A review on the motivations, decision-making factors, attitudes and experiences of couples using pre-implantation genetic testing for inherited conditions.

BACKGROUND: In pre-implantation genetic testing (PGT), fertile couples undergo IVF with genetic testing of embryos to avoid conceptions with a genetic condition. There is an exponentially increasing uptake with over 600 applications listed by the Human Fertilisation and Embryology Authority in the UK. The psychological aspects of the decision-making process and the experience of PGT, however, are relatively underevaluated, with the potential to leave patients unsupported in their journeys. OBJECTIVE AND RATIONALE: In this review, we aim to comprehensively report on every aspect of couples' experiences of PGT. We consider what motivates users, the practical and ethical decisions involved and how couples navigate the decision-making process. Additionally, we report on the social and psychological impact on couples who are actively undergoing or have completed the PGT process. SEARCH METHODS: A systematic search of English peer-reviewed journals of three computerized databases was undertaken following PRISMA guidelines. Studies that examined the motivations, attitudes, decision-making factors and experiences of patients who have been actively engaged in the PGT process were included. No restrictions were placed on study design or date of publication. Studies examining patients using PGT in a hypothetical context or solely using PGT for aneuploidy were excluded. Qualitative data were extracted using thematic analysis. OUTCOMES: The main outcomes were patient motivations, deciding factors and attitudes, as well as the patient experience of coming to a decision and going through PGT.Patients were primarily motivated by the desire to have a healthy child and to avoid termination of pregnancy. Those with a sick child or previous experience of termination were more likely to use PGT. Patients also felt compelled to make use of the technology available, either from a moral responsibility to do so or to avoid feelings of guilt if not. The main factors considered when deciding to use PGT were the need for IVF and the acceptability of the technology, the financial cost of the procedure and one's ethical standpoint on the creation and manipulation of embryos. There was a general consensus that PGT should be applied to lethal or severe childhood disease but less agreement on use for adult onset or variable expression conditions. There was an agreement that it should not be used to select for aesthetic traits and a frustration with the views of PGT in society. We report that couples find it difficult to consider all of the benefits and costs of PGT, resulting in ambivalence and prolonged indecision. After deciding on PGT use, we found that patients find the process extremely impractical and psychologically demanding. WIDER IMPLICATIONS: This review aimed to summarize the current knowledge on how patients decide to use and experience PGT and to make suggestions to incorporate the findings into clinical practice. We cannot stress enough the importance of holistic evaluation of patients and thorough counselling prior to and during PGT use from a multidisciplinary team that includes geneticists, IVF clinicians, psychologists and also patient support groups. Large prospective studies using a validated psychological tool at various stages of the PGT process would provide an invaluable database for professionals to better aid patients in their decision-making and to improve the patient experience.

What are the critical success factors for team training in health care?

BACKGROUND: Ineffective communication among medical teams is a leading cause of preventable patient harm throughout the health care system. A growing body of literature indicates that medical teamwork improves the quality, safety, and cost-effectiveness of health care delivery, and expectations for teamwork in health care have increased. Yet few health care professions' curricula include teamwork training, and few medical practices integrate teamwork principles. Because of this knowledge gap, growing numbers of health care systems are requiring staff to participate in formal teamwork training programs. Seven evidence-based, practical, systematic success factors for preparing, implementing, and sustaining a team training and performance improvement initiative were identified. Each success factor is accompanied by tips for deployment and a real-world example of application. SUCCESS FACTORS: (1) Align team training objectives and safety aims with organizational goals, (2) provide organizational support for the team training initiative, (3) get frontline care leaders on board, (4) prepare the environment and trainees for team training, (5) determine required resources and time commitment and ensure their availability, (6) facilitate application of trained teamwork skills on the job; and (7) measure the effectiveness of the team training program. DISCUSSION: Although decades of research in other high-risk organizations have clearly demonstrated that properly designed team training programs can improve team performance, success is highly dependent on organizational factors such as leadership support, learning climate, and commitment to data-driven change. Before engaging in a teamwork training initiative, health care organizations should have a clear understanding of these factors and the strategies for their establishment.

Sperm DNA fragmentation in subfertile men: the effect on the outcome of intracytoplasmic sperm injection and correlation with sperm variables.

OBJECTIVE: To present the first UK data on sperm DNA fragmentation levels in subfertile men and fertile controls, the correlation with semen variables, and to assess the effect on the outcome of intracytoplasmic sperm injection (ICSI). PATIENTS, SUBJECTS AND METHODS: In all, 56 subfertile men undergoing ICSI (28 with positive and 28 with a negative outcome for paternity) and 10 control fertile semen donors were recruited. The sperm DNA fragmentation index (DFI) was assessed on raw pre-preparation samples using the sperm chromatin structure assay. A mean of 5212 sperm were analysed per sample and DFI data are presented by fertility status, ICSI outcome and correlated with semen variables (assessed using World Health Organisation criteria). RESULTS: Total DFI was significantly higher in subfertile men than in fertile controls (mean and median of 22.8% and 17.0% vs 8.4% and 5.0%; P < 0.001), as was the proportion of both moderate DFI (16.4% and 13.0% vs 6.4% and 4.0%; P = 0.001) and high DFI (6.2% and 6.1 vs 2.0% and 1.0%; P = 0.01). This difference remained significant when the control men were compared only with the subfertile men with successful paternity. There was no significant difference in DFI in the subfertile men when analysed by ICSI outcome (mean and median of 24.5% and 17.0% vs 22.3% and 21.0% for successful and unsuccessful cycles, respectively; P = 0.94). There was a positive statistically significant correlation (r = 0.37; P = 0.02) between the DFI and sperm morphology. CONCLUSIONS: This study confirms a relationship between male subfertility and sperm DFI; we discuss the correct role for genetic testing of sperm in the evaluation of subfertile men. Although DNA fragmentation data might help to decide a suitable treatment, once it is decided to proceed with ICSI, DFI levels have no effect on the outcome.

Use of surgical sperm retrieval in azoospermic men: a meta-analysis.

OBJECTIVE: To compare the outcome of intracytoplasmic sperm injection (ICSI) cycles [1] using epididymal and testicular sperm in patients with obstructive azoospermia (OA); [2] using surgically retrieved sperm in patients with OA and nonobstructive azoospermia (NOA); and [3] using fresh and frozen-thawed sperm. DESIGN: Meta-analysis of published data. SETTING: Assisted conception unit. PATIENT(S): Ten reports (734 cycles: 677 transfers) were identified as suitable to assess source of sperm; 9 reports (1,103 cycles: 998 transfers) to assess etiology; and 17 reports (1,476 cycles: 1,377 transfers) to assess the effect of cryopreservation. INTERVENTION(S): Surgical sperm retrieval/ICSI. MAIN OUTCOME MEASURE(S): Fertilization rate (FR), implantation rate (IR), clinical pregnancy rate (CPR), and ongoing pregnancy rate (OPR) per embryo transfer. RESULT(S): Meta-analysis demonstrated no significant difference in any outcome measure between the use of epididymal or testicular sperm in men with OA. Meta-analysis showed a significantly improved FR (relative risk [RR] 1.18; 95% confidence interval [CI]: 1.13-1.23) and CPR (RR 1.36; 95% CI: 1.10-1.69) in men with OA as compared to NOA with a nonsignificant increase in OPR. There was no difference in either IR or miscarriage rate between the two groups. Comparing fresh with frozen-thawed epididymal sperm there was no difference in FR or IR, a significantly higher CPR (RR 1.20; 95% CI: 1.0-1.42), and no difference in OPR. No difference in fertilization or pregnancy outcome was noted when the testicular cycles were analyzed separately, but IR was significantly impaired using frozen-thawed sperm (RR 1.75; 95% CI: 1.10-2.80). CONCLUSION(S): Meta-analysis of published data confirms that etiology of azoospermia and cryopreservation of surgically retrieved sperm impacts on ICSI outcome, and allows us to make several recommendations for clinical practice. Origin of sperm, in men with similar etiology, does not affect outcome.

Effect of time since vasectomy and maternal age on intracytoplasmic sperm injection success in men with obstructive azoospermia after vasectomy.

OBJECTIVE: To determine the effects of time since vasectomy and maternal age on intracytoplasmic sperm injection (ICSI) outcome in azoospermic men after vasectomy. DESIGN: Retrospective analysis. SETTING: Assisted conception unit. PATIENT(S): Thirty-seven azoospermic men (after vasectomy) who were undergoing 56 cycles of ICSI. INTERVENTION(S): Surgical sperm retrieval and standard ICSI protocol. The ICSI cycles were analyzed in four groups, according to years since vasectomy, and were reanalyzed in three groups, according to maternal age. MAIN OUTCOME MEASURE(S): Fertilization rate, implantation rate, clinical pregnancy rate, and live-birth rate (LBR) per ET. RESULT(S): No effect of time since vasectomy was seen on any outcome. The highest fertilization rate and LBR were found in the group with the longest time interval. These findings could not be explained by differences in either patient characteristics or stimulation regimes. When reanalyzed by maternal age, there was an improvement in implantation rate and LBR with decreasing maternal age. Live birth rates of 38.5%, 22.7%, and 11.8% were achieved for maternal ages of <32, 32-37, and >38 years, respectively. Logistic regression confirmed a statistically significant effect on outcome of maternal age but not time since vasectomy. CONCLUSION(S): Our data suggest that maternal age, and not interval since vasectomy, remains the principal determinant of ICSI success in men with obstructive azoospermia after vasectomy.

The effect of human immunodeficiency virus on sperm parameters and the outcome of intrauterine insemination following sperm washing.

BACKGROUND: This is the first study to assess the outcome of sperm washing and intrauterine insemination (IUI) cycles in human immunodeficiency virus-positive (HIV(+)) men to determine any predictors of success, as well as evaluating the effect of HIV on sperm parameters. METHODS: Semen characteristics were evaluated in 106 HIV(+) men and a control group of 234 HIV(-) men, and the effect of markers of HIV disease assessed. Age, stimulation regime, sperm parameters, markers of HIV disease and the use of anti-retrovirals were assessed as predictors of the outcome of sperm washing/IUI cycles in the HIV(+) men. RESULTS: Ejaculate volume, sperm concentration, total count, progressive motility and normal morphology were all significantly higher in the control group compared to the HIV(+) men (P<0.05). A significant positive correlation was observed between CD4 count and sperm concentration, total count, motility, progressive motility type 'a'+'b' and post-preparation concentration and a significant negative correlation with normal sperm morphology of both raw and post-preparation samples. No correlation was observed between viral load (VL), years since diagnosis, use of anti-retrovirals or duration of use and any sperm parameter. The only factors that significantly improved IUI outcome were a VL <1000 copies/ml and the use of anti-retrovirals. CONCLUSIONS: These data demonstrate that sperm parameters are significantly impaired by the presence of HIV infection and in particular correlate with CD4 count. Undetectable VL and the use of anti-retrovirals improve the outcome of IUI/sperm washing in HIV(+) men.

Synchronous sperm retrieval and sperm washing in an intracytoplasmic sperm injection cycle in an azoospermic man who was positive for human immunodeficiency virus.

OBJECTIVE: To present the first reported case of synchronous sperm retrieval followed by sperm washing before an intracytoplasmic sperm injection (ICSI) cycle in an HIV-positive azoospermic man. DESIGN: Case report. SETTING: Assisted reproduction center. PATIENT(S): A 40-year-old HIV-positive man with obstructive azoospermia due to vasal aplasia. INTERVENTION(S): Synchronous sperm retrieval, sperm washing, nucleic acid-based sequence amplification testing, and intracytoplasmic sperm injection. MAIN OUTCOME MEASURE(S): Successful sperm retrieval sufficient for sperm washing and fertilization. RESULT(S): Sufficient quantity of spermatozoa for washing was obtained at epididymal aspiration. After the wash, HIV ribonucleic acid (RNA) was undetectable with nucleic acid-based sequence amplification testing, enabling injection of oocytes collected after routine gonadotropin superovulation. Of seven oocytes collected from the 39-year-old woman partner, six were injected and five fertilized (83%). Three embryos were transferred on day 2. The pregnancy test was negative on this occasion. CONCLUSION(S): This case demonstrates that sperm washing can be applied in cases of sperm retrieval where sperm volume and density is low, allowing the treatment of azoospermic HIV-positive men.

Frozen embryos generated from surgically retrieved sperm from azoospermic men: are they clinically viable?

PURPOSE: To assess the viability of frozen-thawed embryos derived from intracytoplasmic sperm injection (ICSI) in azoospermic men. METHODS: Retrospective analysis of 154 consecutive ICSI cycles using surgically retrieved sperm from azoospermic men and case-control comparison of subsequent frozen transfer cycles with those using embryos generated from ejaculated sperm. RESULTS: Patient and fresh cycle characteristics were similar in both groups. There were no differences between the two groups in the proportion of pronucleate (54% and 62%), and cleavage-stage embryos thawed (46% and 38%), post-thaw survival rates (retrievals: 69%; ejaculated: 73%) or quality of frozen embryos subsequently transferred. Implantation was significantly lower in frozen cycles where embryos were generated from surgically retrieved sperm (0% versus 11.5%; p = 0.03). Both clinical pregnancy rate (5% versus 21%) and live-birth rate (0% versus 21%) were lower in this group, but only the difference in LBR reached borderline statistical difference (p = 0.10). CONCLUSION: This small series demonstrates a significant impairment in implantation in FET cycles using embryos generated from surgically retrieved sperm and a trend towards a poorer pregnancy outcome.