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Biomedical subjects

Douglas T Carrell

Publications and source records attributed to Douglas T Carrell.

33 records · Page 2Linked to original sources

Pregnancy from intracytoplasmic sperm injection of a sperm head and detached tail.

OBJECTIVE: To evaluate sperm ultrastructure and the efficacy of intracytoplasmic sperm injection (ICSI) with careful positioning of the sperm midpiece next to the sperm head in a patient with easily decapitated sperm syndrome. DESIGN: In vitro fertilization case report with retrospective sperm ultrastructure analysis. SETTING: In vitro fertilization clinic and andrology laboratory. PATIENT(S): A couple seeking treatment for diminished ovarian reserve and male factor infertility using donor oocyte IVF. INTERVENTION(S): Motile sperm inadvertently decapitated during micromanipulation were used for a modified ICSI procedure in which the midpiece was carefully positioned proximal to the sperm head. Sperm were also analyzed by transmission electron microscopy (TEM). MAIN OUTCOME MEASURE(S): Fertilization rate, embryo development, pregnancy, and the incidence of normal sperm ultrastructure. RESULT(S): The ICSI resulted in a fertilization rate of 63% and embryo development of good to moderate quality of 36% of the embryos. Transfer of two embryos resulted in a pregnancy and birth of a healthy child. Normal sperm centrosomes were identified retrospectively. CONCLUSION(S): Pregnancy can result in patients where the sperm are decapitated during immobilization before ICSI if normal centrosomes are present and the head and midpiece are positioned closely together.

Centrosome↗

Use of outcomes-based data in reducing high-order multiple pregnancies: the role of age, diagnosis, and embryo score.

OBJECTIVE: To identify high-risk categories for high-order multiple pregnancy (HMP) in in vitro fertilization (IVF), establish clinic-specific HMP risk data for counseling use, and verify their utility in reducing HMP. DESIGN: Before and after intervention study. SETTING: Two IVF programs using the same embryology laboratory and IVF protocols. PATIENT(S): All IVF patients undergoing fresh embryo transfers. INTERVENTION(S): Use of clinic-specific age, diagnosis, and embryo score (ES) risk data in assessing individual HMP risk during informed consent. MAIN OUTCOME MEASURE(S): HMP and pregnancy outcomes. RESULT(S): In determining clinic-specific high risk categories and developing outcomes-based HMP risk data for counseling, the good outcome rate (GR) was defined as the percentage of singleton or twin deliveries per cycle and the bad outcome rate included no pregnancy or nondelivered pregnancies (miscarriages, multifetal reduction) and HMP per cycle. During 1995 to 1999, age <35 years, calculated morphologic ES, and donor egg (DE) cycles were factors shown by logistic regression to statistically significantly affect the GR. The optimal GRs for DE <35 and >or=35 years (donor age), and non-DE cycles <35 years were achieved with two (57.7%), three (43.2%), and three (43.2%) embryos transferred, respectively. A DE <35 years with >or=3 embryos transferred had the highest risk for HMP. The GR correlated (0.91) with the ES according to the formula: GR = 3.3 + 2.0 ES, when ES range was between 4 and 26. Clinic-specific risks for HMP based on age, diagnosis, and ES were developed and considered while counseling for ET during 2004. The clinic-specific HMP risk data made for a reduction in the HMP rate of 90.9% for DE-IVF (11.8% to 1%) and 53.8% for all IVF (9.1% to 4.2%), without decreases in clinical pregnancy or delivery rates. Physicians showing the greatest decline (64%) in HMP had no reduction in pregnancy or delivery rates. CONCLUSION(S): The use of clinic-specific HMP risk data in counseling based on age, diagnosis, and ES provided a 53% to 64% reduction in HMP without affecting rates of pregnancy or delivery. The clinic-specific ES system correlated closely with good outcomes. A standardized ES system may provide useful information for counseling during ET informed consent.

Adult↗

Improved in vitro fertilization embryo quality and pregnancy rates with intracytoplasmic sperm injection of sperm from fresh testicular biopsy samples vs. frozen biopsy samples.

OBJECTIVE: To compare the outcomes of first-attempt IVF-intracytoplasmic sperm injection (ICSI) cycles when using fresh testicular biopsy samples vs. frozen biopsy samples. DESIGN: Retrospective chart review of 92 consecutive first-attempt IVF-ICSI cycles. SETTING: Two IVF programs. PATIENT(S): Forty consecutive first-attempt IVF-ICSI patients using sperm from fresh testicular biopsy samples and 52 consecutive first-attempt IVF-ICSI cycles using frozen testicular biopsy samples. INTERVENTION(S): Testicular biopsy, IVF-ICSI with fresh and frozen-thawed spermatozoa. MAIN OUTCOME MEASURE(S): Fertilization rates, embryo quality, pregnancy, delivery, and spontaneous abortion rates. RESULT(S): A significantly increased ICSI fertilization percentage was obtained with frozen testicular biopsy samples (76.5% +/- 3.1%) vs. fresh biopsy samples (68.3% +/- 2.6%). However, embryo quality, pregnancy, and delivery rates were higher in the fresh biopsy group. Mean embryo score was 4.54 +/- 0.31 and 3.62 +/- 0.2 in the fresh vs. frozen group, respectively. Chemical pregnancy rates (60% vs. 49.1%), clinical pregnancy rates (56.4% vs. 41.2%), and delivery rates (48.7% vs. 31.2%) were each higher in the fresh group vs. frozen group. Accordingly, the spontaneous abortion rate was lower in the fresh group (21.7%) vs. the frozen group (33.3%). CONCLUSION(S): Although the use of frozen biopsy samples has logistical advantages, we conclude it may be advantageous to use fresh testicular biopsy samples in IVF-ICSI cases whenever possible, as fresh specimens yielded significantly improved embryo quality, generally higher pregnancy rates, and lower spontaneous abortion rates.

Abortion, Spontaneous↗

Seminal infection with Ralstonia picketti and cytolysosomal spermophagy in a previously fertile man.

OBJECTIVE: To determine the origin of large plaque-like cellular and acellular masses of debris found in the semen of a patient with otherwise normal semen quality and secondary infertility. DESIGN: A prospective case study. SETTINGS: Academic andrology laboratory. PATIENT(S): Secondary infertility patient presenting for routine semen evaluation. INTERVENTION(S): Following diagnosis of a seminal infection, the patient was treated with an antibiotic. MAIN OUTCOME MEASURE(S): Semen quality parameters, semen culture, and electron microscopy identification of cytolysosomal spermophagy. RESULT(S): Semen culture identified a rare infection with Ralstonia picketti and electron microscopy showed massive neutrophil and cytolysosomal spermophagy. Both were eliminated after antibiotic therapy. CONCLUSION(S): This case study documents a rare infection of the reproductive tract with Ralstonia picketti. Analysis of large seminal masses determined their origin to be primarily from acellular cytolysosomes. The presence of such masses in semen should be further evaluated, including semen culture.

Adult↗

Elevated sperm chromosome aneuploidy and apoptosis in patients with unexplained recurrent pregnancy loss.

OBJECTIVE: To evaluate sperm chromosome aneuploidy and semen quality in 24 partners of women with unexplained recurrent pregnancy loss and to analyze the data in relation to sperm apoptosis data. METHODS: Semen quality parameters and sperm chromosome aneuploidy for chromosomes X, Y, 13, 18, and 21 were evaluated in the recurrent pregnancy loss patients, fertile controls, and a control group of men from the general population. RESULTS: The mean aneuploidy rate in the recurrent pregnancy loss group was 2.77 +/- 0.22, significantly higher (P <.005) than in either the general population (1.48 +/- 0.12) or in fertile (1.19 +/- 0.11) control groups. In the recurrent pregnancy loss patients, the percentage of aneuploid sperm was correlated to the percentage of apoptotic sperm (r =.62, P <.001). Normal morphology was diminished in the patient group, compared with the general population group (P <.01) and the donor group (P <.001). CONCLUSIONS: These data indicate that some recurrent pregnancy loss patients have a significant increase of sperm chromosome aneuploidy, apoptosis, and abnormal sperm morphology. This study demonstrates a new possible cause of recurrent pregnancy loss.

Abortion, Habitual↗

Human protamines and the developing spermatid: their structure, function, expression and relationship with male infertility.

During spermiogenesis, the protamine proteins play an integral role in spermatid chromatin compaction. Recent research has focused on many facets of protamine biology, including protamine gene and protein structure/function relationships, mechanisms of protamine expression regulation and involvement of the protamines in male fertility. In this paper, we review our current understanding of the structure and function of the protamine-1 (P1) and protamine-2 (P2) proteins and genes, the expression and regulation of these genes and the relationship between the protamines and male fertility. In addition, we offer a brief outlook on future investigation into protamine proteins.

Amino Acid Sequence↗

Prospective, randomized, blinded evaluation of donor semen quality provided by seven commercial sperm banks.

OBJECTIVE: To evaluate variability in donor semen quality between seven commercial donor sperm banks, within sperm banks, and between intracervical insemination and intrauterine insemination. DESIGN: Prospective, randomized, blind evaluation of commercially available donor semen samples. SETTING: An academic andrology laboratory. PATIENT(S): Seventy-five cryopreserved donor semen samples were evaluated. INTERVENTION(S): Samples were coded, then blindly evaluated for semen quality. MAIN OUTCOME MEASURE(S): Standard semen quality parameters, including concentration, motility parameters, World Health Organization criteria morphology, and strict criteria morphology. RESULT(S): Significant differences were observed between donor semen banks for most semen quality parameters analyzed in intracervical insemination samples. In general, the greatest variability observed between banks was in percentage progressive sperm motility (range, 8.8 +/- 5.8 to 42.4 +/- 5.5) and normal sperm morphology (strict criteria; range, 10.1 +/- 3.3 to 26.6 +/- 4.7). Coefficients of variation within sperm banks were generally high. CONCLUSION(S): These data demonstrate the variability of donor semen quality provided by commercial sperm banks, both between banks and within a given bank. No relationship was observed between the size or type of sperm bank and the degree of variability. The data demonstrate the lack of uniformity in the criteria used to screen potential semen donors and emphasize the need for more stringent screening criteria and strict quality control in processing samples.

Cervix Uteri↗

Primordial and pre-antral follicles are not commonly observed in IVF aspirates.

BACKGROUND: Follicular fluid recovered from IVF patients has been proposed to be a valuable source of pre-antral and primary follicles for patient therapy and research. We evaluated the recovery of immature follicles in follicular fluid from 54 patients undergoing IVF using several techniques. METHODS: Fluid from each patient underwent several methods of follicle recovery including: filtration through a cell strainer, Ficoll-Paque density gradient, isolate density gradient, histological slide preparation, and enzymatic digestion with collagenase and DNase. RESULTS: 34 primordial and primary follicles, mean 0.63 +/- 0.27/patient, and 14 pre-antral follicles, mean 0.26 +/- 0.14/patient, were found in this study. The serum estradiol level on the day of HCG injection was significantly lower (P < 0.05) in patients in which immature follicles were recovered, compared with those without immature follicles in the follicular fluid (1779.9 +/- 167.6 versus 2246.6 +/- 153.2 pg/ml). There were no women with advanced maternal age (>39 years) who had immature follicles in the follicular fluid. CONCLUSIONS: Follicular fluid cannot be considered an efficient or reliable source of immature follicles. The presence of any immature follicles appears to be associated with cause of infertility, the random placement of the aspirating needle and may be related to the age of patient.

Adult↗

Body mass index is inversely related to intrafollicular HCG concentrations, embryo quality and IVF outcome.

Decreased periovulatory human chorionic gonadotrophin (HCG) concentrations have been shown to be associated with diminished fertilization rates. This study evaluated if intra-follicular HCG concentration may be related to body mass in 247 IVF patients using their own oocytes and 58 patients receiving donor oocytes, and evaluated if such a relationship might affect IVF outcome. A significant inverse correlation (r = -0.353, P < 0.001) was observed between the body mass index (BMI) and intra-follicular HCG concentration. The mean HCG concentrations were significantly decreased (P < 0.001) in patients with a BMI >30 kg/m(2) compared with patients with a BMI of 20-30 kg/m(2) or BMI <20 kg/m(2) (17.6 versus 45.1 and 52.5%, respectively). The clinical pregnancy rates (P < 0.001) and embryo quality (P < 0.05) were significantly different for the three groups. In donor oocyte recipients, the pregnancy rate was significantly decreased (P < 0.0001) for recipients with a BMI >25 kg/m(2) compared with those with a BMI from 21-25 kg/m(2) and BMI <21 kg/m(2) (43.8 versus 72 and 76.5%, respectively). These data indicate that intra-follicular HCG concentration is inversely related to BMI, and may be related to a concurrent decrease in embryo quality and pregnancy rates.

Journal Article↗

DNA integrity is compromised in protamine-deficient human sperm.

The objective of this study was to examine the relationship between DNA integrity and protamines in human sperm. One hundred forty-nine male infertility patients were included in an Institutional Review Board-approved study. Sperm were evaluated for DNA fragmentation using the DNA Integrity Assay, a test equivalent to the sperm chromatin structure assay (SCSA). Additionally, nuclear proteins were extracted and the protamine-1/protamine-2 ratio (P1/P2), protamine-1 (P1), protamine-2 (P2), and total protamine concentrations were evaluated. We identified 37 patients with abnormally low P1/P2 ratios, 99 patients with normal P1/P2 ratios, and 13 patients with abnormally high P1/P2 ratios. DNA fragmentation was significantly elevated in patients with low P1/P2 ratios (37.1 +/- 6.02) vs those with normal and high P1/P2 ratios (26.7 +/- 1.9 and 23.8 +/- 3.2, respectively; P < .05) and was inversely correlated with the P1/P2 ratio (R(s) -0.18, P < .05), P1 concentration (R(s) -0.29, P < .001), P2 concentration (R(s) - 0.24, P < .005), and total protamine concentration (R(s) -0.28, P < .001). Furthermore, chi2 analysis revealed a significant increase in the incidence of marked DNA fragmentation in patients with diminished levels of either P1 or P2. The present study is the first to report that human sperm protamine content is significantly related to DNA fragmentation. In particular, sperm P1 and P2 concentrations inversely correlate with DNA fragmentation, indicating a protective role of the protamines against sperm DNA damage. In light of recent studies highlighting the negative effect of sperm DNA damage on ART outcomes, these findings indicate a possible clinical significance for human sperm protamine levels.

DNA Fragmentation↗

Comparison of chromatin assays for DNA fragmentation evaluation in human sperm.

Sperm chromatin integrity is vital for successful pregnancy and transmission of genetic material to the offspring. We evaluated chromatin integrity in sperm from 60 infertile men and 7 fertile donors comparing the sperm chromatin structure assay (SCSA), TdT-mediated-dUTP nick end labeling (TUNEL), the sperm chromatin dispersion (SCD) test, and acridine orange staining technique (AOT). The TUNEL and SCD assays showed a strong relationship with the SCSA (r > .866; P < .001) for sperm DNA fragmentation, both in infertile men and donors of known fertility. AOT did not show any relationship with SCSA. The breakdown of the DNA fragmentation index (DFI) into 3 categories (< or =15%, >15%-<30%, and > or =30%) showed that the SCSA, TUNEL, and SCD test predict the same levels of DNA fragmentation. AOT consistently showed higher levels of DNA fragmentation for each DFI category. DNA fragmentation in sperm between infertile men and donor sperm was significantly different (P < .05) under SCSA (22.0 +/- 1.6 vs 11.8 +/- 1.4), TUNEL (19.5 +/- 1.3 vs 11.1 +/- 0.9) and SCD (20.4 +/- 1.3 vs 10.8 +/- 1.1), respectively. DNA fragmentation in sperm evaluated by AOT did not differ (P > .05) between infertile men (31.3 +/- 2.4) and donors (32.7 +/- 4.8). AOT showed extreme variations for sperm DNA fragmentation in semen from both infertile men and donors. The problems of indistinct colors, rapid fading, and the heterogeneous staining were also faced. In conclusion, SCSA, TUNEL, and SCD show similar predictive values for DNA fragmentation, and AOT shows variable and increased levels of DNA fragmentation, which makes it of questionable value in clinical practice.

Chromatin↗