Facilitators and obstacles to sperm banking in young men receiving gonadotoxic chemotherapy for cancer: the perspective of survivors and health care professionals

BACKGROUND: Testicular cancer and Hodgkin's disease are among the most common malignancies to affect young men of reproductive age. Although both are associated with high rates of infertility, sperm banking (SB) remains underutilized by both diagnostic groups. Reasons for this remain elusive. METHODS: This study used a qualitative design. In-depth interviews were conducted with 20 cancer survivors and 18 health care professionals (HCPs) to examine their perspectives on factors that facilitate or hinder SB. Interview data were analysed using a mixed approach and a three-step process of data reduction, data display and conclusion drawing and verification. RESULTS: Eight factors were identified as having an impact on SB, and findings suggest that effective promotion of SB involves adequate communication around the severity and personal risk for infertility, assessing the importance of patients place on having children, emphasizing the benefits of SB and addressing possible obstacles such as cost, misperceptions or cultural and other factors. In addition, the communicator should be perceived as appealing. CONCLUSIONS: These results are conceptually consistent with both the Health Belief Model and the Elaboration Likelihood Model of health promotion and are useful in informing HCPs on how to better promote SB.     

Chlamydia trachomatis in subfertile women undergoing uterine instrumentation. The clinician's role

Most women attending a fertility clinic will undergo uterine instrumentation either diagnostically and/or therapeutically. This places them at potential risk of chlamydial pelvic inflammatory disease. Clinicians remain unclear about the roles of screening, serology and prophylactic antibiotics. A review of the evidence suggests that women <25 years and those older with risk factors, men with risk factors and gamete donors should have their lower genital tract screened for Chlamydia trachomatis by a sensitive test. More information is required before screening men by age can be recommended. Serology in its present form cannot be advocated as a screening tool. Those women with a past history of chlamydial morbidity or a diagnosis of tubal pathology should, in addition to screening, be covered with prophylactic antibiotics when undergoing uterine instrumentation. The partner should be screened for sexually transmitted infections. Non-selective use of prophylactic antibiotics serves only to increase the problem of antibiotic resistance and maintain the bacterial load of chlamydia in the community.     

Donor selection for recipient safety

Before the introduction of testing for transfusion transmissible agents, donor selection criteria made a critical contribution to recipient safety. Currently, for some pathogens, screening questions alone identify donors at risk, whereas for others, questions identify an at-risk population that will undergo selective testing. For many pathogens, such as HIV, HBV and HCV, universal donor testing is done, but deferral criteria developed in the pretesting era are still in place. Ideally, the steps in the donor selection process and specific donor criteria should be evidence based, to avoid deferral of safe donors. Although obtaining evidence to assess criteria is challenging, several approaches have been taken to evaluate actual or potential changes to criteria. The donor selection process and specific criteria should be reassessed over time, as donor testing and pathogen reduction make increasingly important contributions to blood safety.     

ART in recurrent miscarriage: preimplantation genetic diagnosis/screening or surrogacy?

Recently, assisted reproductive techniques have been used to prevent further miscarriages in women with recurrent miscarriage. One approach uses either screening or diagnosis of embryonic chromosomes prior to embryo replacement [preimplantation genetic screening (PGS)/preimplantation genetic diagnosis (PGD)]. The second approach involves surrogacy. However, PGS/PGD assumes that the embryo is chromosomally abnormal, and that the mother should receive a chromosomally normal embryo. Surrogacy assumes that the embryo is normal and that the maternal environment needs to be substituted. This article examines the place of both techniques in different types of recurrent miscarriage, and tries to give guidelines as to which technique is preferable depending on the likelihood of an embryonic chromosome aberration. In repeated fetal aneuploidy or in the older patient, PGS or PGD are preferable. However, with high numbers of miscarriages, or in autoimmune pregnancy loss, surrogacy is preferable. In the light of recent work, it is uncertain which treatment mode is indicated in balanced parental chromosome aberrations. In conclusion, both techniques have a place, but probably only in those patients with a poor prognosis in whom assisted reproductive techniques will be shown to improve the subsequent live birth rate above the spontaneous rate.     

Safety issues in assisted reproduction technology: should ICSI patients have genetic testing before treatment? A practical proposition to help patient information

ICSI is a highly efficient treatment of male factor infertility and therefore increasingly used to treat infertile men successfully. However, when used to treat patients with a genetic cause for their infertility, there may be an increased risk for the offspring. Chromosome aberrations, Y chromosome microdeletions and CFTR (cystic fibrosis transmembrane conductance regulator) mutations alone may explain up to 25% of azoospermia and severe oligozoospermia. These genetic defects could be identified before treatment, in which case informed decisions could be made by the couple to be treated concerning the treatment, prenatal testing or preimplantation genetic diagnosis. Therefore, we propose that men with very low sperm counts (<5 x 10(6)/ml) considering ICSI should always be informed of the possibility of genetic testing. The information should include a precise statement of the implications of the results for the patient, his family and his offspring, and reassurance that a decision to test or not to test, or the subsequent test results will not be used as a reason for withholding treatment. Testing should always remain voluntary, and the couples themselves should decide whether or not they choose to be tested. If an abnormality is identified, patients should be referred to specialist genetic counselling.     

Exercise-induced ovarian torsion in the cycle following gonadotrophin therapy: case report

The incidence of ovarian torsion has been reported to be increased during controlled ovarian hyperstimulation. In this report we describe exercise-induced ovarian torsion in an ovary with a persistent cyst, following a failed gonadotrophin-stimulated intra-uterine insemination cycle. This report suggests that the risk of ovarian torsion persists beyond the treatment cycle and that patients should be instructed to refrain from exercise or strenuous activity if regression to normal ovarian size has not been documented. Ovarian torsion should be high in the differential diagnosis in patients experiencing abdominal pain with a history of recent gonadotrophin stimulation.     

The subsidiarity principle in the context of embryonic stem cell research

Embryonic stem cell research is regulated by different forms of the subsidiarity principle, i.e. research on embryos should only be conducted if no suitable alternatives exist. Four types are discussed: animal versus human material, adult versus embryonic stem cells, affected or at risk embryos versus healthy embryos, and supernumerary versus research embryos. Three major arguments regarding the subsidiarity principle are discussed: the necessity argument, the least offensive moral approach and the 'nothing is lost' argument. It is proposed that the burden of proof should be shifted onto those who oppose embryonic research. When the freedom of research and the moral obligation to relieve human suffering is taken seriously, the opponents of this research should first demonstrate that embryonic stem cells do not work or that adult stem cells work better.     

Biological coagulation findings in third-generation oral contraceptives

An increased risk of venous thrombosis has been demonstrated in women receiving oral contraceptives (OCs). This risk has been primarily associated with the oestrogen content, but recent studies showed that the progestogen may also play a role. A higher risk was found with the so-called third-generation (desogestrel, gestodene) as compared with the second-generation progestogens (levonorgestrel). The risk was approximately two-fold. These unexpected results have been the subject of many debates, and bias--such as selection bias--has been suggested. The existence of bias cannot be completely excluded, but the thrombotic risk seems however to be slightly higher with the third-generation progestins. Haemostatic changes have been observed during OC intake. Both coagulation and fibrinolytic activity are increased: the beneficial profibrinolytic effect may counterbalance the deleterious procoagulant effect. This may explain that the absolute risk of venous thromboembolism is low during OC treatments. Some women who have pre-existing haemostatic abnormalities such as deficiency in antithrombin or activated protein C resistance with factor V Leiden, may be at a higher risk. The biological plausibility of the increased risk related to the third-generation progestogens has been explored. Theoretically, this could be due to an increased coagulation or to a lack of increased fibrinolysis as compared with second-generation progestogens. The only difference presently reported with third-generation OCs is a decreased sensitivity to activated protein C, possibly resulting in a hypercoagulability of greater magnitude. The selection bias suggested in epidemiological studies may also exist for the latter study, as women taking third- or second-generation OCs were not randomized. The possible increased risk related to third-generation OCs should not change the known general contra-indications. Practical guidelines are proposed for women with personal or family history of venous thromboembolism, and for those with a congenital cause of thrombophilia.     

Modern use of clomiphene citrate in induction of ovulation

Clomiphene citrate is the treatment of first choice in the managementof infertility in normally oestrogenized, anovulatory women(WH0 group II). The majority of women with 'pure' anovulatoryinfertility respond to treatment with clomiphene citrate. Therates of pregnancy and miscarriage are close to those expectedin a normal fertile population. Basal hormone concentrationsdo not predict outcome. An increased body mass index is theonly factor which is consistently associated with a decreasedresponse to clomiphene citrate; it follows therefore, that weightreduction should be an important part of therapy in anovulatorywomen. According to our data, only an increased luteinizinghormone value immediately post clomiphene citrate predictedan adverse pregnancy outcome in women who conceived. Clomiphenecitrate, along with other ovulation induction therapies, cancause multiple follicular development, with a risk of ovarianhyperstimulation and multiple pregnancy. Ultrasound monitoringof treatment is important in order to choose the appropriatedose of clomiphene citrate in subsequent cycles and to minimizethe risks of hyperstimulation and multiple pregnancy. When coupleswith other factors contributing to subfertility are excluded,the cumulative conception rate continues to rise after 6 monthsof treatment with clomiphene citrate, reaches a plateau by treatmentcycle 12 and approaches that of the normal population. It hasbeen reported that prolonged use of clomiphene citrate may beassociated with an increased risk of a borderline or invasiveovarian tumour. Taking into consideration these observations,we recommend that anovulatory women responsive to clomiphenecitrate should be treated for at least 6 cycles before consideringmore complex or invasive methods of ovulation induction, andthat treatment should probably be limited to a maximum of 12cycles.     

The changing scene--an unnecessary pill crisis

A number of case-control studies published in 1995/1996 have shown an apparent increase in the risk of venous thromboembolism (VTE) associated with the use of third-generation oral contraceptives (OC). However, it was discussed very early on that these studies were subject to a number of biases or residual confounding that would have increased the risk estimates for third-generation OC while lowering those for second-generation preparations. Six new studies or analyses were performed trying to take into account many of the methodological problems that were discussed for the initial studies: Two population-based database analyses in the UK and Germany, a new analysis of the General Practice Registry database (GPRD) in the UK, an analysis of a new database of the Transnational study, a re-analysis of the original Transnational study with a new technique, and a population-based study in Denmark. These studies could not confirm a higher VTE risk in users of third-generation OC compared with those using second-generation OC. Data on the risk of arterial thromboembolism (ischaemic stroke and myocardial infarction) show no such difference between generations of OC, with a statistically significant reduction in the risk of acute myocardial infarction from first- to third-generation preparations in one major study. Some of the investigators concluded that there is very likely no increased risk of arterial thromboembolism associated with the use of low-dose oestrogen OC in young women who are properly screened for cardiovascular risk factors or for such conditions. These findings should be taken into account when interpreting the results of studies on the risk of VTE in women taking combined OC.     

Consensus statement on the bio-safety of urinary-derived gonadotrophins with respect to Creutzfeldt-Jakob disease

Human transmissible spongiform encephalopathies (TSE) encompass a group of rare neurodegenerative diseases. In April 2004, a group of international experts and regulators met in Buenos Aires, Argentina, to review the safety and to reach consensus on the use of urinary-derived gonadotrophins with respect to TSE. Iatrogenic transmission of Creutzfeldt-Jakob Disease (CJD) from pituitary-derived gonadotrophins has been reported, no infectivity in urine has been demonstrated, and no definite cases of transmission via urine have been reported. It is currently not possible to monitor donor urine or finished product for the presence of prions. Therefore the assessment of risk has to be based on the likelihood of infection in urine, the source of the urine, and the capacity of the manufacturing process to remove any adventitious infection. Urine for the production of medicinal products should be obtained from sources that minimize the possible presence of materials derived from subjects suffering from human TSE. As no strong evidence for TSE infectivity in urine exists, it can be concluded that the risk of disease-generating prions and TSE infectivity being present in donor urine is low. Current evidence indicates that, with respect to the risk of TSE infection, urinary-derived gonadotrophins appear to be safe.     

Transmission risk of hepatitis C virus via semen during assisted reproduction: how real is it?

The risk of viral transmissibility in assisted reproduction is still a much-debated issue, especially for hepatitis C virus (HCV). HCV is a common causative agent for parenterally transmitted viral hepatitis. In addition, it has been incriminated in other routes of transmission, including sexual transmission and nosocomial infections. The management of infertility, in association with HCV, has sparked debates about the potential risk of spread of infection to virus-free individuals, embryos and/or semen. The lack of worldwide-accepted screening policies has helped to fuel this debate. Today, it is evident that there is a potential risk of spread of HCV through biological fluids, including semen, to other individuals. This risk can only be marginalized by the use of well-established criteria for safety in infertility centres, and by the use of proper initial detection and segregation of potentially hazardous materials. Techniques and protocols have been established to help the andrologist and embryologist to safeguard patients against such dangers, and should be imposed in all centres, allowing HCV-positive males to enter their assisted reproduction programmes.     

Managing violence in primary care: an evidence-based approach.

An understanding of the risk factors for violence can help primary care staff to evaluate and manage risk in the primary care setting. They will be able to acknowledge that risk factors are not static but can vary according to time, place, situation, and support networks. General practitioners (GPs) should not ignore their clinical acumen, but should use their knowledge of the patient to form part of a risk assessment. Managing violence in primary care should focus on the individual; for example, in the training of primary care staff. It should also involve an examination of the wider structure of primary care; for example, the safe design of buildings, avoiding long waiting times, and having 'no intoxication' policies for practices. There is a pressing need for primary care-based research in this area. We acknowledge that in our understanding of this topic there are two extremes that should be avoided. The first is that our perceived risk of violence often exceeds the real, absolute risk. Where our perceptions are overstated, patients run the risk of being excluded from primary care or of being inappropriately detained on psychiatric wards under the Mental Health Act. At the other extreme, where risk is understated, staff can play the 'hero' or the 'martyr' in an attempt to defuse a situation without support from other colleagues. Like many other situations in primary care, working in isolation carries real and important risks. Threats of violence are best managed in primary care by having a collaborative practice approach underpinned by a support ethos from primary care organisations.     

Safety of modern oral contraception: the options for women: lessons to be learned

The relatively short history of hormonal contraception has been marked by a series of 'pill scares', all of which--after creating panic among users--were proven to be unfounded in terms of public health impact. The latest pill scare, provoked by regulatory action in the United Kingdom and the Federal Republic of Germany in response to the publication of a series of articles indicating a doubling of risk of deep venous thrombosis in users of oral contraceptives containing third-generation progestins, seems finally settled: both the British and the German Drug Regulatory Authorities have now reverted their verdict. The damage unfortunately stays: hundreds of thousands of women have been compelled to abandon the pill of their choice, often deciding to drop contraception altogether, thereby exposing themselves to unwanted pregnancy and--in a number of cases--to pregnancy termination. This latest episode should be turned into something positive: we need to learn that, in the case of drugs in widespread use, before restrictive action is taken--and except for very rare and specific instances--the scientific community must carry out an exhaustive debate on the reality and importance of the observed effects. Although the public should, in each instance, be properly informed, it is only after this process has been completed that restrictive action should be taken. It is hoped that, after this last episode, all concerned have learned this simple principle and will accept being guided by it from now on.     

Assisted reproductive technologies and the risk of birth defects--a systematic review

BACKGROUND: The risk of birth defects in infants born following assisted reproductive technology (ART) treatment is a controversial question. Most publications examining the prevalence of birth defects in ICSI and IVF infants compared to spontaneously conceived infants have serious methodological limitations; despite this, most researchers have concluded that there is no increased risk. METHODS: We carried out a systematic review to identify all papers published by March 2003 with data relating to the prevalence of birth defects in infants conceived following IVF and/or ICSI compared with spontaneously conceived infants. Independent expert reviewers used criteria defined a priori to determine whether studies were suitable for inclusion in a meta-analysis. Fixed effects meta-analysis was performed for all studies and reviewer-selected studies. RESULTS: Twenty-five studies were identified for review. Two-thirds of these showed a 25% or greater increased risk of birth defects in ART infants. The results of meta-analyses of the seven reviewer-selected studies and of all 25 studies suggest a statistically significant 30-40% increased risk of birth defects associated with ART. CONCLUSIONS: Pooled results from all suitable published studies suggest that children born following ART are at increased risk of birth defects compared with spontaneous conceptions. This information should be made available to couples seeking ART treatment.     

Risk and management of blood-borne infections in health care workers

Exposure to blood-borne pathogens poses a serious risk to health care workers (HCWs). We review the risk and management of human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) infections in HCWs and also discuss current methods for preventing exposures and recommendations for postexposure prophylaxis. In the health care setting, blood-borne pathogen transmission occurs predominantly by percutaneous or mucosal exposure of workers to the blood or body fluids of infected patients. Prospective studies of HCWs have estimated that the average risk for HIV transmission after a percutaneous exposure is approximately 0.3%, the risk of HBV transmission is 6 to 30%, and the risk of HCV transmission is approximately 1.8%. To minimize the risk of blood-borne pathogen transmission from HCWs to patients, all HCWs should adhere to standard precautions, including the appropriate use of hand washing, protective barriers, and care in the use and disposal of needles and other sharp instruments. Employers should have in place a system that includes written protocols for prompt reporting, evaluation, counseling, treatment, and follow-up of occupational exposures that may place a worker at risk of blood-borne pathogen infection. A sustained commitment to the occupational health of all HCWs will ensure maximum protection for HCWs and patients and the availability of optimal medical care for all who need it.     

Chlamydia trachomatis in subfertile women undergoing uterine instrumentation. Screen or treat?

Women who undergo uterine instrumentation are considered at risk for pelvic infections by Chlamydia trachomatis, which may derive either from ascending endocervical infections or from reactivation of micro-organisms persisting in the genital tract after previous chlamydia infections. Women presenting at fertility clinics frequently undergo uterine instrumentation (e.g. hysterosalpingography and laparoscopy with hydrotubation). Studies in subfertile women using DNA amplification techniques have shown that the prevalence of endocervical chlamydia infections is low (1.8%). In contrast, in 30-60% of subfertile women chlamydia IgG antibodies can be found in serum, indicating previous chlamydia infections. It has been demonstrated that, several years after chlamydia infections, viable micro-organisms may still be present in the upper genital tract. Therefore, subfertile women with chlamydia antibodies should be considered at risk for reactivation of persistent chlamydia infections after uterine instrumentation, even after exclusion of endocervical chlamydia infections. Moreover, in subfertile women without chlamydia antibodies, the presence of viable micro-organisms in the genital tract cannot be excluded. As a consequence, prophylactic antibiotics before uterine instrumentation should be considered in all subfertile women, instead of endocervical screening for C. trachomatis and treatment of positive cases only.     

Laparoscopic myomectomy: predicting the risk of conversion to an open procedure

BACKGROUND: Laparoscopic myomectomy (LM) has some advantages over laparotomy; however, it is reputed to be technically difficult, and the risk of conversion to laparotomy might be an obstacle in using this procedure. The aim of this study was to identify the pre-operative factors affecting the risk of conversion to an open procedure (either laparoscopic assisted myomectomy or laparotomy), and to develop a simple prediction model based on available pre-operative data with the use of multiple logistic regression. METHODS: A total of 426 women presenting with a subserous or intramural myoma measuring 20 mm or more underwent LM between March 1989 and October 1999. Of these patients, 378 had successful LM. Forty eight patients [11.3%, 95% confidence interval (CI) 8.3--14.3] had a conversion to an open procedure. A total of 265 women had adequate pre-operative ultrasonography (US) and were used for the analysis. RESULTS: The best prediction model included four pre-operative factors that were found to be independently related to the risk of conversion: size > or = 50 mm at US (adjusted OR = 10.3; 95% CI = 2.8--37.9), intramural type (adjusted OR = 4.3; 95% CI = 1.3--14.5), anterior location (adjusted OR = 3.4; 95% CI = 1.3-9.0) and pre-operative use of gonadotrophin-releasing hormone (GnRH) agonists (adjusted OR = 5.4; 95% CI = 2.0--14.2). The regression coefficients were then scaled and rounded to integers to provide an estimate of the risk for conversion. For a given patient with selected characteristics the predicted risk varied from 0--73%. CONCLUSIONS: This prediction model provides a useful tool that enables multiple criteria to be taken into account simultaneously to help select cases for LM. GnRH agonists should been used only in selected cases. US evaluation is essential before performing LM.     

Partner consent for sperm donation

The current practice of demanding the consent of the spousefor sperm donation is analysed. Three aspects of marriage maybe involved: (i) sexual exclusivity and adultery, (ii) familycomposition and (iii) procreational exclusivity. The differentjustifications for giving the partner the right to participatein the decision-making process are critically scrutinized. Theperspective taken in this article is that the transfer of gametesmust be understood and situated within the moral framework ofthe relationship between donor and partner. Depending on thekind of relationship the donor has with his partner, he maybe morally obliged to consult his procreational partner. Ina close relationship, all decisions concerning the use of one'sreproductive faculties should be joint decisions. However, itis not the task of the clinic or the physician to see that donorshonour their agreements and commitments. The clinic should notseek the partner's consent, although in the counselling sessionsit should be pointed out to the donor that he may have a responsibilityto inform his partner and to confer with her on his donation.     

An information system for drug prescription and distribution in a public hospital

With 773 beds and 3696 employees, the Hospital das Clínicas da Faculdade de Medicina de Ribeir?o Preto (HCFMRP)-Universidade de S?o Paulo, is one of the largest medical institutions in Latin America. The complete process of prescribing and distributing medication at HCFMRP involves the following stages: prescribing (physicians); ordering (infirmary); separating and dispensing (main drugstore); verifying and administering (infirmary). This was a manual process, normally taking place in the morning. Bottlenecks were inevitable and the risk of errors was elevated. An information system (IS) was devised and implemented with a view to controlling such problems. This article addresses the construction of this system and reports on a survey in which different groups of users have evaluated the project.