Autoantibodies in endometriosis--epiphenomenon?
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Autoantibodies↗
Biomedical subjects
N Gleicher
Publications and source records attributed to N Gleicher.
Nonsurgical fallopian tube recanalization for treatment of infertility.
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Catheterization↗
The prevalence of autoantibodies and lupus anticoagulant in healthy pregnant women.
Abnormal autoantibodies have recently been implicated in pregnancy wastage. The normal autoantibody profile of pregnancy has so far, however, not been established. We investigated the effect of pregnancy on autoantibody production prospectively and longitudinally. Forty-three healthy pregnant women were compared with 50 nonpregnant healthy controls matched for age, race, and various obstetric and medical indices. All sera were tested for total immunoglobulin (Ig) levels; IgG, IgM, and IgA isotypes of autoantibodies to six phospholipids; total histone and four histone subfractions; and four polynucleotides. Plasma samples were evaluated for the presence of lupus anticoagulant. Total IgG decreased significantly in pregnant patients. The majority of autoantibody levels in pregnant women were within normal nonpregnant ranges. Only a few autoantibodies were increased in early pregnancy, including IgG antiphosphatidylinositol and H 2B, IgM antiphosphatidylinositol and phosphatidic acid, and IgA antiphosphatidylinositol and H 4. Most autoantibodies, although increased at term, were still within the normal nonpregnant range. Normalizing the data for expanded plasma volume did not significantly alter these results. Adjustment regression analysis excluded age, race, and various medical and obstetric indicators as confounding variables for autoantibody levels. The expected and observed prevalence of positive autoantibody levels in pregnant women was not significantly different from that of nonpregnant controls. None of the pregnant women demonstrated positive lupus anticoagulant. We conclude that in normal pregnancy between 16 weeks' gestation and term, autoantibody levels are largely within the normal range. Alterations occur, if at all, at the time of delivery.
Adult↗
Ovarian stimulation protocol for in vitro fertilization with gonadotropin-releasing hormone agonist widens the implantation window.
Pregnancy rates vary considerably with the type of ovarian stimulation used for in vitro fertilization and embryo transfer (IVF-ET). The window of implantation may represent one of the rate-limiting steps in IVF success. We therefore investigated estimated implantation times of 10 consecutive IVF singleton pregnancies, achieved using pituitary suppression with gonadotropin-releasing hormone agonist (GnRH-a) before and during ovarian stimulation with human menopausal gonadotropins (hMG), and compared those with 9 consecutive IVF pregnancies achieved by hMG stimulation only. Estimated implantation times were calculated by regression analysis of serial human chorionic gonadotropin (hCG) measurements between days 7 and 16 after ET. The GnRH-a/hMG pregnancies implanted between days 7 and 11, whereas hMG pregnancies implanted between days 7 and 9 after ET. The hCG regression curve for the GnRH-a/hMG pregnancies revealed a delay of 1.5 days in estimated implantation time compared with the hMG only group. There were no significant differences in pretransfer in vitro embryos development between the two groups. Thus, the delay in hCG rise probably reflects a delay in embryo implantation. We therefore conclude that a GnRH-a/hMG stimulation protocol appears to widen the implantation window in comparison with a hMG only protocol. This observation may at least in part explain the improved IVF pregnancy success with GnRH-a/hMG stimulation protocols.
Chorionic Gonadotropin↗
Commercial IgG immunoglobulin preparations exhibit IgG and IgA autoantibody reactivity at pharmacologic but not at physiologic concentrations.
IgG immunoglobulin preparations have been increasingly utilized to treat a variety of diseases. Since disease response to this form of therapy in patients with abnormal autoimmune function is often evaluated through the subsequent investigation of autoantibody levels, it is possible that autoantibody positivities reflect autoantibody reactivity of circulating immunoglobulin preparations and not of the patient's inherent B-cell activity. We therefore investigated three commercially available IgG immunoglobulin preparations separately for IgG, IgM and IgA autoantibody reactivity to six phospholipid antigens, total histone and four histone subfractions, and four polynucleotides. Universally, all three preparations demonstrated considerable IgG antiphospholipid and antihistone reactivity at dilutions of up to 1:10(3) but not antipolynucleotide reactivity. Although no IgM reactivity was detected in any of the preparations, in all three preparations surprising IgA reactivity, especially with antihistone specificity, was detected. No autoantibody reactivity was detected at dilutions compatible with physiologic conditions in vivo. Identical observations were made for lupus anticoagulant reactivity, which was evaluated by activated partial thromboplastin time (APTT) and tissue thromboplastin inhibition (TTI). Since autoantibody reactivities and prolonged APTT assays are observed only at pharmacologic dilution levels, it is unlikely that the administration of IgG immunoglobulin preparation will affect the evaluation of autoantibody levels in patients undergoing such treatment.
Autoantibodies↗
The rectus abdominis muscle flap in a combined abdominovaginal repair of difficult vesicovaginal fistulae. A report of three cases.
Conventional repairs had been tried on three patients suffering from vesicovaginal fistulas after abdominal hysterectomies. Separate vaginal and abdominal approaches had been tried and had resulted not only in failure but also in tissue loss and fibrosis. A final synchronous vaginoabdominal approach using a rectus abdominis muscle flap was used successfully in all three patients.
Abdominal Muscles↗
Pooled sequential ejaculates: a way to increase the total number of motile sperm from oligozoospermic men.
We investigated the yield of total number of motile spermatozoa from oligozoospermic men by pooling two closely spaced sequential ejaculates. Semen characteristics were compared between sequential ejaculates (within a period of 1 to 4 hours) of 18 oligozoospermic males (sperm concentration less than 20 X 10(6)/mL and total sperm count less than 40 X 10(6) in the ejaculate) and a control group of 16 normozoospermic men. Whereas the median total number of motile sperm of normozoospermic males significantly decreased from 70 X 10(6) in the first ejaculate to 23 X 10(6) in the second sequential ejaculate, such a decrease was not detected in oligozoospermic males, 3.6 X 10(6) and 3.1 X 10(6), respectively. The percent of normozoospermic and oligozoospermic men who demonstrated a decreased (less than 50%), a comparable (50% to 150%), or an increased (greater than 150%) total motile sperm count in the second ejaculate in comparison with the first ejaculate were 69%, 31%, and 0 versus 39%, 28%, and 33%, respectively. Consequently, pooling of two sequential ejaculates significantly increased the median total number of motile sperm from normozoospermic males by 144% and from oligozoospermic males by 329%, (to 10.2 X 10(6]. We suggest that pooling of two sequential ejaculates from oligozoospermic males is a simple and cost effective method to increase significantly the total number of motile sperm for intrauterine insemination, in vitro fertilization, gamete intrafallopian transfer, or semen cryopreservation.
Body Fluids↗
Obstetric outcome of patients with more than one previous cesarean section.
Records of patients with more than one previous cesarean section were reviewed for a 1-year period. Of 69 such pregnancies, 36 underwent trial of labor in concurrence with an ongoing departmental cesarean section reduction initiative; 80% culminated in vaginal delivery. Twenty of these 69 patients had three or more previous cesarean sections; 9 underwent trial of labor, with 8 subsequent vaginal deliveries. The vaginal delivery rate after more than one previous cesarean section was no different from that of patients with only one previous cesarean section. We conclude that trial of labor in patients with more than one previous cesarean section did not result in a deleterious outcome. Our findings suggest that a trial of labor after more than one previous cesarean section delivery can safely be allowed. Guidelines can be identical to those already established for patients with only one previous cesarean section.
Cesarean Section↗
Breast disease programs in obstetrics and gynecology: a plea for training in mammography.
Obstetrics and gynecology residency programs have started to integrate structured breast disease teaching programs into the curricula. I suggest that mammography training should be the cornerstone of programs on the diagnosis of breast diseases. The implementation of such a program into a teaching department is described in an attempt to facilitate similar efforts elsewhere.
Breast Diseases↗
Reproductive failure because of autoantibodies: unexplained infertility and pregnancy wastage.
Abnormal polyclonal B cell activation has been demonstrated in patients with endometriosis. To determine whether the noted B cell abnormalities were primarily a feature of the disease endometriosis or its manifestations of infertility and pregnancy wastage, we investigated antibody profiles in 26 female patients with unexplained infertility (group A) and 24 patients with unexplained pregnancy wastage (group B) but without documented endometriosis. Group A and B patients exhibited an unusual incidence of gammopathies (10 of 26 patients in group A and 11 of 24 in group B), with a majority representing immunoglobulin M gammopathies. Mean immunoglobulin M values were significantly elevated in both groups (p less than 0.03 and p less than 0.05, respectively, Student t test), whereas immunoglobulin G was significantly increased only among group B patients (p less than 0.05, Student t test). Lupus anticoagulant by tissue thromboblastin inhibition test was abnormally elevated in 2 of 26 group A and 2 of 24 group B patients. Activated partial thromboplastin time values were abnormal in only 3 of 26 group A and 2 of 24 group B women. Immunoglobulin G, immunoglobulin M, and immunoglobulin A autoantibodies to two phospholipid antigens, five histones, and four polynucleotide autoantibodies were detected in 23 of 26 (88%) group A patients and 17 of 24 (70.8%) group B patients. We conclude that some patients with unexplained infertility and pregnancy wastage suffer from polyclonal B cell activation. It is therefore tempting to speculate that autoantibody abnormalities may be causally related to infertility and pregnancy loss.
Abortion, Spontaneous↗
Ovarian development of the female child and adolescent: I. Morphology.
Ovarian morphology of 180 randomly selected females, aged 8-21, was investigated, utilizing standard sector scanning ultrasound techniques, at -1 year (1 year before menarche), year 0 (menarche) and years +1 to +8 (1-8 years postmenarche). According to strict morphologic criteria, seven ovarian patterns were recognized which varied in dominance with age in reference to menarche. Prior to menarche a multifollicular ovarian pattern (Type 1) dominates which after menarche is substituted by a predominantly active ovarian pattern (Type 5). Approximately 20% of postmenarcheal females do not develop this active pattern. In a relatively persistent percentage of females a microcystic (Type 2) ovarian pattern was recognized throughout all postmenarcheal years, suggestive of a normal transitional pattern from Type 1 to Type 5 ovaries. In contrast, multicystic (Type 3), hyperthecosis (Type 4), polycystic ("Mickey Mouse") (Type 6) and silent (Type 7) ovaries appear to represent abnormal ovarian developments. Based on percentage distributions, it is tempting to speculate that multicystic (Type 3) and/or hyperthecosis (Type 4) ovaries represent precursor ovaries to Type 6 (polycystic) ovaries. Confirmation of this hypothesis would have major clinical importance for the early diagnosis of the polycystic ovarian syndrome.
Adolescent↗
Atraumatic antepartum subdural hematoma causing fetal death.
A case of atraumatic antenatal fetal subdural hematoma, severe enough to cause death, is reported. Although it is often associated with traumatic delivery, its occurrence before labor suggests that assumptions of causation require some medical investigation or corroboration before trauma is accepted as the etiologic factor.
Adult↗
Conservative surgical management of interstitial pregnancy.
Conservative management of ampullary and isthmic tubal pregnancies has been increasingly advocated to preserve the affected tubes and results in excellent outcome. A similar approach to interstitial pregnancies is more difficult because of the vascularity of the cornual area. We report here a novel surgical approach to this problem in two patients. Both patients had an unremarkable postoperative course. Hysterosalpingograms performed 5 and 6 months postoperatively demonstrated bilateral tubal patency. It is suggested that conservative surgical management may replace either cornual resection or hysterectomy in selected patients with unruptured interstitial pregnancies.
Female↗
The thromboelastogram and circulating lupus anticoagulant.
Abnormal lupus anticoagulant (LA) levels, as measured with the activated partial tissue thromboplastin and tissue thromboplastin inhibition tests, are associated with a predisposition toward thromboembolic phenomena. Thromboelastogram (TEG) measurements have been proposed as a standardized assay to predict such a predisposition. We therefore correlated LA and TEG assessments in 46 women who were either apparently healthy controls or who had abnormal LA levels with such conditions as endometriosis and repeated pregnancy wastage. The coefficient of correlation (Rho) was .3282 (P = .025). Seven patients with an abnormal LA demonstrated a normal TEG, and eight with a normal LA exhibited an abnormal TEG. Only nine had concomitant LA and TEG abnormalities. We conclude that LA and TEG apparently are not interchangeable as predictors of a hypercoagulable state. While this study did not address which of the two assays has a better predictive value for thromboembolic phenomena, it suggested that each can identify a different patient population.
Abortion, Habitual↗
A successful program to lower cesarean-section rates.
Despite the consensus that national cesarean-section rates are excessive, they continue to rise. Currently, approximately one of every four deliveries is by cesarean section. We developed an initiative to reduce the number of cesarean deliveries to a rate of 11 percent of all deliveries at our inner-city hospital. Participation by attending physicians was voluntary and not linked to any sanction. The program included a stringent requirement for a second opinion, objective criteria for the four most common indications for cesarean section, and a detailed review of all cesarean sections and of individual physicians' rates of performing them. During the first two years of the program, the cesarean-section rate fell from 17.5 percent of 1697 deliveries in 1985 to 11.5 percent of 2301 deliveries in 1987 (P less than 0.05). The proportion of infants with five-minute Apgar scores lower than 7 increased from 3 percent in 1985 to 4.9 percent in 1987 (P less than 0.05), but neither the fetal mortality rate (11.9 per 1000) nor the neonatal mortality rate (11.2 per 1000) in 1987 differed significantly from the rates in 1985. A single maternal death, unrelated to cesarean delivery, occurred during the study. Rates of both primary and repeat cesarean sections decreased, although only the decline in the rate of primary cesarean sections, from 12 to 6.8 percent, was statistically significant (P less than 0.05). During the same period, operative vaginal deliveries (i.e., forceps deliveries and midpelvic procedures) declined from 10.4 to 4.3 percent (P less than 0.05) of total deliveries. We conclude that an initiative within an obstetrics department can reduce cesarean-section rates substantially without adverse effects on the outcome for mother or infant.
Apgar Score↗
Autoantibodies and common idiotypes in men and women with sperm antibodies.
Antisperm antibodies have been implicated as a causative factor of infertility and pregnancy wastage. Since concomitant autoimmune phenomena were reported in men with antisperm antibodies, we investigated known antisperm antibody-positive sera from 25 women, 27 men, and the respective seminal plasma samples. The investigated autoimmune panel included a search for antinuclear antibodies, autoantibodies (in IgG, IgM and IgA isotypes) to seven phospholipids (cardiolipin, phosphatidylserine, phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidic acid), to four histone subfractions (H1, H2A, H3, H4), and to four polynucleotides [ssDNA, dsDNA, poly(I), and poly(dT)], total immunoglobulin levels, and sperm antibody titers. The sera were also evaluated for the presence of a common anti-deoxyribonucleic acid antibody, and anticardiolipin antibody idiotypes. Levels of sperm antibody titers were significantly lower in women than in men. Both men and women with antisperm antibodies demonstrated elevated total IgG levels compared with those of normal control subjects. Only women showed elevated levels of total IgM. Sera from 24% of women and 11% of men with antisperm antibodies demonstrated antinuclear antibody titers greater than 1:40. The most striking autoantibody abnormalities were found among antiphospholipid antibodies. Sera from women with antisperm antibodies demonstrated higher autoantibody production than was found in their male counterparts. A significant correlation was found between antisperm antibodies and IgM anticardiolipin and IgA anti-phosphatidylinositol in women and between sperm antibodies and IgA phosphatidylserine antibodies in men. The presence of anticardiolipin and anti-deoxyribonucleic acid antibody idiotypes was significantly more frequent in women than in men. By means of discriminant analysis and variables selected by this mathematical model, the identification of 24 of 25 women and 26 of 27 men with antisperm antibodies was correctly predicted. These results suggest that women and men respond differently to sperm antigens. The apparent cross-reactivity between sperm antibodies and other autoantibodies, usually associated with autoimmune disease, suggests that a polyclonal B cell activation, similar to that seen in autoimmune diseases, occurs in patients with sperm antibodies.
Adult↗
The reproductive autoimmune failure syndrome.
The association between reproductive failure and abnormal autoimmune function has been recognized for decades in association with such established autoimmune diseases as systemic lupus erythematosus. Recent investigations have expanded this association to women who demonstrate similar humoral abnormalities as patients with defined autoimmune diseases but do not express any of the clinical symptoms required for the diagnosis of an autoimmune disease. The observation that abnormal autoimmune function in clinically asymptomatic patients can lead to reproductive failure has led us to define the reproductive autoimmune failure syndrome as a diagnostic entity. The present article summarizes evidence suggesting that the occurrence of reproductive autoimmune failure syndrome may be teleologically related to the woman's need for increased self-tolerance in face of antigenic exposure to the maternal haplotype of the fetus during normal pregnancy. This need for increased self-tolerance is documented by higher normal autoantibody levels in women than in men and may also be responsible for the highly increased incidence of autoimmune diseases in women in comparison with men. Under this concept, abnormal autoimmune function may lead to reproductive failure at different stages of the reproductive process, depending on the quality and possibly quantity of the abnormal autoimmune response.
Abortion, Habitual↗
Immunologic aspects of IUD action.
Embryo implantation has been demonstrated to depend on specific lymphocyte populations within the uterine cavity. Intrauterine devices (IUD) exert their contraceptive action by prevention of embryo implantation via presently still unknown mechanisms. Therefore, mononuclear cell populations from mice uteri which either contained silastic or copper (Cu) IUD fragments or were sham-operated were evaluated, utilizing monoclonal antibodies against specific cell markers. Uterine horns, bearing IUD fragments, were significantly heavier than sham-operated horns. In Cu-IUD animals this effect extended even into the non-treated contralateral horn. The total number of lymphoid cells in IUD-bearing horns was significantly higher than in sham-operated horns. This observation was also made in non-treated contralateral Cu-IUD horns but not in contralateral horns of silastic-IUD-treated animals. Significant differences in percentages as well as absolute number of various lymphoid cell populations were noted between IUD-treated and sham-operated animals. Again, the effect was more pronounced in Cu-IUD-treated animals and extended in those animals into the contralateral horn. IUD-containing horns also demonstrated a significantly increased number of mast cells, with Cu-IUDs again resulting in a significantly more pronounced effect in both treated and contralateral horns. Sham-operated mice achieved a 67% pregnancy rate in both uterine horns. In contrast, IUD-treated animals demonstrated a significantly reduced pregnancy rate with silastic IUD fragments (15% and 30% for treated and contralateral horn, respectively) and a 0% pregnancy rate for Cu-IUD-treated animals (in either horn).
Animals↗