Biomedical subjects

C B Coulam

Publications and source records attributed to C B Coulam.

193 records · Page 11Linked to original sources

PubMedDate not supplied

Unexplained sporadic and recurrent miscarrage in the new millennium: a critical analysis of immune mechanisms and treatments.

There have been important advances in basic science investigation of mechanisms underlying spontaneous miscarriages which lend support to empirical treatments such as intravenous immunoglobulin G and allogeneic leukocyte immunotherapy. The results from clinical trials of these and other proposed treatments have been problematic. There is only one published meta-analysis of sufficient power and appropriate stratification to qualify as Level 1 evidence, and that deals only with leukocyte immunotherapy. Here we critically review current trials and their flaws, update the meta-analysis, and comment on potential new approaches. Inadequate sample size, better definition of heterogeneity, and proper stratification to minimize the effects of heterogeneity remain as problems. Verification that the experimental or test treatment was active in producing the expected alteration in immunophysiology in the recipient is lacking in most trials; use of stored rather than fresh allogeneic leukocytes appears problematic. Hidden biases that affect trial significance emerge with critical analysis, and the focus on apparent 'high quality' of design in published reports may be misleading. We conclude that there seem to be enough patients to conduct clinical trials of sufficient size to achieve adequate power to test therapies showing promise in pilot studies, but at present, the only Level 1 evidence concerns leukocyte immunotherapy which appears to increase the chance of a live birth if given to appropriate patients.

Abortion, Habitual↗

PubMedDate not supplied

Alteration in platelet count during early pregnancy in the mouse.

Published reports of pregnancy associated thrombocytopenia in mice have utilized the Quackenbush strain. The inability of some laboratories to verify this observation in other mouse strains prompted us to report our findings by using Swiss Albino ICR mice. In Exp. 1, pregnant and pseudopregnant mice were bled prior to mating (time 0) and daily on day 1 (vaginal plug) through day 7. In Exp. 2, media from 24 hr cultures of 2-cell mouse embryos or media from unfertilized oocytes were injected into splenectomized mice. Animals were bled at time 0 (before injection) and at 30, 60, and 120 min after injection. In Exp. 3, splenectomized mice were treated with either media from 2-cell stage embryos or with media supplemented with synthetic platelet-activating factor (PAF: 0.05, 0.1 or 0.2 micrograms). Animals were bled as in Exp. 2. Platelet numbers were determined in duplicate from each blood sample by using a hemacytometer. In Exp. 4, antagonist (SRI 63-441) or vehicle was administered to mated mice on days 1 through 4 of pregnancy. Animals were examined on day 8 to determine number of developing conceptuses. In Exp. 1-3, data were analyzed by using ANOVA for repeated measures, and in Exp. 4 data were analyzed by chi-square analysis. In Exp. 1, there was a treatment x time interaction (P less than .06) due to transient thrombocytopenia in pregnant but not pseudopregnant mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMedDate not supplied

Recurrent spontaneous abortion.

The laboratory diagnosis and clinical management of unexplained recurrent spontaneous abortion (RSA) patients is a controversial issue in contemporary obstetrics. In this report, the results of laboratory investigations and immunotherapy of RSA patients referred to our Center since 1986 are detailed. Our analyses have resulted in grouping RSA patients into primary (1 degree), secondary (2 degrees), and unexplained classifications. Laboratory evaluation criteria included assays for both complement-dependent and complement-independent antipaternal antibodies as well as histocompatibility antigen tissue typing for HLA, A, B, C, and DR antigens. In addition, mixed lymphocyte cultures (MLC) were performed to assess the degree of HLA-D locus compatibility between couples and to test for the presence of MLC inhibitors in maternal blood. Immunotherapy options and the rationale for their use are given and preliminary outcome data are presented from randomized double-blinded, placebo-controlled clinical trials.

Abortion, Habitual↗

PubMedDate not supplied

Occurrence of ectopic pregnancy among women with recurrent spontaneous abortion.

Ectopic pregnancy is a major health problem accounting for about 10% of all maternal mortality. To determine whether patients with a history of recurrent spontaneous abortion (RSA) have a higher frequency of ectopic pregnancy than the general population, the obstetrical histories of 630 patients with a diagnosis of RSA from two centers were studied. Thirty-eight of 376 USA women, (10%) and 10 of 193 British women (5%) previously had suffered an ectopic pregnancy. These data provide an overall prevalence of 9% for ectopic pregnancy among patients who recurrently abort. The total number of pregnancies was 1,716 in the USA group and in the British group was 1,270, for a total of 2,986 including live births, stillbirths, abortions, hydatidiform moles, and ectopic pregnancies. In the US series, 45 of the 1,716 pregnancies were ectopic. If these women had the same relative proportion of ectopic pregnancies as the general population, there should have been 20.6 ectopic pregnancies. This represents a 2.2-fold increase in patients with a history of RSA. There was no association between pregnancy order and occurrence of ectopic pregnancy. The prevalence of known risk factors for ectopic pregnancy in patients with a history of ectopic pregnancy was PID, 3%; tubal surgery, 20%; and used IUD, 3%. Seventy-four percent of the women had no identifiable risk factor. These results suggest a comorbidity for ectopic pregnancy and RSA which may indicate shared etiologies.

Abortion, Habitual↗

PubMedDate not supplied

Evaluation of circulating anti-sperm antibodies in fertile and patient populations.

Several reports have demonstrated the presence of anti-sperm antibodies (ASA) in infertile populations; however there is a paucity of information regarding ASA in fertile populations. The purpose of this study was to establish objective criteria for the interpretation of the Immunobead Binding Test (IBT) based on values obtained from fertile individuals. Sera from 20 fertile couples (n = 40) were assayed by using a modification of the IBT previously described by Clarke et al. An initial lower limit of binding for positivity (lower limit) of 14% was used based upon the mean value for each isotype plus 2 standard deviations (SD) of 4 negative control sera assayed 4 to 7 times each. One-way ANOVA or chi-square analyses were used to analyze these data. There was no difference in percent immunobead binding between males and females in the fertile population (P greater than 0.1); therefore the data were pooled. Percent binding for fertile controls was: IgG, 21.7 + 31.9% (mean + SD); IgA, 19.5 + 25.8%; IgM, 16.9 + 14.9%. Initial analysis indicated no significant difference (P greater than 0.10) in percent binding between fertile and infertile individuals. The corresponding frequency of positive values (for at least one isotype) using a 14% lower limit was 23/40 (57.5%). This was not significantly different (P greater than 0.1) from the frequency observed in the patient population (140/242, 57.8%). New lower limits of positivity for each isotype were established based upon the mean plus 2 SD from the fertile control data: IgG, 85.4%; IgA, 71.1%; IgM, 46.7%.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMedDate not supplied

Sperm antibodies after intraperitoneal insemination of sperm: a preliminary report.

To test the hypothesis that intraperitoneal insemination of sperm induces the expression of anti-sperm antibodies a prospective study was designed. Fifteen women undergoing intraperitoneal insemination (with or without oocyte transfer) were studied with 11 women having evaluation of anti-sperm antibodies. Sperm antibodies were detected by the immunobead test prior to intraperitoneal insemination and after each treatment cycle. Two criteria were used to assess positivity: the first based upon negative controls and the second based upon the evaluation of 20 fertile control couples. Using the first criteria, of 11 of the women undergoing IPI for the first time, 7 were initially negative and 4 were initially positive for at least 1 isotype. After treatment, 3 additional patients were positive (for a total of 7) and 4 patients remained negative. This alteration in sperm antibody frequency was not different (P = .4) as determined by the Fisher's Exact Test. Four of the 11 patients underwent a second cycle of IPI. All 4 patients were negative prior to the first treatment and 3 were negative prior to the second treatment. Subsequent to the second exposure, all 4 of these women were positive for at least 1 isotype. This shift in frequency distribution after 2 cycles was significant (P = .01). The frequency of antisperm antibodies for the same 11 patients was evaluated by using fertile control values as the basis of positivity. Two patients (18%) were positive for anti-sperm antibodies prior to intraperitoneal insemination. There was no change in the frequency of positivity after 1 cycle of IPI.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMedDate not supplied

Update on immunotherapy for recurrent pregnancy loss.

Results of recent, randomized, placebo-controlled clinical trials have raised questions about the efficacy of immunotherapy for recurrent spontaneous abortion (RSA). Most of the clinical trials have shown a 70% successful pregnancy rate with immunotherapy. The controversy comes from variations in success rates in the control populations, which have ranged from 29% to 76%. Explanations for these variations includes small sample sizes and heterogeneity by the populations studied as well as cointervention by the placebo. A meta-analysis has been proposed to investigate these explanations. Because the trials have largely used husband's leukocytes for immunization, alternative forms of immunotherapy have been sought. Two treatments that have been proposed but have not completed testing a randomized, placebo-controlled trials are intravenous immunoglobulin (IVIG) and immunization with seminal plasma. A safe and efficacious method is needed to treat recurrent spontaneous abortion; it is hoped that results of proposed studies will answer this controversy.

Abortion, Habitual↗

PubMedDate not supplied

Association between infertility and spontaneous abortion.

Women experiencing recurrent spontaneous abortion have a higher frequency of infertility than that expected in the general population. To further define the relationships between infertility and spontaneous abortion, the obstetrical histories of 43 women with unexplained secondary infertility were evaluated for the frequency of spontaneous abortion. Of the 88 pregnancies studied, 39 (44%) resulted in spontaneous abortion. Women with unexplained secondary infertility experienced a three-fold increase (P less than 0.0001) in the frequency of spontaneous abortions and half the number of live births (P less than 0.0001) compared with the general population. We conclude that the association between infertility and spontaneous abortion includes a higher frequency of spontaneous abortion among infertile couples as well as a higher prevalence of infertility among recurrent spontaneous aborters compared with the general population.

Abortion, Habitual↗

PubMedDate not supplied

Evaluation of immunological infertility.

To evaluate the frequency with which immunological factors are associated with infertility, 92 couples with unexplained infertility were studied by using assays to detect anti-sperm antibodies (ASA), human leukocyte antigen tissue types (HLA), lymphocytotoxic antibodies (LCA), and inhibitors of mixed lymphocyte culture (MLC) and mouse blastocyst assay (MBA). Seventy-three of the women had blood assayed for antiphospholipid antibodies (APA). The frequencies of APA, ASA, LCA, inhibitors of MLC and MBA, as well as HLA associations previously reported to be related to infertility (B locus blanks, single DQ locus in offspring, greater than 1 DR sharing between mates) among 92 infertile couples were compared with those observed among 41 fertile control couples. No significant differences in the frequencies of APA, ASA, MBA, and HLA associations between fertile and infertile couples were observed. Fertile couples demonstrated the presence of wife anti-husband LCA and MLC inhibitors more frequently than did infertile couples (51% vs. 8%, P = 0.0001 and 29% vs. 4%, P = 0.002, respectively). While APA, ASA, HLA tissue typing, LCA, and MLC and MBA have been previously reported as being markers of autoimmune and alloimmune responses relating to reproductive outcome, the current data suggest that more specific markers are necessary to diagnose immunological components of infertility.

Adult↗

PubMedDate not supplied

New concepts in ovarian regulation: an immune insight.

The purpose of the ovary is to produce eggs. In the human, oocyte production occurs cyclically at monthly intervals. The control of egg production is provided by both the endocrine and immune systems. Successful oocyte production is the result of sophisticated communication between the two systems. These interactions allow adaptive processes necessary for continuation of the species.

Activins↗

PubMedDate not supplied

Sperm antibodies.

Anti-sperm antibodies (ASA) occur in 1% to 30% of infertile couples. Mechanisms by which ASA impair fertility include prevention of fertilization by decreasing acrosome reaction and/or zona pellucida binding, and postfertilization effects. Treatment for ASA involves assisted reproductive technologies.

Animals↗

PubMedDate not supplied

Treatment of endometriosis with the GnRH agonist nafarelin acetate.

Additional details of a multicenter study of nafarelin acetate with particular attention to a unique endometriosis scoring system utilized are reviewed. Additional information regarding the relapse of symptoms of 10 patients treated with nafarelin and danazol during a 6- to 12-month follow-up interval is described. Transient decreases in leukocytes previously reported by other investigators were observed in 3 of 8 patients, but appear to represent a laboratory artifact.

Adolescent↗

PubMedDate not supplied

Ureaplasma urealyticum in semen for artificial insemination: its effect on conception and semen analysis parameters.

Semen specimens from 24 donors in an artificial insemination program--selected for women whose infertile status was determined to be male factor-related and for whom no female factor could be determined--were cultured for the presence of Ureaplasma urealyticum. A life table statistical analysis indicated that conception did not occur sooner in the U. urealyticum-negative group (n = 14) compared with those women inseminated with the U. urealyticum-containing semen (n = 10). In addition, no significant differences were detected in semen analysis count, grade, or motility between semen with or without U. urealyticum. We found no differences in the occurrence of fetal morbidity or mortality in ten conceptions between the women impregnated with Ureaplasma-positive (n = 14) and Ureaplasma-negative (n = 6) semen. Thus, our study does not support the role of U. urealyticum as a cause of male factor-related infertility or early pregnancy loss.

Actuarial Analysis↗