Search

This case report describes a couple suffering from infertility secondary to psychogenic anejaculation, which was refractory to all conservative treatment modalities. A first trial of microsurgical vas aspiration in combination with in-vitro fertilization (IVF) resulted in a pregnancy. After 2 years, three more trials of microsurgical vas aspiration in combination with either IVF or subzonal insemination (SUZI) resulted in embryo transfer without pregnancy. Finally, after 3 years, spermatozoa obtained by rectal probe stimulation under general anaesthesia were cryopreserved. A second intracytoplasmic sperm injection (ICSI) procedure using these cryopreserved spermatozoa also resulted in a second pregnancy. Although sperm concentration was in the normal range, in all samples obtained by either rectal probe electrostimulation or microsurgical vas aspiration, motility was <30% in all but two samples. [ABSTRACT FROM PUBLISHER]

Mindfulness witnessed a substantial popularity surge in the past decade, especially as digitally self-administered interventions became available at relatively low costs. Yet, it is uncertain whether they effectively help reduce stress. In a preregistered (OSF https://doi.org/10.17605/OSF.IO/UF4JZ ; retrospective registration at ClinicalTrials.gov NCT06308744 ) multi-site study (n sites  = 37, n participants  = 2,239, 70.4% women, M age  = 22.4, s.d. age  = 10.1, all fluent English speakers), we experimentally tested whether four single, standalone mindfulness exercises effectively reduced stress, using Bayesian mixed-effects models. All exercises proved to be more efficacious than the active control. We observed a mean difference of 0.27 (d = -0.56; 95% confidence interval, -0.43 to -0.69) between the control condition (M = 1.95, s.d. = 0.50) and the condition with the largest stress reduction (body scan: M = 1.68, s.d. = 0.46). Our findings suggest that mindfulness may be beneficial for reducing self-reported short-term stress for English speakers from higher-income countries., (© 2024. The Author(s).)

Study Question: What is the effect of a blended preconception lifestyle programme on reproductive and lifestyle outcomes of couples going through their first 12 months of IVF as compared to an attention control condition?, Summary Answer: This randomized controlled trial (RCT) was stopped prematurely because of the coronavirus disease 2019 (Covid-19) pandemic but the available data did not suggest that a blended preconception lifestyle programme could meaningfully affect time to ongoing pregnancy or other reproductive and lifestyle outcomes., What Is Known Already: Increasing evidence shows associations between a healthy lifestyle and IVF success rates. Lifestyle programmes provided through a mobile phone application have yet to be evaluated by RCTs in couples undergoing IVF., Study Design Size Duration: A multicentre RCT (1:1) was carried out. The RCT started in January 2019 and was prematurely stopped because of the Covid-19 pandemic, leading to a reduced sample size (211 couples initiating IVF) and change in primary outcome (cumulative ongoing pregnancy to time to ongoing pregnancy)., Participants/materials Setting Methods: Heterosexual couples initiating IVF in five fertility clinics were randomized between an attention control arm and an intervention arm for 12 months. The attention control arm received treatment information by mobile phone in addition to standard care. The intervention arm received the blended preconception lifestyle (PreLiFe)-programme in addition to standard care. The PreLiFe-programme included a mobile application, offering tailored advice and skills training on diet, physical activity and mindfulness, in combination with motivational interviewing over the telephone. The primary outcome was 'time to ongoing pregnancy'. Secondary reproductive outcomes included the Core Outcome Measures for Infertility Trials and IVF discontinuation. Changes in the following secondary lifestyle outcomes over 3 and 6 months were studied in both partners: diet quality, fruit intake, vegetable intake, total moderate to vigorous physical activity, sedentary behaviour, emotional distress, quality of life, BMI, and waist circumference. Finally, in the intervention arm, acceptability of the programme was evaluated and actual use of the mobile application part of the programme was tracked. Analysis was according to intention to treat., Main Results and the Role of Chance: A total of 211 couples were randomized (105 control arm, 106 intervention arm). The hazard ratio of the intervention for time to ongoing pregnancy was 0.94 (95% CI 0.63 to 1.4). Little to no effect on other reproductive or lifestyle outcomes was identified. Although acceptability of the programme was good (6/10), considerable proportions of men (38%) and 9% of women did not actively use all the modules of the mobile application (diet, physical activity, or mindfulness)., Limitations Reasons for Caution: The findings of this RCT should be considered exploratory, as the Covid-19 pandemic limited its power and the actual use of the mobile application was low., Wider Implications of the Findings: This is the first multicentre RCT evaluating the effect of a blended preconception lifestyle programme for women and their partners undergoing IVF on both reproductive and lifestyle outcomes. This exploratory RCT highlights the need for further studies into optimal intervention characteristics and actual use of preconception lifestyle programmes, as well as RCTs evaluating effectiveness., Study Funding/competing Interests: Supported by the Research foundation Flanders (Belgium) (FWO-TBM; reference: T005417N). No competing interests to declare., Trial Registration Number: ClinicalTrials.gov Identifier: NCT03790449., Trial Registration Date: 31 December 2018., Date of First Patient’s Enrolment: 2 January 2019., Competing Interests: The authors declare to have no financial or non-financial conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Objectives: Guidelines advise promoting a healthy lifestyle among patients with fertility problems as the lifestyle of women and men proved to be associated with their fertility. Australian fertility nurses were shown to lack access to structured lifestyle modification programmes, although they value healthy lifestyle promotion. This study aimed to examine whether gynaecologists also value promoting a healthy lifestyle and whether structured lifestyle modification programmes are available in Belgian fertility clinics., Design: An observational study was conducted among health care professionals (HCPs) working in Belgian fertility clinics., Participants/materials, Setting, Methods: An Australian questionnaire on attitudes and practices related to promoting a healthy lifestyle among patients with fertility problems was reciprocally back-to-back translated and three open-ended questions were added. All HCPs of Belgian fertility clinics, including gynaecologists, fertility nurses/midwives, psychologists, and embryologists, were invited by e-mail to complete the questionnaire online. Responses to closed and open-ended questions were analysed with, respectively, descriptive statistics and qualitative thematic analysis. Finally, differences in perspectives between different groups of HCPs were explored., Results: A total of 50 fertility nurses/midwives, 42 gynaecologists, and 19 other HCPs completed the survey (n = 111). Regarding attitudes, all respondents valued informing patients about the impact of lifestyle on fertility. The vast majority of HCPs (n = 96; 86%) stated that fertility clinics have the responsibility to address unhealthy lifestyles prior to offering fertility treatment. Fertility nurses/midwives were significantly more likely than gynaecologists to state that fertility clinics have this responsibility (p = 0.040). Regarding practices, the patient's lifestyle was most commonly discussed by the gynaecologist (n = 107; 96%) during the first appointment (n = 105; 95%). The lifestyle factors that were being addressed, according to the vast majority of respondents, were smoking, weight, age, alcohol, and recreational drugs. Only three HCPs (from three different clinics) stated that their clinic offered a structured lifestyle modification programme. HCPs explained that they lacked the resources and expertise for offering a structured lifestyle modification programme., Limitations: Response rates were limited, but the responding Belgian gynaecologists and fertility nurses/midwives confirmed the findings of the previous study in Australian fertility nurses., Conclusions: HCPs working in Belgian fertility clinics value healthy lifestyle promotion but lack access to structured lifestyle modification programmes to implement in their daily clinical practice. Future studies should focus on developing and evaluating structured lifestyle modification programmes for patients with fertility problems., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Introduction: Infertility and its treatment bring a considerable emotional burden. Increasing evidence demonstrates the effectiveness of smartphone-delivered mindfulness apps for reducing symptoms of emotional distress in both clinical and non-clinical populations. Evidence on this topic in women, men and couples experiencing infertility is currently under-represented. The aim of the MoMiFer study is, therefore, to investigate the efficacy of a stand-alone mobile mindfulness app on symptoms of emotional distress and fertility-related quality of life in people experiencing infertility., Methods and Analysis: This study is an exploratory randomised controlled trial (RCT) with open enrollment. The primary outcomes are symptoms of emotional distress and fertility-related quality of life. Secondary outcomes are mindfulness skills, repetitive negative thinking, self-compassion, user-rated quality of the stand-alone mobile mindfulness app and use of the app. Experience sampling method and standardised self-report questionnaires are combined within a repeated measures design to measure the effects of the stand-alone mobile mindfulness app on the primary and secondary outcomes, apart from the use of the app. The latter will be evaluated through app tracking. People, including women, men and couples, experiencing infertility (n=60) will be randomised to an intervention group receiving the stand-alone mobile mindfulness app for 3 months or a wait-list control group. The app follows the format and content of Mindfulness-Based Stress Reduction. Data will be collected at baseline, at 1.5 months and 3 months after randomisation. Analysis will be according to intention to treat and based on general linear modelling and multilevel mixed-effects modelling., Ethics and Dissemination: This study received approval from the Medical Ethical Committee of the Leuven University Hospital (Belgium). The findings of this exploratory RCT will be disseminated through presentations at public lectures, scientific institutions and meetings, and through peer-reviewed scientific articles., Trial Registration Number: NCT04143828., Competing Interests: Competing interests: KVdG and FR are founders and members of the managing committee of the Leuven Mindfulness Centre Fund. FR and KVdG receive payments for workshops and presentations related to mindfulness., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Cystinosis is an inherited metabolic disorder caused by autosomal recessive mutations in the CTNS gene leading to lysosomal cystine accumulation. The disease primarily affects the kidneys followed by extra-renal organ involvement later in life. Azoospermia is one of the unclarified complications which are not improved by cysteamine, which is the only available disease-modifying treatment. We aimed at unraveling the origin of azoospermia in cysteamine-treated cystinosis by confirming or excluding an obstructive factor, and investigating the effect of cysteamine on fertility in the Ctns -/- mouse model compared with wild type. Azoospermia was present in the vast majority of infantile type cystinosis patients. While spermatogenesis was intact, an enlarged caput epididymis and reduced levels of seminal markers for obstruction neutral α-glucosidase (NAG) and extracellular matrix protein 1 (ECM1) pointed towards an epididymal obstruction. Histopathological examination in human and mouse testis revealed a disturbed blood-testis barrier characterized by an altered zonula occludens-1 (ZO-1) protein expression. Animal studies ruled out a negative effect of cysteamine on fertility, but showed that cystine accumulation in the testis is irresponsive to regular cysteamine treatment. We conclude that the azoospermia in infantile cystinosis is due to an obstruction related to epididymal dysfunction, irrespective of the severity of an evolving primary hypogonadism. Regular cysteamine treatment does not affect fertility but has subtherapeutic effects on cystine accumulation in testis., (© 2021 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)

Study Question: Does male age affect embryo growth or quality in couples undergoing IVF treatment?, Summary Answer: Advanced paternal age (APA) is negatively associated with the chance of an optimal eight-cell embryo on the third day of development., What Is Known Already: Literature shows that APA is associated with decreased sperm quality and fecundity. However, the effect of male age on embryo growth in an IVF setting remains inconclusive. Literature concerning male influences on IVF success is scarce and approaches used to analyse embryo outcomes differ by study., Study Design, Size, Duration: This study was part of the longitudinal Epigenetic Legacy of Paternal Obesity (ELPO) study for which fathers and mothers were followed from pre-pregnancy until the birth of their child. Couples were recruited from April 2015 to September 2017. A total of 1057 embryos from 87 couples were studied., Participants/materials, Setting, Methods: Dutch-speaking couples planning to undergo an IVF treatment were recruited at the Leuven University Fertility Center in Flanders, Belgium. Anthropometrics were documented and compared to the general Flemish population. Semen characteristics, pregnancy rates and the following embryo characteristics were recorded: number of blastomeres, symmetry and percentage fragmentation. Statistical modelling was applied taking into account correlation of within-cycle outcomes and use of multiple cycles per couple., Main Results and the Role of Chance: We observed a significant inverse association between APA and a key determinant for scoring of embryo quality: older men were less likely to produce an embryo of eight blastomeres at Day 3, compared to younger fathers; odds ratio for the effect of 1 year equals 0.960 (95% CI: 0.930-0.991; P = 0.011). Our finding remained significant after adjusting for female age and male and female BMI. Degree of fragmentation and symmetry were not significantly related to male age., Limitations, Reasons for Caution: Because of the study's small sample size and its monocentric nature, a larger study is warranted to confirm our results. In addition, distribution of BMI and level of education were not representative of the general Flemish population. Although we corrected for BMI status, we do not exclude that obesity may be one of the determinants of infertility in our study population. Furthermore, it is known from other European countries that a higher education eases access to fertility treatment. Hence, caution should be taken when interpreting our findings from a fertility setting to the general population., Wider Implications of the Findings: We suggest a heightened need for future research into male age and its potential effects on embryo growth, embryo quality and ART outcomes. Clinical decision-making and preventative public health programmes would benefit from a better understanding of the role of men, carried forward by the Paternal Origins of Health and Disease (POHaD) paradigm. We hope the current finding will encourage others to examine the role of the sperm epigenome in embryo development according to paternal age., Study Funding/competing Interest(s): This work was supported by a research grant from KU Leuven University (OT/14/109). The authors declare no competing financial, professional or personal interests., Trial Registration Number: KU Leuven S57378 (ML11309), B322201523225., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To study the performance of the 'van Loendersloot' prognostic model for our clinic's in vitro fertilisation (IVF) in its original version, the refitted version and in an adapted version replacing previous by current cycle IVF laboratory variables., Methods: This retrospective cohort study in our academic tertiary fertility clinic analysed 1281 IVF cycles of 591 couples, who completed at least one 2nd-6th IVF cycle with own fresh gametes after a previous IVF cycle with the same partner in our clinic between 2010 and 2018. The outcome of interest was the chance on a live birth after one complete IVF cycle (including all fresh and frozen embryo transfers from the same episode of ovarian stimulation). Model performance was expressed in terms of discrimination (c-statistics) and calibration (calibration model, comparison of prognosis to observed ratios of five disjoint groups formed by the quintiles of the IVF prognoses and a calibration plot)., Results: A total of 344 live births were obtained (26.9%). External validation of the original van Loendersloot model showed a poor c-statistic of 0.64 (95% CI: 0.61 to 0.68) and an underestimation of IVF success. The refitted and the adapted models showed c-statistics of respectively 0.68 (95% CI: 0.65 to 0.71) and 0.74 (95% CI: 0.70 to 0.77). Similar c-statistics were found with cross-validation. Both models showed a good calibration model; refitted model: intercept=0.00 (95% CI: -0.23 to 0.23) and slope=1.00 (95% CI: 0.79 to 1.21); adapted model: intercept=0.00 (95% CI: -0.18 to 0.18) and slope=1.00 (95% CI: 0.83 to 1.17). Prognoses and observed success rates of the disjoint groups matched well for the refitted model and even better for the adapted model., Conclusion: External validation of the original van Loendersloot model indicated that model updating was recommended. The good performance of the refitted and adapted models allows informing couples about their IVF prognosis prior to an IVF cycle and at the time of embryo transfer. Whether this has an impact on couple's expected success rates, distress and IVF discontinuation can now be studied., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Infertility and in vitro fertilisation (IVF; with or without intracytoplasmic sperm injection) result in considerable emotional and financial burden. Increasing evidence suggests that lifestyle factors, including diet, physical activity and personal well-being, are associated with IVF-success rates. Currently, IVF is not routinely combined with a lifestyle programme. The preconception lifestyle (PreLiFe) randomised controlled trial (RCT) assesses the effects of a new mobile PreLiFe programme in couples undergoing IVF., Methods and Analysis: A multicentre RCT including 460 heterosexual couples starting IVF in Belgian fertility clinics. IVF couples are randomised between an attention control group or the PreLiFe programme for a period of 12 months or until an ongoing pregnancy is confirmed by ultrasound. The attention control programme includes a mobile application with treatment information (ie, appointments and medication instructions) in addition to standard care. The PreLiFe programme includes a mobile application with the same treatment information in combination with a lifestyle programme. This new lifestyle programme includes tailored advice and skills training on diet, physical activity and mindfulness in combination with text messages and telephone interaction with a healthcare professional trained in motivational interviewing. The primary outcome of this RCT is the cumulative ongoing pregnancy rate within 12 months after randomisation. Secondary outcomes include changes in diet, physical activity, emotional distress, body mass index, waist circumference, quality of life and other reproductive outcomes including IVF discontinuation, clinical pregnancy rate and time to pregnancy. Additionally, partner support and the feasibility (use and acceptability) of the PreLiFe programme will be evaluated in the intervention group. Analysis will be according to intention to treat., Ethics and Dissemination: This study has been approved by the Medical Ethical Committee of the Leuven University Hospital (Belgium) and the other recruiting clinics. The findings of this RCT will be disseminated through presentations at international scientific meetings and peer-reviewed publications., Trial Registration Number: NCT03790449; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Ovarian stimulation with low-dose human menopausal gonadotrophin (HMG) is superior to clomiphene citrate in intrauterine insemination (IUI) cycles with respect to clinical pregnancy rate, but it is unclear whether HMG is also the more cost-effective option. The aim of this study was to compare the cost-effectiveness of ovarian stimulation with low-dose subcutaneously administred HMG (37.5-75 IU per day) to orally administred clomiphene citrate (50 mg/day from day 3-7) in an IUI programme for subfertile couples. A cost-effectiveness analysis was conducted using the results of a randomized trial, including 620 IUI cycles. The primary outcome was the incremental cost-effectiveness ratio (ICER) of using HMG versus clomiphene citrate. Results are presented from the healthcare payer perspective. The total cost per patient associated with one IUI treatment with HMG is €764, whereas it is €558 if clomiphene citrate is used, resulting in an incremental cost of €206 for HMG per treatment. The incremental clinical pregnancy rate of using HMG instead of clomiphene citrate, however, is also 5.7 percentage points higher, resulting in an ICER of HMG versus clomiphene citrate of €3615 per additional clinical pregnancy achieved. On average, HMG was found to be more cost-effective than clomiphene citrate., (Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Morphometric and morphokinetic evaluation of in vitro cultured human embryos allows evaluation without time restriction and reduces intra- and inter-observer variability. Even though these technologies have been reported to improve the quality of cleavage stage embryo evaluation during fresh culture, possible advantages in the evaluation of cryopreserved embryos have been scarcely explored. This study aims to compare morphometric and morphokinetic parameters between slow frozen and vitrified embryos and to determine their relationship to embryo survival and implantation rate (IR) after thawing/warming., Methods: During fresh culture, morphometric characteristics (Total Cell Volume (TCV), symmetry, fragmentation and number of blastomeres) were measured in 286 thawed/warmed embryos. Likewise, after thawing/warming, similar morphometric characteristics were measured in 135 survived embryos. Moreover, morphokinetic parameters (time to mitosis resumption and time to compaction) were measured in 90 embryos after thawing/warming. Then, using linear regression, we investigated the differences between vitrified and slow frozen embryos and the relation of the measured characteristics to embryo survival and IR. Statistical corrections were applied to account for data clustering and for multiple testing., Results: Vitrified embryos resume mitosis and start compaction significantly earlier than slow frozen embryos. Mitosis resumption rate was 82% for vitrified and 63% for slow frozen embryos and median time to mitosis resumption was 7.6 h and 13.1 h (p = 0.02), respectively. Compaction rate was 62% in vitrified and only 23% in slow frozen embryos. Median time to compaction was 18.1 h for vitrified embryos but, for slow frozen could not be computed since less than half of the slow frozen embryos reached compaction (p = 0.0001). Moreover, intact embryos resume mitosis significantly earlier than not intact ones regardless of the freezing method (rate: 79% vs. 66%, median time: 7.6 h vs 14.6 h, respectively, p = 0.03). Regarding morphometrics, slow frozen embryos showed lower TCV and higher blastomere symmetry after thawing than vitrified embryos despite having similar blastomere number. IR was related to blastomere number at cryopreservation in slow frozen embryos, but not in vitrified ones., Conclusions: Interestingly, vitrified/warmed embryos undergo mitosis resumption and compaction significantly earlier than slow frozen/thawed embryos. However, the clinical use of this morphokinetic parameters still remains to be investigated in larger studies., Trial Registration: Retrospectively registered on December 15, 2015 NCT02639715 .

Belgian legislation limiting the number of embryos for transfer has been shown to result in a 50% reduction of the multiple live birth rate (MLBR) per cycle without having a negative impact on the cumulative delivery rate per patient within six cycles or 36 months. The objective of the current study was to evaluate the cost saving associated with a 50% reduction in MLBR. A retrospective cost analysis was performed of 213 couples, who became pregnant and had a live birth after one or more assisted reproductive technology treatment cycles, and their 254 children. The mean cost of a singleton (n = 172) and multiple (n = 41) birth was calculated based on individual hospital invoices. The cost analysis showed a significantly higher total cost (assisted reproductive technology treatment, pregnancy follow-up, delivery, child cost until the age of 2 years) for multiple births (both children: mean €43,397) than for singleton births (mean: €17,866) (Wilcoxon-Mann-Whitney P < 0.0001). A 50% reduction in MLBR resulted in a significant cost reduction related to hospital care of 13%., (Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Human follicular fluid (FF) is a unique biological fluid in which the oocyte develops in vivo, and presents an optimal source for non-invasive biochemical predictors. Oocyte quality directly influences the embryo development and hence, may be used as a predictor of embryo quality. Peptide profiling of FF and its potential use as a biomarker for oocyte quality has never been reported., Methods: This study screened FF for peptide biomarkers that predict the outcome of in vitro fertilization (IVF). Potential biomarkers were discovered by investigating 2 training datasets, consisting both of 17 samples and validating on an independent experiment containing 32 samples. Peptide profiles were acquired by nano-scale liquid chromatography coupled to tandem mass spectrometry (nano LC-MS/MS)., Results: From the training datasets 53 peptides were found as potential biomarker candidates, predicting the fertilization outcome of 24 out of the 32 validation samples blindly (81.3% sensitivity, 68.8% specificity, AUC = 0.86). Seven potential biomarker peptides were identified. They were derived from: insulin-like growth factor binding protein-5, alpha-2-antiplasmin, complement component 3, inter-alpha-trypsin inhibitor heavy chain H1, serum albumin, protein diaphanous homolog 1 and plastin-3., Conclusions: The MS-based comprehensive peptidomic approach carried out in this study, established a novel panel of potential biomarkers that present a promising predictive accuracy rate in fertilization outcome, and indicates FF as an interesting biomarker resource to improve IVF clinic routine.

Background: Characteristics routinely used to evaluate embryo quality after thawing include number of blastomeres survived and presence of mitosis resumption after overnight culture. It is unknown to which extent symmetry and fragmentation affect implantation after warming and whether application of stricter criteria either before vitrification or after warming would improve implantation rate (IR) of vitrified/warmed embryos. This study aimed to find new parameters to improve selection criteria for vitrification and for transfer after warming., Methods: Firstly, we evaluated standard morphological characteristics (intact survival, mitosis resumption, number of blastomeres, symmetry and fragmentation) of 986 warmed day 3 embryos and, from a subset of 654, we evaluated morphometric characteristics (fragmentation, symmetry and volume change). Secondly, we tested the hypothesis that IR of day 3 vitrified/warmed embryos is influenced by morphometric characteristics. IR per embryo transferred was calculated using embryos that were transferred in a single embryo transfer (SET) or a double embryo transfer (DET) with either 0 or 100 % implantation (830/986). We investigated the significant differences in IR between the different categories of a specific characteristic. These categories were based on our standard embryo evaluation system. The statistical tests Chi-square, Fisher's exact or Cochrane-Armitage were used according to the type and/or categories of the variable., Results: The 986 embryos were transferred in 671 FET cycles with 16.9 % (167/986) IR. After exclusion of DET with 1 embryo implanted, IR per embryo transferred was 12.4 % (103/830). Embryo symmetry, fragmentation and volume change in vitrified/warmed day 3 embryos were not associated with IR. However, when mitosis resumption was present after overnight culture, intact embryos reached significantly higher IR than non-intact embryos and only when the embryo compacted after overnight culture the number of cells damaged after warming had no effect on IR. Concretely, embryos with 8 cells after warming or >9 cells after overnight culture-including compacted embryos-reached the highest IR (>15 %) while embryos with <6 cells after warming or with ≤6 cells after overnight culture had extremely low IR (<1 %)., Conclusions: IR of vitrified embryos is determined by the number of cells lost, by the occurrence of mitosis resumption, and by the specific number of blastomeres present but not by fragmentation, blastomere symmetry or volume change. Unselecting embryos for cryopreservation because of fragmentation >10 % and/or symmetry < 75 % only leads to unwanted loss of embryos with acceptable implantation potential., Trial Registration: Retrospectively registered NCT02639715 .

Background: Embryo selection has been based on developmental and morphological characteristics. However, the presence of an important intra-and inter-observer variability of standard scoring system (SSS) has been reported. A computer-assisted scoring system (CASS) has the potential to overcome most of these disadvantages associated with the SSS. The aims of this study were to construct a prediction model, with data mining approaches, and compare the predictive performance of models in SSS and CASS and to evaluate whether using the prediction model would impact the selection of the embryo for transfer., Methods: A total of 871 single transferred embryos between 2008 and 2013 were included and evaluated with two scoring systems: SSS and CASS. Prediction models were developed using multivariable logistic regression (LR) and multivariate adaptive regression splines (MARS). The prediction models were externally validated with a test set of 109 single transfers between January and June 2014. Area under the curve (AUC) in training data and validation data was compared to determine the utility of the models., Results: In SSS models, the AUC declined significantly from training data to validation data (p < 0.05). No significant difference was detected in CASS derived models. Two final prediction models derived from CASS were obtained using LR and MARS, which showed moderate discriminative capacity (c-statistic 0.64 and 0.69 respectively) on validation data., Conclusions: The study showed that the introduction of CASS improved the generalizability of the prediction models, and the combination of computer-assisted scoring system with data mining based predictive modeling is a promising approach to improve the selection of embryo with the highest implantation potential.

Objective: To determine the mean number of follicular flushings needed to retrieve the maximal number of oocytes and to investigate the correlation between the number of flushings and oocyte/embryo quality as well as reproductive outcome., Methods: This prospective study included 154 oocyte retrieval cycles in 138 patients undergoing assisted reproductive technology treatment. During oocyte retrieval, aspirate and flushes were collected in four separate collections (A, F1, F2, F3) and inspected for the presence of an oocyte-cumulus complex (OCC). Outcome variables included oocyte recovery rate, percentage of mature oocytes, fertilization rate, day 2/day 3/day 5 embryo quality and clinical pregnancy rate/live birth rate., Results: Out of 1,495 OCCs collected, 91% were obtained in collections A or F1. Significantly more mature oocytes were obtained in collection A (p = 0.03). The fertilization rate was similar for oocytes obtained in the four separate collections (p = 0.50). The proportion of good-quality day 2/day 3/day 5 embryos was similar (p = 0.93, p = 0.85 and p = 0.14, respectively). Clinical pregnancy rate and live birth rate were not significantly affected by the first two flushes. No live birth emanated from oocytes obtained from the third flush onwards., Conclusion: More than 90% of all recovered OCCs were obtained after follicular aspiration followed by follicular flushing up to two times (collections A and F1). Follicular flushing may increase the oocyte recovery rate and does not have a negative influence on fertilization rate, day 2/day 3/day 5 embryo quality or pregnancy rate., (© 2015 S. Karger AG, Basel.)

This study compared the developmental and implantation potential of tetrahedrally arranged versus non-tetrahedrally arranged 4-cell-stage embryos. If the cleavage planes of a 4-cell-stage embryo were perpendicularly orientated, blastomeres were defined as tetrahedrally arranged, while embryos with parallel-orientated cleavage axes were considered as non-tetrahedral embryos. The 4-cell-stage embryos (n=862) examined in this study were obtained from 299 patients aged <36 years. A total of 299 embryos were transferred as a single-embryo transfer on day 3. This study showed that tetrahedral embryos developed into a 8-cell-stage embryo on day 3 more frequently (307, 45% versus 42, 24%; P<0.0001) and also developed more frequently into good-quality embryos (461, 67% versus 67, 38%; P<0.0001) and into excellent-quality embryos (290, 42% versus 34, 19%; P<0.0001). Tetrahedral embryos had a significantly higher implantation potential (98, 38% versus 9, 21%; P=0.038), ongoing pregnancy rate (84, 33% versus 7, 16%; P=0.032) and live birth rate (84, 33% versus 7, 16%; P=0.032). In conclusion, tetrahedral 4-cell-stage embryos on day 2 developed into embryos of better quality on day 3 with a higher implantation potential and live birth rate compared with non-tetrahedral 4-cell-stage embryos. In this study, an additional characteristic of 4-cell-stage embryos has been evaluated. The aim of the study was to evaluate the spatial arrangement of blastomeres in a 4-cell-stage embryo. If the cleavage planes of a 4-cell-stage embryo were perpendicularly orientated (indicating that both axes meet a right angle), blastomeres were defined as tetrahedral arranged while the other embryos were considered as non-tetrahedral embryos. The 4-cell-stage embryos (n=862) examined in this study were obtained from 299 patients aged <36 years. A total of 299 embryos were transferred as a single-embryo transfer on day 3. This study showed that tetrahedral embryos developed into an 8-cell-stage embryo on day 3 more frequently (307, 45% versus 42, 24%; P<0.0001) and also developed more frequently into good-quality embryos (461, 67% versus 67, 38%; P<0.0001) and excellent-quality embryos (290, 42% versus 34, 19%; P<0.0001). Tetrahedral embryos had a significantly higher implantation potential (98, 38% versus 9, 21%; P=0.038), ongoing pregnancy rate (84, 33% versus 7, 16%; P=0.032) and live birth rate (84, 33% versus 7, 16%; P=0.032). In conclusion, tetrahedral 4-cell-stage embryos on day 2 developed into embryos of better quality on day 3 with a higher implantation potential and live birth rate compared with non-tetrahedral 4-cell-stage embryos., (Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Ovarian tissue cryopreservation by vitrification is an attractive technique for fertility preservation in women. However, this technique has not been optimized. The aim of this study was to evaluate the baboon as a model for the preclinical study of ovarian tissue cryopreservation by vitrification and thawing., Methods: Ovarian cortical tissues (1-mm cubes) were obtained surgically from adult female olive baboons (n = 9) maintained in captivity and vitrified using dimethyl sulphoxide and ethylene glycol protocol. The proportion of morphologically intact follicles (primordial, primary and secondary) in paired fresh and cryopreserved (vitrified-thawed) ovarian tissues was compared., Results: Overall, 67.1% of follicles were morphologically normal after vitrification. When compared to fresh ovarian tissue, vitrified-thawed ovarian tissue contained a comparable number of intact primordial follicles (48.9 vs. 52.9%), and a lower number of both primary (14.8 vs. 29.5%; p < 0.05) and secondary (2.0 vs. 0.7%; p < 0.05) follicles., Conclusion: After vitrification and thawing, baboon ovarian tissue retains about 67% of morphologically normal follicles, which is comparable to results for human ovarian tissue, and suggests that the olive baboon is a promising animal model for preclinical assessment of ovarian vitrification, thawing and autotransplantation studies., (Copyright © 2013 S. Karger AG, Basel.)

The biological effects of khat (Catha edulis) on reproduction and fertility are inadequately investigated and controversial, hence we determined the effects of oral administration of high-dose khat on sperm parameters and male hormonal levels in olive baboons. In this study, 6 male baboons received a high dose of khat (500 g/week) during 1 month. Electroejaculation for sperm studies (concentration, motility and chromatin integrity) and plasma collection for hormonal analysis (testosterone, prolactin and cortisol) were done weekly during 1 month before and 1 month during khat administration as well as 2 weeks after the last dose of khat administration. Administration of khat extract induced a significant reduction in sperm motility (p = 0.008), sperm count (p = 0.041), sperm chromatin integrity (p = 0.0003), testosterone levels (p = 0.035) and prolactin levels (p = 0.0115), but not in cortisol levels and sperm volume (p > 0.05). The results suggest that high-dose khat decreases sperm quality and testosterone and hence may contribute to male infertility., (Copyright © 2012 S. Karger AG, Basel.)

Background: Development of a reproducible baboon in vitro fertilization (IVF) system require optimized and reproducible sperm parameters. The objective of this study was to document basic spermatology values and investigate the reproducibility of these variables in the same baboons 1 or 3 months later in a larger number of baboons., Methods: In this prospective study, sperm quality (semen volume, pH, concentration, motility, morphology and size) was evaluated in 27 sperm samples obtained from 9 baboons electroejaculated three times with a time interval of 1 month (between first and second sample collection) and 3 months (between second and third round sample collection)., Results: Baseline sperm values for semen volume (0.5 ± 0.3 ml), pH (7.5 ± 0.3), concentration (54.2 ± 19.3 million/ml), motility (67.3 ± 18.5%) and morphology (89.2 ± 4.8%) were similar to sperm samples obtained after 1 or 3 months (P > 0.05). Head, midpiece and tail abnormalities were rarely observed (0-9%). Sperm dimensions were characterized by a tail length of 69.6 ± 13.9 μm, a head width of 2.41 ± 0.43 μm and a head length of 3.49 ± 0.6 μm., Conclusion: Sperm quality was not affected by repeated electroejaculation with time intervals of 1 or 3 months, suggesting that the same baboon can participate multiple times in reproductive research., (© 2012 John Wiley & Sons A/S.)

Background: Cell-cell communication and adhesion are essential for the compaction process of early stage embryos. The aim of this study was to develop a non-invasive objective calculation system of embryo compaction in order to test the hypothesis that embryos with a larger mean contact surface result in a higher live birth rate compared to embryos with a lower mean contact surface., Methods: Multilevel images of 474 embryos transferred on day 3 were evaluated by the Cellify software. This software calculates the contact surfaces between the blastomeres. The primary outcome of this study was live birth. An ideal range of contact surface was determined and the positive and negative predictive value, the sensitivity, the specificity and the area under the curve for this new characteristic were calculated., Results: In total, 115 (24%) transferred embryos resulted in a live birth. Selection of an embryo for transfer on its mean contact surface could predict live birth with a high sensitivity (80%) and high negative predicting value (83%) but with a low positive predictive value (27%), a low specificity (31%) and low area under the ROC curve (0.56). The mean contact surface of embryos cultured in a single medium was significantly higher compared to the mean contact surface of embryos cultured in a sequential medium (p = 0.0003)., Conclusions: Neither the mean contact surface nor the number of contact surfaces of a day 3 embryo had an additional value in the prediction of live birth. The type of culture medium, however, had an impact on the contact surface of an embryo. Embryos cultured in a single medium had a significant larger contact surface compared to embryos cultured in the sequential medium.

Background: Although different techniques for sperm immobilization have been described, their value has not been assessed in an adequately powered randomized study. The aim of this study was to compare two types of sperm immobilization methods prior to ICSI and to test the hypothesis that triple touch immobilization (TTIm) would lead to a higher (5% -65% up to 70%) fertilization rate (FR) than single touch immobilization (STIm)., Methods: A total of 3056 metaphase II (MII) oocytes, from 290 patients, were randomly assigned to the STIm group (n = 1528 oocytes; 145 cycles) or to the TTIm group (n = 1528 oocytes; 138 cycles). A total of 1478 oocytes (STIm group) and 1476 oocytes (TTIm group) were used in the statistical analysis. The primary outcome variable was FR. Secondary outcome variables included: number of good quality embryos (GQE) on day 2 and day 3, implantation rate (IR) and implantation with foetal heart beat rate (FHB). Statistical analysis was done using the Fisher Exact test with a significance level of 0.05., Results: The results showed no differences in FR between both groups. The proportion of good quality embryos on day 3, was significantly higher in the STIm group (37.5%) compared to the TTIm group (31.8%; p = 0.02)., Conclusions: In this RCT, the hypothesis that the post-ICSI FR would be higher after TTIm than after STIm was not confirmed and the number of good quality embryos on day 3 was significantly lower in the TTIm group than in the STIm group. These data suggest that more 'aggressive' TTIm technique has no advantages compared to the STIm technique.

Since 2004, assisted conception is encompassed by the European Directive on the Quality and Safety of Tissues and Cells (2004/23/EC). The aim of a standard for quality and safety is to minimize risks of errors, contamination, and accidents and to maximize efficiency of use. This article presents a case study of the implementation of the Tissues and Cells Directive in the Leuven University Fertility Center (LUFC) with a focus on the assisted reproductive technologies laboratory with respect to laboratory facilities, quality management system, traceability, storage conditions as well as serological screening. Although the current European Union (EU) Directive can be considered a step in the right direction to improve patient safety, questions remain as to whether the implementation of this EU Directive, requiring extra time and money, has resulted in higher quality with respect to the quality dimensions of effectiveness, efficiency, timeliness, equity, and patient centeredness., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Quality management according to ISO 9001:2008 guidelines includes infertility care quality assessment and improvement. This study aimed to describe the development process of a questionnaire for infertility management. A literature review, qualitative interviews with experts and patients resulted in a content-valid and face-valid questionnaire. Three cross-sectional surveys were performed in 2004, 2007 and 2008 in a tertiary university infertility centre. First (2004), the questionnaire – measuring eight a-priori dimensions of infertility management – was tested. Second (2007), improvement projects for infertility management were evaluated. Third (2008), factor analysis was performed and internal consistency was documented. The developed patient questionnaire to evaluate infertility management and pre-set desired levels of agreement served to set targets for and assess quality improvement projects. The final patient questionnaire to evaluate infertility management within an ISO framework was valid and reliable and contained 14 items covering four dimensions of infertility management: Telephone Access, Reception, Information and Patient-centeredness. ISO 9001:2008-certified infertility centres can evaluate infertility management with this 14-item questionnaire. This top-down approach to evaluate the patients’ perspective on quality aspects selected by health professionals can be complementary to the bottom-up approach evaluating the patients’ complete experiences of quality of care.

Background: Quality control programs are necessary to maintain good clinical practice. Embryo grading has been described as one of the external quality assurance schemes. Although the evaluation of embryos is based on the assessment of morphological characteristics, considerable intra- and inter-observer variability has been described. In this multicentre study, the variability in the embryo evaluation has been evaluated using morphological characteristics on day 1, day 2 and day 3 of embryo development., Methods: Five embryologists of four different IVF centers participated in this study. Multilevel images of embryos were presented on a website at different time points to evaluate intra-and inter-observer agreement in the assessment of embryo morphology. The embryos were evaluated on day 1, day 2 and day 3 of their development and each embryologist had to decide if the embryo had to be transferred, cryopreserved or discarded., Results: Both intra-observer agreement and inter-observer agreement were good to excellent for the position of the pronuclei on day 1, the number of blastomeres on day 2 and day 3 and the clinical decision (transfer, cryopreservation, discard). For all other characteristics (size of pronuclei, presence of cytoplasomic halo, degree of fragmentation and size of blastomeres) the intra- and inter-observer agreement was moderate to very poor., Conclusions: Mono- or multicentre quality control on embryo scoring by morphological assessment can easily be performed through the design of a simple website. In the future the website design can be adapted to generate statistical feedback upon scoring and can even include a training module.

Embryo selection is based on embryo developmental and morphological characteristics. Standard embryo evaluation has some disadvantages. New technology using multilevel images combined with a computer-assisted scoring system (CASS) has the potential to overcome these disadvantages. The aim of this study was to compare the value of a computer-assisted scoring system (CASS) versus a standard scoring system (SSS) in predicting implantation and live birth. This prospective study included 3185 embryos obtained during 502IVF/intracytoplasmic sperm injection cycles with single-embryo transfer on day 3. Embryos were evaluated with two scoring systems: SSS and CASS. Logistic regression analyses were performed using implantation and live birth as outcomes. According to multiple regression analysis, implantation was influenced by number and size of blastomeres on day 3 using CASS and by all embryo parameters on day 3 using SSS. Combined analysis of both scoring systems revealed that implantation was affected by number and size of blastomeres using CASS and by the degree of embryo fragmentation using SSS. Using live birth as outcome, only the number of blastomeres on day 3, evaluated by SSS and CASS, was predictive. Prediction of implantation and live birth may be superior using CASS when compared with SSS. Embryo selection is currently based on embryo developmental and morphological characteristics of an embryo using a standard scoring system. This evaluation system is limited by a number of disadvantages. New technology using multilevel images combined with a computer-assisted scoring system has the potential to overcome these disadvantages. The aim of this study was to compare the value of such computer-assisted scoring system versus a standard scoring system in predicting implantation and live birth rate. This study included 3185 embryos obtained during 502 IVF or intracytoplasmic sperm injection cycles with single-embryo transfer on day 3. All the embryos were evaluated with two types of scoring systems: a standard scoring system and a computer-assisted scoring system. According to the statistical analysis, the implantation of an embryo was influenced by the number and size of blastomeres on day 3 when evaluated with the computer-assisted scoring system, and by all embryo parameters on day 3 using the standard scoring system. Combined analysis of both scoring systems revealed that implantation was affected by number and size of blastomeres using the computer-assisted scoring system and by the degree of embryo fragmentation using the standard scoring system. Live birth was influenced by the number of blastomeres on day 3 evaluated by both scoring systems. Prediction of embryo implantation and live birth was superior using the computer-assisted scoring system. In conclusion, a computer-assisted scoring system may be superior to a standard scoring system in the prediction of implantation and live birth., (Copyright © 2011 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: To compare different methods of ovarian stimulation (OS) for assisted reproductive technology in baboons., Design: Prospective randomized study., Setting: Institute of primate research., Animal(s): Baboons (n = 10) were randomized into two groups (of five animals each) during three different cycles to compare six protocols of OS., Intervention(s): Cycle 1: clomiphene citrate (CC) alone (group CC) versus CC and GnRH agonist (group CC-Ag); cycle 2: recombinant gonadotropins (GON) without GnRH agonist (group GON) versus GON and depot GnRH agonist (group GON-AgDepo-1); cycle 3: GON and depot GnRH agonist (group GON-AgDepo-2) versus GON and daily GnRH agonist in a classic long protocol (group GON-Ag). Oocyte aspiration was performed 34-36 hours after injecting 5,000 IU rhCG, followed by fertilization via intracytoplasmic sperm injection (ICSI)., Main Outcome Measure(s): Number and quality of oocytes retrieved and their fertilization rate., Result(s): More metaphase II (MII) oocytes were retrieved using the GON-AgDepo-1 (n = 12; 64% MII), GON-AgDepo-2 (n = 9; 79% MII), GON-Ag (n = 16; 88% MII), and GON (n = 6; 59% MII) protocols compared with the CC (n = 9; 15% MII) and CC-Ag (n = 14; 20% MII) protocols. Fertilization by ICSI varied between 43% and 71%., Conclusion(s): In baboons, long and depot protocols yield similar numbers of MII oocytes; however, depot protocol may be preferable because only one injection of GnRH agonist is needed., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

The attitude of patients with reproductive disorders regarding the use of nonhuman primates (NHPs) in preclinical reproductive research and its determinants was examined. A survey was conducted on 299 patients with fertility problems and/or endometriosis in a European fertility center (RR = 80%). The main outcome measure was the attitude toward reproductive research on NHPs. In total, 70.6% accept and 29.4% reject NHP research. Factors significantly positively related to acceptance are confidence in researchers and previous pregnancy. Factors significantly negatively related to acceptance include having a pet, membership of a nature organization, vegetarian, and having lived abroad. To the best of our knowledge, this study is the first on patients' perspective on NHP research. The majority of the patients accept reproductive research on NHPs. Trust in researchers was the most important positively related factor; therefore, researchers are advised to actively try to gain the trust of patients and the public.

Objective: To compare quality of life and fertility aspects after laparoscopic inguinal hernia repair in men using a heavyweight or lightweight mesh., Summary Background Data: The use of lightweight meshes in laparoscopic inguinal hernia repair could have beneficial effects on quality of life and preservation of the spermatic structures due to a decreased foreign-body reaction., Methods: A total of 59 male patients planned for primary, unilateral or bilateral inguinal hernia repair were randomized between a standard polypropylene (Marlex) or lightweight mesh (Vypro II, TiMesh). Main outcome measures were fertility aspects, assessed preoperatively and at 1-year follow-up by semen analysis and scrotal ultrasonography. Secondary outcomes were quality of life (SF-36 and McGill Pain Questionnaire) and recurrence up to 1 year postoperatively., Results: Patients operated on with a VyproII or TiMesh mesh exhibited a decreased sperm motility (vs. preoperatively) compared with Marlex patients, respectively -9.5% and -5.5% versus +2% (P = 0.013). When the results after uni- and bilateral hernia repair were analyzed separately, this difference only remained significant in the bilateral hernia subgroup: -10% for VyproII and -17% for TiMesh versus +1% for Marlex (P = 0.037). Other fertility parameters (sperm concentration, morphology, and alpha-glucosidase level) were unchanged. There were no differences at any study point between the 3 groups regarding quality of life. Only for resumption of sport activities was a small advantage noted for VyproII versus Marlex patients (P = 0.045). After 1 year, no recurrences were observed; 3 patients (6%) complained of chronic disabling pain., Conclusions: Our data suggest that the use of lightweight meshes for laparoscopic inguinal hernia repair in male patients negatively influences sperm motility, without any benefit on quality of life. These alterations might be important in a subgroup of young male patients operated on laparoscopically for a bilateral hernia. This study was registered in the clinicaltrials.gov database (ID number NCT00925067).

Background: The success of in vitro fertilization techniques is defined by multiple factors including embryo culture conditions, related to the composition of the culture medium. In view of the lack of solid scientific data and in view of the current general belief that sequential media are superior to single media, the aim of this randomized study was to compare the embryo quality in two types of culture media., Methods: In this study, the embryo quality on day 3 was measured as primary outcome. In total, 147 patients younger than 36 years treated with IVF/ICSI during the first or second cycle were included in this study. Embryos were randomly cultured in a sequential (group A) or a single medium (group B) to compare the embryo quality on day 1, day 2 and day 3. The embryo quality was compared in both groups using a Chi-square test with a significance level of 0.05., Results: At day 1, the percentage of embryos with a cytoplasmic halo was higher in group B (46%) than in group A (32%). At day 2, number of blastomeres, degree of fragmentation and the percentage of unequally sized blastomeres were higher in group B than in group A. At day 3, a higher percentage of embryos had a higher number of blastomeres and unequally sized blastomeres in group B. The number of good quality embryos (GQE) was comparable in both groups. The embryo utilization rate was higher in group B (56%) compared to group A (49%)., Conclusions: Although, no significant difference in the number of GQE was found in both media, the utilization rate was significantly higher when the embryos were cultured in the single medium compared to the sequential medium. The results of this study have a possible positive effect on the cumulative cryo-augmented pregnancy rate., Trial Registration Number: NCT01094314.

Background: Improvement of baboon sperm capacitation is necessary for achieving high in vitro fertilization (IVF) rates in baboons. In this study, we evaluated separate and combined effects of caffeine and dbcAMP on baboon sperm capacitation., Methods: Sixteen male baboons (n = 16) were electroejaculated. Each sperm sample was divided into two aliquots: one for chemical activation and the other untreated control. Group 1: dbcAMP (n = 6); Group 2: caffeine (n = 6) and Group 3: combination of caffeine and dbcAMP (n = 4). In each aliquot, sperm motility after 30 minutes of incubation was evaluated as well as zona pellucida (ZP) binding ability after overnight incubation with 4-5 ZP from unfertilized human oocytes., Results: Sperm motility and ZP binding ability in all chemically activated groups increased significantly as compared to their respective controls (P < 0.05)., Conclusion: Combined and separate effects of caffeine and dbcAMP increases baboon sperm motility and ZP binding ability and may improve baboon IVF.

Objective: To test the hypothesis that patients with advanced maternal age (AMA) have a higher implantation rate (IR) after embryo transfer of embryos with a normal chromosomal pattern for the chromosomes studied with preimplantation genetic screening (PGS) compared with patients who had an embryo transfer without PGS., Design: Prospective randomized controlled trial (RCT)., Setting: Academic tertiary setting., Patient(s): Patients with AMA (> or =35 years)., Intervention(s): In an RCT, the clinical IR per embryo transferred was compared after embryo transfer on day 5 or 6 between the PGS group (analysis of chromosomes 13, 16, 18, 21, 22, X, and Y) and the Control group without PGS., Main Outcome Measure(s): No differences were observed between the PGS group and the Control group for the clinical IR (15.1%; 14.9%; rate ratio 1.01; exact confidence interval [CI], 0.25-5.27), the ongoing IR (at 12 weeks) (9.4%; 14.9%), and the live born rate per embryo transferred (9.4%; 14.9%; rate ratio 0.63; exact CI, 0.08-3.37). Fewer embryos were transferred in the PGS group (1.6 +/- 0.6) than in the Control group (2.0 +/- 0.6). A normal diploid status was observed in 30.3% of the embryos screened by PGS., Conclusion(s): In this RCT, the results did not confirm the hypothesis that PGS results in improved reproductive outcome in patients with AMA., (Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: The aim of this study was to determine the intra- and inter-observer variability in the evaluation of embryo quality. Multilevel images of embryos on day 1, day 2 and day 3, were analysed using different morphological parameters., Methods: Multilevel images of embryos on day 1, day 2 and day 3, were analysed using a standard scoring system. The kappa coefficient was calculated to measure intra- and inter-observer variability before and after training sessions., Results: Good to excellent intra-observer agreement was present for most parameters exceptions being scoring the position of pronuclei and the presence of a cytoplasmic halo on day 1, multinucleation on day 2 and the size of fragments on day 3. Inter-observer agreement was only good to excellent for the number of blastomeres on day 2 and day 3 and the orientation of the cleavage axes on day 2. Training sessions had a positive impact on inter-observer agreement., Conclusion: In conclusion, assessment of morphological characteristics of early stage embryos using multilevel images was marked by a high intra-observer and a moderate inter-observer agreement. Training sessions were useful to increase inter-observer agreement.

Objective: To determine the prevalence of histologically proven endometriosis in a subset of infertile women., Design: Retrospective case series with electronic file search and multivariable logistic regression analysis., Setting: Tertiary academic fertility center., Patient(s): Two hundred twenty-one infertile women without previous surgical diagnosis for infertility with regular cycles (variation, 21-35 days) whose partners have a normal semen analysis., Intervention(s): Diagnostic laparoscopy and, if necessary, operative laparoscopy with CO(2) laser excision., Main Outcome Measurement(s): The prevalence of endometriosis and of fertility-reducing nonendometriotic tubal and/or uterine pathology., Result(s): The prevalence of endometriosis was 47% (104/221), including stage I (39%, 41/104), stage II (24%, 25/104), stage III (14%, 15/104), and stage IV (23%, 23/104) endometriosis, and was comparable in patients with (54%, 61/113) and without (40%, 43/108) pelvic pain. The prevalence of fertility-reducing nonendometriotic tubal and/or uterine pathology was 29% in all patients (15% in women with and 40% in women without endometriosis). A multivariate logistic regression model including pain, ultrasound data, age, duration of infertility, and type of fertility was not or not sufficiently reliable for the prediction of endometriosis according to the revised American Fertility Society (rAFS) classifications I-II and rAFS III-IV, respectively., Conclusion(s): Reproductive surgery is indicated in infertile women belonging to the study population, regardless of pain symptoms or transvaginal ultrasound results, since half of them have endometriosis and 40% of those without endometriosis have fertility-reducing pelvic pathology.

The aim of this review paper is to provide a scientific basis for the development of ovarian stimulation (OS) protocols for in vitro fertilization (IVF) in baboons. Firstly, the evidence available regarding OS for assisted reproduction in baboons is reviewed based on available published data, assessed by a Pub Med search of papers published between 1970 and 2008 using the following key words: baboon, assisted reproduction, IVF, embryo, oocyte. Secondly, we discuss how state-of-the-art or potentially new OS protocols used in humans and in rhesus monkeys may offer guidance for the development of standardized and reliable OS protocols for IVF in baboons. Based on this review and discussion, we conclude that more randomized trials are needed to improve standardization of OS protocols for IVF in baboons with respect to gonadotrophin type, dose, duration of stimulation, ultrasound monitoring, and time interval between ovulation trigger and oocyte retrieval.