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Biomedical subjects

E Confino

Publications and source records attributed to E Confino.

At least 37 records · Page 2Linked to original sources

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↗

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↗

Preliminary experience with transcervical balloon tuboplasty.

We developed a new technique, transcervical balloon tuboplasty, an adaptation of established balloon angioplasty techniques that facilitates recanalization of proximally occluded oviducts. Sixteen patients with obstruction of the proximal portion of one or two fallopian tubes (based on at least two hysterosalpingograms and one laparoscopic examination) were selected for the procedure. Four patients (25%) were found to have patent oviducts on intraoperative third tubal patency evaluation and were therefore excluded from study. Of the remaining 12 patients, tubal patency was achieved in at least one fallopian tube in 7 patients (58%), as demonstrated by hysterosalpingogram immediately after the transcervical balloon tuboplasty procedure. On follow-up 2 months to 1 year afterward, two pregnancies and one delivery occurred. We conclude that transcervical balloon tuboplasty appears to represent a useful and safe technique to achieve patency in selected cases of tubal interstitial obstruction. Reocclusion rates, long-term complication rates, and pregnancy rates after transcervical balloon tuboplasty remain to be established before the procedure should be considered a recommended alternative for either surgical tuboplasty or in vitro fertilization.

Adult↗

Spontaneous recanalization of cornual tubal occlusion following a pregnancy achieved by in vitro fertilization.

A patient with bilateral tubal occlusion conceived by IVF and delivered a healthy infant vaginally. Four months postpartum, the patient again conceived spontaneously and carried to term. Recanalization of one fallopian tube was demonstrated on HSG performed after delivery of the second infant. Mechanical stretching and pregnancy-induced hormonal changes may explain spontaneous recanalization of obstructed fallopian tubes.

Adult↗

Improved penetration of spermatozoa into uterine fluids of women with abnormal postcoital tests.

Cervical mucus-uterine fluid cross-penetration of husbands' and control sperm was assessed in 13 couples with poor or negative postcoital tests. Cervical mucus scoring and tray agglutination test identified six women with sperm-agglutinating antibodies and seven women with cervical dysmucorrhea. All males were normozoospermic, with penetration into control cervical mucus and control uterine fluids. Control sperm penetrated into cervical mucus and uterine fluids of three and five of the women with sperm-agglutinating antibodies and cervical dysmucorrhea, respectively. Penetration of husbands' spermatozoa into uterine fluids of patients with sperm-agglutinating antibodies was lower than that of control semen (P less than .05). Control and husbands' sperm penetration into uterine fluids of women with cervical dysmucorrhea were identical. In both groups, husbands' and control sperm penetrated uterine fluids more frequently than cervical mucus (75 versus 12%; P less than .001). On a six-month follow-up and midcycle intrauterine inseminations, six patients (46%) conceived. We conclude that uterine fluids of patients with sperm-agglutinating antibodies and cervical dysmucorrhea may provide a better milieu for spermatozoa than cervical mucus. This observation suggests a rationale for intrauterine inseminations to achieve pregnancy.

Antibodies↗

Acute salpingitis in sterilized women.

Previously sterilized women are generally considered protected against salpingitis. However, when we diagnosed salpingitis by laparoscopy in 48 patients during a 16-month period, we found four (8%) who had been previously sterilized. Therefore, contrary to generally stated belief, salpingitis may occur after interruption of tubal continuity.

Acute Disease↗

Is endometriosis an autoimmune disease?

Among 59 laparoscopically staged endometriosis patients, 28.8% tested positive for antinuclear antibody. Of 44 patients, 45.5% were lupus anticoagulant positive (greater than 1.3) and 20.5% were within a borderline range (1.2-1.3). Antinuclear antibody positivity was inversely related to stage of disease (P = .009); lupus anticoagulant positivity exhibited a similar trend, but did not reach statistical significance. Of 31 endometriosis patients, 64.5% exhibited immunoglobulin G (IgG) autoantibodies and 45.2% demonstrated IgM autoantibodies to at least one of 16 antigens investigated. Among IgG autoantibodies, those to phospholipids were most frequently detected, followed in order of frequency by antibodies to histones and nucleotides. The incidence of IgM autoantibodies was inverted, with antinucleotides appearing most frequently and antiphospholipids least frequently. A strong correlation was noted between the presence of lupus anticoagulant and antinuclear antibody with both IgG and IgM autoantibodies. These observations suggest that endometriosis is associated with abnormal polyclonal B cell activation, a classic characteristic of autoimmune disease. This contention is further supported in that immunoglobulin levels (particularly IgG) are elevated in patients with endometriosis, and more so in lupus anticoagulant-positive than lupus anticoagulant-negative endometriosis patients (P = .021).

Antibodies, Antinuclear↗

Penetration of bacteria and spermatozoa into bovine cervical mucus.

It has been reported that bacteria may attach to motile spermatozoa, be carried through the cervix and uterus to the fallopian tubes, and cause acute salpingitis. In an attempt to mimic these conditions in vitro, we incubated Escherichia coli, Streptococcus faecalis, Pseudomonas aeruginosa, and Staphylococcus aureus with motile spermatozoa which then were allowed to migrate through a capillary filled with bovine cervical mucus. After satisfactory sperm migration through the mucus, the capillaries were broken and cultured at different distances from the original insemination site. Mucus fractions in proximity to bacterial inocula grew varying amounts of the pathogens. More distal fractions of mucus columns were generally culture-negative even though they contained motile sperm which had been exposed to bacteria. Migration of spermatozoa exposed to bacteria through bovine cervical mucus did not result in enhanced bacterial penetration.

Animals↗

Chlamydia trachomatis attached to spermatozoa recovered from the peritoneal cavity of patients with salpingitis.

Five in a series of ten patients with laparoscopically demonstrated salpingitis had cultures positive for Chlamydia trachomatis obtained from tubal and peritoneal surfaces. Spermatozoa were observed in the peritoneal fluid of three of these patients, and two had cultures positive for C trachomatis. C trachomatis was attached to spermatozoa recovered from the peritoneal cavity in both patients. This observation suggests that spermatozoa may serve as vectors for C trachomatis and spread this pathogen to the peritoneal surfaces of the uterus and fallopian tubes.

Ascitic Fluid↗

Correlation between peripheral blood and follicular fluid autoantibodies and impact on in vitro fertilization.

Total immunoglobulins, C3 and C4 complement, and autoantibodies to phospholipid antigens, histones, histone subfractions, and nucleotides were measured in serum and follicular fluids of 26 patients undergoing in vitro fertilization. Immunoglobulins and complement fractions appeared in statistically lower concentrations in follicular fluid than in serum. This gradient was clearly larger for immunoglobulin M (IgM) than for IgG, IgA, C3, or C4. Ten patients who were autoantibody positive to one or more of the evaluated antigens demonstrated statistically higher total IgG and IgM levels and lower C3 and C4 than 16 autoantibody negative patients. With regard to follicular fluid, positive patients had significantly elevated IgM levels in comparison with negative control patients, and significantly decreased C3 and C4 concentrations. Patients who were autoantibody positive in serum also exhibited uniformly abnormal follicular fluid autoantibodies. Positive patients had significantly higher IgG antiphospholipid antibodies in follicular fluid than controls, and demonstrated a similar trend for IgM and IgA antiphospholipid antibodies. Positive patients demonstrated no significant differences from negative patients in number of in vitro fertilization attempts, number of oocytes retrieved, fertilization rate, cleavage rate, and number of abnormal (granular) oocytes. However, positive patients experienced a lower pregnancy rate (5.4%) than negative patients (26.1%), although the difference did not reach statistical significance (P = .07). This observation strongly suggests that the presence of abnormal autoantibodies in the female may reduce the chance of pregnancy for in vitro fertilization patients. A similar effect of abnormal autoantibodies can then also be expected in attempts at spontaneous conception.

Autoantibodies↗

Non-vascular transplantation of the rabbit uterus.

Transplantation of the uterus may be an optimal solution in young hysterectomized patients, in women with agenesis of the uterus or in severe uterine anomalies. In the human model, attempted tubal and ovarian homografts have usually failed. Eighteen rabbits underwent unilateral non-vascular uterine transplantation. Four rabbits underwent total unilateral uterine autograft. Three uteri showed severe inflammation and necrosis 72 h, 1 week and 1 month postoperatively. Thereafter, the operative technique was modified to avoid contamination from the vagina and four rabbits underwent supravaginal unilateral non-vascular autograft. Three uteri had preserved endometrial and myometrial structure on relaparotomy. The following four rabbits underwent homotransplantation of the uterus and showed acute rejection of the transplant. Under cyclosporine therapy three homotransplanted rabbits developed pelvic abscesses while three other rabbits showed preserved myometrial and endometrial structures.

Animals↗

Decreased gestational sac volumes in pregnancies induced by human menopausal gonadotropin.

Mean gestational sac volumes of 9 singleton pregnancies induced by human menopausal gonadotropin (hMG) measured by ultrasound were compared with mean gestational sac volumes obtained from 37 normal singleton pregnancies, 6 to 8 weeks from the last menstrual period. HMG-induced gestational sacs were smaller at 6 and 7 weeks of gestation, compared with normal pregnancies. Despite the initial lag in gestational sac volume, hMG-induced pregnancies subsequently demonstrated appropriate fetal growth as measured by crown-rump length measurements between 8 and 12 weeks. These pregnancies also demonstrated normal fetal growth patterns in the second and third trimesters of pregnancy, as assessed by clinical evaluation and ultrasound. These preliminary data suggest that early growth development in hMG-induced pregnancies may be different from that in spontaneously occurring pregnancies.

Embryonic and Fetal Development↗

Histopathological findings in 226 women with post-menopausal uterine bleeding.

Histopathological findings in 226 post-menopausal bleeding women were reviewed retrospectively. Adenocarcinoma of the endometrium was diagnosed in 7% and hyperplastic endometrium in 15%. The incidence of malignancy showed a definite rise with advancing age, increasing amount and duration of bleeding, prolonged time interval between the menopause and onset of bleeding, and enlarged uterus. Adenocarcinoma of the endometrium was associated in 40% of the patients with either obesity, diabetes mellitus, or hypertension. The most frequent histopathological finding was atrophic endometrium (45%).

Adenocarcinoma↗

Pitfalls in sonographic imaging of the incompetent uterine cervix.

Artifacts interfering with sonographic imaging of the uterine cervix in pregnancy are described. Increasing the amount of fluid in the urinary bladder closes the cervix and alters the configuration of the lower uterine segment, while increased intra-uterine pressure results in reciprocal changes. Angulation of the transducer and manual pressure thereon distort sonographic findings. It is concluded that, contrary to recent reports in the literature, sonography cannot reliably demonstrate changes in cervical compliance during pregnancy. Vaginal examination remains the ultimate diagnostic modality for the diagnosis of the incompetent cervix, while sonography may be used as an adjunct only.

Cervix Uteri↗