Testing a Prostate Cancer Educational Intervention in High-Burden Neighborhoods.

To better capitalize on our enhanced understanding of prostate cancer (PCa) risk factors, it is important to better understand how knowledge and attitudes contribute to ethnic disparities in PCa outcomes. The goal of this study was to test the impact of a targeted PCa educational intervention vs. a healthy lifestyle educational control intervention on levels of knowledge, concern, and intention to screen for PCa.We recruited 239 men from neighborhoods with the highest PCa burden in Philadelphia. We assigned 118 men from two of the neighborhoods to the control group 121 men from 2 other neighborhoods to the intervention group. Repeated outcome assessment measures were obtained by administering the survey at baseline, post-session, 1 month post-session, and 4 months post-session.We conducted descriptive statistics to characterize the study sample and linear mixed effect regression models to analyze the intervention's effect on the outcomes. At baseline, we observed no differences in the outcomes between the PCa-targeted intervention and healthy lifestyle control groups.We found that knowledge of PCa and intention to screen increased significantly over time for both the control and intervention groups (p ≤ 0.01 at the 4-month follow-up). In contrast, change in the level of PCa concern was only significant for the intervention group immediately post-session and at 1-month follow-up (p = 0.04 and p = 0.01, respectively).This study showed that gathering at-risk men for discussions about PCa or other health concerns may increase their PCa knowledge and intention to talk to a doctor about PCa screening.

Antithrombotic medication in cancer-associated thrombocytopenia: Current evidence and knowledge gaps.

In cancer patients, antithrombotic medications (i.e. anticoagulation or antiplatelet therapy) are frequently prescribed for prior or new indications such as venous thromboembolism or stoke prevention in atrial fibrillation. Balancing the risks of bleeding and thrombosis during periods of thrombocytopenia represents a significant challenge. Management is informed mainly by expert opinion and several recent retrospective studies on venous thromboembolism. The main management options include no change, temporarily withholding antithrombotic therapy, reducing dose, changing the regimen, and increasing the platelet transfusion threshold. Important recent advances in knowledge include the prognostic importance and apparent safety of aspirin in acute myocardial infarction and thrombocytopenia and data suggesting a low risk of recurrent venous thromboembolism in autologous stem cell transplantation patients who had anticoagulation withheld. This paper will review the literature on antithrombotic medication in thrombocytopenic patients with cancer. The significant knowledge gaps will be summarized and considerations for practice and research will be provided.

Transcriptional characteristics of different sized follicles in relation to embryo transferability: potential role of hepatocyte growth factor signalling.

STUDY HYPOTHESIS: We hypothesized that a better discrimination between follicles containing oocytes with high developmental competence and those containing oocytes with low competence, based on a combination of a follicle's size and transcriptomic signature, will provide a reliable method to predict embryonic outcome of IVF. STUDY FINDING: This study provides new insights on the impact of follicular size on oocyte quality as measured by embryonic development and demonstrates that medium follicles yield a better percentage of transferable embryos. WHAT IS KNOWN ALREADY: Although it is generally accepted that large ovarian follicles contain better eggs, other studies report that a better follicular size subdivision and a better characterization are needed. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: Individual follicles (n = 136), from a total of 33 women undergoing IVF, were aspirated and categorized on the basis of their follicular liquid volume (small, medium or large) and the embryonic outcome of the enclosed oocyte: poor or good development. Comprehensive gene expression analysis between cells from the different sized follicles was performed using microarrays and quantitative RT-PCR to find molecular markers associated with follicular maturity and oocyte developmental competence. MAIN RESULTS AND THE ROLE OF CHANCE: The analysis of embryonic outcome in relation to follicular size indicates that the medium-sized follicles category yielded more transferable embryos (35%) compared with the largest follicles (30%) (NS). Gene expression analysis revealed expression markers with significant (P < 0.05) discrimination between the poor development groups for all three follicle sizes, and good development medium-size follicles, including up-regulation of thrombomodulin, transforming growth factor, beta receptor II and chondrolecti, and those associated with hyaluronan synthesis, coagulation and hepatocyte growth factor signalling. LIMITATIONS, REASONS FOR CAUTION: These analyses were performed in a single cohort of patients coming from a single clinic and the biomarkers generated will require validation in different geographical and biological contexts to ensure their global applicability. WIDER IMPLICATIONS OF THE FINDINGS: Medium-size follicles seem to be the optimal size for a positive embryonic outcome and are associated with competence markers that may help in understanding the ideal differentiation status during late folliculogenesis. LARGE SCALE DATA: The data discussed in this publication have been deposited in The National Center for Biotechnology Information Gene Expression Omnibus database and are accessible through GEO Series accession number GSE52851. STUDY FUNDING AND COMPETING INTERESTS: This study was supported by Canadian Institutes of Health Research (CIHR) and Natural Sciences and Engineering Research Council of Canada (NSERC) to M.A.S. There are no competing interests to declare.

Advances in recombinant DNA technology: corifollitropin alfa, a hybrid molecule with sustained follicle-stimulating activity and reduced injection frequency.

BACKGROUND: Recombinant DNA technologies have been used to develop longer-acting therapeutic proteins. One approach is to introduce sequences containing additional glycosylation sites. Using this technique, a new chimeric gene has been developed containing the coding sequences of the FSH beta-subunit and the C-terminal peptide of the hCG beta-subunit, which bears four O-linked oligosaccharide binding sites. Co-expression of the alpha-subunit and the chimeric FSH beta-subunit produces a new recombinant molecule, named corifollitropin alfa, with a prolonged elimination half-life and enhanced in vivo bioactivity compared with wild-type FSH. METHODS: Medline searches by subject and additional searching by hand. RESULTS: Initial studies in pituitary suppressed female volunteers confirmed the extended half-life of the compound. Phase II studies have shown that corifollitropin alfa is able to induce and sustain multi-follicular growth for an entire week in women undergoing ovarian stimulation using GnRH antagonist co-treatment for IVF. Corifollitropin alfa regimens have been developed with dosages of 100 and 150 microg, for patients with body weight 60 kg, respectively. CONCLUSIONS: Corifollitropin alfa is the first long-acting hybrid molecule with sustained follicle-stimulating activity developed for the induction of multi-follicular growth along with GnRH antagonist co-treatment for IVF. This new treatment option may be simpler and more convenient for patients compared with conventional long protocols of daily FSH injections in combination with GnRH agonist co-treatment. The safety and efficacy of such regimens is currently being evaluated in large comparative phase III clinical trials. The development of corifollitropin alfa is the first step towards a new generation of recombinant gonadotrophins.

Paternal age and birth defects: how strong is the association?

BACKGROUND: Although the association between maternal age and the risks of birth defects has been well studied, the evidence from population data linking paternal age with birth defects was limited and inconsistent. METHODS: We conducted a population-based retrospective cohort study of 5,213,248 subjects from the 1999-2000 birth registration data of the USA. Multiple logistic regressions were used to estimate the independent effect of paternal age on all birth defects and 21 specific defects groups after adjusting for potential confounding of maternal age, race, education, marital status, parity, prenatal care initiation, maternal smoking and alcohol drinking during pregnancy. RESULTS: A total of 77,514 (1.5%) birth defects were recorded in the study cohort. The adjusted odds ratios were 1.04 (1.01, 1.06), 1.08 (1.04, 1.12), 1.08 (1.02, 1.14) and 1.15 (1.06, 1.24), respectively, for infants born to fathers 30-35, 40-44, 45-49 and over 50 years (test for trend, P = 0.0155), when compared with those infants born to fathers aged 25-29 for any birth defect. Advanced paternal age was associated with increased risks of heart defects, tracheo-oesophageal fistulaoesophageal atresia, other musculoskeletal/integumental anomalies, Down's syndrome and other chromosomal anomalies. Fathers under 25 years of age were also at increased risks of spina bifida/meningocele, microcephalus, omphalocele/gastroschisis and other musculoskeletal/integumental anomalies. CONCLUSIONS: Infants born to older fathers have a slightly increased risk of birth defects. Young paternal age is also associated with slightly increased risk of several selected birth defects in their offspring. However, given the weak association, paternal age appears to play a small role in the aetiology of birth defects.

Improved monofollicular ovulation in anovulatory or oligo-ovulatory women after a low-dose step-up protocol with weekly increments of 25 international units of follicle-stimulating hormone.

OBJECTIVE: To compare the effectiveness and efficiency of two low-dose step-up protocols for ovulation induction in women with anovulatory infertility (World Health Organization group II). DESIGN: Open-label, prospective, randomized, group-comparative, multicenter study. SETTING: Eighteen infertility centers in Europe and Canada. PATIENT(S): One hundred fifty-eight anovulatory or oligo-ovulatory infertile women. INTERVENTION(S): Patients were randomly assigned to one of two protocols for one cycle of follitropin beta (rFSH) using a pen device. The starting dosage was 50 IU/day for 7 days. In the absence of follicles > or =12 mm, the daily dosage was increased by either 25 or 50 IU per week. MAIN OUTCOME MEASURE(S): The percentage of all subjects treated who ovulated after one treatment cycle (efficacy) and the total rFSH dose to reach ovulation (efficiency). RESULT(S): The 25-IU group had a higher incidence of monofollicular growth (41.3% of 80 vs. 21.8% of 78 women) and ovulation (81.3% vs. 60.3%), a lower cumulative rFSH dose (887 IU vs. 984 IU), and fewer cancellations due to hyperresponse (>3 follicles > or =15 mm; 5.0% vs. 20.5%). Both protocols were well tolerated. CONCLUSION(S): Weekly increments of 25 IU in the daily dose were more effective and efficient than 50-IU increments.

Treatment with the GnRH antagonist ganirelix prevents premature LH rises and luteinization in stimulated intrauterine insemination: results of a double-blind, placebo-controlled, multicentre trial.

BACKGROUND: This study was designed to assess whether the use of ganirelix in women undergoing stimulated IUI could prevent the occurrence of premature LH rises and luteinization (LH+progesterone rises). METHODS: Women of infertile couples, diagnosed with unexplained or male factor infertility, were randomized to receive either ganirelix (n=103) or placebo (n=100) in a double-blind design. All women were treated with an individualized, low-dose rFSH regimen started on day 2-3 of cycle. Ganirelix (0.25 mg/day) was started if one or more follicles>or=14 mm were visualized. Ovulation was triggered by HCG injection when at least one follicle>or=18 mm was observed and a single IUI was performed 34-42 h later. The primary efficacy outcome was the incidence of premature LH rises (+/-progesterone rise). RESULTS: In the ganirelix group, four subjects had a premature LH rise (value>or=10 IU/l), one LH rise prior to the start of ganirelix and three LH rises during ganirelix treatment, whereas in the placebo group 28 subjects had a premature LH rise, six subjects prior to the start of placebo and 22 subjects during placebo treatment. The incidence of LH rises was significantly lower in ganirelix cycles compared to placebo cycles (3.9 versus 28.0%; P=0.003 for ITT analysis). When excluding subjects with an LH value>or=10 IU/l before the start of ganirelix/placebo the incidence of LH rises was also significantly lower in ganirelix cycles compared to placebo cycles (2.9 versus 23.4%; P=0.003 for ITT analysis). Premature luteinization (LH rise with concomitant progesterone rise>or=1 ng/ml) was observed in one subject in the ganirelix group and in 17 subjects in the placebo group of which three subjects had a premature spontaneous ovulation. Ongoing pregnancy rates per attempt were 12.6 and 12.0% for the ganirelix and placebo groups respectively. CONCLUSIONS: Treatment with ganirelix effectively prevents premature LH rises, luteinization in subjects undergoing stimulated IUI. Low-dose rFSH regimen combined with a GnRH antagonist may be an alternative treatment option for subjects with previous proven luteinization or in subjects who would otherwise require insemination when staff are not working.

Stroke in ovarian hyperstimulation syndrome in early pregnancy treated with intra-arterial rt-PA.

Ovarian hyperstimulation syndrome (OHSS) caused by fertility medications can predispose women to thrombosis. The authors present a case of a previously healthy woman who underwent in vitro fertilization and experienced a middle cerebral artery thrombosis that was subsequently lysed with intra-arterial recombinant tissue plasminogen activator (rt-PA). To the authors' knowledge, this is the first reported case of successful use of rt-PA to lyse a cerebral arterial thrombus resulting from severe OHSS. The patient made a near complete neurologic recovery and delivered a healthy infant at term, illustrating that intra-arterial thrombolysis can be used with relative safety even in very early pregnancy.

Sulfogalactosylglycerolipid is involved in human gamete interaction.

Recent results from our laboratory have revealed the role of sulfogalactosylglycerolipid (SGG) in mouse sperm-zona pellucida (ZP) binding. In this report, we demonstrated the presence of SGG in Percoll-gradient centrifuged (PGC) human sperm by high performance thin layer chromatography with orcinol and Azure A staining, specific for glycolipids and sulfolipids, respectively. SGG in human PGC sperm was quantified by its affinity to Azure A to be 12-15 mol% of sperm lipids. Indirect immunofluorescence revealed that SGG existed on both live and aldehyde fixed human sperm in the head region. Pretreatment of human PGC sperm with affinity purified antiSGG Fab markedly inhibited sperm binding to the ZP in a concentration dependent manner, without any changes in the spontaneous acrosome rate or sperm motility parameters. Fluorescently labeled SGG liposomes also bound uniformly to isolated human ZP, while fluorescently labeled galactosylglycerolipid (GG, SGG's parental lipid) or phosphatidylserine (PS, negatively charged like SGG) liposomes did not. All of these results suggested the role of human sperm SGG in ZP binding.

Anti-SLIP1-reactive proteins exist on human spermatozoa and are involved in zona pellucida binding.

Sulpholipid immobilizing protein 1 (SLIP1) is an evolutionarily conserved 68 kDa plasma membrane protein, present selectively in germ cells. We have previously shown that mouse sperm SLIP1 is involved in sperm-zona pellucida (ZP) binding. In this report, we extended our study to the human system. Immunoblotting demonstrated that anti-SLIP1-reactive proteins (mol. wt 68 and 48 kDa) could be extracted from human spermatozoa by an ATP-containing solution, a result that is consistent with observations in other species. Direct immunofluorescence, using Cy3-conjugated anti-SLIP1 IgG, revealed SLIP1 staining over the acrosomal region, with higher intensity at the posterior area. Using the human sperm-ZP binding assay, we demonstrated that pretreatment of human spermatozoa from three donors with anti-SLIP1 IgG revealed lower numbers of zona-bound spermatozoa, as compared to the corresponding control spermatozoa treated with normal rabbit serum IgG. This decrease in zona pellucida binding was not from an antibody-induced decline in sperm motility or an increase in the premature acrosome reaction. The results strongly suggest that anti-SLIP-reactive proteins on human spermatozoa play an important role in ZP binding.

Efficacy and safety of ganirelix acetate versus leuprolide acetate in women undergoing controlled ovarian hyperstimulation.

OBJECTIVE: To assess the efficacy, safety, and local tolerance of ganirelix acetate for the inhibition of premature luteinizing hormone (LH) surges in women undergoing controlled ovarian hyperstimulation (COH). DESIGN: Phase III, multicenter, open-label randomized trial. SETTING: In vitro fertilization (IVF) centers in North America. PATIENT(S): Healthy female partners (n = 313) in subfertile couples for whom COH and IVF or intracytoplasmic sperm injection were indicated. INTERVENTION(S): Patients were randomized to receive one COH cycle with ganirelix or the reference treatment, a long protocol of leuprolide acetate in conjunction with follitropin-beta for injection. OUTCOME MEASURE(S): Number of oocytes retrieved, pregnancy rates, endocrine variables, and safety variables. RESULT(S): The mean number of oocytes retrieved per attempt was 11.6 in the ganirelix group and 14.1 in the leuprolide group. Fertilization rates were 62.4% and 61.9% in the ganirelix and leuprolide groups, respectively, and implantation rates were 21.1% and 26.1%. Clinical and ongoing pregnancy rates per attempt were 35.4% and 30.8% in the ganirelix group and 38.4% and 36.4% in the leuprolide acetate group. Fewer moderate and severe injection site reactions were reported with ganirelix (11.9% and 0.6%) than with leuprolide (24.4% and 1.1%). CONCLUSION(S): Ganirelix is effective, safe, and well tolerated. Compared with leuprolide acetate, ganirelix therapy has a shorter duration and fewer injections but produces a similar pregnancy rate.

Lack of correlation between oocyte-corona-cumulus complex morphology and nuclear maturity of oocytes collected in stimulated cycles for intracytoplasmic sperm injection.

OBJECTIVE: To evaluate the usefulness of morphology grading of the oocyte-corona-cumulus complex (OCCC) as a marker of oocyte nuclear maturity, fertilizability, embryo cleavage, and likelihood of pregnancy. DESIGN: Prospective cohort study. SETTING: Academic fertility center. PATIENT(S): Eighty-three infertile couples undergoing IVF-ET/intracytoplasmic sperm injection treatment. INTERVENTION(S): All patients underwent a long stimulation protocol of GnRH agonist therapy followed by hMG administration and transvaginal oocyte recovery. MAIN OUTCOME MEASURE(S): All OCCCs, oocytes, and embryos were assessed. The relation among OCCC morphology and the nuclear maturity of denuded oocytes, the fertilization rate, and embryo development to the cleavage stage were analyzed. RESULT(S): Of 909 OCCCs collected from 92 cycles, 2.5%, 4.2%, 79.9%, and 13.4% were prophase I, metaphase I, metaphase II, and degenerating, respectively. No statistically significant differences were found in the percentage of intact metaphase II oocytes, the fertilization rate, or the cleavage rate among complexes with different morphologic grades. The morphologic grade of the OCCCs of transferred embryos in the pregnant group was not different from that in the nonpregnant group. CONCLUSION(S): Most oocytes were in metaphase II at the time of retrieval after ovarian stimulation. However, no relation was observed between the OCCC morphologic grade and oocyte nuclear maturity, the fertilization rate, or embryo cleavage. These observations suggest that OCCC morphology grading is a poor marker of oocyte quality.

A prospective, randomized, double-blind clinical trial to study the efficacy and efficiency of a fixed dose of recombinant follicle stimulating hormone (Puregon) in women undergoing ovarian stimulation.

A prospective, randomized, double-blind, multicentre (n = 5) study was conducted to compare the influence of either a 100 or 200 IU daily fixed-dose regimen of recombinant follicle stimulating hormone (FSH) on the number of oocytes retrieved and the total dose used in down-regulated women undergoing ovarian stimulation. Fertilization was done by intracytoplasmic sperm injection or conventional in-vitro fertilization. A total of 199 women were treated with FSH, 101 subjects with 100 IU and 98 subjects with 200 IU. In subjects of the 200 IU treatment group, significantly more oocytes were retrieved compared to the 100 IU group (10.6 versus 6.2 oocytes, P < 0.001). The total dose needed to develop at least three follicles with a diameter of > or = 17 mm was significantly lower in the 100 IU treatment group (1114 IU versus 1931 IU, P < 0.001). In the low-dose group, significantly lower serum concentrations of oestradiol, progesterone and FSH were observed at the day of human chorionic gonadotrophin administration. Although more cycle cancellations due to low response were seen in the 100 IU group (n = 24 versus n = 3), the clinical pregnancy rate per started cycle was similar (24.7% in the 100 IU group versus 23.3% in the 200 IU group). In the high-dose group, more side-effects, in particular more cases of ovarian hyperstimulation syndrome, were noted. It is concluded that compared to 200 IU, the use of a 100 IU fixed dose is less efficacious in terms of the number of oocytes retrieved, but more efficient as indicated by a lower total dose.

Hyperreactio luteinalis associated with chronic renal failure.

Hyperreactio luteinalis is a rare benign condition characterized by bilateral ovarian enlargement associated with pregnancies where high concentrations of maternal serum human chorionic gonadotrophins are present. This condition may mimic the ovarian hyperstimulation syndrome. We report a case of a 34 year old woman with a history of chronic renal failure on haemodialysis who presented at 10 weeks' gestational age with hyperreactio luteinalis which was treated conservatively. Because of chronic renal failure, the presentation and course of the disease was different from that which has been previously reported.

Uterine artery embolization--a successful treatment to control bleeding cervical pregnancy with a simultaneous intrauterine gestation.

A case of a woman suffering from a bleeding heterotopic cervical pregnancy is described. The concurrent cervical pregnancy and intrauterine gestation were diagnosed by ultrasound and bleeding was initially controlled with selective fluoroscopic uterine artery embolization. A selective fetal reduction was done with ultrasound-guided intracardiac potassium chloride. Uterine artery embolization has been used successfully to control haemorrhage in cervical pregnancies when the main goal was to allow preservation of the uterus, thus maintaining potential fertility. This is the first report of arterial embolization used to control bleeding for maintaining a concurrent intrauterine heterotopic pregnancy in an in-vitro fertilization patient. Unfortunately, subsequent conservative measures led to undesired outcome. This procedure initially controlled the bleeding without disrupting the intrauterine fetal cardiac activity.

An allergic reaction following intrauterine insemination.

Intrauterine insemination is a common procedure used for the treatment of different causes of infertility. Adverse reactions associated with this procedure are very rare and usually the procedure is well tolerated by the patient. We report a case of an allergic reaction after intrauterine insemination. The patient developed fever, difficulty breathing and wheezing in both lung fields. Although a low concentration of penicillin in the medium was used, it caused a significant allergic reaction. When intrauterine insemination was performed in subsequent cycles with an antibiotic-free medium, no allergic reaction occurred, and the procedure was well tolerated by the patient. A careful allergy history is essential in patients pursuing infertility treatment where antibiotics are utilized. Patients who are known to be allergic to penicillin should have semen prepared by an antibiotic-free medium.

A novel approach to the treatment of ascites associated with ovarian hyperstimulation syndrome.

Ascites is a clinical manifestation of severe ovarian hyperstimulation syndrome (OHSS) which may complicate the induction of ovulation using exogenous gonadotrophins. In severe OHSS severe ascites may occur and can lead to dyspnoea, abdominal discomfort and oliguria. To relieve ascites paracentesis is performed two to three times weekly as needed. We report three cases where an indwelling peritoneal catheter was used to decrease the need for repeated paracentesis. Under ultrasound guidance a closed system Dawson-Mueller catheter with 'simp-loc' locking design was inserted to allow continuous drainage of the ascitic fluid. A total of 23 l of the ascitic fluid were drained from the first, 20 l from the second and 28 l from the third patient with significant decrease in abdominal discomfort and improvement in the urine output. No complications or adverse reactions were noted. Continuous drainage of the ascitic fluid is efficient. It quickly decreases the abdominal discomfort, improves the urine output and prevents the need for multiple abdominal paracenteses which some patients may require.