First Irish delivery following sequential, two-stage embryo and blastocyst transfer.

BACKGROUND: The timing of embryo transfer (ET) after in vitro fertilisation (IVF) remains controversial, and there are no reliable guidelines available to prospectively identify which patients would benefit from either day-3 or blastocyst transfer. While blastocyst transfer is generally favoured over day-3 transfers, very few IVF patients get both in the same treatment cycle. CASE DESCRIPTION: We report on a 35.5-year-old female with tubal factor infertility who underwent IVF, which included transfer of a fresh day-3 embryo and a thawed blastocyst frozen at day 6. Transfer occurred on two separate days (days 3 and 6) in a two-stage/dual catheter fashion and resulted in a healthy term singleton livebirth. CONCLUSIONS: While combined day-3 and day-5 ET has been available elsewhere for several years, this is the first description of its successful application in Ireland and confirms the effectiveness of coordinated two-stage transfer in a single IVF treatment cycle

Lake Breezes in Southern Ontario and Their Relation to Tornado Climatology

Geostationary Operational Environmental Satellite (GOES) imagery is used to demonstrate the development of lake-breeze boundaries in southern Ontario under different synoptic conditions. The orientation of the gradient wind with respect to the shorelines is important in determining the location of such lines. When moderate winds (5–10 m s21) are parallel to straight sections of coastlines, cloud lines can extend well inland. In the region between Lakes Huron and Erie lake-breeze lines merge frequently, sometimes resulting in long-lasting stationary storms and attendant heavy rain and flooding. The influence of the lakes is apparent in the tornado climatology for the region: tornadoes appear to be suppressed in regions visited by lake-modified air and enhanced in regions favored by lake-breeze convergence lines. The cloud patterns in the case of a cold front interacting with merging lake-breeze boundaries are shown to be similar to those on a major tornado outbreak day. Two of the cases discussed are used as conceptual models to explain many of the features in the patterns of tornado touchdown locations. In general, it appears that the lakes suppress tornadoes in southern Ontario, compared with neighboring states and in particular in areas where southwest winds are onshore, but enhance tornado likelihood locally in areas of frequent lake-breeze activity. 1

Blastocyst transfer for multiple prior IVF failure: a five year descriptive study

Patients with recurrent IVF failure are generally regarded as having a poor prognosis, and when female age exceeds 35yrs such patients face a particularly bleak outlook. This study reported on blastocyst transfer (BT) performed over a five-year interval in patients seeking “second opinion” after multiple failed IVF cycles. Clinical features and reproductive outcomes were compared between two sets of poor-prognosis IVF patients undergoing BT for the first time, the initial group underwent treatment in 2002 (n=66) and a second group presented five years later (n=392). The two clinical sets had no patients in common. The 2002 group had an average of 3.5(±1.1) prior failed IVF cycles at baseline, and mean (±SD) patient age was 36.4(±3.9)yrs. Average number of oocytes retrieved in this group was 10.4(±5.3) with a fertilisation rate of 58.8%. Although embryo arrest resulted in no transfer for 19 patients (28.8%), clinical pregnancy was achieved for 59.6% of transfers. Five years later, 392 patients underwent BT, but this group had an average of 4.5(±2.3) prior failed IVF cycles. Mean (±SD) female age was 36.0(±3.9)yrs, and the average number of oocytes retrieved in this group was 9.1(±5.4); the fertilisation rate was 59.5%. No blastocysts were available for transfer in 99 cases (25.3%); clinical pregnancy was achieved for 50.0% of transfers. The number of blastocysts transferred was similar in the two groups (1.6 vs. 1.3; p=0.06); the twinning rate rose slightly from 8.2% to 15.1% (p=0.12) despite an increased utilisation of single embryo transfer in 2007 (19.7% vs. 22.2%; p=0.40). Comparisons from 2002 and 2007 found no important differences between the two patient groups, except for a significantly higher rate of prior failed cycles in the 2007 group (

The evolution of health policy guidelines for assisted reproduction in the Republic of Ireland, 2004-2009

This analysis reports on Irish regulatory policies for in vitro fertilisation (IVF) from 2004-2009, in the context of membership changes within the Medical Council of Ireland. To achieve this, the current (2009) edition of the Guide to Professional Conduct & Ethics was compared with the immediately preceding version (2004). The statutory composition of the Medical Council from 2004-2009 was also studied. Content analysis of the two editions identified the following differences: 1) The 2004 guide states that IVF "should only be used after thorough investigation has failed to reveal a treatable cause of the infertility", while the 2009 guide indicates IVF "should only be used after thorough investigation has shown that no other treatment is likely to be effective"; 2) The 2004 stipulation stating that fertilized ovum (embryo) "must be used for normal implantation and must not be deliberately destroyed" is absent from the 2009 guidelines; 3) The option to donate "unused fertilised ova" (embryos) is omitted from the 2009 guidelines; 4) The 2009 guidelines state that ART should be offered only by "suitably qualified professionals, in appropriate facilities, and according to the international best practice"; 5) The 2009 guidelines introduce criteria that donations as part of a donor programme should be "altruistic and non-commercial". These last two points represent original regulatory efforts not appearing in the 2004 edition. The Medical Practitioners Act 2007 reduced the number of physicians on the Medical Council to 6 (of 25) members. The ethical guidelines from 2004 preceded this change, while the reconstituted Medical Council published the 2009 version. Between 2004 and 2009, substantial modifications in reproductive health policy were incorporated into the Medical Council's ethical guidelines. The absence of controlling Irish legislation means that patients and IVF providers in Ireland must rely upon these guidelines by default. Our critique traces the evolution of public policy on IVF during a time when the membership of the Medical Council changed radically; reduced physician contribution to decision-making was associated with diminished protection for IVF-derived embryos in Ireland. Considerable uncertainty on IVF practice in Ireland remains

Clinical experience with intravenous immunoglobulin and tnf-a inhibitor therapies for recurrent pregnancy loss

We report on a 22 year-old non-smoking nulligravida who presented with her husband for in vitro fertilisation (IVF). She was in good general health and had five prior unsuccessful IVF treatments, all with implantation failure. While her TSH and T4 were normal, a strongly positive (1:25,600) thyroid peroxidase antibody (ATA) titre was noted. Their sixth IVF cycle included IVIG infusion x3 as had been used in the immediately preceding cycle. However, etanercept (Enbrel®; Immunex Corp., Thousand Oaks, California USA) was added for the first time as a series of 25mg subcutaneous injections commencing four weeks before ovulation induction and continued on four-day intervals thereafter. Eight etanercept injections were given until commencement of gonadotropins, and then discontinued. Two blastocysts were transferred fresh and two were frozen at day five. Following an unremarkable obstetrical course, the patient delivered male/male twins by Caesarean at 34½ weeks\u27 gestation. While the strongly positive ATA titre finding in our patient was concerning, we admitted that the mechanism of how ATA impacts reproductive outcome is presently unknown. ATA have been documented more often in women with recurrent pregnancy failure than controls, and a prospective clinical trial of women with “immunologic abortion” evaluating multiple autoimmune variables found ATA to be the most frequently encountered immunopathology—present in 53% of patients.Our case, believed to be the first published report of its kind in Ireland, is parallel with those who have described a highly-circumscribed use of immunomodulators for refractory cases where an immune diathesis exists and given only under closely monitored conditions. While immunomodulators are inappropriate in IVF for unselected populations and should not be regarded as first-line therapy, dampening of immune responses antagonistic to implantation and embryo development may be a derivative of IVIG + etanercept therapy. Should our patient decide to enlarge her family and return for transfer of cryopreserved embryos in future, the role of further immunomodulator treatment will require consideration

A pharmacogenomic assessment of psychiatric adverse drug reactions to levetiracetam

OBJECTIVE: Levetiracetam (LEV) is an effective anti-seizure medicine, but 10-20% of people treated with LEV report psychiatric side-effects and up to 1% may have psychotic episodes. Pharmacogenomic predictors of these adverse drug reactions (ADRs) have yet to be identified. We sought to determine the contribution of both common and rare genetic variation to psychiatric and behavioural ADRs associated with LEV. METHODS: This case-control study compared cases of LEV-associated behavioural disorder (n=149) or psychotic reaction (n=37) to LEV-exposed people with no history of psychiatric ADRs (n=920). All samples were of European ancestry. We performed GWAS analysis comparing those with LEV ADRs to controls. We estimated the polygenic risk scores (PRS) for schizophrenia and compared cases with LEV-associated psychotic reaction to controls. Rare variant burden analysis was performed using exome sequence data of cases with psychotic reactions (n=18) and controls (n=122). RESULTS: Univariate GWAS found no significant associations with either LEV-ADR. PRS analysis showed that cases of LEV-associated psychotic reaction had an increased PRS for schizophrenia relative to controls (p = 0.0097, estimate = 0.4886). The rare-variant analysis found no evidence of an increased burden of rare genetic variants in people who had experienced LEV-associated psychotic reaction relative to controls. SIGNIFICANCE: The polygenic burden for schizophrenia is a risk factor for LEV-associated psychotic reaction. To assess the clinical utility of PRS as a predictor, it should be tested in an independent and ideally prospective cohort. Larger sample sizes are required for the identification of significant univariate common genetic signals or rare genetic signals associated with psychiatric LEV-ADRs

IVF for premature ovarian failure: first reported births using oocytes donated from a twin sister

BACKGROUND: Premature ovarian failure (POF) remains a clinically challenging entity because in vitro fertilisation (IVF) with donor oocytes is currently the only treatment known to be effective. METHODS: A 33 year-old nulligravid patient with a normal karyotype was diagnosed with POF; she had a history of failed fertility treatments and had an elevated serum FSH (42 mIU/ml). Oocytes donated by her dizygotic twin sister were used for IVF. The donor had already completed a successful pregnancy herself and subsequently produced a total of 10 oocytes after a combined FSH/LH superovulation regime. These eggs were fertilised with sperm from the recipient\u27s husband via intracytoplasmic injection and two fresh embryos were transferred to the recipient on day three. RESULTS: A healthy twin pregnancy resulted from IVF; two boys were delivered by caesarean section at 39 weeks\u27 gestation. Additionally, four embryos were cryopreserved for the recipient\u27s future use. The sister-donor achieved another natural pregnancy six months after oocyte retrieval, resulting in a healthy singleton delivery. CONCLUSION: POF is believed to affect approximately 1% of reproductive age females, and POF patients with a sister who can be an oocyte donor for IVF are rare. Most such IVF patients will conceive from treatment using oocytes from an anonymous oocyte donor. This is the first report of births following sister-donor oocyte IVF in Ireland. Indeed, while sister-donor IVF has been successfully undertaken by IVF units elsewhere, this is the only known case where oocyte donation involved twin sisters. As with all types of donor gamete therapy, pre-treatment counselling is important in the circumstance of sister oocyte donation

Statements of Agreement From the Targeted Evaluation and Active Management (TEAM) Approaches to Treating Concussion Meeting Held in Pittsburgh, October 15-16, 2015

Conventional management for concussion involves prescribed rest and progressive return to activity. Recent evidence challenges this notion and suggests that active approaches may be effective for some patients. Previous concussion consensus statements provide limited guidance regarding active treatment

Chemical Abundances along the 1G Sequence of the Chromosome Maps: The Globular Cluster NGC 3201

The Hubble Space Telescope (HST) UV Legacy Survey of Galactic Globular Clusters (GCs) has investigated multiple stellar populations by means of the “chromosome map” (ChM) diagnostic tool that maximizes the separation between stars with different chemical compositions. One of the most challenging features revealed by ChM analysis is the apparent inhomogeneity among stars belonging to the first population, a phenomenon largely attributed to He variations. However, this explanation is not supported by uniformity in the p-capture elements of these stars. The HST survey has revealed that the GC NGC 3201 shows exceptionally wide coverage in the DF275W,F814W parameter of the ChM. We present a chemical abundance analysis of 24 elements in 18 giants belonging to the first population of this GC and having a wide range in DF275W,F814W. As far as the p-capture elements are concerned, the chemical abundances are typical of first-generation (1G) stars, as expected from the location of our targets in the ChM. Based on radial velocities and chemical abundance arguments, we find that the three stars with the lowest DF275W,F814W values are binary candidates. This suggests that at least those stars could be explained with binarity. These results are consistent with evidence inferred from multiband photometry that evolved blue stragglers (BSs) populate the bluest part of the 1G sequence in the ChM. The remaining 15 spectroscopic targets show a small range in the overall metallicity by ∼0.10 dex, with stars at higher DF275W,F814W values having higher absolute abundances. We suggest that a small variation in metals and binarity governs the color spread of the 1G in the ChM and that evolved BSs contribute to the bluest tail of the 1G sequence.This work has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research innovation program (grant agreement ERC-StG 2016, No. 716082 “GALFOR,” PI: Milone) and the European Union’s Horizon 2020 research and innovation program under Marie Skłodowska-Curie grant agreement No. 797100. A.P.M. and M.T. acknowledge support from MIUR through the FARE project R164RM93XW “SEMPLICE.” H.J. acknowledges support by the Australian Research Council through the Discovery Project DP150100862

Consensus Statement on Concussion in Sportâ The 4th International Conference on Concussion in Sport Held in Zurich, November 2012

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147044/1/pmr2255.pd