Thomas L. Toth

Body mass index in relation to semen quality, sperm DNA integrity, and serum reproductive hormone levels among men attending an infertility clinic

OBJECTIVE To examine the association between body weight and measures of male reproductive potential. DESIGN Cross-sectional study. SETTING Fertility clinic in an academic medical center. PATIENT(S) Four hundred eighty-three male partners of subfertile couples. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Standard semen analysis, sperm DNA fragmentation, and serum levels of reproductive hormones. RESULT(S) As expected, body mass index (BMI) was positively related to estradiol levels and inversely related to total testosterone and sex hormone-binding glogulin (SHBG) levels. There was also a strong inverse relation between BMI and inhibin B levels and a lower testosterone:LH ratio among men with a BMI > or = 35 kg/m(2). Body mass index was unrelated to sperm concentration, motility, or morphology. Ejaculate volume decreased steadily with increasing BMI levels. Further, men with BMI > or = 35 kg/m(2) had a lower total sperm count (concentration x volume) than normal weight men (adjusted difference in the median [95% confidence interval] = -86 x 10(6) sperm [-134, -37]). Sperm with high DNA damage were significantly more numerous in obese men than in normal-weight men. CONCLUSION(S) These data suggest that despite major differences in reproductive hormone levels with increasing body weight, only extreme levels of obesity may negatively influence male reproductive potential.

Semen quality and sperm DNA damage in relation to urinary bisphenol A among men from an infertility clinic.

Bisphenol A (BPA) impairs spermatogenesis in animals, but human studies are lacking. We measured urinary BPA concentrations, semen quality, and sperm DNA damage (comet assay) in 190 men recruited through an infertility clinic. BPA was detected in 89% of samples, with a median (interquartile range [IQR]) concentration of 1.3 (0.8-2.5) ng/mL. Urinary BPA concentration was associated with slightly elevated, though not statistically significant, odds for below reference sperm concentration, motility, and morphology. When modeled as continuous dependent variables, an IQR increase in urinary BPA concentration was associated with declines in sperm concentration, motility, and morphology of 23% (95%CI -40%, -0.3%), 7.5% (-17%, +1.5%), and 13% (-26%, -0.1%), respectively, along with a 10% (0.03%, 19%) increase in sperm DNA damage measured as the percentage of DNA in comet tail. In conclusion, urinary BPA may be associated with declined semen quality and increased sperm DNA damage, but confirmatory studies are needed.

Beneficial effect of microinjected trehalose on the cryosurvival of human oocytes

OBJECTIVE To determine the effectiveness of trehalose as an intracellular cryoprotectant for the cryopreservation of human oocytes. DESIGN In vitro comparative study. SETTING Clinical and academic research environment at a medical school teaching hospital. PATIENT(S) Women undergoing in vitro fertilization (IVF). INTERVENTION(S) Discarded human oocytes, obtained from IVF patients, were randomly distributed into three groups: control group (no trehalose), extracellular trehalose group (0.5 M extracellular trehalose), and intracellular trehalose group (0.15 M intra- and 0.5 M extracellular trehalose). Trehalose was introduced into oocytes by microinjection. The oocytes in each group were cooled to different temperatures (i.e., -15 degrees C, -30 degrees C, and -60 degrees C) at rate of 1 degrees C/minute and thawed at ambient air temperature. Survival was examined after overnight culture. MAIN OUTCOME MEASURE(S) Survival of human oocytes cryopreserved in the presence and absence of trehalose. RESULT(S) The majority of oocytes in the intracellular trehalose group survived cooling to -15 degrees C (63%), -30 degrees C (53%), and -60 degrees C (66%). In contrast, only a small number of oocytes in both the control (13%) and extracellular trehalose group (22%) survived cooling to -15 degrees C, while all oocytes degenerated when cooled to -30 degrees C and -60 degrees C. CONCLUSION(S) Small amounts of intracellular trehalose in the absence of any other cryoprotectant provide a significant protection against freeze-associated stresses. Our results suggest that sugars such as trehalose should be considered as intracellular cryoprotectants for cryopreservation of human oocytes.

Alterations of the Cytoskeleton and Polyploidy Induced by Cryopreservation of Metaphase II Mouse Oocytes

OBJECTIVE To determine cryopreservation-induced alterations in the cytoskeleton of metaphase II mouse oocytes and the implications of these alterations in functionality of the cytoskeleton and polyploidy after fertilization. DESIGN Comparative study. SETTING Clinical and academic research environment at a medical school teaching hospital. INTERVENTION(S) Oocytes were frozen using a slow-cooling (0.5 degrees C/min) and slow-thawing (8 degrees C/min) protocol in 1.5 M dimethyl sulfoxide and 0.2 M sucrose and were analyzed before and after fertilization. MAIN OUTCOME MEASURE(S) Cytoskeletal alterations, fertilization, and polyploidy rates. RESULT(S) When analyzed immediately after thawing, the oocytes displayed dramatic cytoskeletal alterations. Only slight recovery was observed upon removal of the cryoprotectants. However, incubation after thawing of 1 hour at 37 degrees C completely reestablished a normal microfilament and microtubule pattern while partially restoring normal spindle morphology and chromosome alignment. Accordingly, insemination immediately after removal of cryoprotectants resulted in a significantly decreased fertilization rate and aberrant dynamics of cytoskeleton-dependent events, whereas oocytes inseminated after the post-thaw incubation displayed fertilization rates and cytoskeletal dynamics comparable to those in controls. Cryopreservation did not increase polyspermy but significantly increased digyny when the oocytes were inseminated after the post-thaw incubation. All digynic eggs displayed an abnormal spindle remnant in comparison with diploid or polyspermic eggs. CONCLUSION(S) A brief period of incubation after thawing allows recovery and positively affects fertilization and cytoskeletal dynamics. Cryopreservation does not impair the functionality of microfilaments and cytoplasmic microtubules during postfertilization events. Our findings suggest that the increased rate of digyny in cryopreserved oocytes may be related to the spindle disorganization, leading to failure in segregation of the chromosomes, rather than to direct malfunction of the microfilaments in polar body formation.

Dose reduction and compliance with pediatric CT protocols adapted to patient size, clinical indication, and number of prior studies.

PURPOSE To assess compliance and resultant radiation dose reduction with new pediatric chest and abdominal computed tomographic (CT) protocols based on patient weight, clinical indication, number of prior CT studies, and automatic exposure control. MATERIALS AND METHODS The study was institutional review board approved and HIPAA compliant. Informed consent was waived. The new pediatric CT protocols, which were organized into six color zones based on clinical indications and number of prior CT examinations in a given patient, were retrospectively assessed. Scanning parameters were adjusted on the basis of patient weight. For gradual dose reduction, pediatric CT (n = 692) examinations were performed in three phases of incremental stepwise dose reduction during a 17-month period. There were 245 male patients and 193 female patients (mean age, 12.6 years). Two radiologists independently reviewed CT images for image quality. Data were analyzed by using multivariate analysis of variance. RESULTS Compliance with the new protocols in the early stage of implementation (chest CT, 58.9%; abdominal CT, 65.2%) was lower than in the later stage (chest CT, 88%; abdominal CT, 82%) (P < .001). For chest CT, there was 52.6% (9.1 vs 19.2 mGy) to 85.4% (2.8 vs 19.2 mGy) dose reduction in the early stage of implementation and 73.5% (4.9 vs 18.5 mGy) to 83.2% (3.1 vs 18.5 mGy) dose reduction in the later stages compared with dose at noncompliant examinations (P < .001); there was no loss of clinically relevant image quality. For abdominal CT, there was 34.3% (9.0 vs 13.7 mGy) to 80.2% (2.7 vs 13.7 mGy) dose reduction in the early stage of implementation and 62.4% (6.5 vs 17.3) to 83.8% (2.8 vs 17.3 mGy) dose reduction in the later stage (P < .001). CONCLUSION Substantial dose reduction and high compliance can be obtained with pediatric CT protocols tailored to clinical indications, patient weight, and number of prior studies.

Soy food and isoflavone intake in relation to semen quality parameters among men from an infertility clinic

BACKGROUND High isoflavone intake has been related to decreased fertility in animal studies, but data in humans are scarce. Thus, we examined the association of soy foods and isoflavones intake with semen quality parameters. METHODS The intake of 15 soy-based foods in the previous 3 months was assessed for 99 male partners of subfertile couples who presented for semen analyses to the Massachusetts General Hospital Fertility Center. Linear and quantile regression were used to determine the association of soy foods and isoflavones intake with semen quality parameters while adjusting for personal characteristics. RESULTS There was an inverse association between soy food intake and sperm concentration that remained significant after accounting for age, abstinence time, body mass index, caffeine and alcohol intake and smoking. In the multivariate-adjusted analyses, men in the highest category of soy food intake had 41 million sperm/ml less than men who did not consume soy foods (95% confidence interval = -74, -8; P, trend = 0.02). Results for individual soy isoflavones were similar to the results for soy foods and were strongest for glycitein, but did not reach statistical significance. The inverse relation between soy food intake and sperm concentration was more pronounced in the high end of the distribution (90th and 75th percentile) and among overweight or obese men. Soy food and soy isoflavone intake were unrelated to sperm motility, sperm morphology or ejaculate volume. CONCLUSIONS These data suggest that higher intake of soy foods and soy isoflavones is associated with lower sperm concentration.

Automatic Patient Centering for MDCT: Effect on Radiation Dose

OBJECTIVE The purpose of this study was to determine with phantom and patient imaging the effect of an automatic patient-centering technique on the radiation dose associated with MDCT. SUBJECTS AND METHODS A 32-cm CT dose index (CTDI) phantom was scanned with 64-MDCT in three positions: gantry isocenter and 30 and 60 mm below the isocenter of the scanner gantry. In each position, surface, peripheral, and volume CTDIs were estimated with a standard 10-cm pencil ionization chamber. The institutional review board approved the study with 63 patients (36 men, 27 women; mean age, 51 years; age range, 22-83 years) undergoing chest (n = 18) or abdominal (n = 45) CT using the z-axis automatic exposure control technique. Each patient was positioned according to the region being scanned and then was centered in the gantry. Before scanning of a patient, automatic centering software was used to estimate patient off-centering and percentage of dose reduction with optimum recentering. Data were analyzed with linear correlation and the Students t test. RESULTS Peripheral and surface CTDIs increased approximately 12-18% with 30-mm off-center distance and 41-49% with 60-mm off-center distance. Approximately 95% (60/63) of patients were not positioned accurately in the gantry isocenter. The mean radiation dose saving with automatic centering of all patients was 13.0% +/- 0.9% (range, 2.6-29.9%). There was strong correlation between off-center distance and percentage of surface CTDI reduction with recentering of patients in the gantry isocenter (r2 = 0.85, p < 0.0001). CONCLUSION Surfaces doses can be reduced if radiologic technologists can better center patients within the CT gantry. Automatic centering technique can help in optimum patient centering and result in as much as 30% reduction in surface dose.

Fertilization and in vitro development of cryopreserved human prophase I oocytes

OBJECTIVE To determine the potential for in vitro maturation, fertilization, and cleavage after cryopreservation of immature, prophase I human oocytes. DESIGN Immature oocytes obtained in excess of the number required by the patient were randomized and cryopreserved at the prophase I stage or cultured as control. After thawing and maturation in vitro, test and control oocytes were inseminated with husbands sperm and evaluated for fertilization and cleavage in vitro. SETTING In vitro fertilization program. PATIENTS Consenting patients undergoing controlled ovarian hyperstimulation for the purposes of IVF. MAIN OUTCOME MEASURES Rates of maturation to metaphase II, fertilization, and cleavage were compared between control and cryopreserved oocytes. RESULTS Upon thaw, 58.5% (72/123) of prophase I oocytes were viable. Control oocytes demonstrated a 74.8% (98/131) maturation rate to metaphase II, a 56.5% (52/92) fertilization rate, and an 11.5% (6/52) blastocyst rate. Cryopreserved oocytes showed a 83.3% (60/72) rate of maturation, a 57.7% (30/52) fertilization rate, and a 3.3% (1/30) blastocyst rate. No significant differences were noted between any of these parameters. CONCLUSIONS These results demonstrate that prophase I oocytes from stimulated IVF cycles are able to survive cryopreservation and resume meiosis to achieve full nuclear maturation post-thaw. In addition, cryopreserved oocytes retain the same capacity for fertilization and development as control oocytes.

Dietary fat and semen quality among men attending a fertility clinic

BACKGROUND The objective of this study was to examine the relation between dietary fats and semen quality parameters. METHODS Data from 99 men with complete dietary and semen quality data were analyzed. Fatty acid levels in sperm and seminal plasma were measured using gas chromatography in a subgroup of men (n = 23). Linear regression was used to determine associations while adjusting for potential confounders. RESULTS Men were primarily Caucasian (89%) with a mean (SD) age of 36.4 (5.3) years; 71% were overweight or obese; and 67% were never smokers. Higher total fat intake was negatively related to total sperm count and concentration. Men in the highest third of total fat intake had 43% (95% confidence interval (CI): 62-14%) lower total sperm count and 38% (95% CI: 58-10%) lower sperm concentration than men in the lowest third (P(trend) = 0.01). This association was driven by intake of saturated fats. Levels of saturated fatty acids in sperm were also negatively related to sperm concentration (r= -0.53), but saturated fat intake was unrelated to sperm levels (r = 0.09). Higher intake of omega-3 polyunsaturated fats was related to a more favorable sperm morphology. Men in the highest third of omega-3 fatty acids had 1.9% (0.4-3.5%) higher normal morphology than men in the lowest third (P(trend) = 0.02). CONCLUSIONS In this preliminary cross-sectional study, high intake of saturated fats was negatively related to sperm concentration whereas higher intake of omega-3 fats was positively related to sperm morphology. Further, studies with larger samples are now required to confirm these findings.

The influence of patient centering on CT dose and image noise

Although x-ray intensity shaping filters (bowtie filters) have been used since the introduction of some of the earliest CT scanner models, the clinical implications on dose and noise are not well understood. To achieve the intended dose and noise advantage requires the patient to be centered in the scan field of view. In this study we explore the implications of patient centering in clinical practice. We scanned various size and shape phantoms on a GE LightSpeed VCT scanner using each available source filter with the phantom centers positioned at 0, 3, and 6 cm below the center of rotation (isocenter). Surface doses were measured along with image noise over a large image region. Regression models of surface dose and noise were generated as a function of phantom size and centering error. Methods were also developed to determine the amount of miscentering using a scout scan projection radiograph (SPR). These models were then used to retrospectively evaluate 273 adult body patients for clinical implications. When miscentered by 3 and 6 cm, the surface dose on a 32 cm CTDI phantom increased by 18% and 41% while image noise also increased by 6% and 22%. The retrospective analysis of adult body scout SPR scans shows that 46% of patients were miscentered in elevation by 20-60 mm with a mean position 23 mm below the center of rotation (isocenter). The analysis indicated a surface dose penalty of up to 140% with a mean dose penalty of 33% assuming that tube current is increased to compensate for the increased noise due to miscentering. Clinical image quality and dose efficiency can be improved on scanners with bowtie filters if care is exercised when positioning patients. Automatically providing patient specific centering and scan parameter selection information can help the technologist improve workflow, achieve more consistent image quality and reduce patient dose.