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Biomedical subjects

J A Politch

Publications and source records attributed to J A Politch.

At least 19 recordsLinked to original sources

Factors associated with the formation of triploid zygotes after intracytoplasmic sperm injection.

OBJECTIVE: To determine whether clinical or laboratory factors influence development of triploid (3PN) zygotes after ICSI. DESIGN: Retrospective review. SETTING: The assisted reproductive technology program of Brigham and Women's Hospital. PATIENT(S): Patients undergoing ICSI. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Cycles were divided into two groups: group A, cycles with one or more 3PN zygotes after ICSI, and group B, cycles with no 3PN zygotes. Age, amount of gonadotropin administered, peak estradiol levels, number of follicles, number of oocytes retrieved and injected, time between retrieval and injection, oocyte abnormalities, sperm type and motile count, percentage of diploid zygotes, and ongoing pregnancy rates were compared between groups. RESULT(S): Compared with patients in group B, those in group A received fewer ampoules of gonadotropins, had higher estradiol levels, and had more follicles on the day of hCG administration, oocytes, immature oocytes and oocytes injected and lower percentages of diploid zygotes. However, ongoing pregnancy rates did not differ between groups. CONCLUSION(S): Patients who produce 3PN zygotes after ICSI are high responders to ovarian stimulation. The appearance of such embryos is not associated with lower ongoing pregnancy rates and should not necessarily dictate alterations in ovarian stimulation protocols.

Adult↗

Factors associated with increased levels of human immunodeficiency virus type 1 DNA in semen.

Human immunodeficiency virus type 1 (HIV-1)-infected cells have been isolated from semen and may be a major source of transmissible virus. Quantitative polymerase chain reaction (PCR) assay was used to determine HIV proviral DNA load in cellular fractions of semen from 74 antiviral therapy-naive HIV-1-seropositive men and 53 paired blood samples. HIV-1 DNA was detected in 65% of semen (range: <10-5000 copies/mL) and 100% of blood samples (range: 20-2500 copies/mL). HIV-1 DNA copy numbers in semen correlated significantly with those in blood, but for most cases, the concentration of blood HIV-1 DNA was higher (mean blood-to-semen ratio = 2.9). Factors associated with elevated HIV-1 provirus levels in semen included reduced peripheral CD4 cell count and asymptomatic genital tract inflammation (>10(6) white blood cells/mL of semen). These data provide evidence that genital tract inflammation and reduced peripheral CD4 cell count may be associated with enhanced sexual transmission of HIV-1 because of increased numbers of HIV-1-infected cells in semen.

CD4 Lymphocyte Count↗

Optimized assay for antisperm cell-mediated immunity.

Previous studies on antisperm cell-mediated immunity (CMI) have been confounded by the presence of immunogenic leukocytes in sperm antigen preparations. In this study we isolated pure populations of viable spermatozoa on discontinuous Percoll gradients, and utilized sonicated and cavitated extracts, as well as live motile spermatozoa, to measure cellular immunity to spermatozoa in vasectomized men, men with proven fertility, infertile women, fertile women and umbilical cord blood. Using a thymidine incorporation assay to assess lymphocyte proliferation, nine out of 13 (69%) vasectomized men and five out of 10 (50%) fertile men responded to sperm extracts. Lymphocyte proliferation to sperm extracts was also observed in both infertile and fertile women (27 and 50% respectively). In addition, viable sperm preparations promoted lymphocyte responses in five out of eight (63%) fertile women, seven out of 11 (63%) healthy men and four out of 11 (45%) cord blood specimens. Furthermore, four out of 11 (36%) healthy normal men responded to autologous spermatozoa. No relationship between serum antisperm antibodies, as measured with the Immunobead test, and sperm CMI was observed in any group. This study provides evidence that lymphocytes from fertile as well as infertile men and women and sperm-naive newborn infants proliferate when exposed to viable spermatozoa or sperm extracts. Thus the lymphocyte proliferation assay does not appear to be useful in the diagnosis of immunological infertility, but immunological recognition of spermatozoa may be a common feature that could have a role in fertility.

Adult↗

Is leukocytospermia clinically relevant?

OBJECTIVE: To evaluate the relationship between seminal leukocytes and abnormal semen parameters in a large population of infertility patients. DESIGN: Prospective clinical study. SETTING: Center for Reproductive Medicine at Brigham and Women's Hospital, Boston, Massachusetts. PATIENT(S): One thousand seven hundred ten male partners in infertile couples attending the Center for Reproductive Medicine. MAIN OUTCOME MEASURE(S): Seminal leukocyte concentrations, sperm count, motility and morphology, and the prevalence of samples with < 10 x 10(6) motile sperm per ejaculate (a parameter defined by IVF as the most clinically significant predictor of male infertility). RESULT(S): There was a strong relationship between increasing leukocyte concentrations in semen and abnormal semen parameters. Statistically significant differences in sperm concentrations and morphology were observed at leukocytospermia thresholds of 5 x 10(5) and 2 x 10(6) granulocytes/mL, respectively. The percentage of suboptimal semen specimens as defined by IVF criteria (< 10(7) total motile sperm per ejaculate) significantly increased with increasing seminal granulocyte concentrations. A twofold increased prevalence in such suboptimal semen specimens was observed at the leukocytospermia threshold of 2 x 10(6) granulocytes/mL. CONCLUSION(S): There is a relationship between increasing seminal granulocyte concentrations and poor semen parameters. At seminal granulocyte concentrations > 2 x 10(6)/mL, semen parameter abnormalities were observed that were both statistically and clinically significant.

Fertilization in Vitro↗

Antibiotic therapy and leukocytospermia: a prospective, randomized, controlled study.

OBJECTIVE: To determine the efficacy of common antibiotic therapies for treatment of leukocytospermia of unknown etiology. DESIGN: Prospective, randomized, controlled clinical study. SETTING: Fertility and Endocrinology Unit at Brigham and Women's Hospital, Boston, Massachusetts. PATIENTS: One thousand seven hundred ten male partners in infertile couples attending the Fertility and Endocrinology Unit. INTERVENTIONS: Concentrations of seminal peroxidase-positive granulocytes were determined during all routine semen analyses performed over a 30-month period. Of 119 men found to have leukocytospermia (> 10(6) granulocytes/mL semen) on first visit, 54 agreed to be randomized into one of three groups, and 41 patients completed the study. Group I (n = 13) and their wives received a 14-day course of oral doxycycline, 100 mg twice per day. Group II (n = 11) and their wives received a 14-day course of oral trimethoprim 160 mg-sulfamethoxazole 800 mg twice per day. Group III (n = 17) and their wives received no therapy. Four weeks after randomization, repeat semen analyses and granulocyte quantitations were done. RESULTS: Neither of the antibiotic regimens resulted in a significantly higher rate of resolution of leukocytospermia over that seen in the control group. CONCLUSIONS: There is a high rate of spontaneous resolution of leukocytospermia after one positive test. Antibiotics are no more beneficial than no therapy for treatment of this condition.

Adult↗

The effects of disease progression and zidovudine therapy on semen quality in human immunodeficiency virus type 1 seropositive men.

OBJECTIVE: To investigate the effects of disease progression and zidovudine antiretroviral therapy on semen parameters in human immunodeficiency virus type 1 (HIV-1) seropositive men. DESIGN: Cross-sectional analysis of semen parameters of 166 HIV-1 seropositive men in various stages of disease progression as defined by peripheral CD4+ cell count. Clinical symptoms and zidovudine therapy status were obtained from medical records and clinical interviews. PATIENTS: Human immunodeficiency virus type 1 seropositive men participating in clinical studies at the Fenway Community Health Center (Boston, MA), the University of San Francisco (San Francisco, CA), and Brown University (Providence, RI). MAIN OUTCOME MEASURES: Ejaculate volume; sperm concentration, motility, forward progression, morphology, total sperm count; seminal immature germ cell; and white blood cell (WBC) concentrations. RESULTS: Human immunodeficiency virus type 1 seropositive men that were not on zidovudine therapy and were in early disease stage (> 200 CD4+ cells/mm3) had normal semen parameters as defined by World Health Organization criteria. In contrast untreated men in advanced disease stage (< or = 200 CD4+ cells/mm3) had significant reductions in sperm concentration and total sperm count and an increased percentage of abnormal sperm forms. Men receiving zidovudine antiretroviral therapy, regardless of disease stage, had normal semen parameters similar to those of untreated early disease stage patients. Seminal WBC concentrations were not affected significantly by disease progression but were reduced in patients receiving zidovudine. CONCLUSION: Most HIV-1-infected men in this study had semen parameters consistent with fertility. Disease progression was associated with reduced semen quality, but this effect appeared to be abrogated by zidovudine therapy. Zidovudine was also associated with a significant reduction of WBC numbers in semen. As seminal WBC are principal HIV-1 host cells in ejaculates of HIV-1-infected men, this effect could explain recent laboratory and epidemiological evidence that zidovudine therapy is associated with a reduced prevalence of HIV-1 in semen and a lower rate of sexual transmission.

Acquired Immunodeficiency Syndrome↗

Seminal white blood cells and recurrent abortion.

The incidence of leukocytospermia (> 1 million white blood cells/ml semen) and concentrations of white blood cell populations in semen from men whose partners experience unexplained recurrent spontaneous abortion by conventional testing criteria are described and compared to those of men whose partners have normal reproductive histories. Comparable seminal granulocyte and total white blood cell concentrations between groups suggest that couples with unexplained recurrent abortion do not have an abnormally high incidence of subclinical genital tract infections for which leukocytospermia could serve as a marker. However, a significantly higher prevalence of elevated CD4+ and CD8+ T lymphocyte concentrations in semen from men whose partners have cellular immunity to sperm antigens (i.e. produce embryotoxic factors in response to sperm antigen stimulation) warrants further investigation.

Abortion, Habitual↗

Sperm morphology and recurrent abortion.

In 98 men whose partners experienced three or more spontaneous abortions, there were no significant differences in ejaculate volume, concentration of sperm, the percentage of total abnormal sperm, or the percentage of individual sperm defects as compared with normal WHO standards and 17 men fathering successful pregnancies. These data indicate that neither abnormal sperm concentration nor abnormal sperm morphology are significantly associated with recurrent spontaneous abortion.

Abortion, Habitual↗

Comparison of methods to enumerate white blood cells in semen.

Seminal WBC counts obtained by an mAb-based immunohistologic method correlated well with seminal granulocyte counts obtained with a simple peroxidase method (rho = +0.70; P < 0.0001). However, total WBC counts were significantly higher than granulocyte counts for most samples. With the immunohistologic method, 17 of 112 samples (15.2%) contained > 10(6) WBC/mL semen, whereas the peroxidase method resulted in only 10 samples (8.9%) with > 10(6) WBC/mL. When the threshold defining leukocytospermia was set at 1 x 10(6) positive cells/mL for both methods, the specificity of the peroxidase test compared with the immunohistology technique was 100% (10/10), but the sensitivity was only 58.8% (10/17). When the threshold for leukocytospermia in the peroxidase test was lowered to 5 x 10(5) positive cells/mL semen, the sensitivity relative to the immunohistology technique increased to 94.1% (16/17), and specificity remained 100% (16/16). Likewise, good interassay sensitivity and specificity values were obtained with thresholds of 10(6) WBC/mL for the peroxidase assay and 2 x 10(6) WBC/mL for the immunohistology assay. We conclude that either peroxidase or immunohistology assays can be used to screen for leukocytospermia, but that more research is needed to establish thresholds for pathological levels of WBC in semen using these two approaches. Total round cell counts are of no value for enumerating WBC in semen.

Analysis of Variance↗

Effects of disease stage and zidovudine therapy on the detection of human immunodeficiency virus type 1 in semen.

OBJECTIVE: To determine the prevalence and temporal expression of infectious human immunodeficiency virus type 1 (HIV-1) in the semen of HIV-1 seropositive men and to determine whether the detection of HIV-1 in semen is associated with disease stage, zidovudine treatment status, or other clinical factors. DESIGN: A microculture technique was used to detect infectious HIV-1 in semen from a cohort of 95 seropositive men. In addition, semen cultures were performed monthly for at least 6 months for 14 of the men. Information was obtained by interview and extracted from medical records to identify clinical variables associated with HIV-1 in semen. PATIENTS: Sixty HIV-1 seropositive homosexual men participating in clinical studies at the Fenway Community Health Center, Boston, Mass, and 35 HIV seropositive bisexual or heterosexual men participating in the California Partner Study of the University of California, San Francisco. MAIN OUTCOME MEASURES: Semen HIV-1 culture results, seminal leukocyte counts, Centers for Disease Control (CDC) disease stage, peripheral CD4+ cell counts, zidovudine therapy, HIV risk category. RESULTS: In the cross-sectional study, HIV-1 was cultured from the semen of nine (9%) of 95 men. Factors associated with detection of HIV-1 in semen were peripheral CD4+ cell counts of 0.20 x 10(9)/L (200/microL) or less (adjusted odds ratio [OR], 23.33; 95% confidence interval [Cl], 2.89 to 175.63); symptomatic (CDC class IV) disease (adjusted OR, 6.56; 95% Cl, 1.02 to 66.76); and seminal leukocytosis (greater than 1 x 10(9) white blood cells per liter of semen) (adjusted OR, 7.02; 95% Cl, 1.28 to 39.29). Zidovudine therapy was associated with decreased detection of HIV-1 in semen (adjusted OR, 0.04; 95% Cl, 0.00 to 0.63). In the longitudinal study of 14 men who had neither peripheral CD4+ cells counts of 0.20 x 10(9)/L or less nor seminal leukocytosis, seminal HIV-1 was detected in at least one sample from six men (43%). CONCLUSION: HIV-1 is more commonly found in semen from men with advanced HIV-1 infection and seminal leukocytosis but can also be cultured from semen of men with neither of these conditions. Zidovudine therapy may decrease the prevalence and/or titer of seminal HIV-1. However, all HIV-1-infected persons should continue to assume that they are potentially infectious through sexual contact.

CD4-Positive T-Lymphocytes↗

Leukocytospermia is associated with poor semen quality.

Semen samples from 179 infertility patients were analyzed for type and number of white blood cells (WBC) by a combination of immunologic techniques. Forty-one (23%) had more than 10(6) WBC/mL semen (leukocytospermia). Semen parameters in patients with less than 10(6) WBC/mL were similar to those of 15 fertile donors. In contrast, the leukocytospermic group had significant reductions in total sperm number, percent sperm motility, sperm velocity, motility index, and total number of motile sperm. Patients with high concentrations of monocytes/macrophages (greater than 5 X 10(5)/mL; n = 27) had significantly reduced ejaculate volume; patients with high numbers of T lymphocytes (greater than 10(5)/mL; n = 19) had a significant reduction in sperm velocity; and patients with high levels of granulocyte elastase in semen (greater than 1,000 ng/mL; n = 26) had significant reductions in ejaculate volume, total sperm number, and total motile sperm number. There was no correlation between the presence of antisperm antibodies and leukocytospermia. Our data suggest that leukocytospermia may occur frequently in male infertility patients and show that elevated levels of WBC in semen are associated with poor semen quality. This provides further rationale for white blood cell testing in semen of male infertility patients, since antibiotic or anti-inflammatory therapy may be helpful in appropriately selected cases.

Cell Degranulation↗

TfmLac: a second isolation of testicular feminization in mice.

TfmLac, a new occurrence of the X-linked mutation testicular feminization, has been isolated in a stock of mice and mapped to the same region as the original TfmH mutation. We compared these two mutants to determine if there are differences in their putative residual androgen receptors or androgen responsiveness. Such differences have been reported for Tfm mutations in humans. We found no evidence for induction of ornithine decarboxylase (ODC) activity in TfmLac despite androgen treatment for up to 3 weeks. This is in agreement with findings for TfmH. Both of these mutants expressed small amounts of androgen binding activity which shared some properties with the normal androgen receptors in mouse kidney. The binding was distinguishable between the two mutants, however, as determined by hormone saturation experiments utilizing DNA-cellulose chromatography. These findings confirm the independence of the two mutations and are consistent with their being allelic: both result in severe deficits of androgen binding and response.

Androgen-Insensitivity Syndrome↗

Effects of soluble products of activated lymphocytes and macrophages (lymphokines and monokines) on human sperm motion parameters.

Experiments were conducted to evaluate the effects of supernatants from activated leukocyte cultures and purified lymphokine and monokine preparations on sperm motion. An automated semen analyzer was used to obtain accurate measurements of several parameters of sperm motion. Supernatants from activated peripheral blood leukocyte cultures significantly decreased sperm motility. In studies of effects of individual lymphokines and monokines, significant antimotility effects were observed when spermatozoa were incubated with the lymphokine gamma-interferon and the monokine tumor necrosis factor. Subnormal fertility may result from defective sperm function caused by lymphokines and monokines elaborated by activated lymphocytes and macrophages residing in the reproductive tracts of infertile men and women.

Colony-Stimulating Factors↗

Androgen and estrogen receptors in adult zebra finch brain.

Androgens and estrogens have been implicated in the activation of a variety of sexually-dimorphic, hormone-dependent behaviors in the adult zebra finch. In the present report, several biochemical characteristics of two putative sex steroid receptors, androgen- and estrogen-binding activities, were determined by DNA-cellulose chromatography in brain tissues from these birds. High-affinity, limited-capacity receptors for androgens and estrogens were found in cytosolic extracts of telencephalon, diencephalon-mesencephalon, and metencephalon-myelencephalon from adult male and female zebra finches. Androgen-binding activity reproducibly adhered to DNA-cellulose and was eluted within the 110-150 mM NaCl region of a linear salt concentration gradient. Estrogen receptors adhered to DNA-cellulose and exhibited elution maxima between 170 mM and 210 mM NaCl. Collectively these data indicate that brain regions of zebra finches contain steroid receptors that are similar to those found in the brains of other vertebrates and that their biochemical properties are similar in males and females. Quantitatively, males consistently exhibited higher androgen binding than females in both anterior and posterior telencephalic areas. Females treated with estradiol immediately after hatching exhibited adult levels of androgen binding corresponding to those detected in males. Masculinization of the androgen receptor system by early steroid exposure is discussed.

Animals↗

Growth hormone-secretory patterns in androgen-resistant (testicular feminized) rats.

To investigate the role of androgen receptors in the expression of the male GH-secretory pattern in adult rats, the GH-secretory patterns in androgen-resistant (testicular feminized) rats were compared with their normal male and female littermates. All animals were prepared with intraatrial Silastic catheters and bled every 15 min for 8 h (0800-1600 h). Normal male littermates displayed a characteristic low frequency, high amplitude pattern of GH secretion with bursts of GH occurring every 2.5-3 h and separated by prolonged trough periods where GH values remained low or undetectable (less than 5 ng/ml) for 45-90 min. Normal female littermates showed a characteristic high frequency, low amplitude pattern of GH secretion with pulses of GH occurring every hour. Compared to normal male littermates, females had lower individual GH peak amplitudes and shortened GH-trough periods which contain higher GH levels. GH-secretory profiles displayed by testicular-feminized animals qualitatively and quantitatively resembled those of the normal female littermates. These data suggest that androgen receptors are necessary for the expression of masculine GH-secretory patterns.

Age Factors↗