Progesterone supplementation to prevent recurrent miscarriage and to reduce implantation failure in assisted reproduction cycles

Implantation failure has been questioned for many cases of recurrent miscarriage and unsuccessful assisted reproduction. The exact cause of implantation failure is not known, but luteal phase defect is encountered in many of these cases. Consequently, women with recurrent miscarriages have been treated with progesterone supplementation with various degrees of success, and a recent meta-analysis has shown trends for improved live birth rates in those women. Progesterone probably acts as an immunological suppressant blocking T-helper (Th)1 activity and inducing release of Th2 cytokines. Numerous studies have confirmed that ovarian stimulation used in assisted reproduction is associated with luteal phase insufficiency, even when gonadotrophin-releasing hormone antagonists are used. In those patients, advanced endometrial histological maturity and a decrease in the concentration of cytoplasmic progesterone receptors are observed. Progesterone supplementation results in a trend towards improved ongoing and clinical pregnancy rates, except in patients treated with human menopausal gonadotrophin-only regimens, in whom ongoing pregnancy rates increase significantly. More randomized controlled trials are needed to increase the power of the currently available meta-analyses to further evaluate progesterone supplementation in both conditions.     

Mortality and major morbidity in premature infants less than 31 weeks gestational age in the decade after introduction of surfactant

OBJECTIVE: Population- but also center-based mortality and major morbidity rates of premature infants are essential for prenatal counseling and quality control. METHODS: Records of all infants <30 + 6 weeks (n=674) admitted (1991-2000) to a single neonatal intensive care unit were reviewed and compared to the state-wide mortality. RESULTS: Six hundred and ninety-one infants were born in or transferred to the hospital and 600 infants (89%) survived. The mean (SD) birth weight was 1018 g (+/-314) and the mean gestational age 27+5 weeks (+/-2.0). Mortalityand morbidity did not change significantly over the 10-year period but correlated inversely with gestational age from 45% at 23(0/7) weeks to 5% at 30(6/7) weeks. Study center mortality rate for extremely low birth weight infants with birth weight <750 g was significantly lower than reported for the entire state (local 25%; Bavaria 36% p = 0.0003). Thirty-four per cent (251/600) of the survivors had one or more major complications: intracranial hemorrhage III-IV 8% (88/600), periventricular leucomalacia 6% (41/600), bronchopulmonary dysplasia with oxygen requirement at 36 weeks 20% (128/600), necrotizing enterocolitis 6% (43/600), and retinopathy of prematurity grade III-IV 9% (55/600). Survival without major morbidity increased from 32% at 23 weeks to 92% at 30 weeks. CONCLUSIONS: Despite changes in obstetric and neonatal care during the 1990s, mortality and major morbidity rates did not change significantly after the introduction of surfactant in 1991. Comparison of local, regional, national, and international mortality and morbidity rates are becoming more important in allocating resources and in decision-making at the limits of viability.     

Reproductive outcome after laparoscopic treatment of minimal and mild endometriosis using Helica Thermal Coagulator

OBJECTIVE: To investigate the reproductive outcome following Helica Thermal Coagulator (Helica TC) in an infertile population with early-stage endometriosis. DESIGN: A clinical observational trial conducted in a NHS tertiary referral centre for treatment of endometriosis. Forty-four healthy infertile women (mean age 21 years, range 18-34 years) with laparoscopically confirmed diagnosis of minimal (stage I) or mild (stage II) endometriosis were included. All visible endometriotic lesions and adhesions were treated using Helica TC at the same time of diagnostic laparoscopy. Following laparoscopy, women attempted to conceive spontaneously and were followed for 12 months or until delivery. No hormonal therapy for endometriosis was given whatsoever. RESULTS: One woman was lost to follow-up and the remaining 43 women were considered in the final analysis. The cumulative pregnancy rate was 23.2% (10/43). All pregnancies occurred spontaneously and neither miscarriages nor ectopic pregnancies were observed. Pregnancy rate did not differ between women with stage I and those with stage II endometriosis. The time-to-pregnancy was similar in women with different stage endometriosis. No surgical complications were encountered. CONCLUSIONS: These findings suggest that Helica TC is a simple and safe conservative laparoscopic surgery for early-stage endometriosis. Helica TC appears to improve reproductive outcome in women with otherwise unexplained infertility. Large RCTs are needed to define these preliminary data.     

Chemoprevention of asbestos-linked cancers: a systematic review

Asbestos has been used extensively and, in spite of many countries having banned most of its uses, professional, domestic and environmental exposure has not ceased worldwide. Inhaled asbestos fibers can lead to malignant mesothelioma, lung cancer and non-cancerous conditions, while the substance persists indefinitely in the lung and pleural tissue, resulting in continuous damage. Exposed individuals may be offered medical surveillance or compensation, but nothing is currently being done to lower their specific cancer risk: chemoprevention seems a promising approach. A web search and a PubMed review of the literature on chemoprevention trials in individuals exposed to asbestos have been conducted. Forty-six articles on five projects were found and newly reviewed but, surprisingly, no novel trials have been set up for twenty years, although considerable advances have been gained in cancer chemoprevention. A re-consideration of possibilities offered by chemoprevention should be encouraged. New trials based on the most recently characterized molecules should be planned, taking into account specific issues such as the need for a very large number of participants and a long follow up or, alternatively, the use of biomarkers as surrogate endpoints. The long latency of asbestos related diseases may offer delayed intervention opportunities. The lack of chemoprevention trials for asbestos exposure highlights the urgent need for research in this field.     

Polycomb regulates NF-κB signaling in cancer through miRNA

The mechanisms leading to the constitutive activation of NF-κB in cancers and the pathways upstream and downstream of this activation are not fully understood. In this issue of Cancer Cell, Yamagishi et al. demonstrate that Polycomb-mediated silencing of miR-31 is implicated in the aberrant activation of NF-κB signaling in tumors.     

BCL2L10 is a predictive factor for resistance to azacitidine in MDS and AML patients

Azacitidine is the leading compound to treat patients suffering myelodysplastic syndrome (MDS) or AML with less than 30% of blasts, but a majority of patients is primary refractory or rapidly relapses under treatment. These patients have a drastically reduced life expectancy as compared to sensitive patients. Therefore identifying predictive factors for AZA resistance is of great interest to propose alternative therapeutic strategies for non-responsive patients. We generated AZA-resistant myeloid cell line (SKM1-R) that exhibited increased expression of BCL2L10 an anti-apoptotic Bcl-2 member. Importantly, BCL2L10 knockdown sensitized SKM1-R cells to AZA effect suggesting that increased BCL2L10 expression is linked to AZA resistance in SKM1-R. We next established in 77 MDS patients that resistance to AZA is significantly correlated with the percentage of MDS or AML cells expressing BCL2L10. In addition, we showed that the proportion of BCL2L10 positive bone marrow cells can predict overall survival in MDS or AML patients. We propose a convenient assay in which the percentage of BCL2L10 expressing cells as assessed by flow cytometry is predictive of whether or not a patient will become resistant to AZA. Therefore, systematic determination of BCL2L10 expression could be of great interest in newly diagnosed and AZA-treated MDS patients.