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The scope of female fertility preservation through cryopreservation of oocytes or ovarian cortex has widened from mainly oncological indications to a variety of fertility-threatening conditions. So far, no specific universally accepted denomination name has been given to cryopreservation of oocytes or ovarian cortex for the prevention of age-related fertility decline. We argue that the commonly used phrases 'social' and 'nonmedical freezing' to denote the indication for cryopreservation are not entirely correct. We suggest 'AGE banking', as this has not only the advantage of being catchy but also depicts the exact indication for the strategy, anticipated gamete exhaustion. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the extent to which test accuracy studies published in two leading reproductive medicine journals in the years 1999 and 2004 adhered to the Standards for Reporting of Diagnostic Accuracy (STARD) initiative parameters, and to explore whether the introduction of the STARD statement has led to an improved quality of reporting. Design: Structured literature search. Articles that reported on the diagnostic performance of a test in comparison with a reference standard were eligible for inclusion. For each article we scored how well the 25 items of the STARD checklist were reported. These items deal with the study question, study participants, study design, test methods, reference standard, statistical methods, reporting of results, and conclusions. We calculated the total number of reported STARD items per article, summary scores for each STARD item, and the average number of reported STARD items per publication year. Setting: Not applicable. Patient(s): Not applicable. Intervention(s): Not applicable. Main Outcome Measure(s): Quality of reporting. Result(s): We found 24 studies reporting on test accuracy in reproductive medicine in 1999 and 27 studies in 2004. The mean number of reported STARD items for articles published in 1999 was 12.1 ± 3.3 (range 6.5–20) and 12.4 ± 3.2 (range 7–17.5) in 2004, after publication of the STARD statement. Overall, less than half of the studies reported adequately on 50% or more of the STARD items. The reporting of individual items showed a wide variation. There was no significant improvement in mean number of reported items for the articles published after the introduction of the STARD statement. Conclusion(s): Authors of test accuracy studies in the two leading fertility journals poorly report the design, conduct, methodology, and statistical analysis of their study. Strict adherence to the STARD guidelines should be encouraged. [Copyright &y& Elsevier]

Are unmet needs for psychosocial counselling, peer support and friends/family support in parents directly and/or indirectly related to the mental health of parents and their donor-children? A cross-sectional sample of 214 parents participated in this quantitative study via an online questionnaire. The sample comprised mothers and fathers in a heterosexual relationship (n = 85), mothers in a lesbian relationship (n = 67) and single mothers (n = 62). Parents were recruited via three Dutch fertility clinics and four network organizations. Unmet support needs were measured with an adapted version of the Unmet Needs for Parenting Support questionnaire, changing the original items into items about donor conception. The items were derived from a qualitative study and checked by experts in donor conception. The parents' mental health was measured with the Adult Self Report and the donor-children's mental health with the Child Behaviour Checklist. A multigroup mediation analysis was conducted to explore relationships between parents' unmet support needs and their child's mental health, with the parents' mental health as a possible mediator. There were no direct relations between parents' unmet support needs and the mental health of donor-children. Unmet needs for psychosocial counselling, peer support and friends/family support for parents and children's mental health were indirectly related through the mental health of the parents: 0.074 (CI 95% = 0.013–0.136; P = 0.017), 0.085 (CI 95% = 0.018–0.151; P = 0.036) and 0.063 (CI 95% = 0.019–0.106; P = 0.013), respectively. We recommend that fertility clinics, network organizations and authorities for infertility counsellors make their support available to parents for extended periods after their treatment. Further qualitative studies are necessary to assess how to relieve unmet support needs during donor sperm treatment. [ABSTRACT FROM AUTHOR]

The article presents a study on staining of haematoxylin and eosin and the expression of the mammalian target of rapamycin (mTOR) signalling pathway proteins in various developmental stage testes in rats. It informs that the study included an eight-week old rat and mTOR immunohistochemistry in the testis was noted at several developmental stages. The study shows that mTOR affect spermatogenesis through regulation of spermatogonia proliferation.

Women who face age-related fertility decline have the option to safeguard future reproductive potential by banking oocytes or ovarian tissue. What are the methods that women prefer and what factors are important in their decision-making? Qualitative interview study, participants were recruited through monthly information sessions at a university hospital on oocyte banking, postings on social media, websites and newsletters and snowball sampling. Women had to be aged 35 years or older, single, childless and with a possible future desire for motherhood. Key concepts of the Health Belief Model were used as framework for the analyses. In total, 15 women participated in this qualitative study. For oocyte banking, they mentioned chances of success, extra time and faith in the technique and healthcare professionals as benefits. Risks for themselves or future children and costs were considered to be barriers in decision making. For ovarian tissue banking, the chances of success, the possibility of natural conception, the time investment and effect on menopausal symptoms were seen as benefits, and lack of experience and lack of information were considered barriers for themselves or their future children. Overall, they considered the procedures involved in oocyte banking as relatively 'easy', whereas ovarian tissue banking was seen as a more invasive procedure. Most women preferred oocyte banking over ovarian tissue banking because of its relative convenience. Future quantitative research in a larger cohort is necessary to confirm the findings and provide more insight into the relative importance of the different factors influencing women's decision. [ABSTRACT FROM AUTHOR]

The techniques of vitrification of oocytes and the subsequent warming process being used today are now producing results far superior to the results that are obtained with slow-freezing techniques, and it would seem that this is the method of female fertility preservation that will be widely used in the near future. The reported success of the use of this method should stimulate a renewed debate on oocyte storage for fertility preservation without a medical indication. [Copyright &y& Elsevier]

Abstract Research question What are the reproductive outcomes of women who bank oocytes for fertility preservation? Design A prospective follow-up study of a cohort of 327 women who banked their oocytes for fertility preservation was carried out between July 2009 and August 2015. The indications for oocyte banking and outcomes of ovarian stimulation were collected from medical files. Follow-up data were obtained from an additional questionnaire. Results In total, 243 out of 327 women (74%) responded and 228 women (70%) consented to participate and returned the questionnaire. The median time to follow-up of these women was 31 months. A total of 101 women (44%) were trying, or had tried, to become pregnant after oocyte banking, of which 66 became pregnant (65%). Five women reported an unintended pregnancy. Of these, 71 women became pregnant, 76% conceived naturally, 7% through intracytoplasmic sperm injection with their vitrified–warmed oocytes and 17% by other medically assisted reproduction treatments. Six women attempted to achieve a pregnancy using their banked oocytes. Of the six pregnancies achieved in five women, two resulted in a live birth. A total of thirty-eight women reported a live birth at the time of follow-up. Conclusion : Oocyte banking can be considered a form of risk management or preventive medicine because it is not certain that the women will experience sterility in the future. [ABSTRACT FROM AUTHOR]

What is the risk of hypogonadism in men with obstructive azoospermia, non-obstructive azoospermia (NOA) or Klinefelter syndrome after testicular sperm extraction (TESE)? This prospective longitudinal cohort study was carried out between 2007 and 2015. Around 36% of men with Klinefelter syndrome, 4% of men with obstructive azoospermia and 3% of men with NOA needed testosterone replacement therapy (TRT). Klinefelter syndrome was strongly associated with TRT while no association was found between obstructive azoospermia or NOA and TRT. Irrespective of the pre-operative diagnosis, a higher testosterone concentration before TESE was associated with a lower chance of needing TRT. Men with obstructive azoospermia or NOA have a similar moderate risk of clinical hypogonadism after TESE, while this risk is much larger for men with Klinefelter syndrome. The risk of clinical hypogonadism is lower when testosterone concentrations are high before TESE. [ABSTRACT FROM AUTHOR]

The selection of embryos based on morphology is still the core of daily laboratory practice in IVF/intracytoplasmic sperm injection. At present, the selection of embryos is primarily based on experience and local protocols. Since an evidence-based ranking strategy for embryos on day 3 is currently lacking, this work constructed a multivariable prediction model to rank embryos according to their implantation potential. A total of 6021 fresh embryo transfers between January 2004 and July 2009 were included, eight potential predictive factors were evaluated and a prediction model was developed using multivariable logistic regression. The model was externally validated with data from couples treated between August 2009 and September 2011 in the same clinic. Five factors were included in the final prediction model: early cleavage, number of blastomeres on days 2 and 3 and morphological score and presence of morula on day 3. With validation, the model showed moderate discriminative capacity (c-statistic 0.70) and calibrated well and was able to distinguish embryos with high ongoing implantation potential from embryos with moderate or low ongoing implantation potential. The model can be used by embryologists as an objective tool to rank embryos according to implantation potential, thereby aiding the selection of embryos for transfer. [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 investigate patient preferences and trade-offs for laparoscopic electrocautery of the ovaries relative to ovulation induction with recombinant FSH (rFSH) in patients with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). Design: Assessment of preferences and trade-offs in a randomized controlled trial. Setting: Academic hospital. Patient(s): Thirty-two CC-resistant patients with PCOS who had been randomly assigned to either laparoscopic electrocautery of the ovaries or ovulation induction with rFSH and 32 control patients with PCOS under treatment with CC. Intervention(s): Preference for laparoscopic electrocautery relative to rFSH was established during an interview. Trade-offs between treatment burden and effectiveness were evaluated by varying hypothetical pregnancy rates after laparoscopic electrocautery until patients switched in their initial preference. Main Outcome Measure(s): Preference for laparoscopic electrocautery of the ovaries; trade-off between burden and effectiveness of treatment. Result(s): The majority of the patients would prefer electrocautery of the ovaries over ovulation induction with rFSH if both treatment strategies resulted in similar pregnancy rates. However, most patients were willing to trade off their preference for increased effectiveness: the percentage of patients who preferred electrocautery over rFSH sharply declined when the difference in hypothetical pregnancy rates was more than 5% in favor of rFSH. Conclusion(s): Patients with polycystic ovary syndrome are well able to express an informed preference for laparoscopic electrocautery of the ovaries or ovulation induction with rFHS. Preferences are guided by features of the respective treatments but seem to be dominated by their effectiveness and safety. [Copyright &y& Elsevier]

What are the unmet needs after psychosocial counselling and mental health of women who opt for donor sperm treatment (DST), and are unmet counselling needs related to their mental health? This quantitative study included women in a heterosexual relationship (n = 19), women in a lesbian relationship (n = 25) and single women (n = 51) who opted for DST. Women were included if they had passed the DST intake procedure at a Dutch fertility clinic, were not pregnant and had no previous donor-child. Unmet needs were measured by a self-developed questionnaire based on specific topics identified in a previous qualitative study with added items from experts in the field of DST. The Adult Self Report was used to measure mental health. Relationships between unmet counselling needs and mental health were explored by multiple regression analyses. Fifty-two women (55%) reported unmet counselling needs. Women in heterosexual relationships mostly had unmet counselling needs on the topics of the decision to opt for DST (n = 11, 58%) and non-genetic parenthood (n = 11, 58%); women in lesbian relationships (n = 10, 40%) and single women (n = 14, 27%) mostly had unmet needs on the topic of choosing a sperm donor. In general, women had good mental health, but 13 (14%) met the criteria for clinical mental health problems. Women with more unmet counselling needs also had more mental health problems. Evidence-based guidelines for psychosocial counselling in DST should be developed. Only then can counselling be improved and be fit for purpose. [ABSTRACT FROM AUTHOR]

What valid guideline-based quality indicators can measure quality of care in early pregnancy assessment units (EPAU)? The systematic RAND-modified Delphi method was used to develop an indicator set from four evidence-based guidelines. An international expert panel was assembled to extract recommendations from these guidelines to establish quality indicators. A total of 119 recommendations were extracted. Eleven recommendations received a high median score and top five score above the 75th percentile and were selected as key recommendations. The expert panel reassessed 15 high score recommendations and top five score between the 50th and 75th percentile as well as one high score recommendation without consensus. Eight of these 16 recommendations were selected in the second round as key recommendations. The key recommendations were formulated into a set of 19 quality indicators, summarized as follows: women referred to an EPAU could be seen within 24 h and receive a clear explanation on treatment options; designated senior staff members could be responsible for the unit and staff could have had ultrasound training; protocols could be available for daily practice covering all treatment options for miscarriage and ectopic pregnancy; and an EPAU could have access to urine pregnancy testing and serum HCG assays. Nineteen quality indicators to measure early pregnancy care provided by EPAU were identified. [ABSTRACT FROM AUTHOR]

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? 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. 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. 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. [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]

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). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Trials assessing effectiveness in medically assisted reproduction (MAR) should aim to study the desired effect over multiple cycles, as this reflects clinical practice and captures the relevant perspective for the couple. The aim of this study was to assess the extent to which multiple cycles are reported in MAR trials. A sample of randomized controlled trials (RCT) was collected on MAR, published in four time periods, in 11 pre-specified peer-reviewed journals; 253 trials were included: 196 on IVF, 37 on intrauterine insemination and 20 on ovulation induction. Forty-eight (19%) reported on multiple cycles, which was significantly more common in trials on intrauterine insemination and ovulation induction compared with trials on IVF ( P < 0.01). Both trials on IVF were multi-centre trials, and those using live birth as primary outcome, reported significantly more often on multiple cycles (OR 3.7 CI 1.1 to 12.5) and (OR 8.7 CI 1.8 to 40.3), respectively. Trials designed to compare protocol variations reported multiple cycles less often (OR 0.07 CI 0.01 to 0.74). Most RCT on MAR, especially those on IVF, do not report cumulative pregnancy rates. As not all women become pregnant in their first cycle, the clinical significance of these trials is limited. [ABSTRACT FROM AUTHOR]

Objective: To compare dropout rates in couples undergoing conventional in vitro fertilization with single embryo transfer (IVF-SET), in vitro fertilization in a modified natural cycle (IVF-MNC) or intrauterine insemination with ovarian stimulation (IUI-OS).Study Design: Secondary analysis of a multicentre randomized controlled trial between January 2009 and February 2012. 602 couples with unexplained or mild male subfertility, allocated to IVF-SET (N=201), IVF-MNC (N=194) and IUI-OS (N=207).Main Outcome Measures: Dropouts, defined as couples who discontinued their allocated three cycles of IVF-SET, six cycles of IVF-MNC or IUI-OS, without having achieved a pregnancy. We classified dropouts as "following medical advice" or "patient initiated".Result(s): Thirty couples (15%) allocated to IVF-SET dropped out and 45 couples (23%) allocated to IVF-MNC, compared to 26 couples (13%) allocated to IUI-OS; relative risk (RR) 1.2 (95%CI; 0.73-1.9) for IVF-SET and 1.9 (95%CI; 1.2-2.9) for IVF-MNC, both compared to IUI-OS. Nine couples (4.5%) allocated to IVF-SET, 14 (7.2%) allocated to IVF-MNC and 14 (6.8%) allocated to IUI-OS dropped out following medical advice; RR of 0.51 (95%CI; 0.21-1.2) for IVF-SET and 0.84 (95%CI; 0.39-1.80) for IVF-MNC, both versus IUI-OS. Twenty-one couples (10%) allocated to IVF-SET were patient initiated dropouts, as were 31 (16%) allocated to IVF-MNC and 12 (5.8%) allocated to IUI-COS; RR 1.8 (95%CI; 0.91-3.6) for IVF-SET and 2.8 (95%CI; 1.5-5.2) for IVF-MNC both versus IUI-OS.Conclusion(s): IVF-SET and IUI-OS result in comparable drop-out rates, while drop-out rates after IVF-MNC are almost twice as high, mainly driven by patient preferences. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To assess the capacity of the postcoital test (PCT) to predict pregnancy in WHO II anovulatory women who are ovulatory on clomiphene citrate (CC). In these women, an abnormal PCT result could be associated with lower pregnancy chances, but this has never been proven or refuted.Study Design: Prospective cohort study was performed between December 2009 and September 2012 for all women who started ovulation induction with CC in one university clinic and two teaching hospitals in the Netherlands. A PCT was performed in one of the first three ovulatory cycles. Ovulation induction with CC was continued for at least six cycles. The PCT was judged to be positive if at least one progressive motile spermatozo was seen in one of five high power fields at 400× magnification. The primary outcome was time to ongoing pregnancy, within six ovulatory cycles.Results: In 152 women the PCT was performed. 135 women had a reliable, well-timed PCT. The ongoing pregnancy rate was 44/107 (41%) for a positive and 10/28 (36%) for a negative PCT. The hazard rate for ongoing pregnancy was 1.3 (95% CI 0.64-2.5) for a positive versus a negative PCT. Thirty five of 77 (46%) women with clear mucus had an ongoing pregnancy versus 12 of 45 (27%) women in whom the mucus was not clear (HR 2.0; 95% CI 1.02-3.84, p=0.04).Conclusion: The present study suggests that the outcome of the postcoital test in women with WHO-II anovulation that undergo ovulation induction with CC does not have a large effect on ongoing pregnancy chances over time. [ABSTRACT FROM AUTHOR]

Objective: Acute fertility preservation for women is an interdisciplinary treatment that requires adequate information provision and early referral. This quality management project aimed to improve fertility preservation care by using a practical tool: Strengths, Weaknesses, Opportunities and Threats (SWOT) analysis.Study Design: Quality management project was executed between May 2011 and July 2013. This project has been executed in a university affiliated IVF-clinic in cooperation with two oncological sites and used a four-step strategy: (1) monitoring baseline referral process, (2) exploring baseline fertility preservation program by Strengths, Weaknesses, Opportunities and Threats' (SWOT)-analysis, (3) setting up a new fertility preservation program and (4) evaluating the new fertility preservation program by means of SWOT-analysis.Results: During the three-months monitoring period, fertility preservation was requested for a total of 126 women. The mean age of the women was 33.8 years old (range 1-42 years old). Most requests came from women who wanted to cryopreserve oocytes because of age-related decline of fertility (n=90; 71%). Most requests for acute fertility preservation concerned women with breast cancer (n=16; 57%). Information leaflets and pre-consultation questionnaires for women improved the quality of first fertility preservation consultation as evaluated by final SWOT-analysis. Collaboration with oncological centres and information about fertility preservation improved the referral process.Conclusions: SWOT-analysis proved useful for setting up a new fertility preservation-program and can be recommended as a tool to improve the management and organisation of new types of reproductive care. [ABSTRACT FROM AUTHOR]

Objective To study the impact on health-related quality of life (HRQoL) of treatment with systemic methotrexate (MTX) or expectant management in women with ectopic pregnancy or pregnancy of unknown location (PUL) with low and plateauing serum hCG concentrations. Study design HRQoL was assessed alongside a randomized clinical trial (RCT) with the use of standard self-administered psychometric measure questionnaires. Patients and setting All women who participated in the multicenter RCT comparing treatment with systemic MTX to expectant management in women with ectopic pregnancy or persisting PUL were eligible for the HRQoL measurements. Main outcome measure HRQoL measures of three standardized questionnaires (SF-36, RSCL, HADS). Results Data were available for 64 of 73 women (78%) randomized in the RCT. We found no difference in HRQoL between the two treatment groups. The need for additional treatment, i.e. additional MTX injections or surgical intervention, had no impact on HRQoL. Conclusion Women treated with MTX or expectant management for an ectopic pregnancy or persisting PUL have comparable quality of life. [ABSTRACT FROM AUTHOR]

In this observational study, the effect of the introduction of the first Early Pregnancy Assessment Unit (EPAU) in a university hospital in The Netherlands in 2008 on early pregnancy care is analysed. Derivatives of quality of care were measured before and after the establishment of the EPAU, with the aim of reducing unnecessary care. Care within three time periods was measured: 2006, 2009 and 2012. In 2006, 14% of women who had experienced a miscarriage were admitted to the hospital, whereas in 2009 and 2012 no women were admitted. The surgical management rate for miscarriage decreased from 79% (2006) to 6% (2009) and 28% (2012). Karyotyping of couples who had experienced recurrent miscarriage decreased from 100% (2006) to 17% (2009) and 33% (2012). The surgical management rate for ectopic pregnancy decreased from 50% (2006) to 25% (2009) and 29% (2012). The mean total cost per woman treated in 2006 was €1111 (95% CI €808 to 1426), €436 (95% CI €307 to 590) in 2009 and €633 (95% CI €586 to 788) in 2012. We can therefore conclude that an EPAU results in higher quality and cost-effective care, and has a positive effect on early pregnancy care. [ABSTRACT FROM AUTHOR]

Intrauterine insemination (IUI), with or without ovarian stimulation, IVF and intracytoplasmatic sperm injection (ICSI) are frequently used treatments for couples with male subfertility. No consensus has been reached on specific cut-off values for semen parameters, at which IVF would be advocated over IUI and ICSI over IVF. The aim of this study was to evaluate the cost-effectiveness of interventions for male subfertility according to total motile sperm count (TMSC). A computer-simulated cohort of subfertile women aged 30 years with a partner was analysed with a pre-wash TMSC of 0 to 10 million. Three treatments were evaluated: IUI with and without controlled ovarian stimulation; IVF; and ICSI. Main outcome was expected live birth; secondary outcomes were cost per couple and the incremental cost-effectiveness ratio. The choice of IVF over IUI with ovarian stimulation and ICSI over IVF depends on the willingness to pay for an extra live birth. If only cost per live birth is considered for each treatment, above a pre-wash TMSC of 3 million, IUI is less costly than IVF and, below a pre-wash, TMSC of 3 million ICSI is less costly. Effectiveness needs to be confirmed in a large randomized controlled trial. [ABSTRACT FROM AUTHOR]

Objective To study the value of a population view in assessing assisted reproductive technology (ART) multiple-gestation infants. Design Descriptive comparison of ART treatment and population statistics in seven developed countries (United States [U.S.], South Korea, United Kingdom, the Netherlands, Australia, Belgium, Denmark) with varying ART utilization and single-embryo transfer (SET) rates. Setting Not applicable. Patient(s) Not applicable. Intervention(s) None. Main Outcome Measure(s) The contribution of ART multiple-gestation infants to the total number of multiple-gestation infants in a population was calculated in relation to utilization of ART and SET rates. Result(s) The number of ART treatments leading to embryo transfer varied from 304 per million inhabitants in the U.S. to 1,518 in Denmark. The percentage of ART cycles that utilized SET varied from 8.8% in South Korea to 53.3% in Australia. Reflecting both utilization rates and SET rates, the percentage of multiple-gestation infants in the population attributed to ART ranged from 14.7% in South Korea to 29.0% in Denmark. Conclusion(s) In seven countries, the contribution of ART multiple-gestation infants to all multiple-gestation infants varies from 14.7% to 29.0%, a percentage that was influenced by both the SET rate per cycle and ART utilization rates. In the monitoring of safety and efficacy of fertility treatment, registration of the percentage of SET cycles alone might not be sufficient. [ABSTRACT FROM AUTHOR]

This study evaluated the cost-effectiveness of treatments for women with polycystic ovary syndrome (PCOS) who ovulate on clomiphene citrate but do not conceive after six cycles. A decision-analytic framework was developed for six scenarios: (1 ) three cycles of IVF; (2) continuation of clomiphene citrate for six cycles, followed by three cycles of IVF in case of no birth; (3) six cycles of gonadotrophins and three cycles of IVF; (4) 12 cycles of gonadotrophins and three cycles of IVF; (5) continuation of clomiphene citrate for six cycles, six cycles of gonadotrophins and three cycles of IVF; (6) continuation of clomiphene citrate for six cycles, 12 cycles of gonadotrophins and three cycles of IVF. Two-year cumulative birth rates were 58%, 74%, 89%, 97%, 93% and 98% and costs per couple were €9518, €7530, €9711, €9764, €7651 and €7684 for scenarios 1-6, respectively. Scenario 2 was the lowest cost option. The extra cost for at least one live birth in scenario 5 was €629 and in scenario 6 €630. In these subjects, continuation of treatment for six cycles of clomiphene citrate, 6 or 12 cycles of gonadotrophins and IVF is potentially cost-effective. These results should be confirmed in a randomized clinical trial. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To assess long-term effects of laparoscopic electrocautery of the ovaries compared with ovulation induction with gonadotropins in women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS) on the incidence of pregnancy complications like gestational diabetes, hypertensive disorders, and metabolic or cardiovascular disease. Design: Long-term follow-up study. Setting: Twenty-eight hospitals within the Netherlands. Patient(s): One hundred sixty-eight CC-resistant women who had participated in a randomized controlled trial between 1998 and 2001 comparing electrocautery and gonadotropins. Intervention(s): Postal questionnaire, search in medical files. Main Outcome Measure(s): Pregnancy complications, metabolic or cardiovascular disease. Result(s): Eighty-two percent of follow-up data were obtained. Thirteen of 68 women (19%) allocated to electrocautery, and 14 of 63 women (22%) allocated to gonadotropins had evidence for pregnancy complications (relative risk 0.86; 95% confidence interval 0.43–1.7). At follow-up, 12 of 69 (17%) women allocated to electrocautery, and 13 of 69 (19%) women allocated to gonadotropins had evidence for metabolic or cardiovascular disease (relative risk 0.90; 95% confidence interval 0.39–2.1). The risk of these was modified by body mass index (BMI), but not by female age or treatment allocation. This study is based on questionnaires and data from medical files. In the absence of routine screening, under-reporting in our follow-up study is likely. Conclusion(s): Electrocautery in women with CC-resistant PCOS does not affect pregnancy complications or metabolic or cardiovascular disease later in life compared with ovulation induction with gonadotropins. [ABSTRACT FROM AUTHOR]

Abstract: 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 &y& Elsevier]

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]

A tailored embryo transfer policy based on the prognostic profile of the couple was prospectively evaluated. Single-embryo transfer (SET) was performed, followed by double-embryo transfer (DET) in frozen--thawed embryo transfer cycles in women with a good prognosis (<35 years, first cycle, ≥1 top-quality embryo). DET was performed in both fresh and frozen cycles in women with an intermediate prognosis (<35 years, first cycle and no top-quality embryo available, or <35 years and ≥1 failed cycles, or 35-38 years). Triple-embryo transfer (TET) in both fresh and frozen cycles was performed in women with a poor prognosis (≥39 years). The cumulative ongoing pregnancy rate in the cycles of women with a good prognosis was 43% with a multiple pregnancy rate of 2%, in the cycles of women with an intermediate prognosis 27% and 23% and in the cycles of women with a poor prognosis 18% and 13%, respectively. These findings can be used to guide current practice: i.e. performing SET in women with a good prognosis and TET in women with a poor prognosis. The embryo transfer strategy in women with an intermediate prognosis requires further improvement, possibly by refining the prognosis according to the ovarian response after ovarian stimulation. [ABSTRACT FROM AUTHOR]

Nowadays ectopic pregnancy often can be diagnosed before the woman’s condition has deteriorated, which has altered the former clinical picture of a life-threatening disease into a more benign condition. This review describes the historical developments in the diagnostic and therapeutic management of ectopic pregnancy leading up to current clinical practice. The first attempts to diagnose ectopic pregnancy originate from the beginning of the 20th century. [ABSTRACT FROM AUTHOR]

Objective: To determine if human oocytes can be infected with HIV-1 via intracytoplasmic injection and to determine the infection threshold. Design: Twenty-eight donated immature and unfertilized human oocytes from HIV-negative women were injected with 4 × 104 HIV-1 virions and 13 oocytes were used as uninjected controls. To determine the infection threshold, 543 cat oocytes were injected with 4 × 104, 4 × 102, or 40 copies of feline immunodeficiency virus (FIV) and 376 oocytes were used as controls. Setting: Academic hospital. Patient(s)/Animal(s): Donated immature human oocytes and mature cat oocytes. Intervention(s): Injection with HIV-1 or FIV. Main Outcome Measure(s): Viral integration as measured by fluorescent in situ hybridization with HIV-1-specific probes or by nested FIV polymerase chain reaction. Result(s): We detected viral integration in three of 28 (11%) human oocytes injected with 4 × 104 copies of HIV-1. When injected with high dose FIV (4 × 104 copies) 16%–49% of cat oocytes showed viral integration. This decreased to 2%–7% and 0.6%–1.8% when an intermediate (4 × 102 copies) or low (40 copies) dose was injected, respectively. Conclusion(s): Human and cat oocytes can be infected with HIV-1 and FIV respectively, when injected with high amounts of virus. The probability of viral integration is extremely low when small amounts of virus particles are injected. Taking into account the small volume injected during intracytoplasmic injection, the chances of viral integration are 0.00002%. [ABSTRACT FROM AUTHOR]

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 &y& Elsevier]

Objective: To study the association between patient-related risk factors and severe maternal morbidity in women with tubal ectopic pregnancy (EP). Furthermore, to identify substandard care factors in clinical care management of EP. Design: Case-control study. Setting: Not applicable. Patient(s): Case subjects were from the LEMMoN study, a prospective nationwide cohort study. Control subjects were from the ESEP study, an international multicenter randomized controlled trial. Intervention(s): Case subjects were women with tubal EP complicated by severe intra-abdominal hemorrhage necessitating blood transfusion of ≥4 units of packed red blood cells peri- or postoperatively. Control subjects were women with tubal EP who were hemodynamically stable and surgically treated. Main Outcome Measure(s): Patient-related risk factors as: maternal age, gestational age, previous EP, Chlamydia infection, pelvic inflammatory disease, assisted reproductive techniques, and serum hCG level. Substandard care categories classified as unawareness of the clinician, misdiagnosis, and nonadherence to the guideline on EP. Result(s): Twenty-nine case subjects and 99 control subjects were included. The mean serum hCG level was significantly higher in case subjects compared with control subjects, but we found no reliable cutoff level of serum hCG to rule out maternal morbidity. Other risk factors did not differ significantly. Substandard care was scored more often in case subjects (43%) than in control subjects (14%), mainly concerning misdiagnosis. Conclusion(s): No patient-related risk factors for severe intra-abdominal hemorrhage in women with tubal EP were identified. Our findings underpin the importance of awareness of EP among young fertile women and care providers and clinical care management according to the guidelines to prevent severe maternal morbidity. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the capacity of the postcoital test (PCT) to predict spontaneous pregnancy in a large cohort study of subfertile couples. Design: Prospective study. Setting: Department of reproductive medicine of 38 hospitals in the Netherlands. Patient(s): Between January 2002 and February 2004, we prospectively included consecutive subfertile couples who had not been evaluated previously for subfertility. Intervention(s): We estimated the contribution of the PCT result to the existing prediction model for spontaneous pregnancy by calculating the adjusted hazard ratio (HR) of an abnormal PCT result. We constructed a second prediction model (PCT model) based on the reference model including the PCT. Main Outcome Measure(s): Primary endpoint in this study was ongoing pregnancy. We evaluated the performance of the PCT model in comparison with the reference model by calculating goodness of fit, discrimination, calibration, and the “net reclassification improvement”. Result(s): We included 3,021 couples of whom 537 (18%) had a spontaneous pregnancy and 55 (1.8%) a nonsuccessful pregnancy; 1,316 (44%) started treatment within 12 months, 824 (27%) neither started treatment nor became pregnant, and 289 (10%) became lost to follow-up within 12 months. The adjusted HR for an abnormal PCT was 0.76 (95% confidence interval [CI]: 0.62 to 0.94). The adjusted HR for an abnormal PCT was 0.63 (95% CI: 0.47 to 0.84) in case of no spermatozoa, 0.81 (95% CI: 0.57 to 1.2) in case of nonmotile spermatozoa, and 1.2 (95% CI: 0.8 to 1.8) in case of motile, nonprogressive spermatozoa. Adding the PCT result to the reference model did not improve goodness of fit. Discrimination was equally poor for the PCT model and the reference model. The calibration plots of both models showed comparably good calibration. The net reclassification improvement of the predictions of the PCT model compared with the reference model was −1.1%. Conclusion(s): This study demonstrated that the PCT has prognostic value but does not add substantially to a prognostic model for spontaneous pregnancy. [Copyright &y& Elsevier]

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 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 (CVw) for five semen parameters. The CVw 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 CVw 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. [ABSTRACT FROM AUTHOR]