Paul D. Manganiello

A double-blind, placebo-controlled study of the use of methylprednisolone in infertile men with sperm-associated immunoglobulins * †

Forty-three men with antibody-mediated infertility identified by measuring sperm-associated immunoglobulin with a direct radiolabeled antiglobulin assay were enrolled in a double-blind, placebo-controlled protocol to judge the efficacy of corticosteroids in this condition. In the active drug group, men were given 96 mg methylprednisolone in three divided doses for 7 days followed by a 2-day tapering of the drug. The control group was given placebo in the same manner. Both regimens were repeated three times approximately 1 month apart on the basis of their female partners menstrual cycle. There was not a favorable effect of corticosteroids over placebo on the mens semen parameters, the results of assays for sperm-associated IgA and plasma IgG antisperm antibodies, or the mens subsequent fertility. There was a statistically significant effect on sperm-associated IgG in men given methylprednisolone compared with men given placebo.

A comparison of clomiphene citrate and human menopausal gonadotropin for use in conjunction with intrauterine insemination

OBJECTIVE To compare the outcome of superovulation using clomiphene citrate (CC) versus hMG in conjunction with IUI. DESIGN Sequentially assigned, observational study. Couples initially were assigned to receive either CC or hMG for three cycles. SETTING The Clinical Outpatient Department of the Dartmouth-Hitchcock Medical Center. PATIENT(S) Eighty-three infertile couples. INTERVENTION(S) IUI with hMG use. MAIN OUTCOME MEASURE(S) Conception rate, term pregnancy rate (PR), and pregnancy complications, such as spontaneous miscarriage and multiple gestation. RESULT(S) Of 83 couples who underwent at least one treatment cycle, 29 (35%) conceived during the study period. The relative rate of conception for hMG versus CC was 2.08 (95% confidence interval [CI], 0.93 to 4.68). The relative term PR was 2.10 (95% CI, 0.77 to 5.73) for hMG versus CC. There was no difference in the miscarriage rate for hMG versus CC. CONCLUSION(S) Both the conception rate and the term PR were higher using hMG, compared with CC, in combination with IUI, and showed a trend toward statistical significance.

A 10-year prospective study of women with a history of recurrent fetal losses fails to identify Listeria monocytogenes in the genital tract

An attempt was made to isolate L. monocytogenes from the cervix and endometrium of patients who presented to the Dartmouth-Hitchcock Medical Centers Reproductive Counseling Unit with a history of two or more fetal losses. Endometrial tissue and endocervical swabs were cultured in a prospective fashion for the presence of L. monocytogenes. During the 10-year study period, none of the patients with recurrent fetal losses were found to harbor the organism in their genital tract. It would appear that L. monocytogenes contributes to fetal loss, but probably not on a recurrent basis. Routine culturing for L. monocytogenes in the asymptomatic patient in a clinical setting is not cost-effective and is therefore unwarranted. The portal of entry is possibly the GI tract, with bacteremia and transplacental spread to the fetus. Ascending infection through the introduction of L. monocytogenes into the vagina and cervix may occur. Because of the difficulty in identifying L. monocytogenes in the feces, as well as the self-limiting nature of listeriosis, it would appear unwarranted to give routine administration of antibiotics in patients who have had a history of a fetal loss because of L. monocytogenes.

Human Immunodeficiency Virus–Specific and CD3-Redirected Cytotoxic T Lymphocyte Activity in the Human Female Reproductive Tract: Lack of Correlation between Mucosa and Peripheral Blood

CD8(+) T cell phenotype and function were assessed in the female reproductive tracts (FRTs) of 3 human immunodeficiency virus (HIV)-positive patients who had undergone hysterectomy. FRT cytotoxic T lymphocyte (CTL) lytic activity from 1 patient (patient 872) was detected by using CD3-dependent redirected-lysis assay and HIV-specific assay, concomitant with the presence of CD8(+) cells. In contrast, samples from the 2 other HIV-positive patients (patients 1356 and 1364), who also were asymptomatic for HIV-associated illnesses, demonstrated no CTL activity in any solid tissue tested by either assay, despite activity by autologous peripheral blood mononuclear cells (PBMC). This absence of CTL activity was correlated with a relative absence of CD8(+) cells in the FRT, whereas CD8(+) cells were present in PBMC. Thus, CTL activity in PBMC may fail to correlate with mucosal activity. The finding of CTL activity in the FRT of patient 872 represents the first description of CTL in upper and lower FRT tissues of an HIV-positive woman.

Antisperm antibodies in women: variability in antibody levels in serum, mucus, and peritoneal fluid.

OBJECTIVE To look for patterns of antisperm antibody expression in women by exploring the levels of antisperm antibodies in different body fluids. This was achieved by studying sequential serum samples from individual patients and by comparing the levels of antisperm antibodies in serum from a number of patients with the levels of antisperm antibodies in cervical mucus or peritoneal fluid (PF). DESIGN Prospective studies were performed on sequential serum samples within a menstrual cycle. Retrospective studies were done to compare antisperm antibodies in serum and mucus or PF. The immunobead assay was used to measure antisperm antibodies in these fluids. SETTING Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. PATIENTS A random sample of patients undergoing evaluation for infertility. RESULTS The levels of antisperm antibodies in sera drawn from patients at different points in a menstrual cycle stimulated by the presence of exogenous hormones did not change during the follicular phase of the menstrual cycle. Also, in many samples, the antisperm antibody level in serum did not correlate with the antisperm antibody levels in mucus or PF. CONCLUSIONS The data suggest that measurement of antisperm antibodies at a single point in time or from a single fluid is not sufficient when evaluating a woman for immunological infertility. The data also suggest that numerous and complex factors contribute to the expression of antisperm antibodies in women.

Comparison of the direct radiolabeled antiglobulin assay and the direct immunobead binding test for detection of sperm-associated antibodies.

ABSTRACT: Thirty‐seven semen samples were assayed for sperm‐associated IgG and IgA using the immunobead test. Portions of these sperm samples were sent for testing with a direct radiolabeled antiglobulin assay and the testing results were compared. If the results of the immunobead test when only tail‐tip bead binding was noted are regarded as negative, there was close correlation between the two assay methodologies.

A Bipolar Radiofrequency Catheter Fails to Occlude a Feline Uterine Horn: A Model for Fallopian Tube Occlusion

We developed a retrograde transvaginal-transcervical-transuterine sterilization technique capable of causing occlusive fibrosis and stricture in the human fallopian tube. The procedure is required to induce a lesion at the intramural-isthmic portion of the tube at sufficient depth to damage epithelium underlying the submucosa and inner muscular layer, without acute damage to the outer muscular layer and serosal surface. Nineteen nulliparous purpose-bred cats were induced and maintained in an anestrus state with testosterone cypionate 5 mg/kg intramuscularly and a 6-18-hour light-dark cycle. After laparotomy, all animals had focal radiofrequency lesioning of uterine horns. Ten of 30 treated uterine horns appeared grossly occluded at the time of sacrifice; however, histologic assessment demonstrated only 6 complete occlusions, and 4 horns showed lack of complete lumen occlusion with or without evidence of recanalization. Although no complications were encountered, bipolar radiofrequency failed to provide a consistent obstructive lesion in a tubular structure similar in size and morphology to the human fallopian tube.

Treatment of pain in fibromyalgia patients with testosterone gel: Pharmacokinetics and clinical response.

To test our hypothesis that testosterone deficiency plays an important role in chronic pain, a Phase I/II pilot study was initiated with 12 fibromyalgia patients to verify that a daily dose for 28days with transdermal testosterone gel would 1) significantly and safely increase mean serum testosterone concentrations from low baseline levels to mid/high-normal levels, and 2) effectively treat the pain and fatigue symptoms of fibromyalgia. Pharmacokinetic data confirmed that serum free testosterone concentrations were raised significantly above baseline levels, by assessment of maximum hormone concentration (Cmax) and area under the curve (AUC) parameters: free testosterone Cmax was significantly raised from a mean of 2.64pg/mL to 3.91pg/mL (p<0.05), and 24hour free testosterone AUC was significantly raised from a mean of 35.0pg-hr/mL to 53.89pg-hr/mL. Assessment of the typical symptoms of fibromyalgia by patient questionnaire and tender point exam demonstrated significant change in: decreased muscle pain, stiffness, and fatigue, and increased libido during study treatment. These results are consistent with the hypothesized ability of testosterone to relieve the symptoms of fibromyalgia. Symptoms not tightly related to fibromyalgia were not improved.