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Biomedical subjects

Douglas T Carrell

Publications and source records attributed to Douglas T Carrell.

At least 19 recordsLinked to original sources
PubMed2005

The acceptability of posthumous human ovarian tissue donation in Utah.

BACKGROUND: Infertility due to accelerated loss of ovarian follicles/oocytes may occur through numerous mechanisms. As a result, posthumous human oocyte donation, banking and maturation protocols for research and fertility restoration are current interests in reproductive medicine. METHODS: A computer-generated sample of Utah residents (n = 704) were surveyed regarding demographics, willingness to donate organs, IVF acceptability and posthumous follicle/oocyte donation for: research, fertilization with monitoring to the preembryo stage (eight cells), and fertilization and subsequent transfer of embryos derived from themselves, their partner or non-spousal relative for whom they act as guardian. RESULTS: Ovarian tissue donation for follicle/oocyte retrieval, maturation and scientific investigation without fertilization was acceptable (>or=70%) to a majority of the Utah population. However, fertilization of oocytes or fertilization and transfer of resulting preembyos derived from such donations to cause a pregnancy was less acceptable (58.3% and 57.4%, respectively) in the population responding for their own or partner's oocytes, and more so when the donation was guardian-directed (54.8% and 52.1%, respectively). Similar declines in the level of acceptance were noted when those who had an express interest in such donations (ovarian failure or surgical castration) were surveyed (n = 50). CONCLUSIONS: This study substantiates the ethical recommendation that explicit prior written consent of the donor be obtained when ovarian tissue donations are procured for fertilization, or transfer of a preembryo to cause a pregnancy. In light of the rapid technological advancements in ovarian follicle/oocyte cryopreservation and maturation, the time may have come to provide potential organ donors the opportunity to specify their desires regarding ovarian tissues when registering for organ donation.

Adolescent↗
PubMed2005

Identification and evaluation of a novel sperm protamine abnormality in a population of infertile males.

BACKGROUND: A significant relationship exists between an abnormally high sperm protamine-1 (P1)/protamine-2 (P2) ratio and male infertility. In this study we investigate whether a decreased P1/P2 ratio is also linked to male infertility and we attempt to describe, at the protein expression level, the underlying cause of sperm P1/P2 deregulation. METHODS: P1 and P2 protein concentrations were quantified in sperm from 272 infertility patients and 87 fertile donors. P1/P2 ratios and protamine quantity were correlated with fertility status using semen analysis, sperm penetration capacity, and IVF data. RESULTS: We identified four distinct groups in the study: normal P1/P2 fertile donors, normal P1/P2 patients, low P1/P2 patients, and high P1/P2 patients. P1 and P2 were both under-expressed in patients with a normal P1/P2 ratio, but not in fertile donors. In patients with a low P1/P2 ratio, P1 was under-expressed while P2 was over-expressed; in patients with a high P1/P2 ratio, P1 was normally expressed and P2 was under-expressed. Patients with abnormal P1/P2 ratios displayed significantly reduced semen quality and sperm penetration ability. CONCLUSIONS: We have identified a novel population of infertile males with a reduced P1/P2 ratio. Aberrant P1/P2 ratios arise from an abnormal concentration of P1 and/or P2, either of which is associated with male infertility.

Female↗
PubMed2005

Correlation of sperm penetration assay score with polyspermy rate in in-vitro fertilization.

BACKGROUND: The sperm penetration assay (SPA) is used to predict the fertilizing capacity of sperm. Thus, some programs rely on SPA scores to formulate insemination plans in conjunction with in-vitro fertilization (IVF) cycles. The purpose of this study was to evaluate if a relationship exists between SPA scores and polyspermy rates during conventional IVF cycles. METHODS: A total of 1350 consecutive IVF patients using conventional IVF insemination were evaluated in the study. Oocytes were inseminated three hours post-retrieval by the addition of 150,000 to 300,000 progressively motile sperm. Approximately 18 hours after insemination, the oocytes were evaluated for fertilization by the visualization of pronuclei. The presence of three or more pronuclei was indicative of polyspermy. Polyspermy rates, fertilization success, embryo quality, and pregnancy rates were analyzed retrospectively to evaluate their relationship with SPA score, count, motility, number of progressively motile sperm inseminated, oocyte pre-insemination incubation time, patient age, and diagnosis. RESULTS: A significant positive relationship was observed between SPA score and polyspermy rate (rs = 0.10, p < 0.05). Patients with a normal SPA score had significantly higher polyspermy rates than those with abnormal SPA scores (6.3% +/- 1.5% vs. 2.0% +/- 0.7%, p < 0.05). Fertilization percentage was significantly lower in the group with severely abnormal SPA scores versus all other SPA groups (57.5% +/- 2.1% vs. 70.2% +/- 1.3%, p < 0.005). Although embryo quality was not affected, both clinical pregnancy and implantation rates improved slightly as SPA score increased. In addition, there was a decrease in the rate of spontaneous abortion as SPA score increased. CONCLUSIONS: These data indicate SPA score is positively correlated with polyspermy rates and IVF fertilization percentage. Additionally, there is a slight increase in clinical pregnancy rates, and embryo implantation rates with increased SPA. Furthermore, there is a slight decrease in spontaneous abortions rates related to increased SPA.

Journal Article↗
PubMed2005

Comparison of maturation, meiotic competence, and chromosome aneuploidy of oocytes derived from two protocols for in vitro culture of mouse secondary follicles.

PURPOSE: To compare maturation rates of mouse preantral follicles cultured using two previously reported follicle in vitro follicle culture protocols, and to compare the aneuploidy of oocytes derived from the two protocols with in vivo-matured control oocytes. METHODS: Mouse preantral follicles were either mechanically isolated then cultured in individual microdroplets, or enzymatically isolated and cultured in groups in a modified culture medium. Maturation of the follicles/oocytes and resulting oocyte aneuploidy rates were evaluated and compared. RESULTS: The mechanical isolation and individual culture protocol (M/I) resulted in higher follicle survival than the enzymatic isolation and group culture protocol (E/G) (89.1% versus 79.1%, p < 0.01), and better maturation to the metaphase 2 stage (61.5% versus 39.5%, p = 0.01) The rate of aneuploidy of oocytes not significantly higher in oocytes from the E/G group than the M/I group (15.4% versus 9.9%), but hypoploidy was significantly increased (4.7% versus 0.9%, p < 0.05). Both groups had a higher rate of aneuploidy than the control oocytes (2.9%, p < 0.02). CONCLUSIONS: These results indicate an increased survival and competency of oocytes derived from the M/I protocol, compared to the E/G protocol. The data highlight an increased susceptibility to meiotic errors in early stage follicles undergoing in vitro culture, compared to in vivo-matured oocytes.

Aneuploidy↗
PubMed2005

In vitro oocyte maturation and subsequent delayed fertilization is associated with increased embryo aneuploidy.

Failed fertilization and the appearance of immature oocytes are common in IVF practice; rescue intracytoplasmic sperm injection can be used as a therapy. However, this study indicates that embryos created after in vitro maturation and delayed intracytoplasmic sperm injection contain an increase in aneuploidy (79.7%) over control embryos (60.5%). Therefore, patients should be informed of the possible risk when presented with delayed intracytoplasmic sperm injection.

Adult↗
PubMed2005

Comparison of four media types during 3-day human IVF embryo culture.

The aim of this study was to compare the effectiveness of human tubal fluid (HTF), G1.2, Sage Cleavage and Life Global media for IVF outcome during 3-day culture of human embryos. A three-phase auto-controlled study was conducted in which IVF outcome was compared between (1) HTF and G1.2, (2) HTF and Cleavage, and (3) Cleavage and Life Global. In phase 1, no differences in embryo quality were observed between HTF and G1.2. However, embryos derived from intracytoplasmic sperm injection (ICSI) displayed significantly improved quality when grown in HTF versus G1.2. No differences in pregnancy and implantation rates were observed in cases where embryos transferred were grown exclusively in HTF or G1.2 media. In phase 2, embryo quality was significantly improved for embryos cultured in Cleavage versus HTF media (P < 0.001). However, pregnancy, implantation and spontaneous abortion rates were similar between the two media. In phase 3, there were no differences in embryo quality, pregnancy, implantation, and spontaneous abortion rates between Cleavage and Life Global media. Overall, the data indicate that Life Global and Cleavage media yield similar results in a 3-day IVF culture programme. Cleavage medium is superior to HTF, as evidenced by significantly improved embryo quality (P < 0.001). Meanwhile, HTF medium is superior to G1.2 for ICSI cases.

Cleavage Stage, Ovum↗
PubMed2004

H1FOO is coupled to the initiation of oocytic growth.

We previously reported the discovery of a novel mammalian H1 linker histone termed H1FOO (formerly H1OO), a replacement H1, the expression of which is restricted to the growing/ maturing oocyte and to the zygote. The significance of this pre-embryonic H1 draws on its substantial orthologous conservation, singular structural attributes, selectivity for the germ cell lineage, prolonged nucleosomal residence, and apparent predominance among germ cell H1s. Herein, we report that the intronic, single-copy, five-exon (> or =5301 base pair) H1foo gene maps to chromosome 6 and that the corresponding primary H1foo transcript gives rise to two distinct, alternatively spliced mRNA species (H1foo(alpha) and H1foo(beta)). The expression of the oocytic H1FOO transcript and protein proved temporally coupled to the recruitment of resting primordial follicles into a developing primary follicular cohort and thus to the critical transition marking the onset of oocytic growth. The corresponding potential protein isoforms (H1FOO(alpha) and H1FOO(beta)), both nuclear localization sequence-endowed but export consensus sequence-free and possessing a significant net positive charge, localized primarily to perinucleolar heterochromatin in the oocytic germinal vesicle. Further investigation will be required to define the functional role of the H1FOO protein in the ordering of the chromatin of early mammalian development as well as its potential role in defining the primordial-to-primary follicle transition.

Alternative Splicing↗
PubMed2004

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↗
PubMed2004

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↗
PubMed2004

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↗
PubMed2003

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↗
PubMed2003

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↗
PubMed2003

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↗
PubMed2002

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↗
PubMed2002

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↗