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.     

Can cesarean section be performed without the woman's consent?

Occasionally, an obstetrician can experience conflicts between the mother and her fetus. In a situation where the life of the fetus is in danger, religious, cultural, or other convictions may cause the mother to refuse the physician's recommendations for delivery. When there is a medical indication to perform cesarean section, but the mother refuses, has the obstetrician then a right to perform a cesarean section to save the fetus from possible death or serious injury? In 1987, The Norwegian Directorate of Health made a statement on cesarean section without consent, but later, new legislation on patient rights has been introduced. In Norway, no scientific medical articles have been published on this topic, and no cases have yet been brought to court. Cases of court-ordered cesarean section have been reported from the UK and the USA. In this report, we discuss some of the ethical, moral, and legal aspects of forced cesarean sections.     

Management of cervical cerclage and preterm premature rupture of the membranes: should the stitch be removed?

OBJECTIVE: Our aim was to determine whether retention of cerclage after preterm premature rupture of the membranes occurring before 34 completed weeks' gestation influences pregnancy outcome. STUDY DESIGN: Singleton pregnancies with cerclage and premature rupture of the membranes between 24.0 and 34.9 weeks were reviewed. Women were excluded if they were first seen in labor, had chorioamnionitis, or were delivered within 48 hours. Control subjects consisted of women with premature rupture of the membranes without cerclage. RESULTS: Eighty-one cases of cerclage with premature rupture of the membranes met criteria for inclusion: 30 women (37%) had their cerclage removed at presentation, and 51 (63%) retained the cerclage until delivery. Cases were similar in terms of gestational age at placement and gestational age at premature rupture of the membranes. There was no significant difference between the retained, removed, or control groups in terms of latency, gestational age at delivery, chorioamnionitis, or neonatal morbidity and mortality. CONCLUSIONS: Retention of cervical cerclage after premature rupture of the membranes occurring before 34 completed weeks' gestation is associated with comparable clinical outcomes with respect to latency and perinatal outcome, when compared with removal of the cerclage.     

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.     

What should the management of incest pregnancies be? An ethical view presented via three cases

Incest is a taboo and a neglected social problem. Especially in the adolescent population, which is a very sensitive period of development, it becomes harder for the patients to share their secret with either legal or health authorities. Sometimes pregnancy becomes the only vehicle to uncover this secret. There is a contradiction whether their pregnancies should continue or not. Some authors believe abortion is the best choice for the victim to pull herself together, whereas others advocate that it is just another trauma that will not solve the problem but merely hide it. In this report, three paternal incest cases and their pregnancies will be presented. The aim is not only to discuss the different points of view regarding the management of these pregnancies but also to make the clinicians think about the different choices before making a decision.     

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.     

Refusal to consent: Can it be ignored?

The common law has long recognised the right of competent adults to autonomy and self determination and this has been held to apply to the right to refuse medical and surgical treatment even when refusal could lead to severe detriment to the individual's life and health.Those who work with patients in a health profession can be faced with a refusal to consent to treatment when the best clinical opinion is that the treatment is appropriate and necessary, and considered to be in the patient's best interests. There have been no clear guidelines which health professionals can follow in deciding to treat or not treat in the presence of a patient's refusal. Where the patient continues to be competent there is an opportunity to take the matter up again with him or her as circumstances change However, when the patient loses competence, a clinical dilemma arises.There are documented legal cases in which courts have authorised treatment of competent adults even when they have refused or are refusing treatment. Some of these cases involve saving the life of an unborn child. The question which arises is whether different principles apply when an unborn child is involved.To date most of the cases have been heard in North American courts. However, there have been two recent cases in England where courts have authorised treatment without consent when the subjects have apparently had the capacity to make a decision to refuse treatment. These two cases must be contrasted with a Canadian decision in which a doctor was ordered to compensate a woman for administering a blood transfusion to her at a time she was incompetent to consent to treatment and he had written notice that she was against being the recipient of a blood transfusion in any circumstances.The purpose of this article is to discuss the relevant cases and to draw some conclusions from their outcomes.     

CMV infection: when should medical termination of pregnancy be discussed?

OBJECTIVES: To determine in which circumstances termination of pregnancy (TOP) could be proposed in case of CMV infection. PATIENTS AND METHODS: An inquiry was conducted concerning the practice of doctors working in French foetal medicine units in case of CMV infection. The question asked was: "What is your attitude if confronted to a CMV seroconversion at 23 weeks of amenorrhoea with positive PCR at 28 WA, and normal MRI and ultrasound scan at third trimester?" RESULTS: Thirty-five obstetricians answered. Forty-nine percent do not perform foetal blood sampling (FBS). Among them 1/17 would accept TOP. Fifty-one percent do perform FBS. In this group, 33% would accept TOP in case of negative FBS and 83% if FBS shows foetal infection. DISCUSSION AND CONCLUSION: Techniques available for diagnosis and prognosis of foetal infections are based on PCR on amniotic fluid, ultrasound, MRI and FBS. To date correlation of those tests with foetal outcome has not been fully validated. TOP could therefore be an option in 2 circumstances: when signs of certain severe foetal disease with positive PCR and ultrasound abnormalities; on statistical arguments: if positive PCR, and normal ultrasound, the risk of handicap is approximately 10%, the severity of the handicap being impossible to predict. In this last hypothesis, it is tempting to use additional arguments such as FBS even if the interpretation of the results of this test has not been scientifically validated. Such cases with positive PCR and normal ultrasound in which inconsistent decisions are made are likely to be more frequent because of routine serologic screening policy.     

Age-related changes in growth hormone secretion: should the somatopause be treated?

Growth hormone (GH) secretion declines progressively with aging, and many age-related changes resemble those of the adult GH deficiency (GHD) syndrome, including a decrease in lean body mass; an increase in body fat, especially in the visceral/abdominal compartment; adverse changes in lipoproteins; and a reduction in aerobic capacity. The increase in central obesity can further inhibit GH secretion. GH replacement is effective in reversing many of these changes in adult GHD, and GH is now FDA approved for treatment of adults with documented GHD or hypopituitarism, although there is still only limited experience with its long-term benefits, side effects, and risks. This early experience with GHD has led to speculation that replacing GH or stimulating its secretion may also be beneficial in normal aging, and to widespread off-label use of GH in this context; however, there are still very few well controlled studies of the effects and side effects of GH or GH secretagogues in aging. All published studies are of 6 months or shorter treatment periods. From this limited experience there is a consensus that GH has effects on body composition, but reports disagree on effects on psychological or physical functional performance. Older adults are much more susceptible to the dose-related side effects of GH, including peripheral edema, carpal tunnel syndrome, and a variable decrease in insulin sensitivity; and it is not known whether chronic GH treatment affects the risk of malignancy or has other long-term risks. Thus while short-term results are somewhat encouraging, the evidence on risks and clinically pertinent benefits is still lacking to support the use of GH in normal aging outside of clinical studies. In evaluating patients with clinical features suggesting GHD, which can be quite nonspecific, it is important to assess the presence or absence of true GH deficiency by the context (pituitary disease or its treatment, childhood GHD) and by appropriate GH stimulation tests before considering GH replacement.     

Carrier frequency of autosomal-recessive disorders in the Ashkenazi Jewish population: should the rationale for mutation choice for screening be reevaluated?

BACKGROUND: Ashkenazi Jewish (AJ) population is at increased risk for several recessive inherited diseases. Therefore, carrier testing of AJ members is important in order to identify couples at risk of having offspring with an autosomal recessive disorder. METHODS: In the present study, a database containing the results of 28 410 genotyping assays was screened. Ten thousand seventy eight nonselected healthy members of the AJ population were tested for carrier status for the following diseases; Gaucher disease (GD), cystic fibrosis (CF), Familial dysautonomia (FD), Alpha 1 antitrypsin (A1AT), Mucolipidosis type 4 (ML4), Fanconi anemia type C (FAC), Canavan disease (CD), Neimann-Pick type 4 (NP) and Bloom syndrome (BLM). RESULTS: The results demonstrated that 635 members were carriers of one mutation and 30 members were found to be carriers of two mutations in the different genes related to the development of the above mentioned diseases. GD was found to have the highest carrier frequency (1:17) followed by CF (1:23), FD (1:29), A1AT (1:65), ML4 (1:67) and FAC (1:77). The carrier frequency of CD, NP and BLM was 1:82, 1:103 and 1:157, respectively. CONCLUSIONS: The frequency of the disease-causing mutations screened routinely among the AJ population indicated that there are rare mutations with very low frequencies. The screening policy of the disease-causing mutations should be reevaluated and mutations with a high frequency should be screened, while rare mutations with a lower frequency may be tested in partners of carriers.     

Premenopausal bleeding: When should the endometrium be investigated?—A retrospective non-comparative study of 3006 women

Objective

There is lack of consensus amongst professional organizations as regards the cut-off age for endometrial sampling of premenopausal women presenting with abnormal uterine bleeding (AUB) to exclude endometrial hyperplasia or carcinoma. Therefore we conducted this study to quantify the prevalence of hyperplasia and carcinoma in different age categories in premenopausal women with AUB to identify the appropriate cut-off age for endometrial sampling.

Study design

A retrospective review of the histopathology reports of endometrial samples taken from 3006 women presenting with AUB and aged from ≥30 to ≤50 years at Ipswich Hospital, UK, from 1 January 1998 to 31 December 2007. Women were divided into three subgroups according to age; group 1: 30 to ≤40 (n = 862), group 2: 40 to ≤45 (n = 1035) and group 3: 45 to ≤50 (n = 1109).

Results

Logistic regression revealed that the prevalence of atypical hyperplasia (OR: 3.85; 95% CI: 1.75, 8.49; p = 0.01) and carcinoma (OR: 4.03; 95% CI: 1.54, 10.5; p = 0.04) was significantly higher in women in group 3 when compared to younger women. There was no statistically significant difference as regards simple and complex hyperplasia in the different age categories. All but one of the women (n = 23) who had complex atypical hyperplasia or carcinoma under the age of 45 years, presented with irregular rather than cyclical heavy menstrual bleeding.

Conclusion

Our study, the largest in the literature, suggests using the age 45 years as a cut-off for sampling the endometrium in all women with AUB. However, irregular menstrual bleeding justifies investigating women regardless of their age.