Gulam Bahadur

Detection of human herpesvirus 8 Dna in semen from Hiv-infected individuals but not healthy semen donors

Objective:To ascertain the prevalence of Kaposis sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus (HHV) type 8, and cytomegalovirus (CMV) DNA in semen was investigated. Methods:Amplification by nested polymerase chain reaction was used to detect viral DNA sequences in samples from 24 HIV-infected gay men, 15 of them with Kaposis sarcoma (KS), and 115 healthy donors. Results:Six of the 24 HIV-infected patients had detectable HHV-8 DNA in their semen: three of the 15 patients with KS and three of the nine patients without KS. CMV DNA was detected in 20 semen samples from HIV-infected patients. None of the semen samples from healthy donors had detectable HHV-8 DNA and rates of CMV DNA detection were low (3%). Conclusions:The study demonstrates the presence of HHV-8 in semen from HIV-infected individuals with, or at risk, of developing KS and the potential for sexual transmission of the virus. We found no evidence of HHV-8 in the semen of HIV-uninfected donors.

A comparative study between infertile males and patients with Turner syndrome to determine the influence of sex chromosome mosaicism and the breakpoints of structurally abnormal Y chromosomes on phenotypic sex

The Y chromosome is important for male development as it contains the sex determining gene SRY 1 and many spermatogenesis genes.2 Structural abnormalities of the Y chromosome include rings, deletions, inversions, and dicentrics.3,4 These types of abnormalities are common in infertile males (1.5%), especially those with azoospermia.5,6 However, such rearrangements are unstable and an additional 45,X cell line is frequently present.3 The 45,X cell line has been shown to influence phenotypic sex so that these chromosome constitutions may also be found in patients with ambiguous genitalia and in female patients with gonadal dysgenesis and Turner syndrome.4,7 In fact, from cytogenetic studies about 4-6.2% of female Turner patients show Y chromosome mosaicism8–10 irrespective of the presence of SRY .4,11,12 Mosaicism varies widely between tissues and accurate interpretation depends on the number of cells examined and the number and types of tissues studied.13,14 It has been reported that phenotypic sex is strongly influenced by the percentage and distribution of Y chromosome containing cells in the gonads.15,16 However, studies on gonadal tissue are hindered by the fact that it is rarely available for analysis and alternative, more easily accessible tissue is usually studied. It has also been suggested that the structure of the Y chromosome may indirectly affect phenotypic sex. The repetitive sequences at the euchromatin/heterochromatin boundary of the Y chromosome long arm are thought to have an important stabilising role and loss of this region loses this effect, resulting in mosaicism with a 45,X cell line.17 In dicentrics, which are the most common abnormality of the Y chromosome,3 it has been suggested that the position of the q arm breakpoint in dicentric Yp chromosomes can influence Y chromosome stability. The more proximal the …

Cytogenetic and Y chromosome microdeletion screening of a random group of infertile males.

OBJECTIVE To assess whether to perform routine cytogenetic and Y chromosome microdeletion screening on all infertile male patients. DESIGN A cytogenetic and Y microdeletion study of a random group of infertile men. SETTING University department. PATIENT(S) In total, 40 patients had azoospermia (21 nonidiopathic), 27 had severe oligozoospermia/oligoasthenozoospermia (<or=5 x 10(6)/mL) (5 nonidiopathic), 20 had oligozoospermia/oligoasthenozoospermia (5-20 x 10(6)/mL) (6 nonidiopathic), and 16 had asthenozoospermia (5 nonidiopathic). Many were candidates for intracytoplasmic sperm injection (ICSI). INTERVENTION(S) Collection of blood samples from all patients and buccal cells from one patient. MAIN OUTCOME MEASURE(S) Karyotype analysis, polymerase chain reaction (PCR) screening for Y chromosome microdeletions, and fluorescence in situ hybridization of abnormal chromosomes. RESULT(S) Ten (9.7%) subjects, including one nonidiopathic patient, were found to have an abnormal karyotype. Two idiopathic azoospermic patients were missing large portions of Y chromosome euchromatin, confirmed by PCR analysis and an additional idiopathic azoospermic patient had a Y chromosome microdeletion. CONCLUSION(S) Routine cytogenetic analysis of all infertile male patients is required but it may be advisable to limit routine Y chromosome microdeletion screening to patients with severe male factor infertility (<or=5 x 10(6)/mL).

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.

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 embryos humanity.

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.

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.

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.

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.

Pregnancy and miscarriage rates in 3978 donor insemination cycles: Effect of age, parity and partner's infertility status on pregnancy outcome

The effects of age, parity and male infertility status on pregnancy outcome were studied in a cohort of 720 women receiving donor insemination (DI) treatment. Twenty-two percent of women failed to complete the treatment, leaving 562 women receiving 3202 cycles of DI for assessment. Of the 321 of pregnancies achieved, 57 (17.8%) ended in a mis-carriage. After further DI treatments, 64.7% of mothers who had miscarried succeeded in giving birth. There was some evidence to indicate a trend of decreasing pregnancy rate with increasing maternal age, although this result was not significant (log rank trend statistics = 3.44, P > 0.05). The pregnancy rates of multiparous and primiparous women were significantly different, irrespective of their partners infertility status (azoospermia: log rank statistics = 3.74, P ˇ- 0.05; oligozoospermia: log rank statistics = 4.71, P < 0.03). Furthermore, multiparous women were more likely to become pregnant than primiparous women (azoospermia: hazard ratio = 1.29; oligozoospermia: hazard ratio = 1.50). There was no significant association between miscarriage rate and maternal age (log rank trend statistics = 0.99, P > 0.05). The small number of older women (> 35 years) may confound this result. The mean (± sd) sperm donor age was 23.6 years (± 3.5 years). The implications of these observations are discussed.