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Research Question: What is the cost-effectiveness of gonadotrophins compared with clomiphene citrate in couples with unexplained subfertility undergoing intrauterine insemination (IUI) with ovarian stimulation under strict cancellation criteria?, Design: A cost-effectiveness analysis alongside a randomized controlled trial (RCT). Between July 2013 and March 2016, 738 couples were randomized to gonadotrophins (369) or clomiphene citrate (369) in a multicentre RCT in the Netherlands. The direct medical costs of both strategies were compared. Direct medical costs included costs of medication, cycle monitoring, insemination and, if applicable, pregnancy monitoring. Non-parametric bootstrap resampling was used to investigate the effect of uncertainty in estimates. The cost-effectiveness analysis was performed according to intention-to-treat. The incremental cost-effectiveness ratio (ICER) between gonadotrophins and clomiphene citrate for ongoing pregnancy and live birth was assessed., Results: The mean costs per couple were €1534 for gonadotrophins and €1067 for clomiphene citrate (mean difference of €468; 95% confidence interval [CI] €464-472). As ongoing pregnancy rates were 31% in women allocated to gonadotrophins and 26% in women allocated to clomiphene citrate (relative risk 1.16, 95% CI 0.93-1.47), the ICER was €21,804 (95% CI €11,628-31,980) per additional ongoing pregnancy with gonadotrophins and €17,044 (95% CI €8998-25,090) per additional live birth with gonadotrophins., Conclusions: Gonadotrophins are more expensive compared with clomiphene citrate in couples with unexplained subfertility undergoing IUI with adherence to strict cancellation criteria, without being significantly more effective., (Copyright © 2019. Published by Elsevier Ltd.)

One of the aims in reproductive medicine is to differentiate between couples that have favourable chances of conceiving naturally and those that do not. Since the development of the prediction model of Hunault, characteristics of the subfertile population have changed. The objective of this analysis was to assess whether additional predictors can refine the Hunault model and extend its applicability. Consecutive subfertile couples with unexplained and mild male subfertility presenting in fertility clinics were asked to participate in a prospective cohort study. We constructed a multivariable prediction model with the predictors from the Hunault model and new potential predictors. The primary outcome, natural conception leading to an ongoing pregnancy, was observed in 1053 women of the 5184 included couples (20%). All predictors of the Hunault model were selected into the revised model plus an additional seven (woman's body mass index, cycle length, basal FSH levels, tubal status,history of previous pregnancies in the current relationship (ongoing pregnancies after natural conception, fertility treatment or miscarriages), semen volume, and semen morphology. Predictions from the revised model seem to concur better with observed pregnancy rates compared with the Hunault model; c-statistic of 0.71 (95% CI 0.69 to 0.73) compared with 0.59 (95% CI 0.57 to 0.61)., (Copyright © 2017. Published by Elsevier Ltd.)

Objective: To study the effectiveness of an intrauterine insemination (IUI) program compared to no treatment in subfertile couples with unexplained subfertility and a poor prognosis on natural conception., Study Design: A retrospective matched cohort study in which ongoing pregnancy rates in 72 couples who voluntarily dropped out of treatment with IUI were compared to ongoing pregnancy rates in 144 couples who continued treatment with IUI. Couples with unexplained subfertility, mild male subfertility or cervical factor subfertility who started treatment with IUI between January 2000 and December 2008 were included. Couples were matched on hospital, age, duration of subfertility, primary or secondary subfertility and diagnosis. Primary outcome was cumulative ongoing pregnancy rate after three years. Time to pregnancy was censored at the moment couples were lost to follow up or when their child wish ended and, for the no-treatment group, when couples re-started treatment., Results: After three years, there were 18 pregnancies in the stopped treatment group (25%) versus 41 pregnancies in the IUI group (28%) (RR 1.1 (0.59-2.2)(p=0.4)). The cumulative pregnancy rate after three years was 40% in both groups, showing no difference in time to ongoing pregnancy (shared frailty model p=0.86)., Conclusions: In couples with unexplained subfertility and a poor prognosis for natural conception, treatment with IUI does not to add to expectant management. There is need for a randomized clinical trial comparing IUI with expectant management in these couples., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To compare maternal and perinatal outcomes in dizygotic twin pregnancies conceived after medically assisted reproduction (MAR) with outcomes after natural conception (NC)., Design: Nationwide registry based study., Setting: Academic medical center., Patient(s): Primiparous women who delivered opposite sex twins between January 2000 and December 2012 in the Netherlands, comprising dizygotic twin pregnancies: 6,694 women, 470 after ovulation induction (OI), 511 after intrauterine insemination with controlled ovarian hyperstimulation (IUI-COH), 2,437 after in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI), and 3,276 after NC., Intervention(s): None., Main Outcome Measure(s): Multivariable logistic regression and generalized linear mixed models to evaluate differences in outcomes: maternal outcomes of hypertension, preeclampsia, preterm delivery, hemorrhage, and delivery mode, perinatal outcomes including small for gestational age (SGA) with birth weight <10th percentile, birth weight <1,500 g, 5-minute Apgar score <7, admission to neonatal intensive care unit, congenital anomalies, and perinatal mortality., Result(s): We found no statistically significant differences in maternal or perinatal outcomes after OI compared with NC. Women pregnant after IVF-ICSI had a lower risk for hypertension (adjusted odds ratio [aOR] 0.74; 95% confidence interval [CI], 0.66-0.83) compared with women pregnant after NC. After IUI-COH more children had Apgar scores <7 (adjusted odds ratio (aOR) 1.38; 95% confidence interval (CI) 1.05-1.81) and perinatal mortality rates were higher (aOR 1.56; 95% CI, 1.04-2.33) compared with NC. We found no differences in perinatal outcomes after IVF-ICSI compared with NC., Conclusion(s): Overall, maternal and perinatal risks other than those due to multiplicity are similar for twin pregnancies conceived after MAR and after NC., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: Available treatment options in couples with unexplained or mild male subfertility are intrauterine insemination with controlled ovarian hyperstimulation (IUI-COH) and in vitro fertilisation (IVF). IUI-COH is a less invasive treatment that is often used before proceeding with IVF. Yet as the IVF success rates might be higher and time to pregnancy shorter, expedited access to IVF might be the preferred option. To identify couples that could benefit from immediate IVF over IUI-COH, we assessed whether female age, duration of subfertility or prewash total motile count (TMC) can help to identify couples that would benefit from IVF over IUI-COH., Study Design: We performed a secondary data-analysis of a multicentre open-label randomised controlled trial in three university and six teaching hospitals in the Netherlands. 116 couples with unexplained or mild male subfertility were randomised to one cycle of IVF with elective single embryo transfer with subsequent frozen-thawed embryo transfers or 3 cycles of IUI-COH. The primary outcome was an ongoing pregnancy within 4 months after randomisation. Our aim was to explore a possible differential effect of specific markers on the effectiveness of treatment. We chose to therefore assess female age, duration of subfertility and TMC as these have previously been identified as predictors. For each prognostic factor we developed a logistic regression model to predict ongoing pregnancy with that prognostic factor, treatment and a factor-by-treatment interaction term., Results: Female age and duration of subfertility were not associated with better ongoing pregnancy chances after IVF compared to IUI-COH (p-value for interaction=0.65 and 0.26, respectively). Only when TMC was lower than 110 (×10(6)spermatozoa/mL), the probability of ongoing pregnancy was higher in women allocated to IVF (p-value for interaction=0.06)., Conclusion: In couples with unexplained or mild male subfertility, a low TMC might lead to higher pregnancy rates after IVF than after IUI-COH. This finding needs to be validated in a larger trial before it can be applied in clinical practice., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Couples with unexplained subfertility are often treated with intrauterine insemination (IUI) with ovarian stimulation, which carries the risk of multiple pregnancies. An explorative randomized controlled trial was performed comparing one cycle of IVF with elective single-embryo transfer (eSET) versus three cycles of IUI-ovarian stimulation in couples with unexplained subfertility and a poor prognosis for natural conception, to assess the economic burden of the treatment modalities. The main outcome measures were ongoing pregnancy rates and costs. This study randomly assigned 58 couples to IVF-eSET and 58 couples to IUI-ovarian stimulation. The ongoing pregnancy rates were 24% in with IVF-eSET versus 21% with IUI-ovarian stimulation, with two and three multiple pregnancies, respectively. The mean cost per included couple was significantly different: €2781 with IVF-eSET and €1876 with IUI-ovarian stimulation (P<0.01). The additional costs per ongoing pregnancy were €2456 for IVF-eSET. In couples with unexplained subfertility, one cycle of IVF-eSET cost an additional €900 per couple compared with three cycles of IUI-ovarian stimulation, for no increase in ongoing pregnancy rates or decrease in multiple pregnancies. When IVF-eSET results in higher ongoing pregnancy rates, IVF would be the preferred treatment. Couples that have been trying to conceive unsuccessfully are often treated with intrauterine insemination (IUI) and medication to improve egg production (ovarian stimulation). This treatment carries the risk of multiple pregnancies like twins. We performed an explorative study among those couples that had a poor prognosis for natural conception. One cycle of IVF with transfer of one selected embryo (elective single-embryo transfer, eSET) was compared with three cycles of IUI-ovarian stimulation. The aim of this study was to assess the economic burden of both treatments. The Main outcome measures were number of good pregnancies above 12weeks and costs. We randomly assigned 58 couples to IVF-eSET and 58 couples to IUI-ovarian stimulation. The ongoing pregnancy rates were comparable: 24% with IVF-eSET versus 21% with IUI-ovarian stimulation. There were two multiple pregnancies with IVF-eSET and three multiple pregnancies with IUI-ovarian stimulation. The mean cost per included couple was significantly different, €2781 with IVF-eSET and €1876 with IUI-ovarian stimulation. The additional costs per ongoing pregnancy were €2456 for IVF-eSET. In couples with unexplained subfertility, one cycle of IVF-eSET costed an additional €900 per couple compared to three cycles of IUI-ovarian stimulation, for no increase in ongoing pregnancy rates or decrease in multiple pregnancies. We conclude that IUI-ovarian stimulation is the preferred treatment to start with. When IVF-eSET results in a higher ongoing pregnancy rate (>38%), IVF would be the preferred treatment., (Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: A previous randomized clinical trial (RCT) compared immediate treatment with intrauterine insemination (IUI) to expectant management for six months in subfertile couples with an isolated cervical factor. That study showed higher ongoing pregnancy rates in couples receiving intrauterine insemination. The current study compared the long-term effectiveness and costs of this intervention., Study Design: We followed all couples (N=99) who were previously included in the RCT for three years after randomization and registered pregnancies and treatments. After the initial trial period, couples in both groups were offered further treatment according to local protocol. The primary outcome was an ongoing pregnancy after three years., Results: After three years, there were 36 ongoing pregnancies in the immediate IUI group (N=51 couples) and 38 ongoing pregnancies in the expectant management group (N=48 couples). The ongoing pregnancy rates were 71% and 79% respectively (RR 0.89 (95% confidence interval (CI) 0.7-1.1))., Conclusions: In couples with an isolated cervical factor, a treatment strategy including immediate treatment with IUI does not result in higher ongoing pregnancy rates on the long term. Initial expectant management is therefore justified in these couples and identifying a cervical factor by a post-coital test is unnecessary., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: To evaluate whether baseline characteristics and prognostic profiles differed between couples who drop out from intrauterine insemination (IUI) and couples that continue IUI, and the reasons for couples dropping out from IUI programs., Design: Retrospective observational cohort study., Setting: Fertility centers., Patient(s): Consecutive subfertile couples undergoing IUI., Intervention(s): None., Main Outcome Measure(s): Characteristics and prognosis of ongoing pregnancy after IUI at the start of treatment of couples that dropped out compared with couples that continued treatment or achieved an ongoing pregnancy., Result(s): We studied 803 couples who underwent 3,579 IUI cycles of whom 221 couples dropped out (28%). Couples dropping out completed 2.8 (SD ±1.4) cycles per couple compared with 4.5 (SD ±2.3) cycles per couple for those continuing treatment. Couples dropping out had a higher female age, longer subfertility duration, and higher basal FSH. Mean prognosis to achieve an ongoing pregnancy after IUI at start of treatment was 7.9% (SD ±2.4) per cycle for couples who dropped out and 8.5% (SD ±2.5) per cycle for couples continuing treatment. Of the dropouts, 100 couples (45%) were actively censored from the IUI program, 87 couples (39%) because of poor prognosis; 121 couples (55%) were passively censored from the program, of whom 62 (28%) dropped out owing to personal reasons; 59 couples (27%) were lost to follow-up., Conclusion(s): We found significant differences in prognostic profile between couples continuing treatment and couples dropping out, although these differences seem limited from a clinical perspective. We conclude that overestimation of ongoing pregnancy rates after IUI due to couples dropping out is limited., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the role of corifollitropin alfa, a newly developed weekly administrated long-acting recombinant FSH (rFSH), as an alternative for daily rFSH administration in women undergoing controlled ovarian stimulation in GnRH antagonist down-regulated in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment cycles., Design: Systematic review and meta-analysis of randomized controlled trials., Setting: University and private centers., Patient(s): Infertile women undergoing IVF/ICSI treatment., Intervention(s): Comparing long-acting rFSH corifollitropin alfa versus standard daily administrated rFSH in GnRH antagonist IVF/ICSI cycles., Main Outcome Measure(s): Ongoing pregnancy rate, live birth rate, clinical pregnancy rate, miscarriage rate, duration of stimulation, amount of FSH, number of retrieved oocytes, number of mature oocytes, number of embryos obtained, fertilization rate, ovarian hyperstimulation syndrome (OHSS) incidence, and adverse events. Searches (of literature through November 2011) were conducted in Medline, Embase, Science Direct, the Cochrane Library, and databases of abstracts., Result(s): Four randomized trials involving 2,326 women were included. There was no evidence of a statistically significant difference in ongoing pregnancy rate for corifollitropin alfa versus rFSH. There was evidence of increased ovarian response and risk of OHSS in corifollitropin alfa., Conclusion(s): In view of its equivalence and safety profile, corifollitropin alfa in combination with daily GnRH antagonist seems to be an alternative for daily rFSH injections in normal responder patients undergoing ovarian stimulation in IVF/ICSI treatment cycles., (Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: We recently reported that treatment with intrauterine insemination and controlled ovarian stimulation (IUI-COS) did not increase ongoing pregnancy rates compared with expectant management (EM) in couples with unexplained subfertility and intermediate prognosis of natural conception. Long-term cost-effectiveness of a policy of initial EM is unknown. We investigated whether the recommendation not to treat during the first 6 months is valid, regarding the long-term effectiveness and cumulative costs., Methods: Couples with unexplained subfertility and intermediate prognosis of natural conception (n=253, at 26 public clinics, the Netherlands) were randomly allocated to 6 months EM or immediate start with IUI-COS. The couples were then treated according to local protocol, usually IUI-COS followed by IVF. We followed couples until 3 years after randomization and registered pregnancies and resources used. Primary outcome was time to ongoing pregnancy. Secondary outcome was treatment costs. Analysis was by intention-to-treat. Economic evaluation was performed from the perspective of the health care institution., Results: Time to ongoing pregnancy did not differ between groups (log-rank test P=0.98). Cumulative ongoing pregnancy rates were 72-73% for EM and IUI-COS groups, respectively [relative risk 0.99 (95% confidence interval (CI) 0.85-1.1)]. Estimated mean costs per couple were € 3424 (95% CI € 880-€ 5968) in the EM group and € 6040 (95% CI € 4055-€ 8125) in the IUI-COS group resulting in an estimated saving of € 2616 per couple (95% CI € 385-€ 4847) in favour of EM., Conclusions: In couples with unexplained subfertility and an intermediate prognosis of natural conception, initial EM for 6 months results in a considerable cost-saving with no delay in achieving pregnancy or jeopardizing the chance of pregnancy. Further comparisons between aggressive and milder forms of ovarian stimulation should be performed.

Objective: To evaluate the effectiveness of IVF with elective single embryo transfer (IVF-eSET) vs. IUI with controlled ovarian stimulation (IUI-COS) as an alternative treatment to reduce the risk for a multiple pregnancy., Design: Randomized pilot trial., Setting: Three academic and six teaching hospitals in the Netherlands., Patient(s): Couples with unexplained or mild male subfertility and an unfavorable prognosis for natural conception., Intervention(s): One cycle of IVF-eSET or three cycles of IUI-COS., Main Outcome Measure(s): Ongoing pregnancy per couple., Result(s): We randomly allocated 116 women to IVF-eSET (n = 58) or IUI-COH (n = 58). There were 14 ongoing pregnancies (24%) in the IVF-eSET group and 12 pregnancies (21%) in the IUI-COS group (relative ratio 1.17; 95% confidence interval 0.60-2.30). There were two twin pregnancies in the IVF-eSET group (14%) and two twin pregnancies and one triplet pregnancy in the IUI-COH group (25%)., Conclusion(s): In patients with unexplained or mild male subfertility and a poor prognosis for natural conception, one cycle of IVF-eSET might be as effective as three cycles of IUI-COS as primary treatment. Elective single embryo transfer does not seem an effective strategy in preventing multiple pregnancies in this particular population. In the future a strict SET policy (i.e., compulsory SET) might be an option. Our trial provides evidence for the feasibility and highlights the importance of a large definitive trial to determine the effectiveness and side effects of both strategies., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the precise degree of variability that is represented by the reproducibility and reliability of semen analysis. The general assumption is that semen analyses need to be repeated because of a high degree of within-individual variability. However, the precise degree of variability is not well established in male partners of subfertile couples., Design: Retrospective cohort study., Setting: Two university hospitals in the Netherlands, which routinely perform two semen analyses in the male partner of subfertile couples., Patient(s): Male partners of subfertile couples., Interventions: None., Main Outcome Measure(s): We assessed the test-retest reproducibility, by calculating the coefficient of variation (CV(w)) for five semen parameters. The CV(w) expresses, on a relative scale, the degree of closeness of repeated measurements taken in the same subject. We also estimated the reliability of these semen parameters, in terms of the intraclass correlation coefficient, which expresses the ratio of the between-subject variability over the total variability., Result(s): We analyzed the data of 5,240 men and found that the CV(w) of all semen parameters ranged from 28% to 34%. The intraclass correlation coefficients of these semen parameters were moderate to high: volume: 0.70; concentration: 0.89; motility: 0.58; morphology: 0.60; total motile count: 0.73., Conclusion(s): This study affirmed the presumed large within-subject variability and the limited reproducibility of semen analyses in subfertile men. Whether this degree of variability within men justifies one or more repetitions of the semen analysis in view of consequences for clinical management should be the topic of future studies. Until then it seems reasonable to perform two semen analyses., (Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

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., (Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Multiple pregnancies are high risk pregnancies with higher chances of maternal and neonatal mortality and morbidity. In the past decades the number of multiple pregnancies has increased. This trend is partly due to the fact that women start family planning at an increased age, but also due to the increased use of ART.Couples with unexplained or mild male subfertility generally receive intrauterine insemination IUI with controlled hormonal stimulation (IUI COH). The cumulative pregnancy rate is 40%, with a 10% multiple pregnancy rate.This study aims to reveal whether alternative treatments such as IVF elective Single Embryo Transfer (IVF e SET) or Modified Natural Cycle IVF (MNC IVF) can reduce the number of multiple pregnancy rates, but uphold similar pregnancy rates as IUI COH in couples with mild male or unexplained subfertility. Secondly, the aim is to perform a cost effective analyses and assess treatment preference of these couples., Methods/design: We plan a multicentre randomised controlled clinical trial in the Netherlands comparing six cycles of intra-uterine insemination with controlled ovarian hyperstimulation or six cycles of Modified Natural Cycle (MNC) IVF or three cycles with IVF-elective Single Embryo Transfer (eSET) plus cryo-cycles within a time frame of 12 months.Couples with unexplained subfertility or mild male subfertility and a poor prognosis for treatment independent pregnancy will be included. Women with anovulatory cycles, severe endometriosis, double sided tubal pathology or serious endocrine illness will be excluded.Our primary outcome is the birth of a healthy singleton. Secondary outcomes are multiple pregnancy, treatment costs, and patient experiences in each treatment arm. The analysis will be performed according tot the intention to treat principle. We will test for non-inferiority of the three arms with respect to live birth. As we accept a 12.5% loss in pregnancy rate in one of the two IVF arms to prevent multiple pregnancies, we need 200 couples per arm (600 couples in total)., Discussion: Determining the safest and most cost-effective treatment will ensure optimal chances of pregnancy for subfertile couples with substantially diminished perinatal and maternal complications. Should patients find the most cost-effective treatment acceptable or even preferable, this could imply the need for a world wide shift in the primary treatment., Trial Registration: Current Controlled Trials ISRCTN 52843371.

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.

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.

Background: In the past 20 years, various recommendations have been made about the maximum number of intrauterine insemination (IUI) cycles that should be performed, because evidence underpinning a possible limit is lacking., Methods: We performed a multicentre, retrospective cohort analysis among couples treated with IUI up to nine cycles. Primary outcome measure was ongoing pregnancy rate (OPR) per cycle. Cumulative OPRs (COPR) after three, six and nine cycles of IUI were calculated using life-table analysis. Univariable and multivariable logistic regression analysis was performed to identify variables possibly affecting OPR's., Results: Overall, 3714 couples with male, cervical or unexplained subfertility underwent 15,303 cycles of IUI. In 70% of cycles, controlled ovarian hyperstimulation (COH) was used (51% clomiphene-citrate, 19% gonadotropins). Mean OPR rate was 5.6% per cycle. OPR in the seventh, eighth and ninth cycle were 5.1%, 6.7% and 4.6%, respectively. Taking censored patients into account, the calculated COPR was 18% after the third cycle, 30% after the seventh cycle and 41% after the ninth cycle. If censored patients were considered to have no chance of conception, a crude COPR of 25% after nine cycles was found. Multivariable regression analysis showed no significant impact of age, type of subfertility, diagnosis, use of hyperstimulation or cycle number on OPR after the sixth treatment cycle., Conclusions: OPR in high-order IUI cycles are acceptable, and do not offer a rationale for cancellation before nine cycles. Using this type of very mild COH, it may be reasonable to conduct up to nine cycles.

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.

Objective: To assess the accuracy of our recently developed prediction model in a prospective validation study to predict the outcome of intrauterine insemination (IUI)., Design: Descriptive prospective validation study., Setting: Seven fertility centers in the Netherlands., Patient(s): Couples treated with IUI of whom the female partner had a regular cycle., Intervention(s): Intrauterine insemination with or without controlled ovarian hyperstimulation., Main Outcome Measure(s): Ongoing pregnancy after intrauterine insemination. Performance of the prediction model was assessed with calibration and discriminative capacity. Calibration was assessed by comparing the predicted ongoing pregnancy rate with the observed ongoing pregnancy rate. Discriminative capacity was assessed with receiver operation characteristic (ROC) analysis. For daily practice, a score worksheet of the validated model was developed to estimate the chance of an ongoing pregnancy after IUI per treatment cycle., Result(s): We included 1,079 subfertile couples who underwent 4,244 cycles of IUI. There were 278 ongoing pregnancies, that is, an ongoing pregnancy rate of 6.6% per cycle. External validation of the model showed good calibration. The predicted probability never differed by more than 1.5% of the mean observed probability. The area under the ROC curve was 0.56 (95% confidence interval, 0.53-0.59) at external validation., Conclusion(s): The prediction model was able to make a good distinction between couples with a good pregnancy chance and those with a poor pregnancy chance after IUI. This model can help in deciding which couples will benefit from IUI and which couples will not.

The aim of this retrospective study was to assess the results of intrauterine insemination (IUI) in The Netherlands, using data from 2003 taken from hospital annual reports and reports from individual gynaecologists. By extrapolation, the total number of IUI cycles performed that year nationwide, and the related outcomes, was estimated. IUI was performed in 91 of the country's 101 hospitals. Of these, 58 (64%) registered their IUI results and performed 19,846 IUI cycles. The mean pregnancy rate per cycle was 9.0% and the ongoing pregnancy rate per cycle was 7.3%. Multiple pregnancies occurred in 9.5% of the ongoing pregnancies. Extrapolation of the data suggested that approximately 28,500 IUI cycles were performed, of which approximately 2000 resulted in an ongoing pregnancy. The number of multiple pregnancies following IUI was estimated to be 180 (9.0%). According to the national IVF registry, 9761 IVF cycles were started in 2003, resulting in 2,028 ongoing pregnancies (20.8% per cycle) and 439 twin pregnancies (21.6% per ongoing pregnancy). In conclusion, the pregnancy rate per IUI cycle in The Netherlands (9.0%) was comparable with that reported in the international literature (8.7%). The contribution made by IUI to the number of multiple pregnancies in The Netherlands was much smaller than the contribution made by IVF.

Background: Intrauterine insemination with controlled ovarian hyperstimulation is commonly used as first-line treatment for couples with unexplained subfertility. Since such treatment increases the risk of multiple pregnancy, a couple's chances of achieving an ongoing pregnancy without it should be considered to identify those most likely to benefit from treatment. We aimed to assess the incremental effectiveness of intrauterine insemination with controlled ovarian hyperstimulation compared with expectant management in couples with unexplained subfertility and an intermediate prognosis of a spontaneous ongoing pregnancy., Methods: 253 couples with unexplained subfertility and a 30-40% probability of a spontaneous ongoing pregnancy within 12 months were randomly assigned either intrauterine insemination with controlled ovarian hyperstimulation for 6 months or expectant management for 6 months. The primary endpoint of this hospital-based study was ongoing pregnancy within 6 months. Analysis was by intention to treat. This trial is registered with the Dutch Trial Register and as an International Standard Randomised Clinical Trial, number ISRCTN72675518., Findings: Of the 253 couples enrolled, 127 were assigned intrauterine insemination with controlled ovarian hyperstimulation and 126 expectant management. In the intervention group, 42 (33%) women conceived and 29 (23%) pregnancies were ongoing. In the expectant management group, 40 (32%) women conceived and 34 (27%) pregnancies were ongoing (relative risk 0.85, 95% CI 0.63-1.1). There was one twin pregnancy in each study group, and one woman in the intervention group conceived triplets., Interpretation: A large beneficial effect of intrauterine insemination with controlled ovarian hyperstimulation in couples with unexplained subfertility and an intermediate prognosis can be excluded. Expectant management for 6 months is therefore justified in these couples.

Sixteen vignettes of subfertile couples were constructed by varying fertility history, post-coital test, sperm motility, FSH concentration and Chlamydia antibody titre (CAT). Thirty-five gynaecologists estimated probabilities of treatment-independent pregnancy, intrauterine insemination (IUI) and IVF. Thereafter, they chose IUI, IVF or no treatment. The relative contribution of each factor to probability estimates and to subsequent treatment decisions was calculated. Duration of subfertility and maternal age were the most important contributors for gynaecologists' estimates of treatment-independent pregnancy [relative contribution (RC) 41, 26%]. Maternal age and FSH concentration were the most important contributors in the estimates for IUI (RC: 51, 25%) and for IVF (RC: 64, 31%). The decision to start IVF was mainly determined by maternal age, duration of subfertility, FSH concentration and CAT. The relative contribution of maternal age and duration of subfertility was in concordance with existing prediction models, whereas previous pregnancy and FSH concentration were under- and overestimated respectively. In conclusion, maternal age, duration of subfertility and FSH concentration are the main factors in clinical decision-making in subfertility. Gynaecologists overestimate the importance of FSH concentration, but underestimate that of a previous pregnancy, as compared with their importance reported in prediction models and guidelines.

Background: The aim of this study was to compare the effect of three different times of onset of luteal phase support on ongoing pregnancy rate in infertile patients undergoing treatment with GnRH down-regulated IVF and embryo transfer (IVF/ET)., Materials and Methods: All consecutive eligible patients planned to undergo their first IVF treatment cycle were randomly allocated to receive vaginal progesterone as luteal support at three different time points, that is, after HCG administration for final oocyte maturation (HCG group), at the day of oocyte retrieval (OR group) or at the day of ET (ET group). The primary endpoint of this study was ongoing pregnancy rate., Results: A total of 385 women were randomized, 130 were allocated to the HCG group, 128 to the OR group and 127 to the ET group. An ongoing pregnancy rate of 20.8% was found in the HCG group versus 22.7 and 23.6% in the OR group and ET group, respectively. The mean number and quality of the retrieved oocytes and the transferred embryos did not differ., Conclusion: Based on this data, an 18% difference in ongoing pregnancy rate between the three different times of onset of luteal phase support in GnRH agonist down-regulated IVF/ET cycles can be refuted. Smaller clinically meaningful differences may be present.

Background: Intrauterine insemination (IUI) is a commonly used treatment in subfertile couples. We assessed patients' preferences for IUI relative to expectant management., Methods: Forty subfertile couples were offered scenarios in which the treatment-independent pregnancy chance was varied against a fixed pregnancy chance after IUI without or with controlled ovarian hyperstimulation (COH) of 8% and 12% per cycle, respectively. The treatment-independent pregnancy chance within 12 months was initially set at 100%, and subsequently reduced until couples switched preferences. We also investigated the impact of the risks of ovarian hyperstimulation syndrome (OHSS) and multiple pregnancy on couples' preferences., Results: When pregnancy was guaranteed within a year, all couples would opt for expectant management. Most couples switched to IUI without COH at a 60% chance of a treatment-independent pregnancy and to IUI with COH between a 40% and 60% chance. Where the risk of OHSS was set at 10%, a large majority of the couples preferred expectant management to IUI. At a multiple pregnancy risk of 100%, 77% of the couples would still prefer IUI., Conclusions: The majority of couples prefer IUI with or without COH when the treatment-independent pregnancy chance in the next 12 months is <50% and <40%, respectively. The risk of a multiple pregnancy does not affect their preference for IUI, whereas IUI is rejected when the risk of OHSS exceeds 10%.

Objective: To develop a prognostic model for the outcome of IUI., Design: Retrospective cohort study., Setting: Four fertility centers in The Netherlands., Patient(s): Couples of whom the female partners had a regular cycle and who had been treated with IUI., Intervention(s): Intrauterine insemination with and without ovarian hyperstimulation., Main Outcome Measure(s): Ongoing pregnancy., Result(s): Overall, 3371 couples were included who underwent 14968 cycles. There were 1229 (8.2%) pregnancies, of which 1000 (6.7%) pregnancies were ongoing. Logistic regression analysis demonstrated that increasing maternal age, longer duration of subfertility, presence of male factor subfertility, one-sided tubal pathology, endometriosis, uterine anomalies, and an increasing number of cycles were unfavorable predictors for an ongoing pregnancy. Cervical factor and the use of ovarian hyperstimulation were favorable predictors. The area under the receiver operating characteristic curve was 0.59. When couples were divided into four categories based on prognosis, the difference between the predicted and observed chance, that is, the calibration, was less than 0.5% in each of the four groups., Conclusion(s): Although our model had a relatively poor discriminative capacity, data on calibration showed that the selected prognostic factors allow distinction between couples with a poor prognosis and couples with a good prognosis. After external validation, this model could be of use in patient counseling and clinical decision making.

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.

When intended parents choose to have donor sperm treatment (DST), this may entail wide-ranging and long-lasting psychosocial implications related to the social parent not having a genetic tie with the child, how to disclose donor-conception and future donor contact. Counselling by qualified professionals is recommended to help intended parents cope with these implications. The objective of this study is to present findings and insights about how counsellors execute their counselling practices. We performed a qualitative study that included 13 counsellors working in the 11 clinics offering DST in the Netherlands. We held a focus group discussion and individual face-to-face semi-structured interviews, which were fully transcribed and analysed using thematic analysis. The counsellors combined screening for eligibility and guidance within one session. They acted according to their individual knowledge and clinical experience and had different opinions on the issues they discussed with intended parents, which resulted in large practice variations. The counsellors were dependent on the admission policies of the clinics, which were mainly limited to regulating access to psychosocial counselling, which also lead to a variety of counselling practices. This means that evidence-based guidelines on counselling in DST need to be developed to provide consistent counselling with less practice variation. [ABSTRACT FROM AUTHOR]

Background: Obesity in women of reproductive age has deleterious effects on reproductive and offspring health. In this study, we aimed to evaluate the association between the magnitude of periconceptional body-mass index (BMI) change and maternal and neonatal outcomes in obese infertile women who participated in the LIFEstyle study. The LIFEstyle study was a randomized controlled trial, evaluating if a six-month lifestyle intervention program prior to infertility treatment in obese infertile women improved birth rates, compared to prompt infertility treatment. Methods and findings: This is an exploratory post hoc analysis of the LIFEstyle study. We recorded periconceptional BMI change in women with an ongoing pregnancy, pooling data of all women, regardless of randomization arm. Periconceptional BMI change was calculated using weight at randomization and the periconceptional weight (measured in kilograms 12 weeks before or after conception and expressed as BMI change in units BMI (kg/m2)). Subsequently, women were categorized into quartiles according to the magnitude of their periconceptional change in BMI. The odds of maternal and neonatal outcomes were calculated using logistic regression analysis, comparing women in each of the first three weight change quartiles separately, and combined, to women in the fourth quartile. The fourth quartile was chosen as reference group, since these women had the least weight loss. We adjusted for periconceptional BMI, nulliparity and smoking status. In addition, we performed a subgroup analysis for singleton pregnancies. In the LIFEstyle study, 321 obese infertile women achieved an ongoing pregnancy which was conceived within 24 months after randomization. Periconceptional BMI change was available in 244 of these women (76%). Median BMI at randomization was 35.9 kg/m2. Women in the first quartile (Q1) had a periconceptional BMI change of <-2.1 kg/m2, women in the second quartile (Q2) -2.1 to -0.9 kg/m2, women in the third quartile (Q3) -0.9 to 0.1 kg/m2 and women in the fourth quartile (Q4) gained ≥0.1 kg/m2. There were no significant differences between women in the quartiles regarding rates of excessive gestational weight gain (in term pregnancies), gestational diabetes, preterm birth, induction of labor, spontaneous vaginal birth and Caesarean section. Compared to women in Q4, the adjusted odds ratios, aOR, and 95% confidence interval for a hypertensive complication were; 0.55 (0.22–1.42) for women in Q1, 0.30 (0.12–0.78) for women in Q2, 0.39 (0.16–0.96) for women in Q3 and 0.39 (0.19–0.82) for women in Q1 to Q3 combined. In the subgroup analysis, investigating singleton pregnancies only, the statistically significant decreased rate of a hypertensive complication remained in women in Q2 (aOR 0.27, 95% CI 0.10–0.72) and Q3 (aOR 0.39, 95%CI 0.16–0.98) and when comparing women in Q1 to Q3 together to women in Q4 (aOR 0.38, 95%CI 0.18–0.80). Furthermore, there was a significantly decreased aOR (95%CI) of preterm birth in women in Q2 (0.24, 0.06–0.98) and when combining women in Q1 to Q3 (0.37, 0.14–0.97) compared to women in Q4. Conclusions: These results suggest that a periconceptional decrease in BMI in obese infertile women could lead to a decrease of the rates of hypertensive pregnancy complications and preterm birth. The results are limited by the exploratory nature of the analyses and further evidence is necessary to provide more definitive conclusions. [ABSTRACT FROM AUTHOR]

Objective: To study the effect of body mass index (BMI) on semen quality in a cohort of male partners in subfertile couples.Design: Prospective cohort study.Setting: A fertility center based in an academic hospital.Patient(s): Between January 2000 and January 2007, 1466 men visiting the Centre for Reproductive Medicine as part of a subfertile couple.Intervention(s): None.Main Outcome Measure(s): Semen volume (in mL), semen concentration (in millions per mL), percentage of motile spermatozoa, percentage of spermatozoa with normal forms, total sperm count (in millions), and total motile sperm count (in millions).Result(s): After exclusion of men without data on BMI, the data of 1401 men could be analyzed. The group of men with a BMI lower than 20 kg/m2, with a BMI between 25 and 30 kg/m2, and with a BMI>30 kg/m2 had a lower semen volume compared with the group with a BMI between 20 and 25 kg/m2. Other semen parameters were not statistically significantly different. Multivariable analysis (generalized linear model), correcting for confounders, showed no statistically significant association between BMI and semen parameters, including semen volume.Conclusion(s): Semen quality was not statistically significantly affected by BMI in a cohort of male partners in subfertile couples. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness of low doses of gonadotropins and gonadotropins combined with oral compounds compared with high doses of gonadotropins in ovarian stimulation regimens in terms of ongoing pregnancy per fresh IVF attempt in women with poor ovarian reserve undergoing IVF/intracytoplasmic sperm injection (ICSI) treatment.Design: A systematic review and meta-analysis of randomized controlled studies that evaluate the effectiveness of low dosing of gonadotropins alone or combined with oral compounds compared with high doses of gonadotropins in women with poor ovarian reserve undergoing IVF/ICSI treatment.Setting: Not applicable.Patient(s): Subfertile women with poor ovarian reserve undergoing IVF/ICSI treatment.Intervention(s): We searched the PubMed, EMBASE, Web of Science, the Cochrane Library, and the Clinical Trials Registry using medical subject headings and free text terms up to June 2016, without language or year restrictions. We included randomized controlled studies (RCTs) enrolling subfertile women with poor ovarian reserve undergoing IVF/ICSI treatment and comparing low doses of gonadotropins and gonadotropins combined with oral compounds versus high doses of gonadotropins. We assessed the risk of bias using the criteria recommended by the Cochrane Collaboration. We pooled the results by meta-analysis using the fixed and random effects model.Main Outcomes Measure(s): The primary outcome was ongoing pregnancy rate (PR) per woman randomized.Result(s): We retrieved 787 records. Fourteen RCTs (N = 2,104 women) were included in the analysis. Five studies (N = 717 women) compared low doses of gonadotropins versus high doses of gonadotropins. There was no evidence of a difference in ongoing PR (2 RCTs: risk rate 0.98, 95% confidence interval 0.62-1.57, I2 = 0). Nine studies (N = 1,387 women) compared ovarian stimulation using gonadotropins combined with the oral compounds letrozole (n = 6) or clomiphene citrate (CC) (n = 3) versus high doses of gonadotropins. There was no evidence of a difference in ongoing PR (3 RCTs: risk rate 0.90, 95% confidence interval 0.63-1.27, I2 = 0).Conclusion(s): We found no evidence of a difference in pregnancy outcomes between low doses of gonadotropins and gonadotropins combined with oral compounds compared with high doses of gonadotropins in ovarian stimulation regimens. Whether low doses of gonadotropins or gonadotropins combined with oral compounds is to be preferred is unknown, as they have never been compared head to head. A health economic analysis to test the hypothesis that an ovarian stimulation with low dosing is more cost-effective than high doses of gonadotropins is needed.Prospero Registration Number: CRD42016041301. [ABSTRACT FROM AUTHOR]

Background: Small lifestyle-intervention studies suggest that modest weight loss increases the chance of conception and may improve perinatal outcomes, but large randomized, controlled trials are lacking.Methods: We randomly assigned infertile women with a body-mass index (the weight in kilograms divided by the square of the height in meters) of 29 or higher to a 6-month lifestyle intervention preceding treatment for infertility or to prompt treatment for infertility. The primary outcome was the vaginal birth of a healthy singleton at term within 24 months after randomization.Results: We assigned women who did not conceive naturally to one of two treatment strategies: 290 women were assigned to a 6-month lifestyle-intervention program preceding 18 months of infertility treatment (intervention group) and 287 were assigned to prompt infertility treatment for 24 months (control group). A total of 3 women withdrew consent, so 289 women in the intervention group and 285 women in the control group were included in the analysis. The discontinuation rate in the intervention group was 21.8%. In intention-to-treat analyses, the mean weight loss was 4.4 kg in the intervention group and 1.1 kg in the control group (P<0.001). The primary outcome occurred in 27.1% of the women in the intervention group and 35.2% of those in the control group (rate ratio in the intervention group, 0.77; 95% confidence interval, 0.60 to 0.99).Conclusions: In obese infertile women, a lifestyle intervention preceding infertility treatment, as compared with prompt infertility treatment, did not result in higher rates of a vaginal birth of a healthy singleton at term within 24 months after randomization. (Funded by the Netherlands Organization for Health Research and Development; Netherlands Trial Register number, NTR1530.). [ABSTRACT FROM AUTHOR]

Objective: To summarize the evidence for the use of commonly accepted fertility tests in subfertile women with ovulation problems. Design: Systematic review. Setting: Not applicable. Patient(s): The study population included women starting with clomiphene citrate (CC) as first-line treatment, women starting with second-line treatment if CC failed to result in pregnancy, and women starting with second-line treatment if CC failed to result in ovulation (CC resistant). Intervention(s): Performance of a semen analysis or tubal patency test before or during treatment Main Outcome Measure(s): Prevalence of abnormal tests as well as the diagnostic and prognostic performance of these tests. Result(s): Four studies reported on 3,017 women starting with CC as first-line treatment. The prevalence of male factor infertility was 10%, and in 0.3% of couples azoospermia was found (two studies). Semen parameters were not associated with pregnancy chance (one study). The prevalence of bilateral tubal disease was 4% (two studies). Three studies reported on 462 women starting with second-line treatment if CC failed to result in a pregnancy. Semen parameters were not predictive for pregnancy (one study). The prevalence of bilateral tubal disease in these women was 8% (three studies). Two studies reported on 168 CC-resistant women and total motile sperm count did not predict live birth (two studies). For all other outcomes, no studies were available. Conclusion(s): Data on the basic fertility workup in subfertile women with anovulation are scarce. Based on the available data, the workup should contain a semen analysis, and, for women who need to start second-line treatment if CC failed to result in pregnancy or women with CC resistance, assessment of tubal patency. [ABSTRACT FROM AUTHOR]

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 × 106/mL, total sperm count <200 × 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. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

Objective: To evaluate the methodologic quality of economic analyses published in the field of reproductive medicine. Design: Systematic review. Setting: Centers for reproductive care. Patient(s): Infertility patients. Intervention(s): We performed a Medline search to identify economic evaluation studies in reproductive medicine. We included studies that concerned interventions, evaluated costs and effects, and were published in a journal on reproductive medicine, gynecology, or a major general journal from 1997 through May 2011. Main Outcome Measure(s): Number of quality criteria adhered to. Result(s): Our search revealed 5,519 articles, of which 85 met our inclusion criteria. Seventy-seven (91%) of the economic analyses were on treatment, six (7%) on diagnosis, and two (2%) on screening. The mean number of quality criteria adhered to was 20 out of 30 items, and only one article met all 30 criteria. The mean number of criteria adhered to was higher if at least one of the authors was from a methodologic or health economics department (mean 23 [n = 30] versus mean 20 [n = 55]). The most common limitations of published economic evaluation studies were in methodology or presentation of incremental analyses, sensitivity analyses, and discounting. Conclusion(s): Economic analyses published in the past 15 years in the field of reproductive medicine seldom adhere to all recommended methodologic standards. A large majority of these publications evaluated treatments rather than diagnostic interventions. [Copyright &y& Elsevier]