Sildenafil citrate (Viagra) impairs fertilization and early embryo development in mice

Objective: To determine the effects of sildenafil citrate, a cyclic monophosphate-specific type 5 phosphodiesterase inhibitor known to affect sperm function, on fertilization and early embryo cleavage.

Sperm DNA damage measured by the alkaline Comet assay as an independent predictor of male infertility and in vitro fertilization success

Objective: To evaluate sperm DNA fragmentation and semen parameters to diagnose male factor infertility and predict pregnancy after IVF.
Design: Prospective study.
Setting: Academic research laboratory.
Patient(s): Seventy-five couples undergoing IVF and 28 fertile donors.
Intervention(s): Sperm DNA fragmentation was measured by the alkaline Comet assay in semen and sperm after density gradient centrifugation (DGC). Binary logistic regression was used to analyze odds ratios (OR) and relative risks (RR) for IVF outcomes.
Main Outcome Measure(s): Semen parameters and sperm DNA fragmentation in semen and DGC sperm compared with fertilization rates, embryo quality, and pregnancy.
Result(s): Men with sperm DNA fragmentation at more than a diagnostic threshold of 25% had a high risk of infertility (OR: 117.33, 95% confidence interval [CI]: 12.72–2,731.84, RR: 8.75). Fertilization rates and embryo quality decreased as sperm DNA fragmentation increased in semen and DGC sperm. The risk of failure to achieve a pregnancy increased when sperm DNA fragmentation exceeded a prognostic threshold value of 52% for semen (OR: 76.00, CI: 8.69–1,714.44, RR: 4.75) and 42% for DGC sperm (OR: 24.18, CI: 2.89–522.34, RR: 2.16).
Conclusion(s): Sperm DNA testing by the alkaline Comet assay is useful for both diagnosis of male factor infertility and prediction of IVF outcome.

The effect of sperm DNA fragmentation on miscarriage rates: a systematic review and meta-analysis

STUDY QUESTION Is there an association between high levels of sperm DNA damage and miscarriage?SUMMARY ANSWERMiscarriage rates are positively correlated with sperm DNA damage levels.WHAT IS KNOWN ALREADYMost ejaculates contain a subpopulation of sperm with DNA damage, also referred to as DNA fragmentation, in the form of double or single-strand breaks which have been induced in the DNA prior to or following ejaculation. This DNA damage may be particularly elevated in some subfertile men, hence several studies have examined the link between sperm DNA damage levels and conception and miscarriage rates.STUDY DESIGN, SIZE, DURATIONA systematic review and meta-analysis of studies which examined the effect of sperm DNA damage on miscarriage rates was performed. Searches were conducted on MEDLINE, EMBASE and the Cochrane Library without any language restrictions from database inception to January 2012.PARTICIPANTS/MATERIALS, SETTING, METHODSWe used the terms 'DNA damage' or 'DNA fragmentation' combined with 'miscarriage', 'abortion' or 'pregnancy' to generate a set of relevant citations. Data extraction was performed by two reviewers. Study quality was assessed using the Newcastle-Ottawa Scale. Meta-analysis of relative risks of miscarriage was performed with a random effects model. Subgroup analyses were performed by the type of DNA damage test, whether the sperm examined were prepared or from raw semen and for pregnancies resulting from IVF or ICSI treatment.MAIN RESULTS AND THE ROLE OF CHANCEWe identified 16 cohort studies (2969 couples), 14 of which were prospective. Eight studies used acridine orange-based assays, six the TUNEL assay and two the COMET assay. Meta-analysis showed a significant increase in miscarriage in patients with high DNA damage compared with those with low DNA damage [risk ratio (RR) = 2.16 (1.54, 3.03), P <0.00001)]. A subgroup analysis showed that the miscarriage association is strongest for the TUNEL assay (RR = 3.94 (2.45, 6.32), P <0.00001).LIMITATIONS, REASONS FOR CAUTIONThere is some variation in study characteristics, including the use of different assays and different thresholds for DNA damage and the definition of pregnancy loss.WIDER IMPLICATIONS OF THE FINDINGSThe use of methods which select sperm without DNA damage for use in assisted conception treatment may reduce the risk of miscarriage. This finding indicates that assays detecting DNA damage could be considered in those suffering from recurrent pregnancy loss. Further research is necessary to study the mechanisms of DNA damage and the potential therapeutic effects of antioxidant therapy.STUDY FUNDING/COMPETING INTEREST(S)None.

Haptoglobin Phenotype, Preeclampsia and Response to Supplementation with Vitamins C and E in Pregnant Women with Type 1 Diabetes.

Objective The phenotype of the antioxidant and pro-angiogenicprotein haptoglobin (Hp) predicts cardiovascular disease risk andtreatment response to antioxidant vitamins in individuals withdiabetes. Our objective was to determine whether Hp phenotypeinfluences pre-eclampsia risk, or the efficacy of vitamins C and Ein preventing pre-eclampsia, in women with type-1 diabetes.
Design This is a secondary analysis of a randomised controlledtrial in which women with diabetes received daily vitamins C andE, or placebo, from 8 to 22 weeks of gestation until delivery.
Setting Twenty-five antenatal metabolic clinics across the UK (innorth-west England, Scotland, and Northern Ireland).
Population Pregnant women with type-1 diabetes.
Methods Hp phenotype was determined in white women whocompleted the study and had plasma samples available (n = 685).
Main outcome measure Pre-eclampsia.
Results Compared with Hp 2-1, Hp 1-1 (OR 0.59, 95% CI 0.30–1.16) and Hp 2-2 (OR 0.93, 95% CI 0.60–1.45) were notassociated with significantly decreased pre-eclampsia risk afteradjusting for treatment group and HbA1c at randomisation. Ourstudy was not powered to detect an interaction between Hpphenotype and treatment response; however, our preliminaryanalysis sugge sts that vitamins C and E did not prevent pre-eclampsia in women of any Hp phenotype (Hp 1-1, OR 0.77, 95%CI 0.22–2.71; Hp 2-1, OR 0.81, 95% CI 0.46–1.43; Hp 2-2, 0.67,95% CI 0.34–1.33), after adjusting for HbA1c at randomisation.
Conclusions The Hp phenotype did not significantly affect pre-eclampsia risk in women with type-1 diabetes.

Oxidative stress and inflammation in lean and obese subjects with polycystic ovary syndrome

To determine whether polycystic ovary syndrome (PCOS) independently influences oxidative stress and inflammation or if the culprit is the comorbidities of obesity and/or insulin resistance common to this condition.

Innovative interprofessional teaching session on labour and childbirth for undergraduate medical and midwifery students

There is an increasing recognition of the need to improve interprofessional relationships within clinical practice (Midwifery 2020, 2010). Evidence supports the assertion that healthcare professionals who are able to communicate and work effectively together and who have a mutual respect and understanding for one another’s roles will provide a higher standard of care (McPherson et al, 2001; Miers et al, 2005; Begley, 2008). The joint Royal College of Obstetrics & Gynaecologists(RCOG) / Royal College of Midwives (RCM) report (2008 Page 8) on clinical learning environment and recruitment recommended that “Inter-professional learning strategies should be introduced and supported at an early stage in the medical and midwifery undergraduate students' experience and continued throughout training.” Providing interprofessional education within a University setting offers an opportunity for a non-threatening learning environment where students can develop confidence and build collaborative working relationships with one another (Saxell et al, 2009).Further research supports the influence of effective team working on increased client satisfaction. Additionally it identifies that the integration of interprofessional learning into a curriculum improves students’ abilities to interact professionally and provides a better understanding of role identification within the workplace than students who have only been exposed to uniprofessional education (Meterko et al, 2004; Pollard and Miers, 2008; Siassakos, et al, 2009; Wilhelmsson et al, 2011; Murray-Davis et al, 2012). An interprofessional education indicative has been developed by teaching staff from the School of Nursing and Midwifery and School of Medicine at Queen’s University Belfast. The aim of the collaboration was to enhance interprofessional learning by providing an opportunity for medical students and midwifery students to interact and communicate prior to medical students undertaking their obstetrics and gynaecology placements. This has improved medical students placement experience by facilitating them to learn about the process of birth and familiarisation of the delivery suite environment and it also has the potential to enhance interprofessional relationships. Midwifery students benefit through the provision of an opportunity to teach and facilitate learning in relation to normal labour and birth and has provided them with an opportunity to build stronger and more positive relationships with another profession. This opportunity also provides a positive, confidence building forum where midwifery students utilise teaching and learning strategies which would be transferable to their professional role as registered midwives. The midwifery students were provided with an outline agenda in relation to content for the workshop, but then were allowed creative licence with regard to delivery of the workshop. The interactive workshops are undertaken within the University’s clinical education centre, utilising low fidelity simulation. The sessions are delivered 6 times per year and precede the medical students’ obstetric/gynaecology placement. All 4th year medical and final year midwifery students have an opportunity to participate. Preliminary evaluations of the workshops have been positive from both midwifery and medical students. The teaching sessions provided both midwifery and medical students with an introduction to inter professional learning and gave them an opportunity to learn about and respect each other’s roles. The midwifery students have commented on the enjoyable aspects of team working for preparing for the workshop and also the confidence gained from teaching medical students. The medical students have evaluated the teaching by midwifery students positively and felt that it lowered their anxiety levels going into the labour setting. A number of midwifery and medical students have subsequently worked with one another within the practice setting which has been recognised as beneficial. Both Schools have recognised the benefits of interprofessional education and have subsequently made a commitment to embed it within each curriculum.

Prevalence and risk of Down syndrome in monozygotic and dizygotic multiple pregnancies in Europe: implications for prenatal screening

OBJECTIVE: To determine risk of Down syndrome (DS) in multiple relative to singleton pregnancies, and compare prenatal diagnosis rates and pregnancy outcome.

DESIGN: Population-based prevalence study based on EUROCAT congenital anomaly registries.

SETTING: Eight European countries.

POPULATION: 14.8 million births 1990-2009; 2.89% multiple births.

METHODS: DS cases included livebirths, fetal deaths from 20 weeks, and terminations of pregnancy for fetal anomaly (TOPFA). Zygosity is inferred from like/unlike sex for birth denominators, and from concordance for DS cases.

MAIN OUTCOME MEASURES: Relative risk (RR) of DS per fetus/baby from multiple versus singleton pregnancies and per pregnancy in monozygotic/dizygotic versus singleton pregnancies. Proportion of prenatally diagnosed and pregnancy outcome.

STATISTICAL ANALYSIS: Poisson and logistic regression stratified for maternal age, country and time.

RESULTS: Overall, the adjusted (adj) RR of DS for fetus/babies from multiple versus singleton pregnancies was 0.58 (95% CI 0.53-0.62), similar for all maternal ages except for mothers over 44, for whom it was considerably lower. In 8.7% of twin pairs affected by DS, both co-twins were diagnosed with the condition. The adjRR of DS for monozygotic versus singleton pregnancies was 0.34 (95% CI 0.25-0.44) and for dizygotic versus singleton pregnancies 1.34 (95% CI 1.23-1.46). DS fetuses from multiple births were less likely to be prenatally diagnosed than singletons (adjOR 0.62 [95% CI 0.50-0.78]) and following diagnosis less likely to be TOPFA (adjOR 0.40 [95% CI 0.27-0.59]).

CONCLUSIONS: The risk of DS per fetus/baby is lower in multiple than singleton pregnancies. These estimates can be used for genetic counselling and prenatal screening.