Cardiovascular disease risk prediction in scleroderma

SUMMARY OBJECTIVE: Cardiovascular disease risk prediction in scleroderma is important. In this study of scleroderma patients, the aim was to investigate the relationship between cardiac myosin-binding protein-C, sensitive troponin T, and trimethylamine N-oxide and cardiovascular disease risk with the Systematic COronary Risk Evaluation 2 model of the European Society of Cardiology. METHODS: Systematic COronary Risk Evaluation 2 risk groups of 38 healthy controls and 52 women with scleroderma were evaluated. Cardiac myosin-binding protein-C, sensitive troponin T, and trimethylamine N-oxide levels were analyzed with commercial ELISA kits. RESULTS: In scleroderma patients, cardiac myosin-binding protein-C and trimethylamine N-oxide levels were higher than healthy controls but sensitive troponin T was not (p<0.001, p<0.001, and p=0.274, respectively). Out of 52 patients, 36 (69.2%) were at low risk, and the other 16 (30.8%) patients were at high-moderate risk with the Systematic COronary Risk Evaluation 2 model. At the optimal cutoff values, trimethylamine N-oxide could discriminate high-moderate risk with sensitivity 76%, specificity 86% and cardiac myosin-binding protein-C with sensitivity 75%, specificity 83%. Patients with high trimethylamine N-oxide levels (≥10.28 ng/mL) could predict high-moderate- Systematic COronary Risk Evaluation 2 risk 15 times higher than those with low trimethylamine N-oxide (<10.28 ng/mL) levels (odds ratio [OR]: 15.00, 95%CI 3.585-62.765, p<0.001). Similarly, high cardiac myosin-binding protein-C (≥8.29 ng/mL) levels could predict significantly higher Systematic COronary Risk Evaluation 2 risk than low cardiac myosin-binding protein-C (<8.29 ng/mL) levels (OR: 11.00, 95%CI 2.786-43.430). CONCLUSION: Noninvasive cardiovascular disease risk prediction indicators in scleroderma, cardiac myosin-binding protein-C, and trimethylamine N-oxide could be recommended to distinguish between high-moderate risk and low risk with the Systematic COronary Risk Evaluation 2 model.

Psoriasis and family history of psoriasis may not affect disease severity of rheumatoid arthritis.

The incidence of psoriasis in patients with rheumatoid arthritis (RA) is higher than in the general population. In addition, psoriasis may negatively affect the severity of rheumatological diseases in patients with autoinflammatory or autoimmune diseases. In this study, we evaluated the effect of psoriasis or a family history of psoriasis on the characteristics of RA. This is a cross-sectional study. We included 737 RA patients who met the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) RA Classification Criteria, but did not meet the CASPAR psoriatic arthritis criteria. Subsequently, we compared disease activity, the need for biologic therapy, the number of conventional synthetic disease-modifying anti-rheumatic drugs taken, the frequency of erosive disease and extra-articular involvement, glucocorticoid doses and the Stanford Health Assessment Questionnaire scores between patients with and without a history of psoriasis, and patients with and without a family history of psoriasis. Thirteen (1.8%) patients had psoriasis, while 58 (7.9%) had a family history of psoriasis in first- or seconddegree relatives. All outcome parameters were found to be similar between the groups. We show that concomitant psoriasis has no effect on the evaluated disease characteristics of RA.

A case of chronic lymphocytic leukemia still taking etanercept for ankylosing spondylitis.

The possible risk of hematologic malignancies in anti TNF users is a matter of debate. Whether associated with the drug or not, how to behave when a hematologic malignancy is discovered in the course of anti TNF treatment remains unanswered. Here we present a 66 year old male patient who had AS for 30 years and had been on etanercept for the last two years and who is diagnosed with B cell chronic lymphocytic leukemia (CLL) stage 1. The patient is still on etanercept for 5 years after the diagnosis without any progression in CLL.

Successful preimplantation genetic aneuploidy screening in Turkish patients.

Preimplantation genetic diagnosis is a preventive approach for identifying genetic abnormalities in early stages of reproduction. We used preimplantation genetic aneuploidy screening in 230 cycles of patients with indications of advanced maternal age, recurrent implantation failure, recurrent spontaneous abortions, or severe male factor. Biopsied blastomeres from embryos with six to eight blastomeres on day 3 were fixed and fluorescence in situ hybridization was utilized on chromosomes 13, 16, 18, 21, 22, X, and Y. Among 945 morphologically normal embryos, 314 were diagnosed as chromosomally normal. Trisomy and monosomy were observed in 36% of the cases (18% each). Embryo transfer was used in 144 cycles, resulting in 41 pregnancies. Thirty-seven healthy babies were delivered, with a take-home baby rate of 24.2% and an implantation rate of 22%. We recommend preimplantation genetic aneuploidy screening as a valuable technique to select normal chromosome embryos in order to avoid multiple pregnancies due to the multiple embryo transfers that are normally necessary to ensure pregnancy in poor prognosis in vitro fertilization patients.

Luteal phase empirical low molecular weight heparin administration in patients with failed ICSI embryo transfer cycles: a randomized open-labeled pilot trial.

BACKGROUND: The pathology underlying recurrent implantation failures (RIF) is not clear and treatment options proposed are generally not evidence based. Although the effect of heparin on trophoblast biology has not been studied extensively, given the available data suggesting a possible beneficial effect of heparin on embryo implantation, we decided to undertake this pilot study. METHODS: One hundred and fifty women with > or =2 failed assisted reproduction treatment cycles were included in this randomized open-label pilot trial. Participants underwent controlled ovarian stimulation with the long protocol and were randomly allocated to receive 1 mg/kg/day low molecular weight heparin (LMWH) or no treatment in addition to routine luteal phase support (LPS) on the day after oocyte retrieval. LPS and LMWH was continued up to the 12th gestational week in pregnant participants. RESULTS: There were 26 (34.7%) live births in the LMWH group, and 20 (26.7%) in the control group (absolute difference 8.0%, 95% CI -4.2 to 24.9%, P = 0.29). There were 34 (45.3%) and 29 (38.7%) clinical pregnancies in the LMWH and control groups, respectively (absolute difference 6.6%, 95% CI -9.0 to 21.8%, P = 0.41). Implantation rates were 24.5 and 19.8% in the LMWH and control groups, respectively (absolute difference 4.7%, 95% CI -4.7 to 14.1%, P = 0.33). CONCLUSION: Despite lack of statistical significance, observed relative increase by 30% in live birth rates with LMWH may be regarded as a clinically significant trend necessitating further research on the use of empirical LMWH in women with RIF and possibly in all women undergoing assisted reproduction treatment. Failure to demonstrate statistical significance of the observed treatment difference may be due to limited sample size of this pilot study.

Does hepatitis C virus infection increase hematocrit and hemoglobin levels in hemodialyzed patients?

OBJECTIVE: Some case reports indicated that red cell status increased after hepatitis C viral infection. The aim of study was to define the influence of hepatitis C infection (HCV) on red cell status in hemodialyzed patients. MATERIALS AND METHODS: A total of 49 (21 anti-HCV-positive and 28 anti-HCV-negative) patients with ESRD were included in this study. Exclusion criteria were blood transfusion and massive blood loss in the last 6 months preceding the study. None of the patients used any drug containing aluminum. RESULTS: The prevalence of anti-HCV antibody was 42.8%. Mean age was 51.6 +/- 14.3 in anti-HCV (+) group and 50.4 +/- 17.0 in anti-HCV (-) group. There was no statistically significant difference between the ages of the 2 groups. Mean duration time of hemodialysis was significantly longer in patients with anti-HCV antibody (+) group (54.9 +/- 34.2 months) compared to anti-HCV-negative group (12.5 +/- 9.0 months) (p < 0.001). Mean hemoglobin (Hb) and hematocrit (Htc) levels were significantly higher in anti-HCV-positive patients than in anti-HCV-negative patients (Hb: 10.4 +/- 1.8 g/dl, Htc: 30.5 +/- 5.5% vs Hb: 8.8 +/- 1.7 g/dl, Htc: 26.1 +/- 5.3%) (for Hb p < 0.005, for Htc p < 0.007). There was no significant difference regarding the usage ofrHuEPO between the 2 study groups (57.1% in anti-HCV antibody (+)/59.3% in anti-HCV antibody (-)) (p > 0.05). All patients not receiving rHuEPO did so because of economical reasons. Serum AST and ALT levels were significantly higher in the anti-HCV antibody-positive group compared with the anti-HCV antibody-negative group. (AST p < 0.04, ALT p < 0.04). CONCLUSION: Anti-HCV antibody-positive ESRD patients have higher hemoglobin and hematocrit levels compared to HCV-negative patients.

The effect of pronuclear morphology on embryo quality parameters and blastocyst transfer outcome.

BACKGROUND: Embryo quality may be accurately assessed as early as the pronuclear zygote phase, as shown in recent studies. However, it is not known whether good quality zygotes are destined to become good quality cleavage stage embryos and blastocysts. METHODS: In this retrospective study, 86 intracytoplasmic sperm injection-embryo transfer cycles were studied where each available embryo was scored from the zygote until the blastocyst stage. Embryonic normality parameters such as pronuclear pattern, early cleavage, cleavage stage embryo grade, the presence of embryos with > or =8 cells on day 3 and blastocyst quality were recorded. Embryo transfer was undertaken at the blastocyst stage and the outcome was studied according to the pronuclear pattern exhibited by the zygotes. RESULTS: Embryos that showed an ideal pronuclear pattern (0 PN pattern) cleaved earlier and faster and resulted in better quality cleavage stage embryos and blastocysts. The incidence of blastocyst formation was 72% in zygotes showing a 0 PN pattern, compared with 12.7% in zygotes with double pronuclear abnormality. Higher implantation and pregnancy rates were obtained when at least one blastocyst derived from a 0 PN pattern zygote was included in the set of embryos to be transferred. CONCLUSIONS: Our results indicate that the pronuclear pattern of the zygote is closely related to blastocyst formation and quality. Blastocysts derived from 0 PN zygotes have a higher potential for implantation.

Blastocyst-stage transfer of poor-quality cleavage-stage embryos results in higher implantation rates.

OBJECTIVE: To determine the feasibility and success of blastocyst-stage embryo transfers in patients having only fair and poor quality cleavage-stage embryos on day 3. DESIGN: Prospective case study with historic controls. SETTING: Tertiary care private hospital IVF center. PATIENT(S): A total of 158 day 5 embryo transfer cycles in patients with grade 3 and grade 4 cleavage-stage embryos. Control group consisted of 162 day 3 transfer cycles performed with embryos of similar quality. INTERVENTION(S): In vitro culture of embryos up to the blastocyst stage. MAIN OUTCOME MEASURE(S): The percentage of cycles that culminated in the transfer of at least one blastocyst and implantation and pregnancy rate related to the day of transfer. RESULT(S): In the day 3 transfer group, a mean of 5.2 embryos were replaced per patient. This was significantly more than the mean of 2.4 embryos that could be replaced on day 5 (P <.001). The clinical pregnancy rate per embryo transfer was 27.2% and 33.5% in the two groups, respectively (P >.05). The implantation rate per embryo was significantly higher in the day 5 transfer group (15% vs. 5.9%). The multiple pregnancy and abortion rates were similar between the groups. CONCLUSION(S): Transfer of fair and poor quality embryos at the blastocyst stage is feasible and is associated with higher implantation rates as compared to transfer of similar quality embryos on day 3.

Blastocyst transfer following intracytoplasmic injection of ejaculated, epididymal or testicular spermatozoa.

Recent studies indicate a strong paternal influence on embryo development and progression of the embryo to the blastocyst stage. The aim of this study was to compare, during extended culture, the in-vitro development of embryos resulting from intracytoplasmic sperm injection (ICSI) of ejaculated spermatozoa (group 1, n = 347), epididymal (group 2, n = 22) or testicular (group 3, n = 18) spermatozoa from obstructive azoospermic and testicular spermatozoa from non-obstructive azoospermic (group 4, n = 31) subjects. Fertilization and blastocyst formation rates were significantly lower in group 4 (P < 0.05). The incidence of expanded and hatching blastocysts was significantly lower in group 4 (P < 0.05). Overall in 93.2% ejaculate ICSI cycles, blastocysts were transferred on day 5. This was significantly higher than the 62% day 5 transfers in the non-obstructive azoospermic group (P < 0.05). Implantation rate per embryo was significantly higher in the ejaculate ICSI group compared with the other groups (P < 0.05). Clinical pregnancy per transfer was similar between groups; however, significantly fewer multiple pregnancies were encountered in the non-obstructive azoospermic group (P < 0.01). In conclusion, the source of the spermatozoa, most likely to be indicative of the severity of spermatogenic disorder, affects the rate of blastocyst formation and blastocyst implantation. Spermatozoa from non-obstructive azoospermic subjects, when utilized for ICSI, result in embryos that progress to the blastocyst stage at a lower and slower rate and implant less efficiently.

Blastocyst quality affects the success of blastocyst-stage embryo transfer.

OBJECTIVE: To determine the relationship between blastocyst quality and the results of embryo transfer at the blastocyst stage. DESIGN: Retrospective case analysis. SETTING: Tertiary care private hospital IVF center. PATIENT(S): A total of 350 blastocyst-stage embryo transfer cycles. INTERVENTION(S): In vitro culture to the blastocyst stage was undertaken in 350 ICSI cycles where four or more cleavage-stage embryos were available on day 3. MAIN OUTCOME MEASURE(S): Relationship between blastocyst quality and implantation and clinical and multiple pregnancy rates. RESULT(S): Transfer of at least one grade 1 or grade 2 blastocyst or one hatching blastocyst was associated with very high implantation and pregnancy rates. However, transfer of grade 3 blastocysts yielded very low implantation and pregnancy rates. CONCLUSION(S): There appears to be a strong correlation between blastocyst quality and success of blastocyst transfer.

Progression to the blastocyst stage of embryos derived from testicular round spermatids.

Progression to the blastocyst stage of embryos derived from testicular round spermatids in men with non-obstructive azoospermia was studied. A total of 56 men were studied in whom partial spermatogenesis failure had occurred where only very few spermatozoa (fewer than the number of oocytes retrieved) were extracted from multiple testicular biopsy specimens. Oocytes remaining after intracytoplasmic injection of testicular spermatozoa (group 1) were injected with round spermatids (ROSI, group 2). Only embryos derived from group 1 were transferred. Remaining embryos were observed under culture for 8 days and their progression to the blastocyst stage was recorded. Of the 546 oocytes injected with testicular spermatozoa, 404 (73.9%) showed evidence of 2-pronuclear (2PN) fertilization. Injection of testicular round spermatids resulted in 2PN fertilization rate of 50% (P < 0.05). Using a four-point grading system, 53% of the good quality embryos (grade 1 or 2) in group 1 reached the blastocyst stage compared with 25% in group 2 (P < 0.05). The rate of progression to the blastocyst stage of grade 3 and grade 4 embryos was 46 and 8.5% in the two groups respectively (P < 0.05). Using a different three-point grading system for the blastocysts, 75.3% of the blastocysts in group 1 were either grade 1 or grade 2 and 24.7% were grade 3. However, in group 2 all blastocysts were grade 3. All embryos observed in group 1 reached the blastocyst stage by day 5 or 6 compared with 25% of the embryos reaching the blastocyst stage by this time in group 2. While 31.2% of the blastocysts in group 1 showed evidence of spontaneous hatching in vitro, none of the blastocysts in group 2 hatched. In conclusion, progression to the blastocyst stage occurred at a much lower and slower rate in embryos derived from testicular round spermatids. Furthermore, all blastocysts resulting from ROSI were of poor quality and none showed spontaneous hatching. These results may explain the dismal outcome associated with ROSI.

Outcome of testicular sperm retrieval procedures in non-obstructive azoospermia: percutaneous aspiration versus open biopsy.

The aim of this study was to evaluate whether the extraction of testicular spermatozoa with percutaneous versus open biopsy has an effect on the treatment outcome with intracytoplasmic sperm injection (ICSI) in men with non-obstructive azoospermia. Regardless of testicular size, follicle stimulating hormone concentration, and previous biopsy result, percutaneous testicular sperm aspiration (PTSA) using a 21-gauge butterfly needle was attempted first and if this failed testicular sperm extraction (TESE) was performed. In 63 men spermatozoa were found with PTSA whereas in 228 men TESE had to be undertaken. More men in the PTSA group had previously been diagnosed with hypospermatogenesis (82 versus 50%). Compared with the PTSA group, more men in the TESE group had germ cell aplasia (27 versus 10%) or maturation arrest (22 versus 8%). There was no difference between the groups regarding mean age of men and their partners, duration of stimulation, oestradiol concentration on the day of human chorionic gonadotrophin, number of oocytes retrieved, fertilization rate, and embryo quality between the two groups. The number of embryos transferred (4.38 versus 3.90) was significantly higher in the PTSA group (P < 0.05), reflecting the increased number of embryos available for transfer. Implantation rate per embryo was 20.7% in the PTSA and 13.3% in the TESE group (P < 0.05). Clinical pregnancy rates were 46 and 29% in the PTSA and TESE groups respectively (P < 0.05). Clinical abortion rates were similar (21.2 versus 24%). It is concluded that in men with non-obstructive azoospermia, easier sperm retrieval, which is most likely indicative of a more favourable histopathology, is associated with higher implantation rates per embryo.

Comparing two embryo transfer catheters. Use of a trial transfer to determine the catheter applied.

OBJECTIVE: To analyze the performance of two different embryo transfer catheters (Wallace and Frydman) in an in vitro fertilization (IVF)-intracytoplasmic sperm injection (ICSI) program. STUDY DESIGN: Four hundred twenty-eight IVF or ICSI embryo transfer cycles were analyzed. A trial transfer was performed before the initiation of controlled ovarian hyperstimulation to determine the choice of embryo transfer catheter, Wallace or Frydman. Actual transfer was undertaken with the catheter chosen from the trial transfer. RESULTS: During actual embryo transfer, 214 (93.5%) of the intended 229 Wallace transfers were successful, and in 15 transfers the Frydman catheter was used. Of the intended 199 Frydman transfers, all were successful. Clinical pregnancy rate, implantation rate per embryo and ectopic pregnancy rate per transfer for the Wallace catheter were 41.6%, 16% and 0.9%, respectively. Respective rates for the Frydman catheter were 36.0%, 14.4% and 0.9% (P > .05 for all variables). Trial catheterization prevented most of the unanticipated procedural difficulties during the actual transfer. CONCLUSION: Both Wallace and Frydman catheters performed similarly, although there was a slight but nonsignificant increase in clinical pregnancy rates with the Wallace catheter.

Low-dose aspirin does not increase implantation rates in patients undergoing intracytoplasmic sperm injection: a prospective randomized study.

PURPOSE: The aim was to evaluate the effect of aspirin on pregnancy and implantation rates in an unselected group of patients undergoing intracytoplasmic sperm injection (ICSI). METHODS: Two hundred and seventy-nine patients were randomized to receive 80 mg of aspirin (n = 139) or no treatment (r = 136) starting from the first day of controlled ovarian hyperstimulation. RESULTS: Duration of stimulation, gonadotropin consumption, peak estradiol, number of oocytes retrieved, fertilization rate, cleavage rate, and number of embryos transferred were similar in the two groups. Implantation and clinical pregnancy rates were 15.6% and 39.6% versus 15.1% and 43.4% in aspirin treated and untreated groups, respectively (P > 0.05). CONCLUSIONS: Low-dose aspirin administration does not improve implantation and pregnancy rates in an unselected group of patients undergoing ICSI.

Elevated serum progesterone level on the day of human chorionic gonadotropin administration does not adversely affect implantation rates after intracytoplasmic sperm injection and embryo transfer.

OBJECTIVE: To evaluate the association between serum P levels on the day of hCG administration and the outcome of intracytoplasmic sperm injection (ICSI). DESIGN: Retrospective case study. SETTING: Assisted reproduction unit of a tertiary care private hospital. PATIENT(S): Nine hundred eleven ICSI cycles that proceeded to ET were studied. INTERVENTION(S): The decision to administer hCG was based on serum E2 levels and follicle size. Serum P was measured from frozen sera obtained on the day of hCG administration. Cycles were stratified according to serum P levels of <0.9 ng/mL (n = 298) or > or =0.9 ng/mL (n = 613). This cutoff level was selected because it yielded the highest sensitivity and specificity according to a receiver operator characteristic curve. MAIN OUTCOME MEASURE(S): Implantation and clinical pregnancy rates. RESULT(S): In cycles with high serum P levels, more oocytes were retrieved and more embryos were available for transfer. Clinical pregnancy rates per ET in the low and high P groups were 36.9% and 45.4%, respectively (P<.05). The implantation rate per embryo was similar in the two groups (14.9% and 16.4%, respectively, in cycles with P levels <0.9 vs > or =0.9 ng/mL). Abortion rates were 22.7 and 25.8%, respectively (P>.05). CONCLUSION(S): Our data showed no adverse effect of high serum P levels on the day of hCG administration on implantation rates after ICSI and ET.