What is the success of drug treatment in urge urinary incontinence? What should be measured?

Purpose

The aim of this study is to evaluate the efficacy and the tolerability of three classic antimuscarinic drugs used in the treatment of over active bladder syndrome using clinical data and quality of life tests, and to evaluate the parameters affecting the success of these drugs.

Methods

A total of 90 patients with urge urinary incontinence were randomly allocated into three groups either to receive tolterodine (group A), trospium chloride (group B) or oxybutynin (group C). Urogenital distress inventory short form (UDI-6) and Incontinence impact questionnaire short form (IIQ-7) of the Turkish Urogynecology and Pelvic Reconstructive Surgery Association were performed to each patient before and after treatment to evaluate the effectiveness and tolerability of the antimuscarinic drugs. Adverse events were also recorded during treatment.

Results

Improved urodynamic test values were recorded after 6 weeks of treatment in each group. Similarly, statistically significant differences were observed in UDI-6 and IIQ-7 test scores before and after treatment. Complete cure was achieved in 86 % of patients in group A; however, complete cure rates were 67 and 80 % in group B and C, respectively. Although, patients reported comparable tolerability against trospium chloride (77 %) and tolterodine (80 %), only 23 % of patients using oxybutynin considered the drug as tolerable. The most common side effect was dry mouth, followed by insomnia. Both dry mouth and insomnia was highest in group C (50 %). One patient (0.3 %) in group B and two patients (0.7 %) in group C reported that they did not want to continue to use the drug.

Conclusion

Antimuscarinic medications are very successful in the treatment of urge urinary incontinence; however, the success of treatment is not only limited to clinical improvement. Patients do not regard a drug as successful unless it is tolerable, easy to adapt to the daily life and improve the quality of life even it has very successful clinical outcomes.     

How should randomised trials including multiple pregnancies be analysed?

Objective   To compare the effects of four methods of analysis on the results of randomised controlled trials that recruit women with multiple pregnancies and measure outcomes on their babies.
Design   Analysis of one real and two simulated data sets.
Setting   Secondary analysis of perinatal randomised controlled trials.
Population   Randomised controlled trials including women with multiple pregnancies.
Methods   The analytical methods compared were (a) assuming independence among babies, (b) analysing outcomes per women, counting a woman as having an outcome if any of her babies had it (equivalent to selecting the worst outcome among any of a woman's babies), (c) randomly selecting one baby from each set of multiples for inclusion in the analysis, (d) adjustment of the analysis to take account of non-independence of babies from multiple pregnancies, using methods developed for analysis of cluster randomised trials.
Main outcome measures   Odds ratios for trials' main outcomes.
Results   Results from application of cluster trial methods were similar to those from assuming independence among babies, but with slightly wider confidence intervals, reflecting the reduced effective sample size caused by non-independence between babies from the same pregnancy. Results were more variable using the other two methods, and in some cases, departed markedly from the results of the cluster trial methods.
Conclusions   Cluster trial methods provide a simple way of adjusting the analysis to take account of non-independence between babies from the same pregnancy. Random selection and analysis by pregnancy (methods (b) and (c)) have disadvantages and do not report outcomes for all of the babies in the trial. This may cause problems with incorporating trials analysed using these methods into systematic reviews.     

What is the best measure of maternal complications of term pregnancy: ongoing pregnancies or pregnancies delivered?

OBJECTIVE: The purpose of this study was to determine whether rates of hypertensive disorders of pregnancy increase beyond 37 weeks of gestation and to address how best to analyze these rates. STUDY DESIGN: This was a retrospective cohort study of all women delivered beyond 37 weeks' gestational age from 1995 to 1999 at all Kaiser Permanente Medical Care Program delivery hospitals in Northern California. Rates of gestational hypertension, preeclampsia, and eclampsia were calculated by use of both pregnancy delivered (PD) and ongoing pregnancy (OP) as the denominator. Bivariate and multivariate analyses were conducted with use of P<.05 to indicate statistical significance. RESULTS: Among the 135,560 women in this cohort, the rates of gestational hypertension, preeclampsia, and eclampsia were the same or decreased from 37 to 43 weeks' gestation using PD, but all three increased when calculated according to OP (P<.01). CONCLUSION: We found that among complications of pregnancy that are diagnosed ante partum, use of a different denominator led to contradictory conclusions. When hypertensive disorders of pregnancy are analyzed, ongoing pregnancies should be used as the denominator.     

Which issues concerning multiple pregnancies should be addressed during psychosocial counselling?

The global rise in multiple pregnancy rates due to assisted reproductive technology has led to the development of various strategies to diminish these rates without jeopardising pregnancy. Policies at treatment centres may include the option of fetal reduction, although each centre is subject to national laws and its own guidelines. However, personal opinions and goals may also influence practice. The development of clinical decisions, therefore, is complex and subject to change. Primary prevention is the best way to reduce multiple births. For preventative psychosocial counselling, some centres employ counsellors, but if not, this becomes the physician's task. An in-depth assessment is required to define how many embryos to transfer and what risk of multiple birth is acceptable to patients. Counselling should address the following: the relationship between pregnancy rate, multiple pregnancy rate and the number of embryos transferred; benefits and risks of multiple pregnancy; and possibilities for primary and secondary prevention. Patients should voice how they feel facing these issues; which issues are worrisome; how they anticipate these possibilities; and what psychosocial support exists that could be mobilized. In summary, psychosocial counselling reinforces the partnership between couples and the assisted reproductive technology team, allowing for primary prevention and informed consent on multiple pregnancy issues.     

How should the clinical efficiency of oocyte cryopreservation be measured?

Clinical application of oocyte cryopreservation may be in the context of fertility preservation for women about to undergo cytotoxic therapies or may be as an alternative to embryo cryopreservation in routine assisted reproduction. The clinical efficiency of oocyte cryopreservation will be a consequence of the cumulative impact of pre-freeze oocyte quality, postthaw survival and subcellular effects of cryopreservation protocols, which impact on early embryo quality and post-transfer viability, together with the degree of selection which is applied to the available biological material. Any valid assessment must include reference to all the above aspects, particularly when comparing cryopreserved oocytes with non-frozen controls or cryopreserved embryos. Cumulative pregnancy rates from oocyte collections may provide the most relevant index of success. Survival of human oocytes cryopreserved using current methodology is similar to that achieved with early-cleavage-stage embryos. Although evidence suggests that developmental potential may be compromised when current oocyte cryopreservation protocols are applied, there is a paucity of rigorously controlled studies in the literature.     

What prenatal diagnosis should be offered in multiple pregnancy?

The issues surrounding prenatal diagnosis in multiple pregnancy are complex. Accurate determination of chorionicity is vital and an inability to determine this should trigger consideration for referral to a specialist. The choice of screening method for detection of chromosomal abnormality is limited, and existing data demonstrates the advantages of nuchal translucency screening. The possibility of obtaining discordant results and options for management should be discussed in advance. Invasive tests are technically more difficult and associated with a higher risk of procedure-related pregnancy loss than less invasive methods. Repeat invasive testing is required more often in multiple pregnancies than in singleton pregnancies. Selective termination is technically feasible in both mono- and dichorionic pregnancies, although the risks are higher with the former. It is likely to be more acceptable than high-order multifetal reduction performed in the absence of fetal abnormality.     

Dilemmas in management of bilateral ectopic pregnancies—report of two cases and a review of current practice

Simultaneous bilateral ectopic pregnancies occurring spontaneously or following assisted conception techniques, although rare, present the clinician with diagnostic uncertainty and management dilemmas which may have an implication on the patient’s future fertility. A review of available literature suggests that there is no universally accepted management strategy towards this condition, and care needs to be tailored to the needs of the patient, patient’s preferences and the clinical picture. We report two such rare cases of simultaneous bilateral ectopic pregnancies with different management and outcomes highlighting the fact that these cases not only pose diagnostic and management challenges but also has complex ethical issues associated with it.     

Why and how should multiple pregnancies be prevented in assisted reproduction treatment programmes?

Although most professional societies have issued guidelines to diminish the number of embryos to be transferred during assisted reproductive techniques, the incidence of multiple pregnancies remains unacceptably high. The burden of morbidity and mortality seems to increase substantially with each fetus in a multiple gestation. As a result, there has been growing debate on the need to prevent multiple pregnancies. The infertility specialists who can solve the infertility problem are usually shielded from the complications of multiple pregnancies. If they were involved in the delivery and, more particularly in the care of multiple pregnancies (both financially and socially), their attitude would probably change. IVF centres should gradually reduce the mean number of embryos per transfer in terms of the cost:benefit ratio. A further reduction to one single embryo per transfer in good cases would be similarly acceptable. Laboratory expertise is of vital importance, especially in terms of embryo culture, embryo selection, and freezing and thawing techniques in embryo transfer programmes for reducing the number of transferred embryos.     

Ovarian hemangioma—report of three cases and review of the literature

Introduction Ovarian hemangiomas are rare tumors, with less than 50 reported cases in the English literature. This is a low incidence, considering the rich vascular supply of the ovary.Discussion We have encountered three cases of ovarian hemangiomas found incidentally at the time of surgery. Ovarian hemangioma should be considered when a hemorrhagic ovarian tumor is encountered. Although often an incidental finding at surgery, these lesions may rarely be associated with systemic manifestations.     

What is the role of assisted reproduction technology in the management of age-related infertility?

Although in the UK the upper age limit for National Health Service (NHS) provision of in?vitro fertilisation (IVF) is 39 years of age there has been an increase in number of women having fertility treatment in their 40s. However, the success rates of IVF and intra-uterine insemination (IUI) in this group remain low. Human Fertilisation and Embryology Authority (HFEA) data from 2006 showed that the live-birth rate from IVF in the UK was 11% in the age group 40-42, 4.6% in the age group 43-44 and less than 4% in women over 44. We performed a literature search for studies using terms and combinations of terms in online databases and published meta-analyses reporting the outcome of interventions in older women. This review showed that assisted reproduction technologies (ARTs) continue to have low live-birth rates in women over 40. Trials showed that assisted hatching may increase the chance of pregnancy in women with poor history. Blastocyst transfer is associated with better outcome, whereas application of pre-implantation genetic screening (PGS) in older women has not increased the success rates. It appears that, with the exception of egg-donation, ART has no answer yet to age-related decline of female fertility.     

Antenatal care in developing countries. What should be done?

Development of antenatal care from the beginning of the 20th century and its relation to perinatal mortality in developed countries is presented. The role of socioeconomic factors, new diagnostic and therapeutic procedures, extended indications for cesarean section and of neonatal intensive care is also stressed. In the West- and Middle-European countries by the introduction of antenatal care the perinatal mortality (PNM) rate decreased from about 60.0@1000 in the years 1920-1930 to about 40.0@1000 in 1950s. Further decrease to about 25.0@1000 in the 1970s was conditioned by an increase of number of antenatal visits and by extended indications for cesarean section. New technologies (amnioscopy, pH.metry, cardiotocography and ultrasound examinations) decreased the PNM rate to about 13.0@1000 in the year 1980. Regional organization with neonatal intensive care units decreased PNM rate to low values of 5.0-9.0@1000. The echo of the number of antenatal visits to PNM rate is illustrated on 36,855 deliveries at the University Clinic in Zagreb. In developing countries maternal and perinatal mortality is very high. The reason for that is a bad socioeconomic background and a lack of organized antenatal and perinatal health care system. The policy to decrease maternal and perinatal mortality is presented: the improvement of antenatal booking and of the number of prenatal visits of pregnant women; their childbearing under professional assistance. The organizing of maternity health care should be different from country to country, from region to region, respectively.     

Long-term outcomes: what should the focus be?

The neonatal intervention trials of the 1980s and early 1990s focused primarily on short-term outcomes. Contemporary clinical trials have recognized the importance of longer-term outcomes but have rarely been powered to achieve that aim. This review discusses important and clinically relevant outcomes that future trials should be powered to address and identifies the challenges facing the neonatal clinical trials community. These challenges include consensus definitions of relevant outcomes that are objective and validated, variability among centers in populations and practices, and the need for predictive surrogate markers of long-term outcomes. Future trials must be designed and powered to address the potential for harm as well as the prospect of benefit.     

Vasa praevia after IVF: should there be guidelines? Report of two cases and literature review

The paper gives an illustration and reminder of the risk of problems with placentation resulting from IVF and embryo transfer. Reported here is one neonatal death related to vasa praevia when the condition was not diagnosed antenatally and a neonatal survival when vasa praevia was detected antenatally. A search of the English literature was performed using PubMed for 'vasa praevia and in vitro fertilization'. There were four articles that directly addressed this relationship. Case reports of IVF-embryo transfer pregnancies with vasa praevia and also studies that look at the incidence of vasa praevia in such pregnancies are included in this report. Hence, since vasa praevia is thought to be caused by a disturbed orientation of the blastocyst at implantation, it is probably related to the IVF-embryo transfer procedure. Screening of all IVF-embryo transfer pregnancies with transvaginal sonography and colour Doppler to rule out vasa praevia is recommended in the second trimester.