Research Papers
The focus of Professor Minhas's research at Imperial College is improving our understanding of male fertility and to improve fertility outcomes in men.
He works closely with the department of reproductive endocrinology with his colleague Dr Jayasena at Imperial, as a co-investigator/supervisor on a number of research projects.
In this research paper, Prof Minhas and his team highlight the importance of measuring sperm DNA fragmentation in couples who fail IVF treatments and this paper supports the current guidance in this area. In particular SDF is an important predictor of outcomes from fertility treatments.
The value of multi-vitamins and anti-oxidants in the treatment of male factor infertility is a grey area.
In this study Prof Minhas and an expert team from Europe have highlighted that there is some evidence that medical and nutritional supplements eg multi-vitamins may improve semen analysis, although the evidence that anti-oxidant therapy leads to an increase live birth rates, spontaneous pregnancy, or pregnancy following
assisted-reproductive techniques is limited. There seem to be several medical and nutritional treatments, such as pentoxyfylline, coenzyme Q10, L-carnitine, follicle-stimulating hormone, tamoxifen and kallikrein, that appear to improve semen parameters, but the studies have what we term a risk of moderate or high bias.
Opinion: The potential benefits of nutritional supplements or anti-oxidants seems to outweigh any harmful effects and therefore it would be reasonable to consider starting supplements if you have fertility problems.
Professor Minhas is Co-chair of the European Association of Urology Guidelines on male sexual and reproductive health. Working with colleagues from around the world, the group has extensively analysed studies from the scientific literature on male infertility and other Men's health problems and can be found here.
A summary of the section on male fertility has provided specific recommendations on male infertility and can be summarised as follows:
1. When to perform sperm DNA fragmentation testing and its applications and limitations.
2. Highlighted the importance of taking a history, examining and investigating all men with infertility. Tests may include performing Ultrasound scanning of the testicles, evaluation for infections, hormone blood tests and genetic testing.
3. Highlighted that varicoceles are an important cause of male infertility and treatment can also be considered in men with raised sperm DNA fragmentation.
4. Highlighted that the optimum sperm retrieval technique in men with non obstructive azoospermia (no sperm) should be either a conventional TESE or microdissection testicular sperm extraction.
5. When evaluating the couple for male factor infertility and deciding on treatment, it is important to take into account the female partners age at all times and their ovarian reserve.
In this consensus statement the EAU guidelines on male and sexual reproductive health have provided evidence on when to perform sperm DNA fragmentation in men and to perform testicular sperm extraction. There is a lot of evidence in the scientific literature that oxidative stress and sperm DNA fragmentation (SDF) may be an important cause of male infertility including failure from assisted reproductive technologies. There are a number of causes of raised sperm DNA fragmentation including lifestyle, nutrition, varicocele and male genital infections. However, the indications as to when to measure SDF is controversial. Prof Minhas has worked closely with colleagues to provide definitive statements and advice on when to measure SDF in male infertility and the role of using testicular sperm extraction in the setting of raised SDF.
In this paper, we give an update on the management of men with no sperm in the ejaculate or non obstructive azoospermia. Prof Minhas and his colleagues highlight the types of surgery available and potential future treatments that are emerging. We also discuss the limitations of optimising treatment prior to micro dissection testicular sperm extraction including varicocele treatment and hormonal stimulation including hCG and SERM before surgery.
Prof Minhas prefers to perform microdissection testicular sperm extraction in men with non obstructive azoospermia (NOA). He has almost 20 years experience of this technique and is one of the only surgeons in the UK who has published his outcomes in of sperm retrieval rates and live rates after surgery. In a series of papers, he and his team confirm sperm retrieval rates of between 45-55% in men with NOA. In this paper, his team also provide data on ICSI outcomes, which very few clinics do. His previous research has also verified that using frozen sperm in men with NOA is just as good in terms of live birth rates compared to fresh sperm.
In this research paper, Prof Minhas and his team at Imperial highlight the importance of the bacteria in the seminal fluid or the so called semen microbiome. In men this is very varied in both fertile and infertile men. In this study Prof Minhas and his team show that bacteria in the seminal fluid appears to negatively impact on sperm concentration, progressive motility, and DNA fragmentation index.In particular an organism called Ureaplasma urealyticum negatively impacts on sperm concentration and morphology, Enterococcus faecalis negatively impacts on total motility, and Mycoplasma hominis negatively affects concentration, progressive motility and morphology. This study highlights the importance the male seminal fluid and bacteria within it, on male fertility and the value of screening.
About 10-30% of men with non obstructive azoospermia will have low testosterone. This can be associated with either raised FSH (the hormone that stimulates sperm production from the testis) or normal FSH. If the FSH is raised this is termed hypergonadotrophic hypogonadism and simply means that the pituitary gland where FSH is produced is having to work the testis harder. If the FSH is normal then this is termed normogonadtrophic hypogonadism. Sometimes the FSH can be low and the testosterone low, a specific condition called hypogonadotrophic hypogonadism.
In men who have NOA, many Urologists will use drugs such as Clomid or hCG to increase testosterone prior to testicular sperm extraction or TESE. The hope is that a 3-6 month treatment may increase the chances of finding sperm at the time of TESE.
However, in this recent research or meta-analysis, Prof Minhas and his international colleagues have demonstrated no beneficial effects of taking hormone therapy before sperm extraction in men with raised testosterone and high FSH. Although, they do stress that more studies are needed to confirm these results.
Professor Minhas to give an international lecture on Intra-operative factors enhancing surgical sperm recovery at the time of testicular sperm extraction.
Almost half the NOA-men who undergo TESE/mTESE are negative for spermatozoa at the time of surgical sperm extraction. Thus it is of paramount importance to develop pharmaceutical treatments and surgical approaches that may increase the sperm recovery rate post TESE/mTESE; these strategies will be discussed. The administration of pharmaceutical agents to men with NOA is controversial and may stimulate Leydig and Sertoli cellular function. Varicocelectomy prior to TESE may result in improved outcomes from TESE and sperm induction within the ejaculate. Finally, intra-operative techniques and embryological factors may affect surgical outcomes. The overall result may be improving the probability of retrieving sperm for ICSI.
Infertility affects 15% of couples worldwide and in approximately 50% of cases the cause is secondary to an abnormality of the sperm. However, treatment options for male infertility are limited and empirical use of hormone stimulation has been utilised. We review the contemporary data regarding the application of hormone stimulation to treat male infertility. There is strong evidence supporting the use of hormone stimulation in hypogonadotropic hypogonadism but there is inadequate evidence for all other indications.
In total, 170 studies were identified and screened, and 21 studies (570 patients) were included. In general, high-complexity reconstructive procedures (category > III) were performed, with split-thickness skin grafts for shaft reconstruction. The pooled mean operating time was 192.2 min and the mean estimated blood loss range was 57-326 mL. No intra-operative complications were recorded. The incidence of postoperative complications varied across studies (0-80.8%), with >Grade 4 complications reported in 3.1-3.7% of cases. Wound infection and genital lymphoedema were reported in 4.7-33% and 7.1-60% of cases, respectively. The incidence of graft contracture and partial/total loss was 2.4-14.3% and 1.5-21%, respectively. The incidence of recurrence was not systematically reported and ranged from 5.2% to 13%. Postoperative evaluation of functional outcomes demonstrated significant improvements in sexual function, urinary function and cosmesis. Assessment of risk of bias demonstrated a high risk of bias across all studies.
Diabetes mellitus is a rapidly rising metabolic disorder with important systemic complications. Global figures have demonstrated the prevalence of diabetes mellitus has almost quadrupled from 108 million in 1980 to 422 million in 2014, with a current prevalence of over 525 million. Of the male sexual dysfunction resulting from diabetes mellitus, significant focus is afforded to erectile dysfunction. Nevertheless, ejaculatory dysfunction constitutes important sexual sequelae in diabetic men, with up to 35%-50% of men with diabetes mellitus suffering from ejaculatory dysfunction. Despite this, aspects of its pathophysiology and treatment are less well understood than erectile dysfunction. The main disorders of ejaculation include premature ejaculation, delayed ejaculation, anejaculation and retrograde ejaculation. Although ejaculatory dysfunction in diabetes mellitus can have complex multifactorial aetiology, understanding its pathophysiological mechanisms has facilitated the development of therapies in the management of ejaculatory dysfunction. Most of our understanding of its pathophysiology is derived from diabetic animal models; however, observational studies in humans have also provided useful information in elucidating important associative factors potentially contributing to ejaculatory dysfunction in diabetic men. These have provided the potential for more tailored treatment regimens in patients depending on the ejaculatory disorder, other co-existing sequelae of diabetes mellitus, specific metabolic factors as well as the need for fertility treatment. However, evidence for treatment of ejaculatory dysfunction, especially delayed ejaculation and retrograde ejaculation, is based on low-level evidence comprising small sample-size series and retrospective or cross-sectional studies. Whilst promising findings from large randomised controlled trials have provided strong evidence for the licensed treatment of premature ejaculation, similar robust studies are needed to accurately elucidate factors predicting ejaculatory dysfunction in diabetes mellitus, as well as for the development of pharmacotherapies for delayed ejaculation and retrograde ejaculation. Similarly, more contemporary robust data are required for fertility outcomes in these patients, including methods of sperm retrieval and assisted reproductive techniques in retrograde ejaculation.
Erectile dysfunction is associated with diabetes mellitus with an estimated prevalence of 52.5% in the diabetic population. The first-line therapy for erectile dysfunction is phosphodiesterase type 5 inhibitors, but data suggest that diabetic men may be less responsive than non-diabetic men. Thus, other treatments, including intracavernosal injections, intraurethral prostaglandin, vacuum erection devices and penile prosthetic surgery, should be considered in management of diabetic men with erectile dysfunction refractory to phosphodiesterase type 5 inhibitors. Furthermore, combination therapy of phosphodiesterase type 5 inhibitors and other oral treatments such as arginine or l-carnitine may have synergistic effects resulting in better outcomes. In addition, there are novel therapies such as low-intensity shockwave therapy and stem-cell therapy, which may also be effective in targeted treatment modalities. Furthermore, studies suggest that erectile dysfunction can be improved by targeting concurrent comorbidities or metabolic diseases such as depression, hypertension, hypogonadism, and dyslipidaemia. We present an evidence-based narrative review focusing on the management of erectile dysfunction in diabetic men who have not responded to phosphodiesterase type 5 inhibitors.
Conclusions: Both clinicians and patients should be aware of the different management options in diabetic patients who have not responded to phosphodiesterase type 5 inhibitors.
Anabolic steroids (also known as 'steroids') are banned drugs like testosterone, which make muscles bigger in men. These drugs are dangerous because they stop the testes from making natural testosterone and can cause heart attacks. Men stopping steroids have very low testosterone, which makes them feel weak, depressed, suicidal, infertile, and unable to have erections. We surveyed over 100 doctors to find out how they treat men giving up steroids. We report that doctors differ widely in the way they treat these men. Most doctors simply advise men to wait for the natural recovery of testosterone levels to happen. But 20% of doctors give men drugs to boost testosterone and make men feel better. Unfortunately, many patients had not recovered by the time of our survey. In summary, our survey highlights differences and limitations in the treatment of men giving up steroids. The use of steroids is increasing rapidly among young men, so we recommend further work to improve the treatment of men who are motivated to give up steroids.
Infertility affects 15% of couples worldwide and in approximately 50% of cases the cause is secondary to an abnormality of the sperm. However, treatment options for male infertility are limited and empirical use of hormone stimulation has been utilised. We review the contemporary data regarding the application of hormone stimulation to treat male infertility. There is strong evidence supporting the use of hormone stimulation in hypogonadotropic hypogonadism but there is inadequate evidence for all other indications.
Context: The use of scrotal ultrasonography (SUS) has increased the detection rate of indeterminate testicular masses. Defining radiological characteristics that identify malignancy may reduce the number of men undergoing unnecessary radical orchidectomy.
Objective: To define which SUS or scrotal magnetic resonance imaging (MRI) characteristics can predict benign or malignant disease in pre- or post-pubertal males with indeterminate testicular masses.
Evidence acquisition: This systematic review was conducted in accordance with Cochrane Collaboration guidance. Medline, Embase, Cochrane controlled trials and systematic reviews databases were searched from (1970 to 26 March 2021). Benign and malignant masses were classified using the reported reference test: i.e., histopathology, or 12 months progression-free radiological surveillance. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool (QUADAS-2).
Evidence synthesis: A total of 32 studies were identified, including 1692 masses of which 28 studies and 1550 masses reported SUS features, four studies and 142 masses reported MRI features. Meta-analysis of different SUS (B-mode) values in post-pubertal men demonstrated that a size of ≤0.5 cm had a significantly lower odds ratio (OR) of malignancy compared to masses of >0.5 cm (P < 0.001). Comparison of masses of 0.6-1.0 cm and masses of >1.5 cm also demonstrated a significantly lower OR of malignancy (P = 0.04). There was no significant difference between masses of 0.6-1.0 and 1.1-1.5 cm. SUS in post-pubertal men also had a statistically significantly lower OR of malignancy for heterogenous masses vs homogenous masses (P = 0.04), hyperechogenic vs hypoechogenic masses (P < 0.01), normal vs increased enhancement (P < 0.01), and peripheral vs central vascularity (P < 0.01), respectively. There were limited data on pre-pubertal SUS, pre-pubertal MRI and post-pubertal MRI.
Conclusions: This meta-analysis identifies radiological characteristics that have a lower OR of malignancy and may be of value in the management of the indeterminate testis mass.
Recurrent pregnancy loss is a distressing condition affecting 1-2% of couples. Traditionally investigations have focused on the female, however more recently researchers have started to explore the potential contribution of the male partner. Seminal reactive oxygen species have a physiological function in male reproduction but in excess are suspected to generate structural and functional damage to the sperm. Evidence is mounting to support an association between elevated seminal reaction oxygen species and recurrent pregnancy loss. Studies suggest that the rates of sperm DNA damage are higher in the male partners of women affected by recurrent pregnancy loss compared with unaffected men. However, the available pool of data is conflicting, and interpretation is limited by the recent change in nomenclature and the heterogeneity of study methodologies. Furthermore, investigation into the effects of oxidative stress on the epigenome show promise. The value of antioxidant therapy in the management of recurrent pregnancy loss currently remains unclear.
Sperm DNA fragmentation (SDF) has been associated with male infertility and poor outcomes of assisted reproductive technology (ART). The purpose of this study was to investigate global practices related to the management of elevated SDF in infertile men, summarize the relevant professional society recommendations, and provide expert recommendations for managing this condition.
Seminal oxidative stress (OS) is a recognized factor potentially associated with male infertility, but the efficacy of antioxidant (AOX) therapy is controversial and there is no consensus on its utility. Primary outcomes of this study were to investigate the effect of AOX on spontaneous clinical pregnancy, live birth and miscarriage rates in male infertile patients. Secondary outcomes were conventional semen parameters, sperm DNA fragmentation (SDF) and seminal OS.
Anabolic steroids (also known as 'steroids') are banned drugs like testosterone, which make muscles bigger in men. These drugs are dangerous because they stop the testes from making natural testosterone and can cause heart attacks. Men stopping steroids have very low testosterone, which makes them feel weak, depressed, suicidal, infertile, and unable to have erections. We surveyed over 100 doctors to find out how they treat men giving up steroids. We report that doctors differ widely in the way they treat these men. Most doctors simply advise men to wait for the natural recovery of testosterone levels to happen. But 20% of doctors give men drugs to boost testosterone and make men feel better. Unfortunately, many patients had not recovered by the time of our survey. In summary, our survey highlights differences and limitations in the treatment of men giving up steroids. The use of steroids is increasing rapidly among young men, so we recommend further work to improve the treatment of men who are motivated to give up steroids.
Infertility affects 15% of couples worldwide and in approximately 50% of cases the cause is secondary to an abnormality of the sperm. However, treatment options for male infertility are limited and empirical use of hormone stimulation has been utilised. We review the contemporary data regarding the application of hormone stimulation to treat male infertility. There is strong evidence supporting the use of hormone stimulation in hypogonadotropic hypogonadism but there is inadequate evidence for all other indications.
Keywords: Aromatase Inhibitors; Azoospermia; Dopamine Agonists; Eugonadism; Gonadotropin Releasing Hormone; Gonadotropins; Hormone Stimulation Therapy; Hypergonadotropic Hypogonadism; Hypogonadotropic Hypogonadism; Male Infertility; Selective Oestrogen Receptor Modulators.
Context: The use of scrotal ultrasonography (SUS) has increased the detection rate of indeterminate testicular masses. Defining radiological characteristics that identify malignancy may reduce the number of men undergoing unnecessary radical orchidectomy.
Objective: To define which SUS or scrotal magnetic resonance imaging (MRI) characteristics can predict benign or malignant disease in pre- or post-pubertal males with indeterminate testicular masses.
Introduction: Obesity negatively impact on the metabolism of sex hormones, leading to reduced testosterone serum levels. However, how the obesity could negatively impact on the overall gonadal function, particularly on male fertility, remained unclear so far.
Objective: To systematically review evidences regarding the influence of body weight excess on sperm production.
Purpose: The purpose of this meta-analysis is to study the impact of varicocele repair in the largest cohort of infertile males with clinical varicocele by including all available studies, with no language restrictions, comparing intra-person conventional semen parameters before and after the repair of varicoceles.
Background: Selective oestrogen receptor modulators and aromatase inhibitors stimulate endogenous gonadotrophins and testosterone in men with hypogonadism. There are no systematic reviews/meta-analyses assessing the effects of selective oestrogen receptor modulators/aromatase inhibitors on semen parameters in men with secondary hypogonadism.
Objectives: To assess the effect of monotherapy or a combination of selective oestrogen receptor modulators/aromatase inhibitors on sperm parameters and/or fertility in men with secondary hypogonadism.
The male contribution to a couple suffering with adverse early pregnancy outcomes is being increasingly investigated. Seminal oxidative stress is considered to cause sperm DNA damage, thus affecting the functional capacity of the sperm. Multiple lines of evidence support an association between elevated seminal reactive oxygen species (ROS) and infertility. In the setting of assisted reproduction various factors in the in vitro environment, differing from the in vivo environment, may exacerbate oxidative stress. Furthermore, seminal ROS levels have been found to be higher in the male partners of couple's affected by both spontaneous and recurrent pregnancy loss. There are several methods by which to assess ROS levels however they are costly, inconsistent and their incorporation into clinical practice is unclear. The value of ROS assessment lies in the ability to plan targeted therapies to improve pregnancy and live birth rates. As such, further robust study is required before firm conclusions can be made to inform clinical practice. We aim to review the available evidence regarding the role of seminal ROS in infertility and pregnancy loss.
Androgens (also known as anabolic-androgenic steroids; AAS) are increasingly being abused worldwide to enhance body physique or athletic performance. Qualitative studies including interviews provide a wider understanding of androgen abuse and focus specific support needs to this group. This narrative review summarizes recent studies (2021-2023) using interviews with individuals abusing androgens.
For nonazoospermic infertile men with elevated sperm DNA fragmentation (SDF), it is unclear whether the use of testicular sperm for intracytoplasmic sperm injection (ICSI) may offer advantages over ejaculated sperm.
Recommendations regarding the management of penile size abnormalities and dysmorphophobia are important in guiding evidence-based clinical practice.
Currently, most men with infertility cannot be given an aetiology, which reflects a lack of knowledge around gamete production and how it is affected by genetics and the environment.
Priapism is a persistent or prolonged erection, in the absence of sexual stimulation, that fails to subside.
Androgens (also known as anabolic-androgenic steroids; AAS) are increasingly being abused worldwide to enhance body physique or athletic performance. Qualitative studies including interviews provide a wider understanding of androgen abuse and focus specific support needs to this group. This narrative review summarizes recent studies (2021-2023) using interviews with individuals abusing androgens.
The male contribution to a couple suffering with adverse early pregnancy outcomes is being increasingly investigated.
Introduction: Obesity negatively impact on the metabolism of sex hormones, leading to reduced testosterone serum levels. However, how the obesity could negatively impact on the overall gonadal function, particularly on male fertility, remained unclear so far.
Objective: To systematically review evidences regarding the influence of body weight excess on the sperm production.
Mean sperm counts are declining at an accelerated rate and infertility is increasingly becoming a public health concern. It is now understood that human semen, previously considered to be sterile, harbours its own specific microbiome. Via activated leucocytes and the generation of reactive oxygen species, bacteria have the capability of evoking an immune response which may lead to sperm damage. Men with infertility have higher rates of both reactive oxygen species and sperm DNA damage. Due to the lack of sensitivity of routine culture and PCR-based methods, next-generation sequencing technology is being employed to characterise the seminal microbiome. There is a mounting body of studies that share a number of similarities but also a great range of conflicting findings. A lack of stringent decontamination procedures, small sample sizes and heterogeneity in other aspects of methodology makes it difficult to draw firm conclusions from these studies. However, various themes have emerged and evidence of highly conserved clusters of common bacteria can be seen. Depletion or over-representation of specific bacteria may be associated with aberrations in traditional and functional seminal parameters. Currently, the evidence is too limited to inform clinical practice and larger studies are needed.
Mean sperm counts are declining at an accelerated rate and infertility is increasingly becoming a public health concern. It is now understood that human semen, previously considered to be sterile, harbours its own specific microbiome. Via activated leucocytes and the generation of reactive oxygen species, bacteria have the capability of evoking an immune response which may lead to sperm damage. Men with infertility have higher rates of both reactive oxygen species and sperm DNA damage. Due to the lack of sensitivity of routine culture and PCR-based methods, next-generation sequencing technology is being employed to characterise the seminal microbiome. There is a mounting body of studies that share a number of similarities but also a great range of conflicting findings. A lack of stringent decontamination procedures, small sample sizes and heterogeneity in other aspects of methodology makes it difficult to draw firm conclusions from these studies. However, various themes have emerged and evidence of highly conserved clusters of common bacteria can be seen. Depletion or over-representation of specific bacteria may be associated with aberrations in traditional and functional seminal parameters. Currently, the evidence is too limited to inform clinical practice and larger studies are needed.
Conservative and medical treatments are considered the first step in ischemic priapism (IP) management, although there is no clear evidence regarding their efficacy. We conducted a systematic review on behalf of the EAU Guidelines panel on Sexual and Reproductive health to analyse the available evidence on the efficacy and safety of conservative and medical treatment for non-sickle cell disease-related IP. Databases searched for relevant literature investigating efficacy and safety of conservative measures and medical treatment for IP included Medline, EMBASE, Cochrane Libraries and clinicaltrial.gov published up to September 2021. Overall, 41 retrospective, 3 prospective single-arm studies and 3 randomized controlled trials met the inclusion criteria. Intracavernous injection with sympathomimetic (ICIs) agents were the most frequently utilized treatment with efficacy ranging from 0 to 100% of cases. The combination of ICIs with corporeal aspiration with or without irrigation with saline was successful in 70 to 100% of cases. Oral treatment with β2 receptor agonist (e.g., terbutaline) showed mild to moderate efficacy. Conservative methods including ice pack, exercise, cold enema and ejaculation depicted lower effectiveness in resolving priapism (1-55%). Longer time interval from the onset to the resolution of IP was associated with higher rate of erectile dysfunction at follow-up (30-70%), especially after 24 h.
Sickle cell disease (SCD) is an inherited hemoglobin disorder characterized by the occlusion of small blood vessels by sickle-shaped red blood cells. SCD is associated with a number of complications, including ischemic priapism. While SCD accounts for at least one-third of all priapism cases, no definitive treatment strategy has been established to specifically treat patients with SC priapism. The aim of this systematic review was to assess the efficacy and safety of contemporary treatment modalities for acute and stuttering ischemic priapism associated with SCD. The primary outcome measures were defined as resolution of acute priapism (detumescence) and complete response of stuttering priapism, while the primary harm outcome was as sexual dysfunction. The protocol for the review has been registered (PROSPERO Nr: CRD42020182001), and a systematic search of Medline, Embase, and Cochrane controlled trials databases was performed. Three trials with 41 observational studies met the criteria for inclusion in this review. None of the trials assessed detumescence, as a primary outcome. All of the trials reported a complete response of stuttering priapism; however, the certainty of the evidence was low. It is clear that assessing the effectiveness of specific interventions for priapism in SCD, well-designed, adequately-powered, multicenter trials are strongly required.
Sickle cell disease (SCD) is an inherited hemoglobin disorder characterized by the occlusion of small blood vessels by sickle-shaped red blood cells. SCD is associated with a number of complications, including ischemic priapism. While SCD accounts for at least one-third of all priapism cases, no definitive treatment strategy has been established to specifically treat patients with SC priapism. The aim of this systematic review was to assess the efficacy and safety of contemporary treatment modalities for acute and stuttering ischemic priapism associated with SCD. The primary outcome measures were defined as resolution of acute priapism (detumescence) and complete response of stuttering priapism, while the primary harm outcome was as sexual dysfunction. The protocol for the review has been registered (PROSPERO Nr: CRD42020182001), and a systematic search of Medline, Embase, and Cochrane controlled trials databases was performed. Three trials with 41 observational studies met the criteria for inclusion in this review. None of the trials assessed detumescence, as a primary outcome. All of the trials reported a complete response of stuttering priapism; however, the certainty of the evidence was low. It is clear that assessing the effectiveness of specific interventions for priapism in SCD, well-designed, adequately-powered, multicenter trials are strongly required.
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