed to determine whether positive CAT serology is associated with lower spontaneous pregnancy rates in women in whom HSG and/or diagnostic laparoscopy showed no visible tubal pathology. Methods We studied ovulatory women in whom HSG or laparoscopy showed patent tubes. Women were tested for C. trachomatis immunoglobulin G (IgG) antibodies with either micro-immunofluorescence (MIF) or an ELISA. CAT serology was positive if the MIF titre was <1:32 or if the ELISA index was >1.1. The proportion of couples pregnant without treatment was estimated at 12 months of follow-up. Time to pregnancy was considered censored at the date of the last contact when the woman was not pregnant or at the start of treatment. The association between CAT positivity and an ongoing pregnancy was evaluated with Cox regression analyses. Results Of the 1882 included women without visible tubal pathology, 338 (18) had a treatment-independent pregnancy within 1 year [estimated cumulative pregnancy rate 31; 95 confidence interval (CI): 2735]. Because of differential censoring after 9 months of follow-up, regression analyses were limited to the first 9 months after tubal testing. Positive C. trachomatis IgG serology was associated with a statistically significant 33 lower probability of an ongoing pregnancy [adjusted fecundity rate ratio 0.66 (95 CI 0.490.89)]. Conclusions Even after HSG or laparoscopy has shown no visible tubal pathology, subfertile women with a positive CAT have lower pregnancy chances than CAT negative women. After external validation, this finding could be incorporated into existing prognostic models.

Role of semen analysis in subfertile couples (Article)

2011-03-01T00:00:00Z

Objective: To evaluate the associations between the results of the male partner's semen analysis (classified according to the World Health Organization [WHO] criteria) and fathering a child without any treatment. Design: Prospective multicenter cohort study. Setting: Twenty subfertility centers in The Netherlands. Patient(s): A total of 3,345 consecutive couples presenting for subfertility. Intervention(s): None. Main Outcome Measure(s): Associations between the results of the male partner's semen analysis, classified according to the WHO criteria, and fathering a child without any treatment within a time horizon of 1 year. Subsequently, we redefined semen quality criteria and reevaluated the associations. Result(s): Follow-up data of 3,129 couples (94%) were available, of which 517 (17%) had a healthy pregnancy without treatment. The 1-year pregnancy rate in men with WHO normozoospermia did not differ significantly from that in men with WHO impaired semen (24% vs. 23%). In contrast, we observed lower chances of fathering a child for sperm concentrations <40 Ã 106/mL, total sperm count <200 Ã 106, and sperm morphology <20% normal forms. With a multivariable regression model based on the redefined male semen subfertility criteria we were able to make a finer differentiation between subfertile men, with probabilities of fathering a child ranging from 7% to 41%. Conclusion(s): The current WHO criteria for semen quality do not discriminate between fertile and subfertile men. Our redefined and graded semen criteria have strong predictive value. If interpreted correctly, the fast and inexpensive semen analysis remains the gold standard for defining a man's role in subfertility.

Role of semen analysis in subfertile couples (Article)

2011-03-01T00:00:00Z

Time to pregnancy after a previous miscarriage in subfertile couples (Article)

2010-07-01T00:00:00Z

Objective: To assess the time to spontaneous ongoing pregnancy after a previous miscarriage in subfertile couples. Design: A prospective cohort study. Setting: The study was conducted in 38 fertility centers in the Netherlands. Patient(s): Subfertile couples who miscarried after completing their basic fertility work-up. Intervention(s): Expectant management after a miscarriage. Main Outcome Measure(s): Spontaneous ongoing pregnancy. Result(s): We included 5,663 subfertile couples, of which 1,098 (19%) conceived spontaneously. Among these 1,098 couples, 199 (18%) miscarried and these couples were included in the present study. Follow-up was completed for 171 couples, of which 95 conceived again within 24 months of follow-up. Of these 95 pregnancies, 86 (91%) were ongoing. The cumulative spontaneous ongoing pregnancy rate (PR) after 24 months was 70% (95% confidence interval [CI] 59%-81%). Conclusion(s): Subfertile couples, who experience a treatment-independent pregnancy resulting in a miscarriage, have very good prospects of a spontaneous ongoing pregnancy in the near future. This information is useful in counseling couples who had a miscarriage after a previous period of subfertility.

Prediction models in reproductive medicine: A critical appraisal (Article)

2009-08-27T00:00:00Z

Background: Prediction models have been developed in reproductive medicine to help assess the chances of a treatment-(in)dependent pregnancy. Careful evaluation is needed before these models can be implemented in clinical practice. Methods: We systematically searched the literature for papers reporting prediction models in reproductive medicine for three strategies: expectant management, intrauterine insemination (IUI) or in vitro fertilization (IVF). We evaluated which phases of development these models had passed, distinguishing between (i) model derivation, (ii) internal and/or external validation, and (iii) impact analysis. We summarized their performance at external validation in terms of discrimination and calibration. Results: We identified 36 papers reporting on 29 prediction models. There were 9 models for the prediction of treatment-independent pregnancy, 3 for the prediction of pregnancy after IUI and 17 for the prediction of pregnancy after IVF. All of the models had completed the phase of model derivation. For six models, the validity of the model was assessed only in the population in which it was developed (internal validation). For eight models, the validity was assessed in populations other than the one in which the model was developed (external validation), and only three of these showed good performance. One model had reached the phase of impact analysis. Conclusions: Currently, there are three models with good predictive performance. These models can be used reliably as a guide for making decisions about fertility treatment, in patients similar to the development population. The effects of using these models in patient care have to be further investigated.

Predictive value of pregnancy history in subfertile couples: results from a nationwide cohort study in the Netherlands (Article)

2008-09-01T00:00:00Z

Objective: To assess whether pregnancy history can predict the occurrence of a spontaneous ongoing pregnancy in subfertile couples. Design: Prospective cohort study. Setting: Thirty fertility centers in the Netherlands. Patient(s): Subfertile, ovulatory women with at least one patent tube and male partners without severely impaired semen quality. Intervention(s): Fertility work-up, including a detailed pregnancy history. Main Outcome Measure(s): Spontaneous ongoing pregnancy. Result(s): We included 4445 couples, of whom 793 (18%) had a spontaneous ongoing pregnancy within 1 year of follow-up. Previous live birth and miscarriage in current partnership were both associated with higher fecundity as compared with primary infertility (hazard rate ratios for spontaneous pregnancy [HR] 1.4; 95% CI, 1.2-1.7 and 1.3; 95% CI, 1.0-1.5, respectively). Pregnancies in a woman's previous partnerships did not affect the fecundity of the couple. A pregnancy in a previous partnership of the male partner was associated with lower fecundity (HR 0.76; 95% CI, 0.58-0.99). A previous pregnancy after fertility treatment also was associated with lower fecundity (HR 0.52; 95% CI, 0.30-0.90). Conclusion(s): Accurate prediction of the future fertility of a couple requires an exact assessment of the fertility history of both partners.

Obesity affects spontaneous pregnancy chances in subfertile, ovulatory women (Article)

2008-02-01T00:00:00Z

BACKGROUND: Obesity is increasing rapidly among women all over the world. Obesity is a known risk factor for subfertility due to anovulation, but it is unknown whether obesity also affects spontaneous pregnancy chances in subfertile, ovulatory women. METHODS: We evaluated whether obesity affected the chance of a spontaneous pregnancy in a prospectively assembled cohort of 3029 consecutive subfertile couples. Women had to be ovulatory and had to have at least one patent tube, whereas men had to have a normal semen analysis. Time to spontaneous ongoing pregnancy within 12 months was the primary endpoint. RESULTS: The probability of a spontaneous pregnancy declined linearly with a body mass index (BMI) over 29 kg/m2. Corrected for possible related factors, women with a high BMI had a 4% lower pregnancy rate per kg/m2increase [hazard ratio: 0.96 (95% CI 0.91-0.99)]. CONCLUSIONS: These results indicate that obesity is associated with lower pregnancy rates in subfertile ovulatory women.

Immunoglobulin G antisperm antibodies and prediction of spontaneous pregnancy (Article)

2008-01-01T00:00:00Z

Objective: To investigate the predictive capacity of immunoglobulin G ASA (direct MAR test) for spontaneous ongoing pregnancy in subfertile couples. Design: Prospective cohort study. Setting: Nine fertility centers in The Netherlands. Patient(s): Consecutive ovulatory subfertile couples. Intervention(s): A basic fertility workup, including a mixed agglutination reaction test for IgG (MAR test) at first semen analysis. Main Outcome Measure(s): Spontaneous conception resulting in ongoing pregnancy. Result(s): We included 1,794 couples, of which 283 (16%) had a spontaneous ongoing pregnancy within 1 year. When a threshold 50% was used for an abnormal test result, the MAR test was positive in 3% of the couples. In the univariable analysis, a positive MAR test ≥50% reduced, albeit not statistically significant, the probability of spontaneous pregnancy (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.34 to 1.7). In the multivariable analysis, a positive MAR test ≥50% had no contribution in the prediction of spontaneous pregnancy (HR 0.99, 95% CI 0.40 to 2.4). Conclusion(s): This large cohort study shows that the MAR test is not able to predict spontaneous pregnancy chances. Its routine use in the basic fertility workup for identification of couples with low spontaneous pregnancy chances is not justified.

Effectiveness of intrauterine insemination in subfertile couples with an isolated cervical factor: a randomized clinical trial (Article)

2007-12-01T00:00:00Z

After randomization of subfertile couples with an isolated cervical factor to intrauterine insemination for 6 months or expectant management for 6 months, 26 women (51%) vs. 16 women (33%) conceived, respectively. Of these pregnancies, 22 (43%) vs. 13 (27%) were ongoing (relative risk, 1.6; 95% confidence interval, 0.91 to 2.8). There was one multiple pregnancy in the group that was allocated to intrauterine insemination. This trial suggests a beneficial effect of IUI in couples with an isolated cervical factor.

The additional value of ovarian hyperstimulation in intrauterine insemination for couples with an abnormal postcoital test and a poor prognosis: a randomized clinical trial (Article)

2007-12-01T00:00:00Z

Objective: To assess the effectiveness of controlled ovarian hyperstimulation (COH) in intrauterine insemination (IUI) for subfertile couples with an abnormal postcoital test and a poor prognosis. Design: Randomized clinical trial. Setting: Twenty-four fertility centers in the Netherlands. Patient(s): Subfertile couples with a well-timed nonprogressive PCT and additional factors that reduce fertility. Intervention(s): Couples were randomly allocated to three cycles of IUI with COH or three cycles of IUI without COH. Main Outcome Measure(s): Ongoing pregnancy within three IUI cycles. Result(s): We randomly allocated 132 couples to IUI with COH, and 133, to IUI without COH. We observed 33 pregnancies (25%) in the couples allocated to IUI with COH, of which 28 were ongoing (21%), vs. 28 pregnancies (21%) in the couples allocated to IUI without COH, of which 23 were ongoing (17%; relative risk of an ongoing pregnancy, 1.2; 95% confidence interval, 0.75 to 2.0). Two multiple pregnancies occurred in the IUI with COH group, and one, in the IUI without COH group. Conclusion(s): In couples with an abnormal PCT and a poor prognosis, IUI with COH leads to pregnancy rates comparable to those for IUI without COH. We propose to perform IUI without COH in couples with an abnormal PCT.

Identifying subfertile ovulatory women for timely tubal patency testing: A clinical decision rule based on medical history (Article)

2007-10-01T00:00:00Z

Background: The aim of tubal testing is to identify women with bilateral tubal pathology in a timely manner, so they can be treated with IVF or tubal surgery. At present, it is unclear for which women early tubal testing is indicated, and in whom it can be deferred. Methods: Data on 3716 women who underwent tubal patency testing as a part of their routine fertility workup were used to relate elements in their medical history to the presence of tubal pathology. With multivariable logistic regression, we constructed two diagnostic models. One in which tubal disease was defined as occlusion and/or severe adhesions of at least one tube, whereas in a second model, tubal disease was defined as the presence of bilateral abnormalities. Results: Both models discriminated moderately well between women with and women without tubal disease with an area under the receiver-operating characteristic curve (AUC) of 0.65 (95% CI: 0.63-0.68) for any tubal pathology and 0.68 (95% CI: 0.65-0.71) for bilateral tubal pathology, respectively. However, the models could make an almost perfect distinction between women with a high and a low probability of tubal pathology. A decision rule in the form of a simple diagnostic score chart was developed for application of the models in clinical practice. Conclusions: In conclusion, the present study provides two easy to use decision rules that can accurately express a woman's probability of (severe) tubal pathology at the couple's first consultation. They could be used to select women for tubal testing more efficiently.

Reply: Pregnancy is predictable: A large-scale prospective external validation of the prediction of spontaneous pregnancy in subfertile couples [2] (Article)

2007-08-01T00:00:00Z

Predictive value and clinical impact of basal follicle-stimulating hormone in subfertile, ovulatory women (Article)

2007-06-01T00:00:00Z

Context: Basal FSH is a marker for ovarian reserve. Objectives: The objective of the study was to investigate the predictive value of basal FSH on spontaneous ongoing pregnancy in subfertile ovulatory women. Design: This was a prospective cohort study. Setting: The study was conducted in 19 fertility centers in The Netherlands. Participants: Subfertile ovulatory women without two-sided tubal pathology and in whom the man had normal sperm parameters (total motile count ≥ 3 × 106) participated in the study. Interventions: Interventions included a fertility work-up, including a basal FSH measurement on cycle d 3. Main Outcome Measures: Spontaneous ongoing pregnancy was measured. Results: We included 3519 consecutive couples of which 562 (16%) had a spontaneous ongoing pregnancy within 1 yr. Basal FSH levels of 8 IU/liter or higher were associated with a decreased probability of spontaneous ongoing pregnancy [hazard ratio (HR) 0.93/IU·liter (95% confidence interval [CI] 0.87-0.98)]. In a multivariable analysis, female age (HR 0.97/yr, 95% CI 0.95-0.99), cycle length (HR 0.96/d, 95% CI 0.93-1.0), and FSH levels 8 IU/liter or greater (HR 0.93/IU·liter, 95% CI 0.87-0.99) were strong negative predictors for spontaneous ongoing pregnancy. Addition of FSH to a prediction model based on female age, duration of subfertility, previous pregnancy, referral status, and semen analysis changed the probability to conceive spontaneously from 30% or greater to less than 30% in 97 of 3219 couples (3.0%). Conclusions: In ovulatory women, a basal FSH level of 8 IU/liter or higher is associated with decreasing fecundity, independent of female age and cycle length. Because the number of couples in whom the FSH level alters management decisions is low, we do not recommend routine testing of basal FSH in subfertile couples. Copyright

Pregnancy is predictable: A large-scale prospective external validation of the prediction of spontaneous pregnancy in subfertile couples (Article)

2007-02-01T00:00:00Z

Background: Prediction models for spontaneous pregnancy may be useful tools to select subfertile couples that have good fertility prospects and should therefore be counselled for expectant management. We assessed the accuracy of a recently published prediction model for spontaneous pregnancy in a large prospective validation study. Methods: In 38 centres, we studied a consecutive cohort of subfertile couples, referred for an infertility work-up. Patients had a regular menstrual cycle, patent tubes and a total motile sperm count (TMC) >3 × 106. After the infertility work-up had been completed, we used a prediction model to calculate the chance of a spontaneous ongoing pregnancy (www.freya.nl/probability.php). The primary end-point was time until the occurrence of a spontaneous ongoing pregnancy within 1 year. The performance of the pregnancy prediction model was assessed with calibration, which is the comparison of predicted and observed ongoing pregnancy rates for groups of patients and discrimination. Results: We included 3021 couples of whom 543 (18%) had a spontaneous ongoing pregnancy, 57 (2%) a non-successful pregnancy, 1316 (44%) started treatment, 825 (27%) neither started treatment nor became pregnant and 280 (9%) were lost to follow-up. Calibration of the prediction model was almost perfect. In the 977 couples (32%) with a calculated probability between 30 and 40%, the observed cumulative pregnancy rate at 12 months was 30%, and in 611 couples (20%) with a probability of ≥40%, this was 46%. The discriminative capacity was similar to the one in which the model was developed (c-statistic 0.59). Conclusions: As the chance of a spontaneous ongoing pregnancy among subfertile couples can be accurately calculated, this prediction model can be used as an essential tool for clinical decision-making and in counselling patients. The use of the prediction model may help to prevent unnecessary treatment.

Should the post-coital test (PCT) be part of the routine fertility work-up? (Article)

2004-06-01T00:00:00Z

BACKGROUND: This study aimed to determine whether medical history and semen analysis can predict the result of the post-coital test (PCT). METHODS: A previously reported data set of Dutch patients collected between 1985 and 1993 was used. Our study was limited to just patients with an ovulatory cycle. Data were complete for medical history, semen analysis and PCT. We performed logistic regression analysis to evaluate whether these factors could predict the result of the PCT (PCT model). Furthermore, we evaluated the additional contribution of the PCT in the prediction of treatment-independent pregnancy (pregnancy model). RESULTS: Thirty-four percent (179 out of 522) had an abnormal PCT. The PCT model contained previous pregnancy [odds ratio (OR) 2.1; 95% confidence interval (CI) 1.3-3.5], semen volume (OR 0.88; 95% CI 0.77-0.99), sperm concentration (OR 0.96; 95% CI 0.94-0.97), sperm motility (OR 0.97; 95% CI 0.96-0.98) and sperm morphology (OR 2.7; 95% CI 1.2-6.8). The area under the ROC curve of the model was 0.81. In the pregnancy model, the result of the actual PCT could be replaced by the predicted result of the PCT model in about half of the couples, without compromising its predictive capacity. CONCLUSION: The medical history and semen analysis can predict the result of the PCT in approximately 50% of the subfertile couples with a regular cycle, without compromising its potential to predict pregnancy.