Women’s health—what’s new world wide
A roundup of patents, guidelines and trials from around the globe
A patent was granted to Oncomethylome Sciences, on 10 September 2008, to detect cervical cancer by determining the methylation status of estrogen receptor 1 (ESR1). The in vitro method involves use of a kit (comprising a gene-specific primer and an Ayre’s spatula and/or endocervical brush for removing cervical cells from the patient) for determining whether the cytosine residues in the ESR1 gene are hypermethylated (which the patentees believe is a useful marker for detecting the incidence/susceptibility of cervical cancer). The invention may extend further than the promoter regions if the gene is methylated elsewhere.
Van der See A, Wisman B. ESR1 and cervical cancer. Patent No: EP1769087 B1.
Detection of hypermethylated genes in tissue samples using quantitative methylation-specific polymerase chain reaction is a promising tool for the identification of cancer. The specific gene cited in the patent, ESR1 (a ligand-activated transcription factor composed of several domains important for hormone binding, DNA binding and activation of transcription) has also been implicated in other diseases, e.g. breast cancer.
On 8 August 2008, Manchester University submitted a patent application regarding prognostic markers for HPV-related cancer. The invention relates to an in vitro method to measure onzin levels in samples from patients. It is claimed that raised onzin levels indicate a patient may have, or be at risk of developing, cancer. The invention also includes a method to prevent or treat human tumour-related cancers or warts caused by HPV by reducing onzin levels/activity in patients.
Hampson I, Hampson L. Prognostic markers for HPV-related cancer. Application number: WO 2008/093083 A2.
The onzin gene is a novel, negative c-Myc target gene. The c-Myc oncoprotein is a general transcription factor whose target genes dictate the c-Myc phenotype. c-Myc overexpression reduces endogenous onzin levels coinciding with a cell’s increased susceptibility to a variety of apoptotic stimuli. Onzin, therefore, has the potential to act as a biomarker for malignant potential in cervical cancer.
A US patent application has been submitted by Pfizer relating to triazole derivatives, which may be useful as vasopressin antagonists to treat a wide range of disorders, but particularly primary and secondary dysmenorrhoea. The triazole derivative compounds are selective inhibitors of the vasopressin V1a receptor and this invention includes both the preparation process, the method by which they are contained and the use of these compounds.
Bryans J, Johnson P, Roberts L, Ryckmans T. Compounds useful in therapy. Application number: US 2008/0234252 A1.
Vasopressin antagonists have been proposed as a treatment for dysmenorrhoea based on the in vitro evidence that vasopressin, acting on its uterine V1a receptor, contributes to the myometrial hyperactivity associated with this condition. Early clinical studies in the past demonstrated that intrauterine pressure and pain levels fell during administration of another antagonist in spontaneous and vasopressin-induced dysmenorrhoea.
An application has been made to the US Patent Office regarding an invention relating to a portable obstetrics chair. As a result of an increasing number of women wishing to give birth in an upright position, health professionals have had to modify their own position during the delivery to ensure that they are positioned lower than the women. The invention aims to make it easier for health professionals by providing a portable, hygienic, height-adjustable chair to support them while performing a standing delivery.
Topping K. Portable obstetrics chair. Application number: US 2008/0224521 A1.
Priority interventions: HIV/AIDS prevention, treatment and care in the health sector
International efforts to combat HIV/AIDS have increased over the past few years. However, the disease still represents the most serious challenge to global public health and currently undermines achievement of six Millennium Development Goals. This comprehensive report, published by the WHO in August 2008, discusses the essential interventions that healthcare providers should deliver to patients with HIV/AIDS. The priority interventions recommended in this report include: family and partner HIV testing; prevention of sexual transmission of HIV; family planning, counselling and contraception; infant feeding counselling and support. The report provides guidelines on strengthening and expanding healthcare services, building robust strategic information systems and introducing a variety of operational services.
It is intended to be a ‘living’ document and will be updated regularly to ensure that the most current and relevant advice is available to health professionals managing patients with this condition.
Guidelines on antenatal care (parts 1 and 2)
These guidelines, published by the Hong Kong College of Obstetricians and Gynaecologists in September 2008, provide recommendations on the routine care of healthy pregnant women. Part 1 focuses on aspects of care pertaining to the organisation and delivery of antenatal care, lifestyle considerations, management of minor symptoms and clinical examination and part 2 on antenatal screening.
Although the National Institute for Health and Clinical Excellence in the UK (NICE) has produced its own guidelines on the subject, it is still interesting to read how another organisation has interpreted the best available evidence to make similar recommendations.
The balanced counselling strategy: a toolkit for family planning service providers
The Population Council aims to improve the quality of reproductive care worldwide. This strategy has been developed specifically to improve client–provider interactions in family planning services. The toolkit has been designed to be practical and interactive. It provides counselling cards to help health professionals offer and explain a range of methods to women seeking contraceptive advice. Three visual memory aids are used during the consultation: an algorithm (decision tree); a set of counselling cards for different contraceptive methods, and an information brochure discussing each method. The strategy has been tested in Peru and Guatemala and subsequently revised as a result of feedback from users. A user guide to the strategy has also been produced for which the URL is provided below.
Although designed for use primarily in the developing world, the advice contained in the tool kit is so clearly and logically laid out that all health professionals would benefit from using it.
ESHRE position paper: good clinical treatment in assisted reproduction
The European Society for Human Reproduction and Embryology (ESHRE) promotes best practice in the field of assisted reproduction and aims to advise health professionals on the best available evidence for managing fertility problems. This position paper, published by ESHRE in June 2008, discusses differing levels of access to infertility advice and treatment internationally and sets out a number of principles of good clinical practice including: accessibility; investigation of fertility problems; information and counselling; ovulation induction; intrauterine insemination; in vitro fertilisation (IVF); intracytoplasmic sperm injection (ICSI); cryopreservation; multiple pregnancies; single embryo transfer policy and the monitoring of assisted reproduction clinics.
The paper provides very concise and up-to-date advice regarding the management of common fertility problems and assisted reproduction technologies based on ESHRE and NICE guidelines, ESHRE monographs and European IVF-monitoring programme reports.
The evaluation and treatment of hirsutism in premenopausal women
The Endocrine Society has published a comprehensive clinical practice guideline on the management and treatment of hirsutism. The guideline provides evidence-based recommendations including: the definition, pathogenesis and aetiology of hirsutism; the diagnosis and pharmacological and hair removal (temporary and permanent) treatments in premenopausal women.
Clinical trial recruitment
Clinicians keen to keep up-to-date regarding clinical trials that are currently recruiting may find the following informative.
Tacrolimus versus corticosteroids in the treatment of vulval lichen sclerosis
This randomised, double-blind trial aims to evaluate the safety and efficacy of the immunomodulator, tacrolimus in treating vulval lichen sclerosis compared with standard corticosteroid treatment. The trial period is 3 months and cream will be applied once a day.
Inclusion criteria: female; 2 years or older; medical diagnosis of lichen sclerosis; no treatment received within the last 3 months.
Primary outcome measures: efficacy of tacrolimus versus topical corticosteroids in the treatment of vulval lichen sclerosis determined by physical findings and patient reported symptoms.
Secondary outcome measures: comparison of the severity of the adverse effects of both treatments; full blood count, glycaemia, vitamin B12 levels, thyroid-stimulating hormone to find immune-associated disease.
Trial site: Quebec, Canada.
Anticipated trial end date: April 2009.
Tacrolimus is a topical calcineurin inhibitor that has been used in a variety of dermatological conditions (e.g. eczema and vitilgo) because of its immunosuppressive properties. Small studies have reported its efficacy in lichen sclerosis (BJOG 2006 113:832–4) but, to the best of our knowledge, this is the first RCT comparing topical tacrolimus with corticosteroids.
A randomised controlled study comparing two single-incision devices for female urinary stress incontinence
This randomised, controlled, phase IV trial aims to compare the efficacy of two single-incision devices, the MiniArc and the tension-free vaginal tape (TVT) Secur System, for the treatment of female urinary stress incontinence. Eligible patients will be given a baseline assessment that includes anthropometric, clinical, hormonal, ultrasound and urodynamic evaluations. Before surgery, patients will be randomised to receive either a MiniArc or TVT Secur System. The clinical outcomes and adverse experiences of each patient will be evaluated. Data from this study will be analysed using the intention-to-treat principle, with a P value of 0.05 or less being considered significant. Inclusion criteria: female; 18–80 years; genuine stress urinary incontinence. Primary outcome measure: feasibility (degree of surgical difficulty in non-trained surgeons).
Secondary outcome measures: Learning curve; intraoperative complication rate; blood loss; postoperative complication rate; long-term complication rate; postoperative pain; patient satisfaction; sexual function; quality of life; failure rate; recurrence rate; de novo urge incontinence rate.
Trial site: Catanzaro, Italy.
There are now a large number of different devices on the market for the treatment of urinary stress incontinence and little evidence supporting the choice of one device over any other. The development, therefore, of well-designed RCTs to compare the effectiveness and long-term outcomes associated with such devices is to be welcomed.
Postpartum depression: transdermal estradiol versus sertraline
This randomised, double-blind study aims to compare estrogen patches, sertraline (SERT; a selective serotonin reuptake inhibitor) and placebo to determine the efficacy of estrogen patches in treating postpartum major depression (PPMD). Treatment will last 8 weeks but women will continue to be monitored until 6.5 months postpartum. The study will test the efficacy of the treatments; assess the development of infants exposed to mothers with PPMD; evaluate the medications in terms of whether they are transmitted to infants through breastfeeding; assess maternal depression and measure mother–infant serum SERT and estradiol levels.
Inclusion criteria: 18–40 years old; PPMD with pregnancy or postpartum onset (recruit by 3 months of delivery); SIGH-ADS score ≥18 and DSM-IV; current diagnosis of major depression (outpatient care); medically healthy (including normal lipid profile, renal function, liver function, thyroid function, full blood count).
Primary outcome measures: percentage of patients with remission of major depressive event; time to remission of major depressive event; number of venous thromboembolic incidents; endometrial hyperplasia; incident breast cancer cases; irregular vaginal bleeding; undesired discontinuation of breast feeding.
Secondary outcome measures: infant development in 6.5-month-old children (using Bayley Scales of Infant Development) with mothers who have PPMD; serum estradiol concentrations in infants.
Trial site: Pennsylvania, USA.
Anticipated trial end date: May 2012.
Postpartum depression is a difficult clinical problem with limited management options. Although estradiol has been proposed as a treatment, there is little evidence from a recent review to support its effectiveness (CNS Spectr 2005; 10:944–52). Similarly, there is limited evidence available regarding the effect of antidepressants (Cochrane Database Syst Rev 2005: CD 004363). This study appears to be well designed and addresses the important issue of safety.
Effectiveness of the use of the PICSI Dish (hyaluronan microdot) in the selection of sperm for ICSI
This randomised, double-blind trial aims to determine if using a PICSI Dish (hyaluronan microdot) to select sperm for ICSI, in men with a low hyaluronan-binding score, will result in an increased pregnancy rate.
Inclusion criteria: 18–40 years; IVF patients requiring ICSI that are being managed by participating clinical and scientific staff.
The head of a mature (but not immature) sperm carries a hyaluronan-specific receptor that enables mature sperm to bind to hyaluronan—the main component of the cumulus layer surrounding the oocyte. In routine ICSI, sperm are visually selected for injection on the basis of their morphology and motility. However, this approach does not reflect the genomic integrity of the sperm and its ability to provide the ‘best’ paternal contribution to the zygote. The PICSI system provides a means potentially to select mature sperm based on their ability to bind to three microdots of hyaluronan hydrogel at the bottom of the dish.
On 4 August 2008, the Supreme Court in Nepal rejected a case aiming to overturn the country’s abortion law. Attorney Achyut Kharel had brought the case to the Supreme Court claiming that the current law, where abortion is legal upon request up until the 12th week of pregnancy, was discriminatory against men as a woman currently does not need to have the consent of her husband to terminate a pregnancy. However, the court was persuaded that requiring consent from a husband would violate a woman’s human rights under both international law and Nepal’s constitution.