Previous Treatment Cycles Research Articles

30-day mortality after systemic anticancer treatment for breast and lung cancer in England: a population-based, observational study

SummaryBackground30-day mortality might be a useful indicator of avoidable harm to patients from systemic anticancer treatments, but data for this indicator are limited. The Systemic Anti-Cancer Therapy (SACT) dataset collated by Public Health England allows the assessment of factors affecting 30-day mortality in a national patient population. The aim of this first study based on the SACT dataset was to establish national 30-day mortality benchmarks for breast and lung cancer patients receiving SACT in England, and to start to identify where patient care could be improved.MethodsIn this population-based study, we included all women with breast cancer and all men and women with lung cancer residing in England, who were 24 years or older and who started a cycle of SACT in 2014 irrespective of the number of previous treatment cycles or programmes, and irrespective of their position within the disease trajectory. We calculated 30-day mortality after the most recent cycle of SACT for those patients. We did logistic regression analyses, adjusting for relevant factors, to examine whether patient, tumour, or treatment-related factors were associated with the risk of 30-day mortality. For each cancer type and intent, we calculated 30-day mortality rates and patient volume at the hospital trust level, and contrasted these in a funnel plot.FindingsBetween Jan 1, and Dec, 31, 2014, we included 23 228 patients with breast cancer and 9634 patients with non-small cell lung cancer (NSCLC) in our regression and trust-level analyses. 30-day mortality increased with age for both patients with breast cancer and patients with NSCLC treated with curative intent, and decreased with age for patients receiving palliative SACT (breast curative: odds ratio [OR] 1·085, 99% CI 1·040–1·132; p<0·0001; NSCLC curative: 1·045, 1·013–1·079; p=0·00033; breast palliative: 0·987, 0·977–0·996; p=0·00034; NSCLC palliative: 0·987, 0·976–0·998; p=0·0015). 30-day mortality was also significantly higher for patients receiving their first reported curative or palliative SACT versus those who received SACT previously (breast palliative: OR 2·326 99% CI 1·634–3·312; p<0·0001; NSCLC curative: 3·371, 1·554–7·316; p<0·0001; NSCLC palliative: 2·667, 2·109–3·373; p<0·0001), and for patients with worse general wellbeing (performance status 2–4) versus those who were generally well (breast curative: 6·057, 1·333–27·513; p=0·0021; breast palliative: 6·241, 4·180–9·319; p<0·0001; NSCLC palliative: 3·384, 2·276–5·032; p<0·0001). We identified trusts with mortality rates in excess of the 95% control limits; this included seven for curative breast cancer, four for palliative breast cancer, five for curative NSCLC, and seven for palliative NSCLC.InterpretationOur findings show that several factors affect the risk of early mortality of breast and lung cancer patients in England and that some groups are at a substantially increased risk of 30-day mortality. The identification of hospitals with significantly higher 30-day mortality rates should promote review of clinical decision making in these hospitals. Furthermore, our results highlight the importance of collecting routine data beyond clinical trials to better understand the factors placing patients at higher risk of 30-day mortality, and ultimately improve clinical decision making. Our insights into the factors affecting risk of 30-day mortality will help treating clinicians and their patients predict the balance of harms and benefits associated with SACT.FundingPublic Health England.

Oocyte competence in invitro fertilization and intracytoplasmic sperm injection patients suffering from endometriosis and its possible association with subsequent treatment outcome: a matched case-control study.

Endometriosis affects up to 15% of women of reproductive age. There is an obvious lack of studies dealing with morphological parameters of oocyte morphology in endometriosis patients in assisted reproduction. One aim of the study is to describe oocyte morphology in patients undergoing intracytoplasmic sperm injection suffering from endometriosis. In addition, the impact of endometriosis on invitro fertilization results is analyzed. Both invitro fertilization and intracytoplasmic sperm injection patients are then matched with an endometriosis-free control group for highlighting the possible association of endometriosis with pregnancy outcome. Oocyte morphology of endometriosis patients was assessed in two groups. Both study group and control group consisted of 129 invitro fertilization/intracytoplasmic sperm injection cycles each. Patients were matched according to anti-Müllerian hormone, female age, previous treatment cycles, and method of fertilization. Endometriosis was graded according to the revised American Society for Reproductive Medicine guidelines of 1997. Patients with endometriosis had a significantly lower rate of mature oocytes (p<0.03) and morphologically normal oocytes (p<0.001). In particular, brownish oocytes (p<0.009; stage I-IV) and the presence of refractile bodies (p<0.001; stage IV) were found to be increased. Endometriosis stage IV was associated with significantly worse-quality oocytes than stages I-III (p<0.01). Fertilization was significantly reduced in conventional invitro fertilization but not in intracytoplasmic sperm injection (p<0.03). This was due to lower fertilization rates in stage III-IV endometriosis compared with stage I-II (p<0.04). No difference was observed with respect to rates of implantation, clinical pregnancy, miscarriage, live birth, and malformation. Endometriosis patients, in particular those with severe endometriosis, present lower-quality oocytes. Once fertilized, no impairment of further preimplantation embryo development and pregnancy outcome right up to healthy live birth rate has to be expected.

MP74-08 REAL-WORLD CLEAN INTERMITTENT CATHETERIZATION RATES AFTER TREATMENT WITH ONABOTULINUMTOXINA IN PATIENTS WITH OVERACTIVE BLADDER

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction I1 Apr 2016MP74-08 REAL-WORLD CLEAN INTERMITTENT CATHETERIZATION RATES AFTER TREATMENT WITH ONABOTULINUMTOXINA IN PATIENTS WITH OVERACTIVE BLADDER Michael Kennelly, Lonny Green, Nancy Fathali, Salim Wehbe, John Joseph Smith, Scott MacDiarmid, Jeffrey Mangel, Marc Schwartz, Tamer Aboushwareb, and Brian Murray Michael KennellyMichael Kennelly More articles by this author , Lonny GreenLonny Green More articles by this author , Nancy FathaliNancy Fathali More articles by this author , Salim WehbeSalim Wehbe More articles by this author , John Joseph SmithJohn Joseph Smith More articles by this author , Scott MacDiarmidScott MacDiarmid More articles by this author , Jeffrey MangelJeffrey Mangel More articles by this author , Marc SchwartzMarc Schwartz More articles by this author , Tamer AboushwarebTamer Aboushwareb More articles by this author , and Brian MurrayBrian Murray More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1705AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Previous randomized controlled trials (RCTs) have reported a 5.0-6.5% incidence of clean intermittent catheterization (CIC) following treatment with onabotulinumtoxinA (onabotA) in patients with overactive bladder (OAB) who were inadequately managed by ≥1 anticholinergic. Retrospective studies with onabotA have reported a higher incidence of CIC. Our goal was to evaluate CIC rates in OAB patients undergoing onabotA treatment in real-world clinical practice with evidence-based exclusion criteria from the RCTs. In a multicenter retrospective chart review, we assessed the rate of voiding dysfunction requiring CIC and the effect of injection technique on the need for CIC. METHODS Patients received onabotA 100U (approved dose) or 200U treatments, administered by experienced injectors, for OAB symptoms between January 2013 and June 2015. As in the onabotA RCTs, patients using CIC or an indwelling catheter for ≥24 hours for voiding dysfunction prior to onabotA injections were excluded. The primary outcome was post-treatment CIC use (lasting >24 hours; based on individual physician's discretion). CIC rates were analyzed by 1st (n=143), 2nd (n=63), and 3rd (n=25) onabotA treatments. Potential baseline predictors of CIC initiation (history of pelvic prolapse, cystocele, diabetes, post-void residual [PVR] urine volume and age) were assessed using a multivariable logistic regression analysis. RESULTS This interim analysis comprised 143 patients; mean age was 66.7 years. CIC was initiated in 2.1% (3/143) of the patients in treatment cycle 1; these CIC patients received the 100U dose. The de novo CIC rate was 2.4% (2/85 patients) in treatment cycles 2 and 3 combined; 3 patients were censored from analysis due to CIC initiation in previous treatment cycles. Overall, 7 CIC events occurred in 5 patients across all treatments (2 patients used CIC in 2 treatment cycles); 4 events had PVR urine volume of 200 to <350 mL, and 3 had PVR >350 mL. None of the baseline characteristics were found to be significant predictors of CIC initiation. CONCLUSIONS In this real-world study of OAB patients treated with onabotA, the incidence of CIC was lower than the rates reported in previous studies, including the onabotA RCTs. There were no significant correlations between baseline characteristics and CIC initiation, although statistical significance may not have been reached due to the low incidence of CIC. Analysis of additional patients and the effect of injection technique on CIC use is ongoing and will be presented. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e972 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Michael Kennelly More articles by this author Lonny Green More articles by this author Nancy Fathali More articles by this author Salim Wehbe More articles by this author John Joseph Smith More articles by this author Scott MacDiarmid More articles by this author Jeffrey Mangel More articles by this author Marc Schwartz More articles by this author Tamer Aboushwareb More articles by this author Brian Murray More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Does age of the sperm donor influence live birth outcome in assisted reproduction?

Does age of the sperm donor have an effect on reproductive outcomes (live birth rate and miscarriage occurrence) of donor insemination or in vitro fertilization treatment using donated sperm? Live birth and miscarriage occurrence in assisted reproduction treatment using donor sperms was not found to be affected by the age of sperm donors up to 45 years old. Literature on the effect of sperm donor age on outcome of medically assisted reproduction is scarce. Most researchers agree that semen parameters deteriorate with increasing paternal age. However, there is no substantial evidence to suggest that this deterioration adversely affects the reproductive outcomes in couples undergoing medically assisted reproduction. This retrospective cohort study analysed 46 078 first donor insemination treatments and fresh in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles using donated sperm from 1991 to 2012. The first fresh donor insemination and IVF/ICSI treatment cycles (46 078 treatment cycles) using donated sperm from the long-term anonymized data registry from 1991 to 2012 of the HFEA, the UK regulator, were analysed by the binary logistic modelling technique for association between sperm donor age and reproductive outcomes (live birth occurrence and miscarriage occurrence). The statistical package SPSS (version 21) was used for analysis and results were considered to be statistically significant if the P-value was <0.05. Of 46 078 women, 84.6% (N = 38 974) underwent donor insemination treatment and the remainder, 15.4% (N = 7104), had IVF/ICSI treatment with donor sperm. The live birth occurrence decreased with increasing female age in both treatment groups; In the donor insemination treatment group, it was 11.1% in 18-34 year old women, 8.3% in 35-37 year old women and 4.7% in 38-50 year old women. The corresponding figures in the IVF/ICSI treatment group were 28.9, 22.0 and 12.9% respectively. In each of these subgroups, no evidence of declining likelihood of live birth with increasing sperm donor age was found (P > 0.05). The miscarriage occurrence (i.e. number of miscarriages per 100 women commencing treatment) was 1.3% in 18-34 year old women, 1.9% in 35-37 year old women and 1.9% in 38-50 year old women undergoing donor insemination treatment. In the sperm donation IVF/ICSI treatment group, these figures were 5.7, 8.4 and 6.8% respectively. The results were not suggestive of any unfavourable effect of advancing sperm donor age on the odds of miscarriage occurrence (P > 0.05). As sperm donors are a select population based on good semen indices, the generalization of results to the paternal population at large may not be possible. Although the study subgroups were controlled for female age, treatment modality and effect of previous treatment cycles, adjustments for certain potential compounding factors, such as smoking status, BMI of women and stimulation protocol used in IVF/ICSI treatment cycles, were not possible. Live birth and miscarriage occurrence following assisted reproduction weren't adversely affected by increasing sperm donor age up to 45 years. In view of the increasing demand for donor sperm, further studies may be required to ascertain the safe upper age limit for sperm donors. No funding was received from any individual or funding agency. NG was on a Commonwealth Scholarship for the duration of the study. The authors do not have any conflicts of interest to declare.

Does infertility history affect the emotional adjustment of couples undergoing assisted reproduction? the mediating role of the importance of parenthood.

ObjectivesThe emotional adjustment of couples undergoing assisted reproductive technology (ART) treatments has been widely studied; however, it remains unclear whether infertility history contributes to couples' adjustment. This study examined the impact of infertility history (duration of infertility and number of previous ART treatment cycles) on the emotional adjustment of couples undergoing an ART cycle and the mediating effect of importance of parenthood on that association.MethodsIn this cross‐sectional study, 70 infertile couples (70 women and 70 men) completed self‐report questionnaires assessing emotional adjustment and infertility stress during the hormonal stimulation phase of an ART cycle. Path models accounting for the dyadic nature of the data examined the direct and indirect effects (by affecting representations about parenthood and childlessness) of infertility history on emotional adjustment.ResultsThe number of previous cycles affected men's, but not women's, emotional adjustment by affecting the representations on the importance of parenthood and of childlessness. Duration of infertility had the opposite effect, as couples with longer infertility reported heightened importance of parenthood, which negatively affected their emotional adjustment.ConclusionsInfertility history was associated with emotional adjustment in men and women, although these associations were complex. The results suggest that progression through treatment is harder for those men and women who attribute higher importance to being parents, which is aggravated by longer infertility. Statement of contribution What is already known about the subject? Infertility is an unexpected and stressful life eventAssisted reproductive treatments (ART) are emotionally demanding What does this study add? The influence of infertility history on adjustment is mediated by the importance of parenthoodMen and women are affected by their past history of infertility differently

The need to improve patient care through discriminate use of intracytoplasmic sperm injection (ICSI) and improved understanding of spermatozoa, oocyte and embryo biology

D. T. Carrell, A. Nyboe Andersen and D. J. Lamb Departments of Surgery (Urology), Obstetrics and Gynecology, and Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, USA, The Fertility Clinic, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark, and The Center for Reproductive Medicine, Scott Department of Urology and the Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA

Treatment by testicular sperm extraction and intracytoplasmic sperm injection of 65 azoospermic patients with non-mosaic Klinefelter syndrome with birth of 17 healthy children.

The aim of this work was to present the clinical and embryological outcomes of 65 azoospermic patients with non-mosaic Klinefelter syndrome (KS), treated by testicular sperm extraction (TESE), followed by intracytoplasmic sperm injection (ICSI), either with fresh or cryopreserved testicular spermatozoa. In total, spermatozoa were recovered in 25/65 (38.5%) of the cases. Of the 48 patients who choose to perform TESE followed by ICSI using fresh testicular spermatozoa (treatment TESE), spermatozoa was recovered in 19 patients (40%), with birth of 12 newborn. Of the 17 patients who choose to perform TESE followed by testicular sperm cryopreservation, spermatozoa were recovered in six patients (35%), with birth of one child. Of the patients who performed treatment TESE, nine went for a new cycle using cryopreserved spermatozoa. Of these, five patients had a previous failed treatment cycle (two patients, three newborn) and four with a previous success went for a new cycle (one patient, one newborn). Overall, the embryological and clinical rates were as follows: 52% of fertilization, 41% of blastocyst, 27% of implantation, 39% of live birth delivery and 47% of newborn. Of the 16 clinical pregnancies, 14 had a successful delivery (12 girls and 5 boys). The 17 newborns had a mean gestation time of 37.2 weeks (35.3% pre-term) and a mean newborn weight of 2781.3 g (37.5% low weight). Comparisons between cycles with fresh and frozen-thaw spermatozoa revealed higher fertilization and clinical pregnancy rates with fresh spermatozoa, with no differences regarding implantation or newborn rates. Of the 17 newborns, no abnormal karyotypes (n = 3) or numerical abnormalities in chromosomes 13, 18, 21, X and Y (n = 14) as evaluated by Multiplex Ligation-dependent Probe Amplification were observed. In conclusion, this study presents further data that reassures that men with KS have no increased risk of transmitting their genetic problem to the offspring.

Classification Issue in the IVF ICSI/ET Data Analysis: Early Treatment Outcome Prognosis

Abstract Infertility is a serious social problem. Very often the only treatment possibility are IVF methods. This study explores the possibility of outcome prediction in the early stages of treatment. The data, collected from the previous treatment cycles, were divided into four subsets, which corresponded to the selected stages of treatment. On each such subset, sophisticated data mining analysis was carried out, with appropriate imputations and classification procedures. The obtained results indicate that there is a possibility of predicting the final outcome at the beginning of treatment.

Autologous Stem Cell Collection In Lymphoma and Myeloma Patients: Single Center Analysis With Intention To Successful Mobilization and Collection Under Restricted Permission For Use Of Plerixafor

High dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplantation (HSCT) rescue is a potentially curative&consolidative therapy for advanced hematological malignancies, and it also permits the administration of higher doses of chemotherapy to overcome tumor cell resistance. In this study, our aim is to evaluate 167 consecutive myeloma (MM) and lymphoma (ML) patients referred to our center between August 2010 and May 2013. Patients data are analyzed in intent to successful hematopoietic stem cell (HSC) mobilization and collection. In our country we have limited access to plerixafor, as salvage HSC mobilizing agent, permitted only after a failed mobilization&collection trial of chemotherapy and G-CSF. Our center's policy is to collect HSC with G-CSF in all MM (exception of prolonged revlimide use and prior autologous HSCT), and non-heavily pretreated ML patients. Candidates for poor mobilization underwent first CT and G-CSF, and second line receive plerixafor. Under these circumstances 86 lymphoma patients (31 Hodgkin and 55 NHL) and 81 MM patients (F/M: 57/110, med. age 52, range 18-72) were included in this study. Nearly >15% of the patients received more than 2 cycles of chemotherapy before HSC collection. Mobilization with G-CSF as a single agent resulted in optimal CD34+ cell yield for 121 (72%) patients. In myeloma G-CSF as first line resulted with 92.7% successful HSC mobilization and collection. Overall 17 patients received plerixafor as 2nd or 3rd line, and resulted with sufficient HSC collection in 57.3%. In three cases (MM:1, ML:2) additional support with autologous bone marrow collection necessary. Only in 9 (5.3%) patients all attempts for mobilization failed including plerixafor. After any type of mobilization regimen median count for pCD34+ cells obtained was 18/mcl. Median yield of 3.3 x 106/kg CD34+ cells/kg was collected with range of 0.2-33.9x106/kg in total apheresis sessions. MM patients have significant high levels of preapheresis circulating CD34+ count in comparison to ML patients (29 vs 15, p=0.001). pCD34+ cell did not correlate with body mass index, age, underlying disease and previous treatment cycles. There is a close correlation between pCD34+ cell count and collected CD34+ cells in all types of mobilization regimens as G-CSF, chemotherapy and plerixafor (relatively; p<0.001, p=0.002 and p=0.001). Successful ASCT is achieved in 144 patients transplanted so far. Mobilization is achieved in almost all multiple myeloma patients and most of lymphoma patients with only G-CSF based regimen in our cohort. Half of patients not mobilized with G-CSF were successfully mobilized with chemotherapy and plerixafor as second or third line regimen. The restricted use of plerixafor resulted in time and expense for additional chemotherapy and collection attempt, whereas this inconvenience did not impact the success of stem mobilization and collection in our current policy within 3 years. Disclosures:No relevant conflicts of interest to declare.

Factors predicting the outcome of intrauterine insemination

Background: Intrauterine insemination (IUI) is a frequently indicated therapeutic modality in infertility and considered to be of low to moderate complexity before the application of more sophisticated assisted reproductive technologies (ART). It is simple and inexpensive treatment in which processed and concentrated motile sperm are placed directly into uterine cavity. IUI is used together with various controlled ovarian hyperstimulation (COH) protocols for many indications such as male infertility, ovulatory disorders, endometriosis and unexplained infertility. Aim of study: Is to identify the important prognostic variables contributing to the successful outcome. Patients and methods: A prospective study was carried out at Assisted Conception Unit of Basra Medical College, A total of 203 cycles were analyzed to identify prognostic factors regarding treatment outcome. The variables selected for analysis were female age, duration and etiology of infertility, sperm parameters, number of preovulatory follicles, and number of previous treatment cycles and the method of COH. Results: The overall pregnancy rate per cycle was 9.3% (19/203). Of 19 pregnancies, 68.4% resulted in live birth, 26.3% in spontaneous abortion, and 5.3% were ectopic pregnancy. The multiple pregnancy rate was 15.8 % (3 twin pregnancies). Three significant variables for successful outcome were total motile sperm count (>10x106), the method of ovarian stimulation (use of r-FSH alone being superior to Clomiphen Citrate (CC) with r-FSH and CC alone), and multifollicular response. There was a tendency to a higher pregnancy rate in women 10x106), controlled ovarian hyperstimulation (COH) with r-FSH and multifollicular response are valuable predictors for pregnancy in COH-IUI cycle.

Efficacy and safety of palonosetron as salvage treatment in the prevention of chemotherapy-induced nausea and vomiting in patients receiving low emetogenic chemotherapy (LEC)

The purpose of this study is to evaluate the efficacy and safety of intravenous (IV) palonosetron in preventing chemotherapy-induced nausea and vomiting (CINV) in patients with cancer who had incomplete control of CINV during their previous cycle of low emetogenic chemotherapy (LEC). Patients with histologically or cytologically confirmed cancer, ≥18 years of age, with a Karnofsky Performance Scale score of ≥50% who had received LEC that induced vomiting and/or at least moderate nausea during their previous treatment cycle received palonosetron 0.25 mg IV 30 min before chemotherapy. Outcomes were recorded in patient diaries over 120 h and at an end-of-study visit on days 6, 7, or 8 after LEC administration. The primary efficacy variable was the complete response rate, defined as no emetic episodes and no rescue medication at 0-24 h (acute post-chemotherapy phase), 24-120 h (delayed phase), and 0-120 h (overall). Complete responses among the intent-to-treat study population (n = 34) were recorded for 88.2 % of patients in the acute phase, 67.6% in the delayed phase, and 67.6% overall. No emetic episodes occurred in 91.2 and 79.4% of patients during the acute and delayed phases, respectively, and no nausea in 73.5 and 52.9%, respectively. Palonosetron was well tolerated; only two patients experienced treatment-related adverse events. Among the patients with cancer who had a history of CINV with LEC, palonosetron was effective in preventing CINV in both the acute and delayed post-chemotherapy phases, and was well tolerated. Randomized comparative studies in larger populations of patients receiving LEC are needed to confirm these findings.

The benefit of artificial oocyte activation is dependent on the fertilization rate in a previous treatment cycle

Following intracytoplasmic sperm injection (ICSI), some patients present low or zero fertilization rates. Artificial oocyte activation has been proposed as a suitable means to overcome this problem. This study applied artificial oocyte activation in patient cohorts with a history of no fertilization (0%, group 1), fertilization between 1 and 29% (group 2) or fertilization between 30 and 50% (group 3) in initial ICSI cycles. In the following treatment cycles, oocytes were activated after ICSI using calcium ionophore. Fertilization, pregnancy and take-home baby rates were compared with the previous cycle without activation. In group 1, fertilization rate was 41.6%, embryos for transfer were available in 82.1% of cycles, giving a clinical pregnancy rate of 18.8% and take-home baby rate of 12.8%. In group 2, despite a lower transfer rate (87.9% versus 100%, P<0.05), there were higher fertilization and clinical pregnancy rates (44.4% versus 19.3% and 31.4% versus 12.8%, respectively, P<0.05) and take-home baby rate was 24.1% versus 12.8%. In group 3, fertilization rates differed (56.1% versus 36.8%; P<0.001) but all other parameters were similar. Artificial oocyte activation has great potential especially in patients showing compromised fertilization rates below 30% after standard ICSI.Following intracytoplasmic sperm injection (ICSI), some patients present very low or even zero fertilization rates after ICSI. Artificial oocyte activation has been proposed as a suitable means to overcome this problem. We applied artificial oocyte activation in patients which presented a history either no fertilization, fertilization between 0 and 30% or fertilization between 30 and 50% in initial ICSI cycles. In the following treatment cycles, oocytes were activated after ICSI using a calcium ionophore. Fertilization, pregnancy and take-home baby rates were compared to the previous cycle without activation. For the groups with previously 0% or 1–29% fertilization, we noted higher fertilization rates and clinical pregnancy rates per embryo transfer. For the group with moderate fertilization, only fertilization rates differed but all other parameters were not significantly different. From these data we conclude that artificial oocyte activation has a great potential especially in patients which show a compromised fertilization rate below 30% in a standard ICSI cycle.

Survival of Civilian and Prisoner Drug-Sensitive, Multi- and Extensive Drug- Resistant Tuberculosis Cohorts Prospectively Followed in Russia

Objective and MethodsA long-term observational study was conducted in Samara, Russia to assess the survival and risk factors for death of a cohort of non-multidrug resistant tuberculosis (non-MDRTB) and multidrug resistant tuberculosis (MDRTB) civilian and prison patients and a civilian extensive drug-resistant tuberculosis (XDRTB) cohort.ResultsMDRTB and XDRTB rates of 54.8% and 11.1% were identified in the region. Half (50%) of MDRTB patients and the majority of non-MDRTB patients (71%) were still alive at 5 years. Over half (58%) of the patients died within two years of establishing a diagnosis of XDRTB. In the multivariate analysis, retreatment (HR = 1.61, 95%CI 1.04, 2.49) and MDRTB (HR = 1.67, 95%CI 1.17, 2.39) were significantly associated with death within the non-MDR/MDRTB cohort. The effect of age on survival was relatively small (HR = 1.01, 95%CI 1.00, 1.02). No specific factor affected survival of XDRTB patients although median survival time for HIV-infected versus HIV-negative patients from this group was shorter (185 versus 496 days). The majority of MDRTB and XDRTB strains (84% and 92% respectively) strains belonged to the Beijing family. Mutations in the rpoB (codon 531 in 81/92; 88.8%), katG (mutation S315T in 91/92, 98.9%) and inhA genes accounted for most rifampin and isoniazid resistance respectively, mutations in the QRDR region of gyrA for most fluroquinolone resistance (68/92; 73.5%).ConclusionsAlarmingly high rates of XDRTB exist. Previous TB treatment cycles and MDR were significant risk factors for mortality. XDRTB patients' survival is short especially for HIV-infected patients. Beijing family strains comprise the majority of drug-resistant strains.

A 2:1 formulation of follitropin alfa and lutropin alfa in routine clinical practice: a large, multicentre, observational study

Background. A 2:1 (150 IU:75 IU) follitropin alfa:lutropin alfa formulation has been developed. A 3-year post-marketing surveillance study is ongoing in Germany to explore the use of this formulation in routine clinical practice.Materials and methods. An 11-month interim analysis of data from assisted reproductive technology (ART) cycles only is described.Results. Data were available from 857 patients undergoing 919 cycles of ART at 19 centres. Most patients (58.7%) were aged ≥35 years, and many (41.3%) were undergoing their first ART cycle. Main reasons cited by physicians for prescribing this formulation were poor response in a previous treatment cycle (n = 303) and low basal luteinizing hormone (LH) level (n = 107). Mean (standard deviation) duration of ovarian stimulation was 10.8 (2.6) days. In 90.7% of cycles, the 2:1 formulation was administered throughout the stimulation period. Most frequent LH daily dose was 75 IU. Embryo transfer was conducted in 741 cycles; clinical pregnancy rate per transfer was 27.5%. Three cases of ovarian hyperstimulation syndrome developed in three patients (3/741 [0.4%] cycles); one required hospitalization. No other major safety events were reported.Conclusion. This interim analysis shows that use of the 2:1 formulation for ovarian stimulation during routine ART procedures is effective in achieving clinical pregnancies and is associated with a positive safety profile.

Prospective longitudinal cohort study on cumulative 5-year delivery and adoption rates among 1338 couples initiating infertility treatment

The objective was to assess crude 5-year delivery rates after assisted reproductive technology (ART) treatment, intrauterine inseminations (IUI), spontaneous conceptions (SC) and adoptions in a large infertile cohort. A prospective longitudinal survey comprised 1338 infertile couples starting public infertility programmes offering IUIs and three free ART cycles during 2000-2001. The cohort was cross-linked with the National Medical Birth Register to obtain delivery rates for all 1338 couples. More detailed data were available from 817 women responding to a 5-year follow-up questionnaire (response rate 74.7%). Fifty-seven percent (466/817) of the couples had received treatment prior to inclusion in the study with an average of 4.1+/-2.8 infertility treatments before referral. Of the 1338 couples, 69.4% had at least one delivery within 5-years of follow-up. For women <35 years 74.9% had delivered compared with 52.2% of those aged > or =35 years. The mean number of children was 1.6, and 52.1% had more than one child. Of the 817 women who provided questionnaire data, 18.2% (149/817) delivered after SC, two-thirds of these after a previous ART delivery. Adoption of a child occurred for 5.9% (48/817) of the women. Positive prognostic factors for delivery were male infertility, female age <35 years, <3 years of infertility and less than three previous treatment cycles. A crude delivery rate of 69.4% in the total population 5 years after referral to tertiary hospital centres with 6.6% deliveries after SC in the subpopulation responding to the questionnaire indicates a high efficacy of modern infertility treatments.

A phase I study of amrubicin (AMR) and irinotecan (CPT-11) in relapsed small cell lung cancer(SCLC)

13548 Background: AMR and CPT-11 have shown excellent activity in extensive small cell lung cancer (SCLC). The aim of this study was to determine the maximum tolerated dose (MTD) of amrubicin in combination with a fixed dose of CPT-11. Methods: Eligibility criteria were patients having pathologically proven SCLC, had relapsed after one or two previous chemotherapies, ECOG performance status (PS) of 0–2 and adequate organ function. Irinotecan was delivered as 50 mg/m2 on days 1 and 8, every 21 days. AMR was delivered on day 1. Doses of AMR were level 1: 80mg/ m2, level 2: 90 mg/m2 and level 3: 100 mg/ m2. Dose elevation was determined using continuous reassessment method (CRM). Tolerability was assessed after the 1st cycle. Another two cycles were conducted when disease progression or unacceptable toxicities were not observed. Results: Between June 2004 and October 2006, 18 patients were enrolled with the following characteristics: male/female, 15/3; median age, 66.3 years (range 57–61); PS 0/1/2: 4/14/0. Median number of previous treatment cycles was 5. A total of 40 courses were conducted. Grade 3/4 hematological toxicities of 1st cycle were: leukocytopenia: 67% (G3/4: 8/4); neutropenia: 89% (G3/4: 6/10), thrombocytopenia: 11% (G3/4: 1/1). Grade 3 febrile neutropenia occurred in 1 patient. Other grade 3 or greater non-hematological toxicities were observed in 4 of 40 courses (grade 3 infection in 3 courses and diarrhea in 1). In the first course, DLT was observed in 2 of 6 patients at dose level 2 (prolonged grade 4 neutropenia, febrile neutropenia), in 1 of 6 at dose level 3 (prolonged grade 4 neutropenia), Both MTD and recommended dose of amrubicin determined by CRM were 100 mg/m2 (level 3). Objective response was obtained in 4 patients (29%). Median survival time was 1.1 year and 1-yr survival rate was 68%. Conclusions: This combination was well tolerated and showed encouraging activities in SCLC. Randomized phase II trials are being planned in chemo naïve SCLC. No significant financial relationships to disclose.

Comparison of multiple dose GnRH antagonist and minidose long agonist protocols in poor responders undergoing in vitro fertilization: a randomized controlled trial

To investigate the efficacy of gonadotropin releasing hormone antagonist (GnRH) in poor responders undergoing in vitro fertilization. Ninety-six patients with poor ovarian response in previous treatment cycles were prospectively randomized into two groups. Forty-four patients were stimulated with GnRH antagonist multidose protocol and 45 patients received a standard long agonist protocol. Ovarian response was evaluated by transvaginal ultrasound and hormonal parameters. Cycle characteristics and treatment outcomes were statistically compared between groups. There was significantly reduced duration of stimulation and consumption of gonadotrophins in the antagonist group when compared to the agonist group. The estradiol concentrations on the day of human chorionic gonadotropin (hCG) injection, the number of oocytes retrieved, and the number of embryos transferred were similar for both groups. In the antagonist group, eight (18.1%) ongoing pregnancies were achieved and in the agonist group, ten (22.2%) clinical pregnancies were achieved but the difference was not statistically significant. The present study was not powered to detect clinically relevant differences between two protocols in outcomes such as pregnancy rate, with confidence.

Évaluation prospective du transfert sélectif d’un embryon : deux années d’expérience

ObjectiveMultiple embryo transfer is responsible for a high rate of multiple pregnancies (ICSI), with subsequent risks of premature birth and perinatal death. This prospective non randomized study aimed to assess the ability of an elective single-embryo transfer (eSET) policy to reduce the twin pregnancy rate, compared to a double embryo transfer (DET) approach. Patients and methodsBetween March 2005 and May 2006, 180 eligible women were proposed to benefit from an eSET transfer rather than a DET. Inclusion criteria were (i) age less than 37 years old; (ii) at least two good quality embryos available (three to five cells at day 2 or six to nine cells at day 3; less than 20% fragmentation and the absence of multinucleates blastomeres), after IVF or ICSI and (iii) no more than one previous failed treatment cycle. Outcome analysis included cycles with frozen-thawed embryo transfer (FET). ResultsAccording to patients’ decision, 107 and 73 women had an eSET (59.4%) and a DET (40.6%) respectively. No differences were found between eSET and DET groups regarding demographics and biologicals parameters. The clinical pregnancy rate (PR) per transfer was 43.9% in eSET group and 57.5% in DET group (p=0.07). The twin pregnancy rates were 0 and 14.3%, in eSET and DET groups, respectively (p=0.007). The cumulative PR per patient, including the outcome of performed FET cycles, was 63.6% in eSET group and 61.6% in DET group. In this case, the cumulative twin pregnancy rates were 2.9 and 15.6% in eSET and DET groups, respectively (p=0.02). Discussion and conclusionOur data show that in a selected population of women, transferring one fresh embryo and then, if required, one or two frozen-thawed embryos significantly reduces the twin pregnancy rate without decreasing the overall pregnancy rate. This study supports the policy of eSET in this subgroup of patients.

Patients' Return to Referring Physicians and Its Relation to Their Infertility Duration

To determine if length of patient-reported infertility prior to referral to a specialist is related to the likelihood that the patient will return to the referring physician for obstetrical care. A review of our medical record database identified 430 consecutive pregnant patients, discharged between January 1, 2003, and March 1, 2004. The name of the referring and discharge obstetrician(s), duration of infertility, prior use of clomiphene citrate, and number of previous clomiphene treatment cycles were recorded. Of the 430 patients, 305 (71%) had information about the referring and discharge obstetrician(s) and complete records regarding prior treatment. Median duration of infertility was 1.3 years (range 0.2-12 years). Fifty-five percent (167 of 305) of patients returned to their referring physician for obstetrical care. If patients were referred prior to 6 months of treatment by the referring obstetrician, 76% (35 of 46) returned. If patients were referred after 6 months to 1 year of treatment, 67% (82 of 122) returned. If after 1-2 years, 35% (33 of 94), and after more than 2 years, 40% (10 of 25) returned to their referring physician. Overall, 25% of patients (77 of 305) patients had preliminary treatment with clomiphene citrate. If the referring physician did not give the patient clomiphene citrate, 55% (128 of 232) returned to that physician; if the patient had been given one to four clomiphene cycles, 54% (37 of 69) returned, and if given more than four cycles, 25% (2 of 8) returned. Although many factors may affect a patient's decision to return to the referring doctor, patient satisfaction with the referring physician may be related to timely referral to a specialist.

A phase I study of amrubicin (AMR) and irinotecan (CPT-11) in relapsed small cell lung cancer

18181 Background: AMR and CPT-11 have shown excellent activity in extensive small cell lung cancer (SCLC). The aim of this study was to determine the maximum tolerated dose (MTD) of amrubicin in combination with a fixed dose of CPT-11. Methods: Eligibility criteria were patients having pathologically proven SCLC, had relapsed after one or two previous chemotherapies, ECOG performance status (PS) of 0–2 and adequate organ function. Irinotecan was delivered as 50 mg/m2 on days 1 and 8, every 21 days. AMR was delivered on day 1. Doses of AMR were level 1: 80mg/ m2, level 2: 90 mg/m2 and level 3: 100 mg/ m2. Dose elevation was determined using continuous reassessment method (CRM). Tolerability was assessed after the 1st cycle. Another two cycles were conducted when disease progression or unacceptable toxicities were not observed. Results: Between June 2004 and October 2006, 18 patients were enrolled with the following characteristics: male/female, 15/3; median age, 66.3 years (range 57–61); PS 0/1/2: 4/14/0. Median number of previous treatment cycles was 5. A total of 40 courses were conducted. Grade 3/4 hematological toxicities of 1st cycle were: leukocytopenia: 67% (G3/4: 8/4); neutropenia: 89% (G3/4: 6/10), thrombocytopenia: 11% (G3/4: 1/1). Grade 3 febrile neutropenia occurred in 1 patient. Other grade 3 or greater non-hematological toxicities were observed in 4 of 40 courses (grade 3 infection in 3 courses and diarrhea in 1). In the first course, DLT was observed in 2 of 6 patients at dose level 2 (prolonged grade 4 neutropenia, febrile neutropenia), in 1 of 6 at dose level 3 (prolonged grade 4 neutropenia), MTD of amrubicin were determined by CRM to be 100 mg/m2 (level 3). Objective response was obtained in 4 patients (28%). Conclusions: This combination was well tolerated and showed activities in SCLC, though hematological toxicities were rather severe. Phase II trials are being planned in chemo naïve SCLC. No significant financial relationships to disclose.