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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]

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]

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]

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]

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]

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]

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]

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 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. [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]

Objective: To determine whether variation in testis-specific protein Y-encoded (TSPY) gene copy number affects semen quality. Design: Nested case-control study. Setting: University hospital. Patient(s): From a consecutive cohort of 1,016 male partners of subfertile couples, unselected for sperm counts, we selected as cases 100 men with the lowest total number of progressively motile sperm (TMC) and as controls, 100 men with the highest total number of progressively motile sperm. Intervention(s): Quantitative real-time polymerase chain reaction (PCR) and Southern blot to determine TSPY copy number. Main Outcome Measure(s): TSPY copy number. Result(s): The quantitative PCR method showed excellent agreement with the Southern blot analysis. Cases had a median TSPY copy number of 35 (range 20–73), whereas controls had a median TSPY copy number of 34 (range 26–76). This difference was not statistically significant. Conclusion(s): We found no association between TSPY copy numbers and severe spermatogenic failure. The observed variation in TSPY copy number therefore appears to have no functional consequences for semen quality. [ABSTRACT FROM AUTHOR]

Objective: To investigate the preference for preimplantation genetic diagnosis (PGD) as an alternative to prenatal diagnosis (PND) in a large group of couples representing a wide array of genetic disorders. We also investigated the couple's familiarity with PGD and presented time trade-off scenarios for PGD versus PND, as PGD treatment is regularly accompanied by waiting lists.Design: Questionnaire study.Setting: Patient organizations representing genetic disorders.Patient(s): A total of 210 couples carrying genetic disorders.Main Outcome Measure(s): Preference for PGD or PND and familiarity with PGD in carrier couples.Result(s): Fifteen organizations representing 38 genetic disorders agreed to participate. Nine hundred eighty-three couples responded. In total 210 couples were in their reproductive years (women 18-40 years) and had a desire to conceive. Ninety couples (42%) had never heard of PGD. After they were informed, 127 couples (60%) wanted to have diagnostic testing (PND or PGD) performed. Ninety-four (74%) of these couples preferred testing with PGD. When no waiting list was used 102 couples (80%) preferred PGD. With a 2-year waiting list for PGD, 58 couples (46%) would opt for PGD.Conclusion(s): Many carrier couples are unaware of the existence of PGD. When informed, most couples prefer PGD more than PND. The preference for PGD decreases with longer waiting lists. [ABSTRACT FROM AUTHOR]

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 &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 semen parameters during the natural course of asymptomatic human immunodeficiency virus-1 (HIV-1) infection. Design: A longitudinal cohort study. Setting: HIV outpatient clinic of the Academic Medical Center in Amsterdam, the Netherlands. Patient(s): 55 men infected with HIV-1, with infection of variable duration but without previous or current antiretroviral therapy. Intervention(s): Biannual blood and semen analyses. Main Outcome Measure(s): We examined the changes in semen parameters over time using a repeated measurements mixed-effects model. Result(s): The mean follow-up period was 77 weeks (interquartile range: 39 to 111 weeks). The mean CD4 cell count showed a statistically significant decline from 480 to 400 cells/mm3, and the mean blood plasma HIV-1 RNA concentration showed a statistically significant increase from 4.1 to 4.3 log10 copies/mL. None of the semen parameters showed any statistically significant change over time. Conclusion(s): Prolonged exposure to asymptomatic, untreated HIV-1 infection does not affect semen quality. These findings should be reassuring for untreated men infected with HIV-1 who wish to father a child, and they also provide relevant background information for studies investigating the potential effect of antiretroviral therapy on semen quality. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

Previous association studies that described the effect of an enlarged CAG repeat length in the Androgen Receptor (AR) gene on spermatogenesis could not prove or refute a true association because of methodological weaknesses. Here, we clearly show that there is no association between CAG repeat length variation and semen quality. [Copyright &y& Elsevier]

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

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. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

Objective: To validate a published model for the prediction of the individual FSH response dose for gonadotropin induction of ovulation in polycystic ovary syndrome (PCOS). Design: Structured, complete, and carefully monitored patient-based data collection to test the external validity of the prediction model. Setting: Twenty-nine hospitals in The Netherlands. Patient(s): Eighty-five clomiphene citrate (CC)–resistant women with PCOS. Intervention(s): Ovulation induction in a chronic low-dose step-up FSH regimen. Main Outcome Measure(s): Predicted individual FSH response dose, defined as follicle growth >10 mm in diameter on ultrasound. Result(s): The model, using the women’s body mass index, CC response, initial serum FSH level, and initial serum insulin-to-glucose ratio was studied in the validation sample. Overall, the FSH response dose predicted by the model was higher than the observed response dose. The predictive performance of the model was poor, with an R 2 of 0.11, and the average prediction error was 35 IU. Conclusion(s): The external validity of the model predicting the individual FSH response dose was inadequate in women with CC-resistant PCOS undergoing ovulation induction with recombinant FSH in a low-dose step-up regimen. [Copyright &y& Elsevier]

To assess the performance and clinical value of the postwash total motile sperm count (postwash TMC) as a test to predict intrauterine insemination (IUI) outcome.Meta-analysis of diagnostic tests.Tertiary fertility center.Patients undergoing IUI.None.We detected 16 studies that reported on postwash TMC at insemination and IUI outcome. Summary receiver operating characteristics (ROC) curves indicated a reasonable predictive performance toward IUI outcome, and, at cut-off levels between 0.8 to 5 million motile spermatozoa, the postwash TMC provided a substantial discriminative performance. At these cut-off levels, the specificity of the postwash TMC, defined as the ability to predict failure to become pregnant, was as high as 100%; the sensitivity of the test, defined as the ability to predict pregnancy, was limited.The postwash TMC at insemination could potentially be used in counseling patients for either IUI or IVF. However, to enable patient counseling before the start of treatment, further studies are needed to establish the accuracy of a postwash TMC during the fertility workup rather than at insemination. [Copyright &y& Elsevier]

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, 3,371 couples were included who underwent 14,968 cycles. There were 1,229 (8.2%) pregnancies, of which 1,000 (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. [Copyright &y& Elsevier]

: ObjectiveTo compare the effectiveness of hMG and recombinant FSH after down-regulation for ovulation stimulation in assisted reproductive cycles.: DesignMeta-analysis.: SettingInfertility centers providing assisted reproductive techniques.: Patient(s)Two thousand thirty women undergoing IVF or ICSI.: Intervention(s)Ovarian hyperstimulation with hMG or recombinant FSH after down-regulation.: Main outcome measure(s)Clinical pregnancy rate, ongoing pregnancy/live birth rate, gonadotropin dose used, oocytes retrieved, implantation rate, miscarriage rate, and multiple pregnancy rate.: Result(s)Six randomized controlled trials were included. In all trials, the group of women treated with hMG had higher pregnancy rates. Pooling the five trials that used a long GnRH agonist protocol resulted in a higher clinical pregnancy rate for hMG compared with recombinant FSH (relative risk, 1.22 [95% CI, 1.03 to 1.44]). However, there was no evidence of a difference in rates of ongoing pregnancy or live birth per woman between hMG recipients and recombinant FSH recipients (relative risk, 1.20 [95% CI, 0.99 to 1.45]). No differences were found in gonadotropin dose used, oocytes retrieved, miscarriage rate, or multiple pregnancy rate.: Conclusion(s)Use of hMG resulted in higher clinical pregnancy rates than did use of recombinant FSH in IVF/ICSI cycles after GnRH agonist down-regulation in a long protocol. [Copyright &y& Elsevier]

Objective: To study the genetic cause of infertility in a family with five infertile brothers.Design: Case report.Settings: Center for reproductive medicine at a university medical center.Patient(s): Five brothers presenting with primary infertility due to severely impaired spermatogenesis; also, their parents and two other paternally related family members.Intervention(s): Fluorescence in situ hybridization and sequence family variant analysis was performed in leukocyte DNA to determine the number of deleted in azoospermia (DAZ) genes. Linkage analysis was performed for X chromosome inheritance, and mitochondrial DNA (mtDNA) was screened for mutations.Main Outcome Measure(s): DAZ gene copy number, X chromosome linkage, and mtDNA sequence.Result(s): With conventional polymerase chain reaction (PCR) analysis, no deletions of the AZFc region were found, but with fluorescence in situ hybridization and sequence family variant analysis, only two DAZ genes instead of four were detected in all individuals tested. The five brothers did not share an identical X chromosomal locus, and no mutations were found in the mtDNA of the index patient.Conclusion(s): A reduced copy number of the DAZ genes is found in five infertile brothers with severely impaired spermatogenesis, as well as in their normospermic father and in two other fertile paternally related family members. This illustrates that the phenotype associated with a reduced copy number of the DAZ genes can be extremely variable. [ABSTRACT FROM AUTHOR]

: ObjectiveTo study the genetic cause of infertility in a family with five infertile brothers.: DesignCase report.: SettingCenter for reproductive medicine at a university medical center.: Patient(s)Five brothers presenting with primary infertility due to severely impaired spermatogenesis; also, their parents and two other paternally related family members.: Intervention(s)Fluorescence in situ hybridization and sequence family variant analysis was performed in leukocyte DNA to determine the number of deleted in azoospermia (DAZ) genes. Linkage analysis was performed for X chromosome inheritance, and mitochondrial DNA (mtDNA) was screened for mutations.: Main outcome measure(s)DAZ gene copy number, X chromosome linkage, and mtDNA sequence.: Result(s)With conventional polymerase chain reaction (PCR) analysis, no deletions of the AZFc region were found, but with fluorescence in situ hybridization and sequence family variant analysis, only two DAZ genes instead of four were detected in all individuals tested. The five brothers did not share an identical X chromosomal locus, and no mutations were found in the mtDNA of the index patient.: Conclusion(s)A reduced copy number of the DAZ genes is found in five infertile brothers with severely impaired spermatogenesis, as well as in their normospermic father and in two other fertile paternally related family members. This illustrates that the phenotype associated with a reduced copy number of the DAZ genes can be extremely variable. [Copyright &y& Elsevier]

: ObjectiveTo determine the number of DAZ gene clusters in the Y-bearing spermatozoa of patients who underwent intracytoplasmic sperm injection (ICSI) and to compare the outcome with the number of clusters found in the spermatozoa of normospermic men.: DesignProspective study.: SettingAcademic hospital.: Patient(s)Forty-seven patients with impaired spermatogenesis who were attending our clinic for ICSI and 56 semen donors.: Intervention(s)Peripheral blood was drawn to obtain somatic DNA for polymerase chain reaction (PCR) analysis and leukocytes for karyotyping and FISH analysis. Three-color FISH was performed on the spermatozoa remaining after ICSI and on the spermatozoa of semen donors to determine the presence of the X and Y chromosome as well as the number of DAZ gene clusters.: Main outcome measure(s)Number of DAZ gene clusters in Y-bearing spermatozoa.: Result(s)Five patients had only one DAZ gene cluster, one patient had a complete AZFc deletion, and one patient had three clusters on average. One of the semen donors also showed three DAZ gene clusters in his Y-bearing spermatozoa. None of the semen donors had only one DAZ gene cluster.: Conclusion(s)Besides complete AZFc deletions, partial deletions are also associated with impaired spermatogenesis. As a result, these partial deletions that are not recognized by routine PCR are reintroduced into the population by the ICSI technique. [Copyright &y& Elsevier]

Objective: To evaluate the capacity of baseline characteristics and total motile sperm count (TMC) to predict total fertilization failure (TFF) in patients undergoing IVF.Design: Retrospective cohort study.Setting: University hospital.Patient(s): Eight hundred ninety-two couples with a total of 1,569 consecutive IVF cycles.Intervention(s): Prewash and postwash TMC during fertility workup and at the time of ovum pickup (OPU).Main Outcome Measure(s): Analysis of logistic regression and the receiver operating characteristic curve were used to determine which variables could be used to predict TFF.Result(s): The area under the curve (AUC) for prewash TMC during fertility workup was 0.72, similar to a combination of pre- and postwash TMC. At the time of OPU, both pre- and postwash TMC had an AUC of 0.73. A model based on selected baseline characteristics (male age, number of IVF cycles, indication for IVF, and prewash TMC during fertility workup) had an AUC of 0.75. A model at the time of OPU, including the number of oocytes, had an AUC of 0.80.Conclusion(s): The use of both models, one before start of the IVF cycle and one at the time of OPU, allows an accurate prediction of the chance of TFF and is useful in counseling patients on whether to opt for IVF or ICSI. [ABSTRACT FROM AUTHOR]

Anxiety and the willingness to undergo ART was assessed by the State-Trait Anxiety Inventory and by trade-off at increasing hypothetical HIV-1 transmission risks in fifty serodiscordant couples undergoing intrauterine inseminations as a risk-reduction strategy. Both men and women displayed high state anxiety levels, but despite their anxiety, women were prepared to take high risks to fulfill their desire for a child. [Copyright &y& Elsevier]

Mutation screening of the BOULE gene in 156 men with azoospermia or severe oligozoospermia revealed no relevant mutations; thus, mutations in BOULE can be eliminated as a major cause of impaired spermatogenesis. [Copyright &y& Elsevier]

The most appropriate primary outcome measure for reproductive medicine has been discussed frequently. In 2003 the European Society for Human Reproduction and Embryology recommended that the outcome measure of assisted reproductive technology (ART) and non-ART should be singleton live birth. Although live birth is indeed the aim of clinical practice, and there is no discussion that it should be reported in infertility trials, we hereby provide arguments that plead for using ongoing pregnancy as the primary outcome in such trials. We feel that ongoing pregnancy best serves the many purposes of a primary outcome and best reflects the effectiveness of a treatment. [Copyright &y& Elsevier]

Objective: To collect published data on spermatogonial quantity in the testes of healthy children and calculate the reference values of spermatogonial quantities throughout prepuberty.Design: Systematic literature search in PubMed and EMBASE focusing on the number of spermatogonia per transverse tubular cross section (S/T) and spermatogonial density per cubic centimeter (cm(3)) of testicular volume (S/V) throughout prepuberty.Setting: None.Patient(s): None.Intervention(s): None.Main Outcome Measure(s): Polynomial meta-regression analyses of S/T and S/V of healthy boys from the ages of 0 to 14 years.Result(s): We found six papers describing original quantitative data on S/T and S/V of healthy boys (total n = 334 and 62, respectively) that were suitable for meta-analysis. Polynomial meta-regression analyses of S/T and S/V demonstrated a clear pattern of spermatogonial quantity throughout prepubertal life. This consisted of a decline during the first 3 years of life, a gradual increase until the ages of 6 to 7 years, a plateau until the age of 11 years, and a sharp incline reaching pubertal numbers at 13 to 14 years of age. The association between S/T and S/V allowed us to perform S/T to S/V extrapolation, creating reference S/V (rS/V) values throughout prepubertal life from a cohort of 372 boys.Conclusion(s): Spermatogonial quantity varies during testicular development toward puberty. The values found in this study may serve as a baseline clinical reference to study the impact of diseases and adverse effects of gonadotoxic treatments on spermatogonial quantity in prepubertal testes. Spermatogonial quantity reference values may also help to evaluate the quality of testicular biopsy samples acquired for fertility preservation of prepubertal boys. [ABSTRACT FROM AUTHOR]

Objective To study risk of birth asphyxia and related morbidity among term singletons born after medically assisted reproduction (MAR). Design Population cohort study. Setting Not applicable. Patient(s) A total of 1,953,932 term singleton pregnancies selected from a national registry for 1999–2011. Intervention(s) None. Main Outcome Measure(s) Primary outcome Apgar score <4; secondary outcomes Apgar score <7, intrauterine fetal death, perinatal mortality, congenital anomalies, small for gestational age, asphyxia related morbidity, and cesarean delivery. Result(s) The risks of birth asphyxia and related morbidity were calculated in women who conceived either through MAR or spontaneously (SC), with a subgroup analysis for in vitro fertilization (IVF). An additional propensity score matching analysis was performed with matching on multiple maternal baseline covariates (maternal age, ethnicity, socioeconomic status, parity, year of birth, and preexistent diseases). Each MAR pregnancy was matched to three SC controls. Relative to SC, the MAR singletons had an increased risk of adverse neonatal outcomes including Apgar score <4 (adjusted odds ratio [OR] 1.29; 95% CI, 1.14–1.46) and intrauterine fetal death (adjusted OR 1.61; 95% CI, 1.35–1.91). After propensity score matching, the risk of an Apgar score <4 was comparable between MAR and SC singletons (OR 0.99; 95% CI, 0.87–1.14). Cesarean delivery for both fetal distress and nonprogressive labor occurred more among MAR pregnancies compared with SC pregnancies. Conclusion(s) Term singletons conceived after MAR have an increased risk of morbidity related to birth asphyxia. Because this is mainly due to maternal characteristics, obstetric caregivers should be aware that the increased rates of cesareans reflect the behavior of women and physicians rather than increased perinatal complications. [ABSTRACT FROM AUTHOR]

Objective: To study whether acute lymphoblastic leukemia (ALL) cells survive in a human testicular cell culture system. Design: Experimental laboratory study. Setting: Reproductive biology laboratory, academic medical center. Patient(s): Acute lymphoblastic leukemia cells from three patients and testicular cells from three other patients. Intervention(s): Acute lymphoblastic leukemia cells were cultured alone or in combination with testicular cells, at various concentrations, in a system that has recently been developed to propagate human spermatogonial stem cells. Main Outcome Measure(s): Viability of ALL and testicular cells during culture was evaluated by flow cytometry using markers for live/dead cells. Furthermore, the presence of ALL cells among testicular cells was determined by highly sensitive (1:10,000 to 1:100,000 cells) patient-specific antigen-receptor minimal residual disease polymerase chain reaction. The presence of spermatogonia at the end of culture was determined by reverse transcription–polymerase chain reaction for ZBTB16, UCHL1, and GPR125. Result(s): The ALL cells cultured separately did not survive beyond 14 days of culture. When cultured together with testicular cells, even at extremely high initial concentrations (40% ALL cells), ALL cells were undetectable beyond 26 days of culture. Reverse transcription–polymerase chain reaction confirmed the presence of spermatogonia at the end of the culture period. Conclusion(s): Our pilot study shows that the described testicular cell culture system not only allows for efficient propagation of spermatogonial stem cells but also eliminates contaminating ALL cells. [ABSTRACT FROM AUTHOR]

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]