Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline PART II.

PURPOSE: The summary presented herein represents Part II of the two-part series dedicated to the Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline. Part II outlines the appropriate management of the male in an infertile couple. Medical therapies, surgical techniques, as well as use of intrauterine insemination (IUI)/in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) are covered to allow for optimal patient management. Please refer to Part I for discussion on evaluation of the infertile male and discussion of relevant health conditions that are associated with male infertility. MATERIALS/METHODS: The Emergency Care Research Institute Evidence-based Practice Center team searched PubMed®, Embase®, and Medline from January 2000 through May 2019. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table[Table: see text]). This summary is being simultaneously published in Fertility and Sterility and The Journal of Urology. RESULTS: This Guideline provides updated, evidence-based recommendations regarding management of male infertility. Such recommendations are summarized in the associated algorithm (figure[Figure: see text]). CONCLUSION: Male contributions to infertility are prevalent, and specific treatment as well as assisted reproductive techniques are effective at managing male infertility. This document will undergo additional literature reviews and updating as the knowledge regarding current treatments and future treatment options continues to expand.

Setting up a fertility preservation programme.

With improved survival rates from cancer, young people can expect to lead a normal life, including having their own children. However, cancer or other serious disease itself, and more often its treatment, often leads to a significant reduction in fertility or premature gonadal insufficiency. There is increasing acknowledgement for the importance of fertility preservation (FP) options to be discussed and offered to young people whose fertility is at risk, ideally before the gonadotoxic therapy begins. FP options currently include oocyte, embryo and ovarian tissue cryopreservation; ovarian protection during chemotherapy and semen, sperm and testicular tissue cryopreservation. A multidisciplinary team consisting of committed and enthusiastic doctors, scientists, nurses, counsellors, administrators and researchers is required to provide a holistic FP service with rapid response capacity for acute consultation and procedures and a robust system for long-term follow-up. This speciality is developing rapidly with exciting scientific advances that have relevance for the whole spectrum of reproductive medicine.

Towards a multidimensional scientific approach to improve clinical practices for infertility treatment.

Polycystic ovary syndrome (PCOS) is the most common metabolic and endocrine disorder in women, leading to infertility. However, there is no general agreement concerning how to diagnose and treat PCOS. The Rotterdam consensus statement from the European Society of Human Reproduction and Embryology/American Society for Reproductive Medicine, the Chinese diagnostic criteria and consensus statement, and the clinical practice guideline from the Endocrine Society in the USA are widely recognized. Guidance has been provided for clinical practice based on a comparative analysis of the above three practice guidelines or consensus statements (Wang et al., 2018a). High body mass index (BMI) has no negative effect on the outcome of in vitro fertilization (IVF) in Chinese patients with PCOS; however, the conclusion may be limited by the retrospective design and potential bias (Pan et al., 2018). Neonatal birth weight is positively affected by both maternal pre-pregnancy body mass index (pre-BMI) and gestational weight gain (Du et al., 2017). Normal body weight is very important for conception. Women with PCOS are almost 3 times more likely to be obese than those without PCOS; however, no specific interventions are available to induce weight loss, and drugs are used to treat other symptoms of the syndrome or obesity in the general population. A network meta-analysis found that the amount of weight loss differed significantly according to the choice of drugs (in descending order): liraglutide, orlistat, and metformin. Liraglutide alone, liraglutide/metformin, and metformin alone significantly reduced waist circumference, but no change was found with orlistat, indicating liraglutide appears superior to the other drugs in reducing weight and waist circumference (Wang et al., 2018b). IVF, as a choice for more than 1 000 000 infertile couples each year, gives rise to the birth of over 3 000 000 babies worldwide.

Acupuncture in reproductive medicine: the motivations of infertile women to participate in a randomised controlled trial.

INTRODUCTION: Randomised controlled trials are the gold standard in medical research and are challenging to conduct successfully since high numbers of participants are needed to produce robust results. Therefore, it is important to understand what motivates patients to participate in one, particularly in Reproductive Medicine where the conduct of RCTs is rare. Just as it is important to evaluate medical interventions, it is equally important that adjuvant therapies are properly assessed. There has been an increased interest in adding acupuncture to in vitro fertilisation (IVF) in the hope of increasing the chance of pregnancy and a live birth. However, evidence that acupuncture assists IVF outcomes is conflicted and insight into the experiences and motivations of infertile women is important. This paper describes how an invitation to participate in an RCT of acupuncture as an adjuvant to IVF was received by infertile women and how they processed their decision to participate. METHODS: In-depth interviews were conducted with 50 infertile women recruited from the RCT sample cohort. Recruitment aimed for maximum variation in social demographics. The data were saturated. Data pertaining to the theme of motivations to participate in an RCT were subjected to semantic thematic analysis. RESULTS: Two subthemes contained categories related to (a) the reasons women put forward for participation in an RCT, and (b) the rationale that underpinned and surrounded their decision. Women described themselves as active agents searching for a better outcome for their infertility or improved outcomes for women in the future. Their decision to participate in an RCT was motivated by factors such as opportunity, novelty and a value of science and was made after weighing various risks and benefits. CONCLUSIONS: The decision to participate in an RCT was an informed one. Infertile women in a stressful treatment situation participated in an RCT in the hope of finding a therapy to improve IVF outcomes for themselves and for other infertile women.

Reproductive medicine involving genome editing: clinical uncertainties and embryological needs.

Genome editing based on site-directed nucleases facilitated efficient and versatile genetic modifications in human cells. However, recent reports, demonstrating CRISPR/Cas9-mediated genome editing in human embryos have raised profound concerns worldwide. This commentary explores the clinical justification and feasibility of reproductive medicine using germline genome editing. Despite the perceived utility of reproductive medicine for treating intractable infertility, it is difficult to justify germline genome editing from the perspective of the prospective child. As suggested by the UK legalization regarding mitochondrial donation, the prevention of genetic disease in offspring by genome editing might be acceptable in limited cases of serious or life-threatening conditions, where no alternative medicine is available. Nonetheless, the mosaicism underlying human embryos as well as the off-target effect by artificial nucleases will likely hamper preimplantation genetic diagnosis prior to embryo transfer. Such considerations suggest that this type of reproductive medicine should not be developed toward a clinical application. However, the clinical uncertainties underscore the need for embryology that can address fundamental questions regarding germline aneuploidy and mosaicism using genome editing.

Complementary Therapies and Medicines and Reproductive Medicine.

Complementary therapies and medicines are a broad and diverse range of treatments, and are frequently used by women and their partners during the preconception period to assist with infertility, and to address pregnancy-related conditions. Despite frequent use, the evidence examining the efficacy, effectiveness, and safety for many modalities is lacking, with variable study quality. In this article, we provide an overview of research evidence with the aim of examining the evidence to inform clinical practice. During the preconception period, there is mixed evidence for acupuncture to improve ovulation, or increase pregnancy rates. Acupuncture may improve sperm quality, but there is insufficient evidence to determine whether this results in improved pregnancy and live birth rates. Acupuncture can be described as a low-risk intervention. Chinese and Western herbal medicines may increase pregnancy rates; however, study quality is low. The evaluation of efficacy, effectiveness, and safety during the first trimester of pregnancy has most commonly reported on herbs, supplements, and practices such as acupuncture. There is high-quality evidence reporting the benefits of herbal medicines and acupuncture to treat nausea in pregnancy. The benefit from ginger to manage symptoms of nausea in early pregnancy is incorporated in national clinical guidelines, and vitamin B6 is recommended as a first-line treatment for nausea and vomiting in pregnancy. The safety of ginger and vitamin B6 is considered to be well established, and is based on epidemiological studies. Acupuncture has been shown to reduce back pain and improve function for women in early pregnancy. There is little evidence to support the use of cranberries in pregnancy for prevention of urinary tract infections, and chiropractic treatment for back pain. Overall the numbers of studies are small and of low quality, although the modalities appear to be low risk of harm.

Acupuncture in clinical and experimental reproductive medicine: a review.

BACKGROUND: Acupuncture has been used as treatment for infertility for hundreds of years, and recently it has been studied in male and female infertility and in assisted reproductive technologies, although its role in reproductive medicine is still debated. AIM: To review studies on acupuncture in reproductive medicine, in experimental and clinical settings. METHODS: Papers were retrieved on PubMed and Google Scholar and were included in the review if at least the abstract was in English. RESULTS: There is evidence of benefit mainly when acupuncture is performed on the day of embryo transfer (ET) in the live birth rate. Benefit is also evident when acupuncture is performed for female infertility due to polycystic ovary syndrome (PCOS). There is some evidence of sperm quality improvement when acupuncture is performed on males affected by idiopathic infertility. Experimental studies suggest that acupuncture effects are mediated by changes in activity of the autonomic nervous system and stimulation of neuropeptides/neurotransmitters which may be involved in the pathogenesis of infertility. CONCLUSIONS: Acupuncture seems to have beneficial effects on live birth rate when performed on the day of ET, and to be useful also in PCOS as well as in male idiopathic infertility, with very low incidence of side effects. However, further studies are necessary to confirm the clinical results and to expand our knowledge of the mechanisms involved.

Sperm toxicity of "nonspermicidal" lubricant and ultrasound gels used in reproductive medicine.

Three commercial, nonspermicidal gels used in fertility practice were found to be toxic to sperm in a 24-hr sperm survival assay; these included Felis, Replens, and Aquasonic Gel, which is used for transvaginal ultrasound during ovulation monitoring. In contrast, Pre-Seed did not cause any sperm toxicity, suggesting its appropriate use by patients who are trying to conceive, as well as clinicians during fertility procedures.

Care closer to home.

In 2008, in total there were 202 158 abortions performed in England and Wales and 13 817 in Scotland, unfortunately one of the most common gynaecological procedures. 'Care closer to home' applied to this service, as part of a holistic integrated care pathway, can improve access and choice and reduce cost whilst continuing to focus on clinical quality and safety and work towards reducing the number of primary and repeat abortions. Whilst constraints remain within Law, there are ways to change services to help reduce barriers to access not just to abortion but also the essential allied interventions of contraception, sexual health and counselling and support. The first will be reflected in the number of women able to have their abortions earlier, therefore more safely and at lesser cost. It would build on service changes to date, which has allowed women more choice of the method of abortion. The integration of contraceptive services should impact positively on the currently high level of repeat abortions. Bringing care closer to home, into the communities within which women spend their lives, is an important strategy in addressing the quality agenda in abortion care.

Gynaecological health care utilization and use of sex hormones--the study of Health in Pomerania.

BACKGROUND: In Germany, there is a lack of population-based data related to the use of gynaecological health care services. The objectives of our analyses utilizing a population-based cross-sectional survey conducted in one geographically defined area [Study of Health in Pomerania (SHIP)] are to assess the prevalences of: (i) attendance of gynaecological outpatient facilities and of (cervical) cancer screening; (ii) gynaecological and breast surgery; (iii) use of oral contraceptives (OC) and menopausal hormone therapy (MHT). METHODS: We analysed socio-demographic factors, reproductive history, gynaecological service utilization, and use of sex hormones in 2186 women aged 20-79 years. We used standard statistics and sex- and age group-specific weighting factors to reflect characteristics of the population of Western Pomerania. RESULTS: Approximately 43% of women reported surgical procedures. Participation in cancer screening at least once was reported by 78% of women (lifetime prevalence). Two-thirds of women stated ever use of OC, 28% (aged >40 years) ever use of MHT. CONCLUSIONS: Women in Western Pomerania reported a high life-time use of both OC and MHT. The use of cervical cancer screening exceeded the national average. Women had an almost 50% risk of undergoing gynaecological, breast or obstetric surgery. The high use of MHT and surgical procedures calls for efforts regarding continuing medical education and health care policy actions.

Preclinical safety testing of biotechnology-derived pharmaceuticals: understanding the issues and addressing the challenges.

The unique and complex nature of biotechnology-derived pharmaceuticals has meant that it is often not possible to follow the conventional safety testing programs used for chemicals, and hence they are evaluated on a case-by-case basis. Nonclinical safety testing programs must be rationally designed with a strong scientific understanding of the product, including its method of manufacture, purity, sequence, structure, species specificity, pharmacological and immunological effects, and intended clinical use. This knowledge, coupled with a firm understanding of the regulatory requirements for particular product types, will ensure that the most sensitive and regulatory-compliant test systems are used to optimize the chances of gaining regulatory approval for clinical testing or marketing authorization in the shortest possible time frame.

Alternative treatments in reproductive medicine. The vexing problem of 'seemingly impeccable trials...'.

The problem of 'seemingly impeccable trials' that produce unbelievable results is approached from basic notions of the philosophy of science: facts and theory are interdependent, and 'crucial experiments' do not exist. This does not lead to an 'anything goes' attitude, but obliges us to consider arguments and counter-arguments in the spirit of the 'crossword' analogy by Susan Haack. The role of editors and readers might be different: while editors might be under some obligation to publish 'seemingly impeccable trials', readers are not obliged to accept the findings.