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The advent of intracytoplasmic sperm injection (ICSI) has contributed to a significant growth in the delivery of assisted conception technique, such that IVF/ICSI procedures are now recommended over other interventions. Even the UK National Institute for Health Care Excellence (NICE) guidelines controversially recommends against intrauterine insemination (IUI) procedures in favour of IVF. We reflect on some of the clinical, economic, financial and ethical realities that have been used to selectively promote IVF over IUI, which is less intrusive and more patient friendly, obviates the need for embryo storage and has a global application. The evidence strongly favours IUI over IVF in selected couples and national funding strategies should include IUI treatment options. IUI, practised optimally as a first line treatment in up to six cycles, would also ease the pressures on public funds to allow the provision of up to three IVF cycles for couple who need it. Fertility clinics should also strive towards ISO15189 accreditation standards for basic semen diagnosis for male infertility used to triage ICSI treatment, to reduce the over-diagnosis of severe male factor infertility. Importantly, there is a need to develop global guidelines on inclusion policies for IVF/ICSI procedures. These suggestions are an ethically sound basis for constructing the provision of publicly funded fertility treatments., (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The article addresses the issue of the ethics of patenting in human embryonic stem (hES) cells. The current stance of the European Patent Office in citing moral objections to patents on hES cells and the monopolistic scope of the Wisconsin Research Alumni Fund/Geron patents granted by the United States Patent and Trademark Office represent twin obstacles to achieving an ethical balance in patent rights in this field. The particular issues and strategies around granting patents on hES cells can be better understood by placing them in the context of the biotechnology industry and its role in the global bioeconomy. Some possible avenues of redress are considered based on the potential to open up cell pluripotency as new terrain for intellectual property offered by new technological breakthroughs such as induced pluripotent cells. Any changes in patent law should be accompanied by increased collaboration through devices such as patent pools.

Background: The aim of this study was to analyse the semen quality of patients before and after gonadotoxic therapy., Patients and Methods: We evaluated semen quality in 314 patients over a 26 year period. The diagnostic categories were leukaemia (n = 13); lymphoma (n = 128); testicular cancer (n = 102); benign conditions (n = 13); and other malignant neoplasms (n = 58). The degree of azoospermia or oligozoospermia for each disease category was recorded. We then analysed the recovery in semen quality over time for each disease category., Results: The mean patient age was 27.9 years (range 13-65 years). A total of 1115 post-treatment semen samples were analysed from 314 patients. There was a significant reduction in the post-treatment sperm concentration, sperm motility and semen volume compared with pre-treatment levels (P < 0.05) in the entire cohort. However, the sperm movement and motility grade remained unaffected. Patients with testicular carcinoma had the lowest pre-treatment sperm concentrations but also the lowest incidence of azoospermia after cancer treatment. Patients with lymphoma and leukaemia had the highest incidence of post-treatment azoospermia and oligospermia. Patients having the largest reductions in their sperm concentration after treatment required the longest recovery period for spermatogenesis. The diagnostic category was the only significant predictor of post-treatment azoospermia., Conclusion: Gonadotoxic treatment results in a significant reduction in sperm quality. The type of cancer or disease, and the pre-treatment sperm concentrations were found to be the most significant factors governing post-treatment semen quality and recovery of spermatogenesis. All categories of patients displayed varying degrees of azoospermia and oligozoospermia, and recovery of gonadal function from these states was not significant. This highlights the importance of ensuring sperm banking before treatment, including for patients with benign conditions. Several factors and associations are discussed further in order to give an insight into the pre- and post-gonadotoxic treatment effects.

The ethical issues raised by advances in reproductive technology allowing the transplantation of testicular stem cells to enable infertile men and cancer patients, including the pre-pubertal, to have children, and to provide new contraceptive prospects for fertile men are discussed. Consideration of respect for the patient's autonomy, the need for informed consent and the health of any offspring resulting from such a procedure are included. Topics covered include: the problems raised by cases needing consent for the transplantation of testicular stem cells from pre-pubertal and adolescent patients; the legal status of stem cells; the arguements for treating such tissue as property which might serve as a means of guaranteeing respect for patients' rights in disputed cases; aspects of patents and the ethics of allowing commercial traffic of such material; questions relating to health and safety, as well as xenotransplantation technology in humans; and posthumous procurement use of germ cells from minors. Proposals are made to enhance informed and effective consent, while supporting patient determination, choice, autonomy and technological advances. The paper appeals to the emerging EU directives in relation to tissue procurement, storing and use of tissue and cells to adopt a pragmatic and meaningful position which will help enhance patient determination and autonomy in relation to the emerging technologies in reproductive medicine, whilst providing a pragmatic way forward for fertility clinics and laboratories to function.

Background: Adult cancer patients are routinely offered pre-treatment sperm cryopreservation. However, only recently has the welfare of adolescent cancer sufferers gained momentum, including their infertility, and unsurprisingly relatively little is known about their semen quality and feasibility of cryopreservation., Methods and Results: A total of 238 adolescent cancer patients referred to our centre between 1991 and 2000, from post-pubertal age up to 19 years 11.9 months, were included. Their semen was processed after appropriate counselling. Semen cryopreservation was possible in 205 of the initial 238 patients referred (86.1%). The pathology of the cancer cases included Hodgkin's lymphoma, non-Hodgkin's lymphoma, osteosarcoma, Ewing's sarcoma, acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML), testicular, leukaemia, and others. The mean sperm counts were broadly uniform across the disease and age groups, except for the AML group. There was no cancer group analysed in which sperm could not be stored. Semen volume was broadly uniform across the disease groups, except the ALL and Ewing's sarcoma groups, which showed relatively lower and higher mean semen volumes respectively. Older adolescent patients appeared to have a higher mean semen volume., Conclusions: Semen cryopreservation was possible in most adolescent cancer cases regardless of age or diagnosis. In all cases the quality of the semen was potentially useful for assisted conception procedures. An offer to freeze sperm in all patients aged >12 years should be made. Adequate support and counselling of both the boys and their parents is essential.

Background: The influence of an accompanying person (parent, guardian or nurse) on the ability of an adolescent (post-pubescent, <20 years of age) to produce a semen sample for cryopreservation, is undetermined, as is the potential for use of urine samples to retrieve sperm in those adolescents that are unable to produce a semen sample., Methods: The records from 1991-2000 inclusive were reviewed to derive those adolescent patients who were unable to produce semen for cryopreservation prior to undergoing treatment for a malignant condition., Results: During the study period 238 adolescents attended our unit of whom 205 (86.1%) banked semen ('producers'). The remaining 33 adolescents (13.9%) were initially unable to produce a sample ('non-producers'), four of these provided a urine specimen for analysis (12.1%) and of these one had sufficient sperm for cryopreservation. Of the 'accompanied' patients 29.7% (19/64) were non-producers while in the 'unaccompanied' patients only 8.0% (14/174) were non-producers (chi(2) = 16.58, P < 0.001). The relative risk (RR) of not producing a semen sample for the accompanied group of patients was greater than that for the unaccompanied group (RR = 3.689, 95% confidence interval: 2.0-6.9). One patient returning alone successfully provided a semen sample for storage., Conclusion: Units should consider the effect of the presence of an accompanying person when an adolescent is unable to produce a semen sample and should consider requesting urine to retrieve sperm.

The complex moral, ethical and legal concerns that have arisen as a result of posthumous assisted reproduction (PAR) are examined in this report. Difficult questions such as what constitutes informed consent, and whether it is ethical to retrieve spermatozoa from patients who are in a coma, are considered. Legal issues, such as whether gametes can be considered as property and the need to clarify the legal definition of paternity in cases of children born in such circumstances, are also discussed, while other points regarding the advisability of PAR, respecting the wishes of the deceased donor and the need to protect the interests of the unborn child, are outlined. The motives of the gestating women, viewing their desire for PAR perhaps as part of the grieving process, and the effects on the children concerned are examined; it is concluded that there appears to be no adverse effect, but this finding might be premature. The report also asserts the need for responsible accounting on the part of fertility clinics, and calls for fairness, transparency and patience to help the bereaved reach an unbiased yet informed decision. This may be achieved by offering ample time for informed and support counselling. Finally, consideration should be expressed for the welfare of unborn child, in a balanced, pragmatic and sensible manner.

The Human Rights Act (HR Act) 1998 (UK) (Human Rights Act, 1998) came into effect on October 2, 2000. Instead of taking a case to the European Court of Human Rights in Strasbourg, litigants can enforce their rights in the UK. The Act will have an unprecedented effect in virtually all areas of the UK legal systems. In line with those countries who have incorporated the 'Convention' in domestic law, litigation is expected to increase. The extensive body of Convention law, as well as decisions of the domestic courts of other states which have incorporated the Convention, now becomes an integral part of UK jurisprudence. Broadly, the Act applies to public and not private bodies. The relevant bodies which embody reproductive issues and concerns are for example the National Health Service (NHS) and the regulatory bodies such as the Human Fertilisation and Embryology Authority (HFEA) (Human Fertilisation and Embryology Authority Act, 1990) and the Human Genetics Advisory Commission (HGAC). A profound impact on the NHS practice, interpretations of the HFEA Act and its Code of Practice can be envisaged in relation to the Convention rights. Cases involving reproductive issues are already emerging in relation to the HR Act and which include sex selection, the present embryo transfer policy, interpretation of fatherless offspring and the provision of fertility services under the NHS. This review is intended to raise awareness of the HR Act 1998 for persons interested in human reproductive issues and how the HR Act could impact on the current laws and practice. Whilst it is only possible to speculate on what might happen in relation to the HR Act, what is certain is that UK law will radically change to accommodate the requirements of the HR Act 1998.

Sperm banking for early adolescent cancer patients requires delicate, sensitive handling and, in the UK, consideration is required of statutory elements. No information at present exists about how adolescents with cancer are normally treated or counselled for sperm banking. Here we highlight the type of issues in relation to fertility preservation faced by clinicians and those faced by adolescents at a sperm storage laboratory. We explore the very real difficulties of bringing together these medical fields of assisted reproduction, oncology and the various pieces of legislation and focus specifically on gaining consent. Attention is paid to counselling and communication to help the patient reach an effective and informed decision to store spermatozoa. The role of parents in contributing towards communication and support, together with the legal constraints in decision making, is acknowledged. How absolute and fully 'informed' consent should be will always remain a contentious issue amongst the various specialists and disciplines. In relation to sperm storage, as a minimum the patients should understand the process that they are undertaking so that it is undertaken freely and without pressure. The practical approach to gaining consent that we are using seems a logical and practical method to help early adolescent patients to store spermatozoa.

Sperm preservation prior to chemotherapy and radiotherapy is common practice in adult males. Spermatozoa are usually retrieved from an ejaculated sample although there are occasions when testicular tissue is used as the source. These techniques of sperm preservation present minimal ethical objections as the patients give their informed consent. Sperm preservation in children presents practical and ethical dilemmas in that the children cannot always give their informed consent, there are no regulatory guidelines and there is no guarantee that spermatogenesis is occurring. With the rapid advances in reproductive technology and the possible future use of immature germ cells by in-vitro maturation or transplantation, the demand for immature testicular tissue preservation is likely to increase. More information for the parents and oncologists with regard to this subject is needed to allow informed decisions to be made on behalf of the children. These issues are discussed using two cases of children having testicular tissue preservation.

In considering gonadal tissue cryopreservation in children about to undergo chemotherapy or radiotherapy for cancer, numerous issues need to be confronted. This relates firstly to a dearth of information available on the subject of children's gonads coupled to ill-defined fertility preservation procedures, technologies and perhaps less well-publicized regulatory, ethical and legal controls. There may be benefits in considering gonadal tissue preservation for children prior to chemotherapy or radiotherapy, in the hope that future technologies can utilize their immature gametes. Whether or not freezing of gonadal tissue is encouraged prior to cancer therapy, there is a growing demand from parents and clinicians for more information to be made available. This paper reviews our current knowledge of children's gonads in terms of physiology and of fertility experience gained after childhood cancer treatment. It further examines the various issues and concerns regarding children's gonadal tissue storage, its potential use, the present law and the demands and pressures under which clinicians find themselves with patients and parents. This information is important for both the counselling process and decision-making when presented with potential fertility issues in paediatric oncology patients.

The detection of the recently discovered Kaposi's sarcoma-associated herpes virus (KSHV) in human immunodeficiency virus-uninfected donor semen and in blood from a normal blood donor has led us to review this new area of health concern, with emphasis on a number of studies conducted into the presence of the virus in semen and the possibility of transmission during assisted conception procedures.

Declining sperm count reports have caused enormous concern to both the scientific community and to society. We reproduced the linear regression analysis and the quadratic model analysis using the 50 year sperm count data published in Carlsen's report and found that neither model adequately described the data. The reported decline in sperm count could be due to observational bias and overinterpretation of linear regression. In fact only 36% of the total variability in sperm count was explained by the linear model and 42% by the quadratic model. The linear model was no longer valid when three new European reports on sperm counts were included in the analysis. The quadratic model, however, suggested an upward trend of sperm count after 1975 (R2 = 0.48, P < 0.0001). Factors other than the 'passage of time' may have contributed to the initial decline of sperm count. An immediate candidate was demography. Our analysis showed that sperm counts in USA were significantly higher in 1938-1956 compared with those in 1957-1974 and 1975-1988, but not in the European or Asian/African/South American countries. The variability of the USA sperm count (1938-1988) explained by the linear and quadratic models was found to be 71 and 70% respectively. The quadratic model importantly indicated that the sperm count in USA decreases asymptotically towards a limiting value and global sperm counts could be increasing since 1970. The non-uniform nature of the global sperm count change suggested that local variations in pollution, diet but not global warming were important determinants of reproductive health.

For patients about to receive chemotherapy, radiotherapy or to undergo a surgical procedure, loss or impairment of fertility is a major issue. For males, sperm banking is a standard accepted procedure to circumvent loss or damage to spermatozoa and this has been undertaken in this unit since 1975 (Steele et al., 1995). For women there is no established procedure for gamete storage. Embryo preservation is not an option for single women or even for those in a stable relationship, as treatment would have to be delayed while ovarian stimulation and oocyte retrieval took place. With the general shortage of donor oocytes, the possibility of maturing primordial follicles from fetal ovaries has become a subject for debate (HFEA 1995: Recent deliberations). In animals, the use of frozen ovarian tissue has been encouraging with a report of a live birth in lamb after orthotopic transplantation (Gosden et al., 1995). Media attention to the future prospect for freezing ovarian tissue has meant that pressure from patients is likely to increase either for information or as requests to freeze the ovarian tissue which could irretrievably be lost as a result of surgery and/or treatment. In the absence of well defined procedures and technologies, should women be given the chance to preserve ovarian tissue prior to receiving intensive chemotherapy or radiotherapy?

The results of in-vitro cervical mucus-sperm penetration tests and cross-hostility tests in 178 couples with repeatedly negative post-coital tests were recorded. Using a protocol of three cycles with intra-uterine inseminations (IUI) followed by three cycles with ovulation induction + IUI, the association between the cause of infertility, results of the in-vitro tests and the outcome of infertility treatment was investigated. We found that repeatedly negative post-coital tests are a good indicator of a cervical mucus-sperm penetration problem. The cross-hostility test clearly differentiates the abnormal factor in this interaction, and a good performance of the donors' spermatozoa in the cervical mucus correlates with increased pregnancy rate. In male factor infertility, failure of the husbands' spermatozoa to penetrate cervical mucus was not indicative of a deficient fertilization potential in vivo. In these patients a serious attempt should therefore be made to reverse the infertility by treatment with IUI or ovulation induction + IUI before attempting assisted reproduction. Women with polycystic ovaries and repeatedly negative post-coital tests should be investigated for sperm receptivity of the cervical mucus. Low receptivity of the cervical mucus may imply that endometrial receptivity and oocyte quality are also low. Ovulation induction and not IUI alone should therefore be used as the preferred mode of treatment to improve pregnancy rate.