Elective freezing of embryos versus fresh embryo transfer in IVF: a multicentre randomized controlled trial in the UK (E-Freeze).

STUDY QUESTION: Does a policy of elective freezing of embryos, followed by frozen embryo transfer result in a higher healthy baby rate, after first embryo transfer, when compared with the current policy of transferring fresh embryos? SUMMARY ANSWER: This study, although limited by sample size, provides no evidence to support the adoption of a routine policy of elective freeze in preference to fresh embryo transfer in order to improve IVF effectiveness in obtaining a healthy baby. WHAT IS KNOWN ALREADY: The policy of freezing all embryos followed by frozen embryo transfer is associated with a higher live birth rate for high responders but a similar/lower live birth after first embryo transfer and cumulative live birth rate for normal responders. Frozen embryo transfer is associated with a lower risk of ovarian hyperstimulation syndrome (OHSS), preterm delivery and low birthweight babies but a higher risk of large babies and pre-eclampsia. There is also uncertainty about long-term outcomes, hence shifting to a policy of elective freezing for all remains controversial given the delay in treatment and extra costs involved in freezing all embryos. STUDY DESIGN, SIZE, DURATION: A pragmatic two-arm parallel randomized controlled trial (E-Freeze) was conducted across 18 clinics in the UK from 2016 to 2019. A total of 619 couples were randomized (309 to elective freeze/310 to fresh). The primary outcome was a healthy baby after first embryo transfer (term, singleton live birth with appropriate weight for gestation); secondary outcomes included OHSS, live birth, clinical pregnancy, pregnancy complications and cost-effectiveness. PARTICIPANTS/MATERIALS, SETTING, METHODS: Couples undergoing their first, second or third cycle of IVF/ICSI treatment, with at least three good quality embryos on Day 3 where the female partner was ≥18 and <42 years of age were eligible. Those using donor gametes, undergoing preimplantation genetic testing or planning to freeze all their embryos were excluded. IVF/ICSI treatment was carried out according to local protocols. Women were followed up for pregnancy outcome after first embryo transfer following randomization. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 619 couples randomized, 307 and 309 couples in the elective freeze and fresh transfer arms, respectively, were included in the primary analysis. There was no evidence of a statistically significant difference in outcomes in the elective freeze group compared to the fresh embryo transfer group: healthy baby rate {20.3% (62/307) versus 24.4% (75/309); risk ratio (RR), 95% CI: 0.84, 0.62 to 1.15}; OHSS (3.6% versus 8.1%; RR, 99% CI: 0.44, 0.15 to 1.30); live birth rate (28.3% versus 34.3%; RR, 99% CI 0.83, 0.65 to 1.06); and miscarriage (14.3% versus 12.9%; RR, 99% CI: 1.09, 0.72 to 1.66). Adherence to allocation was poor in the elective freeze group. The elective freeze approach was more costly and was unlikely to be cost-effective in a UK National Health Service context. LIMITATIONS, REASONS FOR CAUTION: We have only reported on first embryo transfer after randomization; data on the cumulative live birth rate requires further follow-up. Planned target sample size was not obtained and the non-adherence to allocation rate was high among couples in the elective freeze arm owing to patient preference for fresh embryo transfer, but an analysis which took non-adherence into account showed similar results. WIDER IMPLICATIONS OF THE FINDINGS: Results from the E-Freeze trial do not lend support to the policy of electively freezing all for everyone, taking both efficacy, safety and costs considerations into account. This method should only be adopted if there is a definite clinical indication. STUDY FUNDING/COMPETING INTEREST(S): NIHR Health Technology Assessment programme (13/115/82). This research was funded by the National Institute for Health Research (NIHR) (NIHR unique award identifier) using UK aid from the UK Government to support global health research. The views expressed in this publication are those of the author(s) and not necessarily those of the NIHR or the UK Department of Health and Social Care. J.L.B., C.C., E.J., P.H., J.J.K., L.L. and G.S. report receipt of funding from NIHR, during the conduct of the study. J.L.B., E.J., P.H., K.S. and L.L. report receipt of funding from NIHR, during the conduct of the study and outside the submitted work. A.M. reports grants from NIHR personal fees from Merck Serono, personal fees for lectures from Merck Serono, Ferring and Cooks outside the submitted work; travel/meeting support from Ferring and Pharmasure and participation in a Ferring advisory board. S.B. reports receipt of royalties and licenses from Cambridge University Press, a board membership role for NHS Grampian and other financial or non-financial interests related to his roles as Editor-in-Chief of Human Reproduction Open and Editor and Contributing Author of Reproductive Medicine for the MRCOG, Cambridge University Press. D.B. reports grants from NIHR, during the conduct of the study; grants from European Commission, grants from Diabetes UK, grants from NIHR, grants from ESHRE, grants from MRC, outside the submitted work. Y.C. reports speaker fees from Merck Serono, and advisory board role for Merck Serono and shares in Complete Fertility. P.H. reports membership of the HTA Commissioning Committee. E.J. reports membership of the NHS England and NIHR Partnership Programme, membership of five Data Monitoring Committees (Chair of two), membership of six Trial Steering Committees (Chair of four), membership of the Northern Ireland Clinical Trials Unit Advisory Group and Chair of the board of Oxford Brain Health Clinical Trials Unit. R.M. reports consulting fees from Gedeon Richter, honorarium from Merck, support fees for attendance at educational events and conferences for Merck, Ferring, Bessins and Gedeon Richter, payments for participation on a Merck Safety or Advisory Board, Chair of the British Fertility Society and payments for an advisory role to the Human Fertilisation and Embryology Authority. G.S. reports travel and accommodation fees for attendance at a health economic advisory board from Merck KGaA, Darmstadt, Germany. N.R.-F. reports shares in Nurture Fertility. Other authors' competing interests: none declared. TRIAL REGISTRATION NUMBER: ISRCTN: 61225414. TRIAL REGISTRATION DATE: 29 December 2015. DATE OF FIRST PATIENT'S ENROLMENT: 16 February 2016.

Adjuncts in the IVF laboratory: where is the evidence for 'add-on' interventions?

Globally, IVF patients are routinely offered and charged for a selection of adjunct treatments and tests or 'add-ons' that they are told may improve their chance of a live birth, despite there being no clinical evidence supporting the efficacy of the add-on. Any new IVF technology claiming to improve live birth rates (LBR) should, in most cases, first be tested in an appropriate animal model, then in clinical trials, to ensure safety, and finally in a randomized controlled trial (RCT) to provide high-quality evidence that the procedure is safe and effective. Only then should the technique be considered as 'routine' and only when applied to the similar patient population as those studied in the RCT. Even then, further pediatric and long-term follow-up studies will need to be undertaken to examine the long-term safety of the procedure. Alarmingly, there are currently numerous examples where adjunct treatments are used in the absence of evidence-based medicine and often at an additional fee. In some cases, when RCTs have shown the technique to be ineffective, it is eventually withdrawn from the clinic. In this paper, we discuss some of the adjunct treatments currently being offered globally in IVF laboratories, including embryo glue and adherence compounds, sperm DNA fragmentation, time-lapse imaging, preimplantation genetic screening, mitochondria DNA load measurement and assisted hatching. We examine the evidence for their safety and efficacy in increasing LBRs. We conclude that robust studies are needed to confirm the safety and efficacy of any adjunct treatment or test before they are offered routinely to IVF patients.

Single-stage preputial skin flap urethroplasty for long-segment urethral strictures: evaluation and determinants of success.

OBJECTIVE: To determine the overall efficacy and predictors of success of the penile preputial flap in the management of complex urethral strictures >2.5 cm in length. PATIENTS AND METHODS: We performed a retrospective and prospective study of 58 patients undergoing single-stage penile preputial flap urethroplasty for complex long-segment urethral strictures, without lichen sclerosus, repaired between May 2005 and April 2012 at our institution. For obvious reasons circumcised patients were excluded from the study. Results were assessed by univariate analysis of various patient characteristics, preoperative and postoperative patient satisfaction (based on symptoms), and urethral ultrasonography, retrograde urethrography and uroflowmetry. RESULTS: The median (range) follow-up was 42 (6-90) months, the median (range) intra-operative stricture length was 48.5 (26-85) mm and the median (range) operating time was 90 (85-125) min. A total of 87.93% of patients had a satisfactory outcome, with an overall success rate of 81.03%. Diabetes mellitus (relative risk [RR] 5.21, confidence interval [CI] 2.31-64.68, P = 0.003) and smoking (RR 4.19, CI 1.54- 45.0, P = 0.01) were predictors of failure, while postinfective aetiology (RR 2.19), panurethral stricture (RR 2.73), stricture length >70 mm (RR 3.25), previous urethroplasty (RR 2.4) and severe peri-urethral fibrosis (RR 2.37) were also associated with a higher risk of failure. CONCLUSIONS: A urologist should try to gain experience of all the methods of urethroplasty as the techniques may vary according to the circumstances. Single-stage preputial skin flap urethroplasty, in experienced and expert hands, has results equivalent to all other methods of urethroplasty in complex urethral strictures. We prefer this technique in this part of the world where buccal mucosa cannot be used because of dyskeratotic changes as a result of consumption of gutkha, tobacco, pan masala, betel nut.

Diagnosis and treatment of hypogonadism in men seeking to preserve fertility - what are the options?

Male hypogonadism is a clinical syndrome that results in low testosterone levels and frequently leads to infertility. The syndrome occurs due to disruption at one or more levels of the hypothalamic-pituitary-gonadal axis. Testosterone replacement therapy (TRT) is the most common treatment utilised for male hypogonadism. However, long-acting forms of TRT leads to infertility and so is inappropriate for patients wishing to conceive. For patients who wish to remain fertile, nasal TRT, clomiphene citrate, exogenous gonadotropins, gonadotropin releasing hormone and aromatase inhibitors have been used as alternative treatment options with different degrees of success. A review of the literature was performed to identify the safety and efficacy of alternative treatment options. Gonadotropin releasing hormone can successfully induce spermatogenesis but is impractical to administer. Likewise, aromatase inhibitors have limited use due to inducing osteopenia. Nasal TRT may be a good treatment option for these patients, but its efficacy has so far only been demonstrated in small sample sizes. However, clomiphene citrate and exogenous gonadotropins are safe, offer good symptom control and can successfully induce fertility in hypogonadism patients.

Outpatient paracentesis for the management of ovarian hyperstimulation syndrome: study protocol for the STOP-OHSS randomised controlled trial.

INTRODUCTION: Ovarian hyperstimulation syndrome (OHSS) is the most significant short-term complication of pharmacological ovarian stimulation. Symptoms range from mild abdominal discomfort to rare complications such as renal failure, thromboembolism and respiratory distress syndrome.Currently, clinical practice typically involves monitoring the patient until the condition becomes severe, at which point they are admitted to hospital, where drainage of ascitic fluid (paracentesis) may take place. Preliminary studies have indicated that earlier outpatient paracentesis may reduce the progression of OHSS and prevent hospitalisation in women. METHODS AND ANALYSIS: This UK, multicentre, pragmatic, two-arm, parallel-group, adaptive (group sequential with one interim analysis), open-label, superiority, confirmatory, group sequential, individually randomised controlled trial, with internal pilot will assess the clinical and cost-effectiveness and safety of outpatient paracentesis versus conservative management (usual care) for moderate or severe OHSS. 224 women from 20 National Health Service and private fertility units will be randomised (1:1) and followed up for up to 13.5 months. The primary outcome is the rate of OHSS related hospital admission of at least 24 hours within 28 days postrandomisation. The primary analysis will be an intention to treat with difference in hospitalisation rates as measure of treatment effect. Secondary outcomes include time to resolution of symptoms, patient satisfaction, adverse events and cost-effectiveness. A qualitative substudy will facilitate the feasibility of recruitment. Participant recruitment commenced in June 2022. ETHICS AND DISSEMINATION: London-Southeast Research Ethics Committee approved the protocol (reference: 22/LO/0015). Findings will be submitted to peer-reviewed journals and abstracts to relevant national and international conferences, as well as being disseminated to trial participants and patient groups. TRIAL REGISTRATION NUMBER: ISRCTN71978064.

The long-term safety and efficacy of bilateral transplantation of human fetal striatal tissue in patients with mild to moderate Huntington's disease.

Huntington's disease (HD) is a fatal autosomal dominant neurodegenerative disease involving progressive motor, cognitive and behavioural decline, leading to death approximately 20 years after motor onset. The disease is characterised pathologically by an early and progressive striatal neuronal cell loss and atrophy, which has provided the rationale for first clinical trials of neural repair using fetal striatal cell transplantation. Between 2000 and 2003, the 'NEST-UK' consortium carried out bilateral striatal transplants of human fetal striatal tissue in five HD patients. This paper describes the long-term follow up over a 3-10-year postoperative period of the patients, grafted and non-grafted, recruited to this cohort using the 'Core assessment program for intracerebral transplantations-HD' assessment protocol. No significant differences were found over time between the patients, grafted and non-grafted, on any subscore of the Unified Huntington's Disease Rating Scale, nor on the Mini Mental State Examination. There was a trend towards a slowing of progression on some timed motor tasks in four of the five patients with transplants, but overall, the trial showed no significant benefit of striatal allografts in comparison with a reference cohort of patients without grafts. Importantly, no significant adverse or placebo effects were seen. Notably, the raclopride positron emission tomography (PET) signal in individuals with transplants, indicated that there was no obvious surviving striatal graft tissue. This study concludes that fetal striatal allografting in HD is safe. While no sustained functional benefit was seen, we conclude that this may relate to the small amount of tissue that was grafted in this safety study compared with other reports of more successful transplants in patients with HD.

COVID-19 vaccination and fertility: fighting misinformation.

The introduction of vaccination against COVID-19 was associated with widespread misinformation on social media concerning, among other things, the potential effect of the vaccine in reducing fertility and increasing the risk of miscarriage among recipients. Tackling misinformation requires an understanding of the context in which it spreads and careful use of the doctor's knowledge and communication skills. Research into ways of tackling disinformation is still at an early stage, but some measures that are likely to be effective include content moderation, misinformation labelling and improving the level of scientific discussion in public media. Health professionals have a duty to provide unbiased and accurate information, including through the use of social media. This requires the maintenance of empathy, trustworthiness and openness in the face of what may at times be malicious intent.

Video consultations in reproductive medicine: Safety, feasibility and patient satisfaction.

OBJECTIVE: To study the safety and feasibility of virtual consultations in reproductive medicine. DESIGN: This was a descriptive cross-sectional study involving subfertile patients attending a video consultation between September 2021 and August 2022. Clinicians conducting virtual consultations during the same period responded to a parallel survey for healthcare professionals. SETTING: University Hospital in Manchester, UK. PARTICIPANTS: Subfertile patients attending a virtual consultation. Healthcare professionals conducting virtual consultations. INTERVENTION: The survey link was offered in 4,932 consultations. A total of 577 (11.69%) patients responded and 510 completed the questionnaire (88.3%). MAIN OUTCOME MEASURES: Patient satisfaction measured as the percentage of patients preferring virtual to in person consultations. RESULTS: The majority of the patients (475, 91.70%) had a positive experience with the video consultation and just under half of the patients (152, 48.65%) preferred a video consultation to an in person consultation due to cost and time savings. Most patients (375, 72.68%) felt safer and less exposed to COVID-19. When the risk of COVID-19 subsides, 242 patients (47%) would still prefer to attend video consultations, while 169 (32.82%) had no preference. Analysis of the responses from patients reporting a negative experience identified technical problems as a possible cause. The virtual consultations appeared to be suitable for patients with disabilities. The clinicians' survey identified potential legal and ethical concerns. CONCLUSION: Virtual consultations are a safe and feasible alternative to in person consultations for subfertile patients. This large cross-sectional study revealed a high rate of patient satisfaction. Appropriate patient selection accounting for IT literacy, English language understanding and preference is crucial for successful virtual consultations. Further consideration should be given to ethical and legal challenges of virtual consultations. TRIAL REGISTRATION: Research Registry, UIN 6912, https://www.researchregistry.com/browse-the-registry.

Prediction of significant OHSS by ovarian reserve and ovarian response - implications for elective freeze-all strategy.

Ovarian Hyperstimulation Syndrome (OHSS) remains a risk to women undergoing assisted conception despite available preventative measures, which are usually applied on the basis of ovarian response. We performed a retrospective cohort study with robust ascertainment of OHSS cases in women undergoing treatment using GnRH antagonist. FSH dose was based on Anti-Mullerian Hormone concentration. A total of 1492 cycles were carried out over 18 months. Moderate/severe OHSS occurred in 24 cycles (1.6%). AMH of 35 pmol/L and/or AFC of 20 or more identified 18/24 (76%) OHSS cases. The optimal thresholds for predicting OHSS were 22.5 pmol/L for AMH (sensitivity 87.5%, specificity 60.6%), 19.5 for AFC (sensitivity 70.8%, specificity 67%), and 9.5 for egg numbers (sensitivity 83.5%, specificity 62.7%). Peak oestradiol levels had no predictive value. The utility of egg number is limited as it is only known after the ovulatory trigger has been administered. Thus, ovarian reserve parameters are better than ovarian response at predicting the risk of significant OHSS in GnRH antagonist cycles in modern clinical practice. Patients with a high ovarian reserve are at risk of OHSS even if their ovarian response is not excessive. Decisions about preventative measures should be based on ovarian reserve rather than ovarian response.

Transfer of thawed frozen embryo versus fresh embryo to improve the healthy baby rate in women undergoing IVF: the E-Freeze RCT.

BACKGROUND: Freezing all embryos, followed by thawing and transferring them into the uterine cavity at a later stage (freeze-all), instead of fresh-embryo transfer may lead to improved pregnancy rates and fewer complications during in vitro fertilisation and pregnancies resulting from it. OBJECTIVE: We aimed to evaluate if a policy of freeze-all results in a higher healthy baby rate than the current policy of transferring fresh embryos. DESIGN: This was a pragmatic, multicentre, two-arm, parallel-group, non-blinded, randomised controlled trial. SETTING: Eighteen in vitro fertilisation clinics across the UK participated from February 2016 to April 2019. PARTICIPANTS: Couples undergoing their first, second or third cycle of in vitro fertilisation treatment in which the female partner was aged < 42 years. INTERVENTIONS: If at least three good-quality embryos were present on day 3 of embryo development, couples were randomly allocated to either freeze-all (intervention) or fresh-embryo transfer (control). OUTCOMES: The primary outcome was a healthy baby, defined as a live, singleton baby born at term, with an appropriate weight for their gestation. Secondary outcomes included ovarian hyperstimulation, live birth and clinical pregnancy rates, complications of pregnancy and childbirth, health economic outcome, and State-Trait Anxiety Inventory scores. RESULTS: A total of 1578 couples were consented and 619 couples were randomised. Most non-randomisations were because of the non-availability of at least three good-quality embryos (n = 476). Of the couples randomised, 117 (19%) did not adhere to the allocated intervention. The rate of non-adherence was higher in the freeze-all arm, with the leading reason being patient choice. The intention-to-treat analysis showed a healthy baby rate of 20.3% in the freeze-all arm and 24.4% in the fresh-embryo transfer arm (risk ratio 0.84, 95% confidence interval 0.62 to 1.15). Similar results were obtained using complier-average causal effect analysis (risk ratio 0.77, 95% confidence interval 0.44 to 1.10), per-protocol analysis (risk ratio 0.87, 95% confidence interval 0.59 to 1.26) and as-treated analysis (risk ratio 0.91, 95% confidence interval 0.64 to 1.29). The risk of ovarian hyperstimulation was 3.6% in the freeze-all arm and 8.1% in the fresh-embryo transfer arm (risk ratio 0.44, 99% confidence interval 0.15 to 1.30). There were no statistically significant differences between the freeze-all and the fresh-embryo transfer arms in the live birth rates (28.3% vs. 34.3%; risk ratio 0.83, 99% confidence interval 0.65 to 1.06) and clinical pregnancy rates (33.9% vs. 40.1%; risk ratio 0.85, 99% confidence interval 0.65 to 1.11). There was no statistically significant difference in anxiety scores for male participants (mean difference 0.1, 99% confidence interval -2.4 to 2.6) and female participants (mean difference 0.0, 99% confidence interval -2.2 to 2.2) between the arms. The economic analysis showed that freeze-all had a low probability of being cost-effective in terms of the incremental cost per healthy baby and incremental cost per live birth. LIMITATIONS: We were unable to reach the original planned sample size of 1086 and the rate of non-adherence to the allocated intervention was much higher than expected. CONCLUSION: When efficacy, safety and costs are considered, freeze-all is not better than fresh-embryo transfer. TRIAL REGISTRATION: This trial is registered as ISRCTN61225414. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 25. See the NIHR Journals Library website for further project information.

During in vitro fertilisation, eggs and sperm are mixed in a laboratory to create embryos. An embryo is placed in the womb 2­5 days later (fresh-embryo transfer) and the remaining embryos are frozen for future use. Initial research suggested that freezing all embryos followed by thawing and replacing them a few weeks later could improve treatment safety and success. Although these data were promising, the data came from small studies and were not enough to change practice and policy. We conducted a large, multicentre, clinical trial to evaluate the two strategies: fresh-embryo transfer compared with later transfer of frozen embryos. We also compared the costs of both strategies during in vitro fertilisation treatment, pregnancy and delivery. This study was conducted across 18 clinics in the UK from 2016 to 2019, and 619 couples participated. Couples were allocated to one of two strategies: immediate fresh-embryo transfer or freezing of all embryos followed later by transfer of frozen embryo. The study's aim was to find out which type of embryo transfer gave participants a higher chance of having a healthy baby. We found that freezing all embryos followed by frozen-embryo transfer did not lead to a higher chance of having a healthy baby. There were no differences between strategies in the number of live births, the miscarriage rate or the number of pregnancy complications. Fresh-embryo transfer was less costly from both a health-care and a patient perspective. A routine strategy of freezing all embryos is not justified given that there was no increase in success rates but there were extra costs and delays to embryo transfer.

Protocol for developing a core outcome set for male infertility research: an international consensus development study.

STUDY QUESTION: We aim to develop, disseminate and implement a minimum data set, known as a core outcome set, for future male infertility research. WHAT IS KNOWN ALREADY: Research into male infertility can be challenging to design, conduct and report. Evidence from randomized trials can be difficult to interpret and of limited ability to inform clinical practice for numerous reasons. These may include complex issues, such as variation in outcome measures and outcome reporting bias, as well as failure to consider the perspectives of men and their partners with lived experience of fertility problems. Previously, the Core Outcome Measure for Infertility Trials (COMMIT) initiative, an international consortium of researchers, healthcare professionals and people with fertility problems, has developed a core outcome set for general infertility research. Now, a bespoke core outcome set for male infertility is required to address the unique challenges pertinent to male infertility research. STUDY DESIGN SIZE DURATION: Stakeholders, including healthcare professionals, allied healthcare professionals, scientists, researchers and people with fertility problems, will be invited to participate. Formal consensus science methods will be used, including the modified Delphi method, modified Nominal Group Technique and the National Institutes of Health's consensus development conference. PARTICIPANTS/MATERIALS SETTING METHODS: An international steering group, including the relevant stakeholders outlined above, has been established to guide the development of this core outcome set. Possible core outcomes will be identified by undertaking a systematic review of randomized controlled trials evaluating potential treatments for male factor infertility. These outcomes will be entered into a modified Delphi method. Repeated reflection and re-scoring should promote convergence towards consensus outcomes, which will be prioritized during a consensus development meeting to identify a final core outcome set. We will establish standardized definitions and recommend high-quality measurement instruments for individual core outcomes. STUDY FUNDING/COMPETING INTERESTS: This work has been supported by the Urology Foundation small project award, 2021. C.L.R.B. is the recipient of a BMGF grant and received consultancy fees from Exscentia and Exceed sperm testing, paid to the University of Dundee and speaking fees or honoraria paid personally by Ferring, Copper Surgical and RBMO. S.B. received royalties from Cambridge University Press, Speaker honoraria for Obstetrical and Gynaecological Society of Singapore, Merk SMART Masterclass and Merk FERRING Forum, paid to the University of Aberdeen. Payment for leadership roles within NHS Grampian, previously paid to self, now paid to University of Aberdeen. An Honorarium is received as Editor in Chief of Human Reproduction Open. M.L.E. is an advisor to the companies Hannah and Ro. B.W.M. received an investigator grant from the NHMRC, No: GNT1176437 is a paid consultant for ObsEva and has received research funding from Ferring and Merck. R.R.H. received royalties from Elsevier for a book, consultancy fees from Glyciome, and presentation fees from GryNumber Health and Aytu Bioscience. Aytu Bioscience also funded MiOXYS systems and sensors. Attendance at Fertility 2020 and Roadshow South Africa by Ralf Henkel was funded by LogixX Pharma Ltd. R.R.H. is also Editor in Chief of Andrologia and has been an employee of LogixX Pharma Ltd. since 2020. M.S.K. is an associate editor with Human Reproduction Open. K.Mc.E. received an honoraria for lectures from Bayer and Pharmasure in 2019 and payment for an ESHRE grant review in 2019. His attendance at ESHRE 2019 and AUA 2019 was sponsored by Pharmasure and Bayer, respectively. The remaining authors declare no competing interests. TRIAL REGISTRATION NUMBER: Core Outcome Measures in Effectiveness Trials (COMET) initiative registration No: 1586. Available at www.comet-initiative.org/Studies/Details/1586. TRIAL REGISTRATION DATE: N/A. DATE OF FIRST PATIENT'S ENROLMENT: N/A.

Isolated renal artery thrombosis because of blunt trauma abdomen: report of a case with review of the literature.

BACKGROUND: Isolated renal trauma in case of blunt trauma abdomen (BTA) is not common. Renal artery occlusion by thrombosis in such cases is seen very rarely. These cases had been traditionally treated by early nephrectomy, but nowadays, renal preservation is considered whenever possible. Treatment options to do so are being developed. METHODS: Recently we came across one such case of isolated unilateral renal artery thrombosis (RAT) because of BTA. Relevant literature especially on various therapeutic techniques has been critically reviewed briefly along with case presentation. RESULTS: Isolated blunt traumatic RAT has an incidence of less than 1%. Only about 400 cases have been reported. It must be diagnosed and treated as soon as possible to avoid progressive permanent loss of renal function. Contrast-enhanced CT scanning is the preferred modality for evaluation and follow-up of RAT. Conservative treatment is reserved for unilateral cases. For bilateral cases and when RAT occurs in a solitary kidney, revascularization either surgically or more preferably by less invasive percutaneous techniques has been recommended. CONCLUSION: Renal arterial thrombosis because of blunt abdominal trauma is still an underreported entity, treatment for which has not yet been established. Both early nephrectomy and delayed revascularization are not justified treatment options.

Unusual rectal foreign body presenting as intestinal obstruction: a case report.

Colorectal foreign bodies are infrequently encountered, and are mostly associated with increased incidence of homosexuality and anal auto-erotism. The diagnosis may be confirmed by plain abdominal radiographs and rectal examination, but abdominal computerized tomography can be decisive in the further management. Manual extraction is only possible for very low-lying objects; patients with high-lying foreign bodies usually require a major intervention in the operation theater. An early decision of laparotomy should only be made after subjecting the patient to suitable investigations to determine exactly the localization of the object, in order to avoid any inadvertent damage to the adjoining vasculature as well as anal incontinence. We report the case of a young adult male who presented in the emergency department with an incarcerated, large, neglected rectal foreign body, a 'bull horn', causing intestinal obstruction. Emergent laparotomy was required for its removal.

A review of varicocele treatment and fertility outcomes.

Varicoceles are reported to be present in a significant proportion of men presenting with subfertility and are more common amongst this group than in the general population. Opinion still remains divided amongst clinicians managing male factor infertility as to whether varicoceles alter the probability of spontaneous conception and/or pregnancy and live birth rates after fertility treatment. The debate as to whether varicoceles should be treated or not has intensified in recent years. This is due to the concerns regarding the impact of varicoceles on not only conventional semen parameters, but also the potential effects that they may have at the cellular level (an increase in circulating reactive oxygen species (ROS) resulting in sperm DNA fragmentation, even when conventional semen parameters are within the normal reference ranges). It has been suggested that treating the varicocele may result in improvements in the semen parameters, the fertilization and pregnancy rates for both spontaneous pregnancy as well as following in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment. ICSI can still be used for Assisted Reproduction Treatment (ART) in the presence of suboptimal semen parameters. However, it is an invasive and expensive technique with potential adverse effects on the offspring. As far as we are aware, there are no randomized controlled trials comparing the clinical/cost effectiveness of varicocele treatment versus the immediate use of ICSI on pregnancy rates. Previous modelling exercises are old and do not take into consideration current practices and trends such as rising female age and time to pregnancy. The conflicting advice that patients sometimes receive, challenges our commitment to evidence-based practice. The only way to resolve the controversy is to undertake an appropriately powered randomized trial, assessing clinical- and cost-effectiveness and the time to pregnancy following varicocele treatment and comparing this to a no treatment group.

Qualitative risk assessment of follicle stimulating hormone injectable products.

BACKGROUND: Gonadotropin injections for fertility treatment regimens are usually self-injected, typically over 8-12 days during the assisted reproductive technology cycle. Parenteral gonadotropins are available in different formulations and administered through various systems. A user experience study and risk assessment were performed to evaluate different product types for risks to the patient when preparing and administering injections. METHODS: Nine women of child-bearing age each prepared and administered injections of six products representing single- and multidose vials of menotropin for reconstitution (Merional® and Menopur®), follicle stimulating hormone (FSH) reusable pen injectors with (Puregon®), and without cartridges (Gonal-f®), and single-use FSH pre-filled pens (Bemfola®). Risk assessments based on user feedback were made with reference to EU regulations for implementing practices for safe use of injectable products. RESULTS: Products requiring reconstitution with diluent in glass ampoules were associated with medium risk for sharps injury and a lower level of user confidence. Pen injectors were considered easy-to-use, with a low risk of sharps injury. Single-use pens were associated with the lowest risk of dosing errors. CONCLUSIONS: The study identifies differences in the risks for both sharps injuries and dosing errors between FSH delivery options that practitioners should consider when making a treatment choice.

Tunica albuginea urethroplasty for anterior urethral strictures: a urethroscopic analysis.

OBJECTIVE: To assess the efficacy of tunica albuginea urethroplasty (TAU) for anterior urethral strictures. METHODS: We assessed 206 patients with anterior urethral strictures who underwent TAU. The procedure involves mobilization of strictured urethra and laying it open with a dorsal slit. Edges of the slit-open urethra are sutured to edges of the urethral groove with a silicon catheter in situ. Thus in neourethra, the roof is formed by tunica albuginea of the urethral groove. Results were assessed at 6, 12, 24 and 36 months by comparative analysis of patient satisfaction along with retrograde urethrogram, urethrosonogram, uroflowmetry, and were categorized as good, fair and poor. Good and fair results were considered as successful. Thirty patients were taken for postoperative urethroscopic analysis to allow better understanding of both successful and failed cases. RESULTS: Postoperative evaluation at 6 months showed a 96.6% success rate, which decreased to 94.7% at 1 year, 93.2% at 2 years and over 90% at the end of 3 years. The overall failure rate was 9.2%, which required revision surgery. Urethroscopic visualization of the reconstruction site showed wide, patent and distensible neourethra uniformly lined by urothelium over roof formed by tunica albuginea of the corpora cavernosa in successful cases. Failure cases showed diffuse fibrotic narrowing or circumferential scarring. CONCLUSION: Tunica albuginea is a locally available distensible tissue, sufficient to maintain the patency of the neourethra, without any graft or flap. TAU is easier and useful when patients have unhealthy oral mucosa due to tobacco chewing.

Technique of anterior urethroplasty using the tunica albuginea of the corpora cavernosa.

OBJECTIVE: To describe a technique of anterior urethroplasty using the tunica albuginea of the corpora cavernosa. METHODS: We performed this technique on 99 male patients with anterior urethral stricture with follow-up at 6, 12 and 18 months. We assessed preoperative and postoperative patient satisfaction rate based on symptoms along with preoperative and postoperative urethrograms, urethrosonographies and uroflowmetry and labelled outcomes as good, fair and poor. RESULTS: Good and fair results were considered successful. The overall success rate was 95.9%. In our series of patients, the overall success rate of urethroplasty remained the same at 6 months, but decreased to 94.9% at 12 months and 88.1% at 18 months. CONCLUSION: These observations show that anterior urethroplasty by using the tunica albuginea of the corpora cavernosa produced satisfactory results and is comparable with the other techniques of urethroplasty. The merits of using the tunica albuginea for urethroplasty are local availability of tissues, so that there is no need to use anatomically and structurally dissimilar distant tissue such as the buccal mucosa, preputial, penile, or scrotal skin or Teflon grafts. It can be used in our area where most of the patients come with dyskeratotic changes in their buccal mucosa.

Outpatient management of severe ovarian hyperstimulation syndrome: a systematic review and a review of existing guidelines.

Ovarian hyperstimulation syndrome (OHSS) is a potentially serious complication of assisted reproductive treatment. Management of women with severe OHSS has traditionally included hospitalisation for close monitoring and supportive treatment. The aim of this review is to assess the evidence for safety and efficacy of outpatient management of severe OHSS. A systematic review of studies describing outpatient management options was performed. Current guidance from advisory bodies was also reviewed. Outpatient management has been found in observational studies to be safe and cost-effective compared to inpatient management. Paracentesis of ascitic fluid seems to be effective treatment for severe OHSS along with supportive management including maintenance of fluid balance and preventative measures against thrombo-embolism. GnRH antagonist was shown in few studies to be effective in treatment of early severe OHSS although further research is required to assess its role in this context. Appropriate outpatient set up and protocols are essential to provide safe outpatient management for women with severe OHSS.