Retrospective observational RT-PCR analyses on 688 babies born to 843 SARS-CoV-2 positive mothers, placental analyses and diagnostic analyses limitations suggest vertical transmission is possible.

RESEARCH QUESTION: Is there vertical transmission (from mother to baby antenatally or intrapartum) after SARS-CoV-2 (COVID-19) infected pregnancy? STUDY DESIGN: A systematic search related to SARS-CoV-2 (COVID-19), pregnancy, neonatal complications, viral and vertical transmission. The duration was from December 2019 to May 2020. RESULTS: A total of 84 studies with 862 COVID positive women were included. Two studies had ongoing pregnancies while 82 studies included 705 babies, 1 miscarriage and 1 medical termination of pregnancy (MTOP). Most publications (50/84, 59.5%), reported small numbers (<5) of positive babies. From 75 studies, 18 babies were COVID-19 positive. The first reverse transcription polymerase chain reaction (RT-PCR) diagnostic test was done in 449 babies and 2 losses, 2nd RT-PCR was done in 82 babies, IgM tests were done in 28 babies, and IgG tests were done in 28 babies. On the first RT-PCR, 47 studies reported time of testing while 28 studies did not. Positive results in the first RT-PCR were seen in 14 babies. Earliest tested at birth and the average time of the result was 22 hours. Three babies with negative first RT-PCR became positive on the second RT-PCR at day 6, day 7 and at 24 hours which continued to be positive at 1 week.Four studies with a total of 4 placental swabs were positive demonstrating SARS-CoV-2 localised in the placenta. In 2 studies, 10 tests for amniotic fluid were positive for SARS-CoV-2. These 2 babies were found to be positive on RT-PCR on serial testing. CONCLUSION: Diagnostic testing combined with incubation period and placental pathology indicate a strong likelihood that intrapartum vertical transmission of SARS-CoV-2 (COVID-19) from mother to baby is possible.

Adverse outcomes in SAR-CoV-2 (COVID-19) and SARS virus related pregnancies with probable vertical transmission

The global severe acute respiratory syndrome-related coronavirus SARS-CoV-2 (COVID-19) pandemic has had an unprecedented impact on all aspects of daily life and healthcare. Information on the infection risks for pregnant women and their offspring have so far been limited to small case series, until a large UK report on 427 SARS-CoV-2 infected pregnant women was published. Previous SARS epidemic experiences were drawn upon. Diagnostic use of real time polymerase chain reaction (RT-PCR) and IgG and IgM antibody tests are fraught with concerns of non-validation and false negative results, as are sampling methodologies. Virtually no information on controls accompany these reports. Infection of the mother and baby has serious implications for obstetric and neonatal care. Information on early and late stage pregnancy infection and the relationship to severity of infection on fetal development is both useful and clearly warranted. An increasing number of reports centre around mildly infected women showing no evidence of fetal infection while a few reports suggesting vertical transmission require further validation. Vertical transmission from mother to baby however small would have profound health implications for obstetric and neonatal care and fetal abnormalities. Some data suggesting intrapartum vertical transmission from mother to baby cannot be dismissed given the lack of controls and limitations of diagnostic viral tests. This analysis covers some key early reports addressing pregnancy outcomes following SARS-CoV-2 infection. (AU)

Reappraisal of clinical data supports double IUI for improved pregnancy outcomes.

Optimising pregnancy and live birth outcomes for fertility procedures is highly desirable and involves disentangling numerous potentially contributing factors. In IUI procedures would double inseminations within a cycle be beneficial? Despite mistaken belief amongst the fertility practitioners the available evidence including Cochrane review has suggested, there would be beneficial effects of utilising double IUI within a cycle. Here we examine new evidence attempting to clarify the role of double versus single IUI.

First line fertility treatment strategies regarding IUI and IVF require clinical evidence.

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.

Semen characteristics in consecutive ejaculates with short abstinence in subfertile males.

This study reports the favourable semen characteristics of 73 subfertile oligozoospermic men with short abstinence periods up to 40 min. Semen characteristics were compared between initial and consecutive ejaculate showing improved semen parameters: progressive grade A spermatozoa, morphology and sperm concentration. Median concentrations in initial and consecutive ejaculates were 10 million/ml and 17 million/ml, respectively. The second sample had a higher median normal morphology (7% versus 6%, P < 0.001). The median of non-progressive spermatozoa (Grade C) was significantly lower in the consecutive sample than the initial sample (0% versus 5%, P < 0.01). Medians for slow progression spermatozoa (B grade) and immotile spermatozoa (D grade) were lower in the consecutive samples (20% versus 13%, P < 0.01 and 60% versus 50%, P < 0.001, respectively). The median for rapid motility (Grade A) was significantly higher in the consecutive sample than the first (30% versus 5%, P < 0.001). Overall median progressive motility as benchmarked by the WHO 2010 criteria was significantly higher in the consecutive sample (43% versus 25%, P < 0.001). Semen analyses of consecutive semen samples collected 30 min (mean) apart in oligozoospemic men should be checked routinely for diagnostic purposes and for managing potential subfertility treatment.

Beyond the 'embryo question': human embryonic stem cell ethics in the context of biomaterial donation in the UK.

Discussion about the ethics of human embryonic stem cell (ESC) research in the UK tends to be dominated by the divisive and potentially intractable issue of the moral status of the embryo. This can have the effect of silencing or marginalizing other concerns, especially in the context of public engagement with science in this field. One such area of potential public concern is the donation of oocytes and embryos to stem cell research. Contemporary research on the views of donors and potential donors about a wide range of biomaterials, from solid organs to gametes and bone marrow, is reviewed and used to illustrate the range and types of ethical concerns articulated by this important group of stakeholders. Attitudes to donation are found to vary according to the type of tissue being donated or collected, the purpose for which donation is being sought and the nature of the recipient of the donation. Pertinently, attitudes towards donating oocytes are found to differ in some respects from donation of embryos or fetal tissue. The implications of these findings for ensuring ethically robust informed consent and publicly acceptable sourcing of human biomaterials for stem cell research are then considered.

Patenting human pluripotent cells: balancing commercial, academic and ethical interests.

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.

Admixed human embryos and stem cells: legislative, ethical and scientific advances.

This paper examines the regulatory framework currently governing the creation of animal-human hybrids and chimera embryos in stem cell research, and some of the ethical implications of such research. It discusses the findings of a recent government select committee that considered the topic. It considers the debate around the precise definition of a human embryo, and whether such hybrids therefore fall within the remit of the Human Fertilisation and Embryology Authority. It outlines the advantages of such hybrids, in lessening the need for human egg donors, as well as the moral objections to species boundary violation. It calls for an examination of the scientific benefits of such research to inform debate on the question, and argues for the need to take genuine account of the public's views on this matter.

Concerns of sex selection and regulation in the report on Human Reproductive Technologies and the Law.

The House of Commons Science and Technology Select Committee, comprising 11 members, reviewed human reproductive technologies and the law and presented their fifth report of Session 2004-05 on 28 March 2005. They felt 'it necessary to reconnect the Human Fertilisation and Embryology Act of 1990 with the changes in modern science'.

Semen quality before and after gonadotoxic treatment.

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.

Ethics of testicular stem cell medicine.

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.

Mumps epididymo-orchitis with prolonged detection of virus in semen and the development of anti-sperm antibodies.

Epididymo-orchitis is the most common complication of mumps in post-pubertal men. A case of MMR vaccine failure, in whom mumps and mumps-associated unilateral epididymo-orchitis developed, is presented in this article. Mumps virus was isolated from the semen 14 days after onset and mumps RNA was detected in semen for up to 40 days using RT-PCR. Epididymo-orchitis was associated with transient but significant reduction in sperm count and severe abnormalities in sperm morphology. It also led to the appearance of anti-sperm antibodies, which may have potential long-term adverse effects on the patient's fertility. Sequencing of the SH gene of the virus showed this to be a new mumps genotype distinct from the virus circulating currently in the UK.

Novel PDE5 inhibitors for the treatment of male erectile dysfunction.

Erectile dysfunction (ED) affects the lives of approximately 150 million men worldwide. ED may be a cause of male sub-fertility in a significant proportion of patients. There is now an expanding armamentarium for the management of ED, including oral agents such as phosphodiesterase type 5 (PDE5) inhibitors. PDE5 inhibitors may also be useful in situations of temporary ED in couples undergoing IVF. Two novel PDE5 inhibitors have been commercially launched in the European Union in the first quarter of 2003. This article reviews the pharmacology and clinical efficacy of these new agents and their potential role in treating patients with male sub-fertility.

The moral status of the embryo: the human embryo in the UK Human Fertilisation and Embryology (Research Purposes) Regulation 2001 debate.

The use of the embryo in research into birth defects, infertility and the possible therapeutic value of embryonic stem cells, has given rise to vigorous discussion of the ethical, moral and legal status of the embryo. This paper considers the parliamentary debate that surrounded the passing of legislation in the UK in 2000 governing the use of the embryo in research. Underlying disagreement by members of Parliament as to whether embryo research was permissible, were considerable differences regarding when life was thought to begin--whether at the moment of fertilization of the egg, or whether after 14 days, at the time of the beginnings of cell differentiation, and the point after which the embryo can no longer split to form twins. Those who favoured the latter view argued that, while the conceptus might possess a unique genetic formula, it had only the potential for life before 14 days, the development of human life being a gradual and continuous process. They considered it mistaken to accord the embryo full human rights. Those who adopted an opposed standpoint insisted that life was present and actual from the moment of conception and therefore sacrosanct and inviolable. The notion of the pre-embryo, they maintained, merely serves to disguise the embryo's humanity.

Semen quality and cryopreservation in adolescent cancer patients.

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.