Donna Pratt

The association of antithyroid antibodies in euthyroid nonpregnant women with recurrent first trimester abortions in the next pregnancy

OBJECTIVE To evaluate the prognostic value of antithyroid antibodies in euthyroid women with a history of recurrent first trimester abortions on future pregnancy loss. DESIGN The sera of 42 euthyroid women with a history of three or more consecutive first trimester abortions were evaluated for the presence of antibodies to thyroglobulin and thyroid peroxidase before pregnancy and again as soon as the diagnosis of pregnancy was made. SETTING Medical school-affiliated private infertility center. PATIENTS Forty-two women with a history of three or more consecutive first trimester abortions who were planning to conceive again. MAIN OUTCOME MEASURE The presence of antithyroid antibodies in the nonpregnant state and their association with pregnancy loss in the next gestation. RESULTS Thirteen of 42 women (31%) were positive for the presence of antithyroid antibodies at the initial screening before pregnancy. All 13 maintained positivity by the time their next pregnancy was diagnosed. Only 12 of those 42 women (29%) experienced a first trimester abortion. Eight of these 12 women (67%) were positive for one or more antithyroid antibody. In contrast, among 30 nonaborting women, only 5 of 30 (17%) exhibited thyroid antibody positivity. The detection of thyroid antibodies before conception carried an increased risk of pregnancy loss in the next pregnancy (8 of 13, 62% versus 4 of 29, 14%). CONCLUSION The presence of antithyroid antibodies in nonpregnant women with a history of recurrent abortion identifies a subgroup of women at significantly increased risk for yet another pregnancy loss in their next gestation. Because organ-specific autoantibodies thus demonstrate similar prognostic significance to nonorgan-specific autoantibodies, it is tempting to conclude that peripheral autoantibody abnormalities seen in habitual aborters only reflect an underlying T-lymphocyte defect, which may be the actual cause of pregnancy loss.

Antithyroid antibodies and the association with non-organ-specific antibodies in recurrent pregnancy loss.

OBJECTIVES The purpose of our study was to evaluate the incidence of antithyroid antibodies and non-organ-specific antibodies in women who have had three or more recurrent spontaneous abortions. STUDY DESIGN Sera from 45 women for the presence of antithyroid antibodies to thyroglobulin and thyroid peroxide and for the non-organ-specific autoantibodies to 6 phospholipids, 5 histones, and 4 polynucleotides were analyzed. Sera from 100 apparently health blood donors served as controls. RESULTS The test results of 14 (31%) of 45 study subjects were positive for one or both antithyroid antibodies compared with 19 (19%) of controls. Five (11%) of 45 patients had positive test results for one or more non-organ-specific antibodies, and 4 (8%) of 45 had positive test results for the lupus anticoagulant by either activated partial thromboplastin, tissue thromboplastin time, or both. Only 3 (21%) of 14 subjects whose test results were positive for thyroid antibodies also demonstrated non-organ-specific autoantibodies. COMMENTS The incidence of antithyroid antibodies in women who have had recurrent abortions appears not to be significantly increased compared with a normal random control population. Antithyroid antibodies do occur, however, with significantly greater frequencies in women with recurrent spontaneous abortions than non-organ-specific autoantibodies (p = 0.02). Organ-specific and non-organ-specific autoantibodies may serve as independent markers of risk for repeated pregnancy loss in patient populations where pregnancy loss is associated with abnormal autoimmune function.

WHAT DO WE REALLY KNOW ABOUT AUTOANTIBODY ABNORMALITIES AND REPRODUCTIVE FAILURE: A CRITICAL REVIEW

CONDENSATION The diagnosis and treatment of autoantibody-associated forms of reproductive failure is critically reviewed. OBJECTIVE To critically evaluate the published literature in reference to autoantibody-associated forms of reproductive failure. LOCATION Medical School-affiliated private Infertility Center. MATERIALS A review of over 200 published papers reflecting on the topic. RESULTS Autoantibody associated reproductive failure, characterized by a decrease in fecundity and an increase in the risk of pregnancy loss, appears established. Autoantibody abnormalities, as routinely detected by standard laboratory assays, are, however, neither immunologically nor biologically specific since cross reactivities between autoantibodies are frequent and a specific autoantibody may cause a biological effect in one but not in another affected individual. CONCLUSIONS The evaluation of autoantibody abnormalities in all cases of suspected autoimmune-associated reproductive failure is valuable and will improve clinical care of affected patients. Clinicians need, however, to recognize the limitations of autoantibody testing and have to adjust their clinical management to the degree and quality of autoantibody evaluation available to them in their community.

Autoantibody profiles and immunoglobulin levels as predictors of in vitro fertilization success

OBJECTIVE Our aim was to determine the predictive value of autoantibody and immunoglobulin determinations as indicators of the success of in vitro fertilization. STUDY DESIGN This was a blinded study in which laboratory evaluations were performed on coded samples obtained from another institution. Codes were broken and data were analyzed after results of all laboratory tests had been reported out. One hundred five infertility patients who had undergone in vitro fertilization were randomly chosen. Among those, 46 were considered low responders (six or fewer oocytes were retrieved) and 59 as high responders (13 to 30 oocytes were retrieved). Total immunoglobulin G, M, and A levels and 15 autoantibody levels (6 antiphospholipids, 5 antihistones, and 4 antipolynucleotides) were determined separately for immunoglobulin G, immunoglobulin M, and immunoglobulin A isotypes. RESULTS High and low responders demonstrated an unusual incidence of autoantibody (25% and 30%, respectively) and immunoglobulin (46% and 48%, respectively) abnormalities. They did not differ from each other, however, in either immunoglobulin or autoantibody parameters. Autoantibody and immunoglobulin abnormalities alone or in combination did not predict pregnancy success (24% vs 16%), incidence of chemical pregnancies (15% vs 24%), or clinical pregnancy loss (9% vs 11%) when such women were compared with those without either abnormality. However, the occurrence of hypergammaglobulinemias, in contrast to hypogammaglobulinemias, was associated with a significant decrease in the clinical pregnancy rate (6% vs 24%, p = 0.05). CONCLUSIONS Neither autoantibody abnormalities nor total immunoglobulin abnormalities allow differentiation between high and low responders in in vitro fertilization cycles. The presence of autoantibody and total immunoglobulin abnormalities also does not predict low clinical pregnancy rates. Within a group of women with immunoglobulin abnormalities, those with hypergammaglobulinemias appear, however, at significant risk for low pregnancy rates with in vitro fertilization. This observation suggests that high total immunoglobulin levels may serve as a marker for an as yet to be determined immunologic factor that adversely affects the chance of conception. The evaluation of total immunoglobulin levels may be indicated as part of a routine infertility workup.

The limited value of hysterosalpingography in assessing tubal status and fertility potential

DESIGN To determine whether the diagnostic accuracy and prognostic value of hysterosalpingography (HSG) could be improved if routine spot films were replaced by an on-line recorded gynecoradiologic study. SETTING Medical school-affiliated private infertility center. PATIENTS In 1992, a review of 152 infertile women with infertility who demonstrated a normal HSG, by standard criteria of spot film evaluation, in 117 (77%). They were further investigated by gynecoradiologic study if the HSG revealed asymmetrical tubal filling, an increased perfusion pressure, and/or evidence for abnormal tubal spill. In 1993, 47 women with normal HSG by spot film criteria underwent bilateral selective salpingography and were subdivided into those with normal (group I, n = 23) and abnormal (group II, n = 24) tubal perfusion pressures. INTERVENTION Patients in both study groups then were treated for their infertility independently of pressure perfusion measurements. MAIN OUTCOME MEASURE Clinical pregnancy rates (PRs) over the ensuing 6 to 10 months. RESULTS Among 117 women with apparently normal spot film HSG, 64 (55%) demonstrated asymmetrical tubal filling, 32 (27%) demonstrated abnormal spillage into the peritoneal cavity, and 55 (47%) demonstrated abnormally elevated injection pressures. Among 98 women who underwent bilateral selective salpingography, 43 (44%) demonstrated bilaterally normal tubal perfusion pressures and 55 (56%) showed an abnormally elevated pressure in at least one oviduct. Of 47 women that were followed prospectively in 1993, patients with normal perfusion pressure (group I) demonstrated a significantly higher PR than women with elevated tubal pressure (group II) from 2 months and on after the procedure. CONCLUSIONS Routine spot film HSG is of limited value in assessing tubal status beyond the determination of tubal patency. Especially with regard to fertility potential, HSG should be replaced by gynecoradiologic study.

A randomized prospective comparison between intrauterine insemination and fallopian sperm perfusion for the treatment of infertility

OBJECTIVE To determine if the pregnancy rates (PRs) in infertile women could be improved with fallopian sperm perfusion in comparison with IUI. DESIGN Randomized prospective analysis. SETTING Academically affiliated infertility center. PATIENTS Consecutive patients undergoing controlled ovarian hyperstimulation (COH). INTERVENTIONS After hCG administration, patients were randomized to either IUI or fallopian sperm perfusion. MAIN OUTCOME MEASURES Pregnancy rates with the two treatment modalities. RESULTS Of 240 COH cycles, those randomized to IUI included 44 clomiphene citrate (CC) (group I) and 76 gonadotropin (group III) cycles. Patients receiving fallopian sperm perfusion included 44 cycles of CC (group II) and 76 cycles of gonadotropin (group IV) treatment. The overall PRs per cycle (10.8% versus 10.8%) were similar for IUI and fallopian sperm perfusion, respectively. The PRs were also similar when compared for ovulation induction with CC (6.8% versus 9.1%) and gonadotropins (13.2% versus 11.8%). CONCLUSION We conclude that fallopian sperm perfusion offers no advantage over IUI. Because the process of fallopian sperm perfusion is more time consuming and more costly (because of increased media usage), fallopian sperm perfusion does not seem indicated as a routine infertility therapy and should not replace IUI.

Standardization of hysterosalpingography and selective salpingography: a valuable adjunct to simple opacification studies *

OBJECTIVE To investigate the correlation between opacification and perfusion pressures during hysterosalpingography (HSG) and selective salpingography under the assumption that the latter may add to the diagnostic capabilities of the procedures. DESIGN Perfusion pressures were uniformly evaluated by standardizing injection volume per time interval of contrast medium and the delivery system. Pressures were measured in a closed system through a digital manometer and recorded on tracing paper. SETTING Fully ambulatory gynecoradiology suite at academically affiliated infertility center. PATIENTS Thirty infertility patients. INTERVENTION Hysterosalpingography and selective salpingography for diagnostic purposes. MAIN OUTCOME MEASURE Correlation between opacification patterns and perfusion pressures. RESULTS The evaluation of perfusion pressures during HSG is unreliable because they may be affected by uterine factors and will only reflect the oviduct of least resistance. In contrast, perfusion pressures during selective salpingography are reflective of only the investigated tube. They appear to lie within a functionally normal range of up to 350 mm Hg. Tubes by opacification judged as normal exhibited a pressure range of 429 +/- 376 mm Hg, which was significantly lower than that of abnormally appearing oviducts (957 +/- 445 mm Hg; P = 0.001). CONCLUSIONS The concomitant performance of perfusion pressure studies during selective salpingography further enhances the diagnostic capability of selective salpingography over HSG in the diagnostic evaluation of fallopian tubes.

Laparoscopic removal of twin cornual pregnancy after in vitro fertilization

The laparoscopic management of tubal pregnancies by salpingostomy has become a clinical standard of care (5). Those surgeries usually are performed for tubal pregnancies that are located distally to the cornua and the intramural piece of the tube. We previously reported on the conservative surgical management of interstitial pregnancies (3). To our knowledge, cornual pregnancies have never before been approached laparoscopically. Such a surgical approach is reported here, involving a twin gestation in the left uterine cornua conceived by IVF in a women with bilaterally absent tubes.

Elevated tubal perfusion pressures during selective salpingography are highly suggestive of tubal endometriosis.

OBJECTIVE To investigate the possible etiologies of elevated tubal perfusion pressures. DESIGN Analysis of 48 consecutive female patients with infertility who underwent laparoscopy and a gynecoradiological investigation as part of their infertility work-up. SETTING Academically affiliated infertility center. INTERVENTIONS A gynecoradiological investigation was performed using a previously reported standardized contrast injection system. Laparoscopy was performed routinely. RESULTS Patients who demonstrated by laparoscopy to have endometriosis showed a significantly increased incidence of tubal blockage during initial hysterosalpingography (HSG) (12/26, 46.1%) compared with controls (2/14, 14.3%). Patients with endometriosis also demonstrated significantly more frequently elevated tubal perfusion pressures (22/26; 84.6%) than women without disease (2/14, 14.3%) and significantly higher mean tubal perfusion pressures than women with normal pelvises (576 +/- 264 versus 450 +/- 268 mm Hg). CONCLUSION Tubal blockage during initial HSG and elevated tubal perfusion pressures during selective salpingography are highly suggestive of tubal endometriosis. These data are the first evidence that tubal involvement with endometriosis may be more frequent than previously suspected. They also suggest that the performance of a gynecoradiological investigation, inclusive of selective salpingography, can greatly contribute to a presumptive diagnosis of endometriosis.

Transvaginal intratubal insemination by tactile sensation: a preliminary report

Transvaginal catheterization of the fallopian tube has gained increased popularity for transfer of embryos and gametes. Forty-five ITIs were performed on 32 patients using the novel approach of tubal transfer via tactile sensation. This group of patients had undergone an average of 5.2 IUIs before ITI. There were a total of 11 pregnancies, 6 occurring with hMG stimulation and 5 with CC-stimulated cycles (34% PR per patient). Three pregnancies ended with spontaneous abortion, and one patient developed acute salpingitis necessitating laparotomy. These data suggest ITI may be effective in assisted reproduction but, as other invasive procedures, is not without risk.