Incidence and risk factors for incomplete HBV DNA suppression in HIV/HBV-co-infected patients initiating tenofovir-based therapy.

Suppression of hepatitis B virus (HBV)-DNA to undetectable levels is an important goal for HIV/HBV-co-infected patients receiving anti-HBV-active antiretroviral therapy (ART), and current guidelines recommend that this outcome should be reached by 1 year of treatment. However, the proportion of patients that fail to achieve an undetectable HBV DNA at this time point and its determinants remain unknown in clinical practice. The objective of this study was to determine the incidence and risk factors for incomplete HBV suppression following 1 year of tenofovir-based ART. We performed a cohort study among tenofovir-treated HIV/HBV-co-infected patients. Patients had HBV viraemia, initiated tenofovir-based ART and had HBV DNA measured at 1 year of therapy. The primary outcome was incomplete HBV suppression (HBV DNA ≥2.6 log IU/mL) at 1 year. Logistic regression determined odds ratio (ORs) of incomplete HBV suppression for risk factors of interest. Among 133 patients, 54% (95% CI, 46-63%) had incomplete HBV suppression at 1 year. Incomplete suppression was associated with higher baseline HBV DNA (OR, 1.46 per log IU/mL increase; 95% CI, 1.1-1.94) and detectable HIV viraemia at 1 year (OR, 2.52; 95% CI, 1.19-5.32). Among 66 patients with suppressed HIV RNA at 1 year, 28 (42%) failed to achieve an undetectable HBV DNA. Failure to suppress HBV DNA by 1 year occurred in a sizeable proportion of tenofovir-treated HIV/HBV-co-infected patients. Higher HBV DNA and detectable HIV viraemia were risk factors for incomplete HBV suppression.

A near-fatal hypersensitivity reaction to abacavir: case report and literature review.

A near-fatal hypersensitivity reaction to abacavir developed in a 62-year-old HIV-seropositive man who had been sensitized 17 months before presentation. Six days after he was rechallenged, acute respiratory distress developed, requiring mechanical ventilation for 2 weeks. Four days after extubation, he was again rechallenged. Hours later, the patient experienced anaphylactic shock, requiring mechanical ventilation for 3 weeks, aggressive volume resuscitation, and vasopressor support. Recovery was complicated by acute tubular necrosis, digital necrosis, and a GI bleed. This report reviews the mechanisms of action, efficacy, and adverse reactions of abacavir and illustrates the danger of serially rechallenging patients with this agent.

Qualitative and quantitative evaluation of six algorithms for correcting intensity nonuniformity effects.

The desire to correct intensity nonuniformity in magnetic resonance images has led to the proliferation of nonuniformity-correction (NUC) algorithms with different theoretical underpinnings. In order to provide end users with a rational basis for selecting a given algorithm for a specific neuroscientific application, we evaluated the performance of six NUC algorithms. We used simulated and real MRI data volumes, including six repeat scans of the same subject, in order to rank the accuracy, precision, and stability of the nonuniformity corrections. We also compared algorithms using data volumes from different subjects and different (1.5T and 3.0T) MRI scanners in order to relate differences in algorithmic performance to intersubject variability and/or differences in scanner performance. In phantom studies, the correlation of the extracted with the applied nonuniformity was highest in the transaxial (left-to-right) direction and lowest in the axial (top-to-bottom) direction. Two of the six algorithms demonstrated a high degree of stability, as measured by the iterative application of the algorithm to its corrected output. While none of the algorithms performed ideally under all circumstances, locally adaptive methods generally outperformed nonadaptive methods.

Elevated basal estradiol levels have no negative prognosis in young women undergoing ART cycles.

The objective of this study was to determine the relationship between serum estradiol levels on day 2 of an in vitro fertilization and embryo transfer (IVF-ET) cycle and the chance of pregnancy and implantation rates according to age. Two hundred and forty-eight cycles of IVF-ET in patients treated with gonadotropin-releasing hormone analog (GnRHa, follicle-stimulating hormone (FSH) and human menopausal gonadotropin (hMG) were divided into several groups according to the basal serum concentrations of estradiol (E2):A < 25 pg/ml, B 26-50 pg/ml, C 51-75 pg/ml, D 76-100 pg/ml, E > 100 pg/ml. Furthermore, the patients were subdivided into two subgroups according to age: I younger; and II, older than 35 years. Pregnancy and implantation rates were analyzed for each subgroup according to basal E2 level and age. Statistical analysis was performed using analysis of variance, chi2 and Fisher's test. The number(s) of cycles for each subgroup were 164 and 84 for I and II, respectively. Even though there were no significant differences among groups for the pregnancy rates for individual groups, there was a tendency for a decreased rate with increasing levels of E2 only in women older than 35 years of age. When pregnancy rates of all women with E2 levels above 25 pg/ml were calculated, the differences between those observed in subgroup I (< or = 35 years) and II (> 35 years) was significant: p = 0.02 (38.7% vs. 18.7%, respectively). When implantation rates in the same groups and subgroups were analyzed, we found that again the differences were statistically significant: p = 0.001 (13.1%vs, 4.3% for I and II). The results of the present studies reveal that basal levels of E2 are a marker of poor prognosis for implantation and pregnancy in assisted reproduction (ART) cycles only in patients over the age of 35 years. These data cast doubt on the use of basal levels of E2 to screen women below the age of 35 prior to initiating an ART cycle. In addition, high levels of basal E2 per se may not be deleterious for reproductive efficiency in younger women, since pregnancy and implantation rates did not differ among patients younger than 35 years old (IA to E).

Anti-endothelial cell antibodies: another cause for pregnancy loss?

PROBLEM: Previous studies demonstrated that unique tissue-specific antigens expressed on vascular endothelial cells can serve as immunogens, and the apparent association between transplant rejection and antiendothelial cell (EC) antibodies is well established. A common feature of some placentas from women with recurrent pregnancy loss is the diffuse formation of microthrombi associated with changes in thromboresistant properties of endothelial cells, similar to the findings in rejected organs. Therefore, the prevalence of anti-EC antibodies in patients with recurrent pregnancy loss and the role of these antibodies in cultured human endothelial cells from umbilical cord vein were studied. METHOD OF STUDY: To evaluate the frequency of anti-EC antibodies, sera from 160 nonpregnant patients with recurrent pregnancy loss after absorption with pooled platelets and pooled leukocytes were tested using cultured human umbilical cord vein endothelial cells (HUVEC) by flow cytometry. To study the role of anti-EC antibodies, purified anti-EC IgGs were added to HUVEC cultures and hemostatic, fibrinolytic, and anticoagulation pathway markers (tissue factor, tissue plasminogen activator, palsminogen-activator inhibitor, thrombomodulin, heparan-sulfate proteoglican, antithrombin III, von Willebrand factor, CD54, human leukocyte antigens-DR, and transferin receptor) were detected by specific antibodies and flow cytometry. Immunoblotting analyses were done by using purified anti-EC IgGs against cell membrane proteins from endothelial cells and leukocytes extracted by detergent solubilization. RESULTS: Thirty-nine (24%) of the patients were positive for EC antibodies. Antipaternal lymphocyte antibodies were tested as well and were found in 37 (23%) of the patients as 25 sera (15.6%) showed reactivity with both EC and lymphocytes. Certain patient sera were reactive with HUVEC lines from some but not other umbilical cords, which suggests allotypy. Sera from 70 normal healthy male and nonpregnant female controls did not react with any of the individual HUVEC lines used. The purified anti-EC immunoglobulin G (IgGs) recognized bands, from HUVEC surface membrane protein preparations, with molecular weights of 120 kDa. Both hemostatic and fibrinolytic pathway markers were found activated in the presence of anti-EC IgGs, suggesting an altered endothelial cell surface activation state. CONCLUSIONS: The results indicate that anti-EC antibody is another marker for a subset of recurrent spontaneous aborters who may have activation of hemostasis and fibrinolysis as a mechanism involved in their losses.

Immunotherapy for recurrent pregnancy loss: analysis of results from clinical trials.

PROBLEM: Up to 80% of unexplained recurrent spontaneous abortions (RSA) are thought to have an immunologic mechanism. Yet clinical trials using immunotherapy to treat women experiencing RSA have low treatment effects. The present study was undertaken to explain the low treatment effects. METHODS: Results of clinical trials using allogeneic leukocyte immunization and intravenous (IV) immunoglobulin (Ig) are compared. The mechanisms of pregnancy loss are reviewed in light of data on frequency of karyotype abnormalities in trophoblast of failing pregnancies. RESULTS: Results of two independent analyses using allogeneic leukocyte immunization as immunotherapy for all women with RSA revealed live birth ratios of 1.16 (P = 0.03) and 1.21 (P = 0.02). When the analysis was limited to primary aborters, the live birth ratio increased to 1.46 (P = 0.006). Live birth ratio after immunotherapy for all RSA using IVIg was 1.88 (P = 0.04). Because of low treatment effects, confounders to treatment success of maternal age and number of previous abortions were studied. Chromosomal abnormalities have been identified in 55% of concepti from RSA. The frequency of chromosomal abnormalities remained constant for up to six pregnancy losses. Women with a history of primary compared to secondary RSA had a higher frequency of karyotypically abnormal concepti (chi 2 = 4.54, P < 0.05). Risk factors for RSA also include number of previous losses. CONCLUSION: Chromosomal abnormalities are a significant confounder when evaluating efficacy of immunotherapy for treatment of RSA. Some women with RSA have a high risk of recurrent chromosomal problems.

Frequency of abnormal karyotypes among abortuses from women with and without a history of recurrent spontaneous abortion.

OBJECTIVE: To compare the frequency of chromosomal abnormalities in products of conception from women with and without a history of recurrent spontaneous abortion. DESIGN: Retrospective analysis of prospectively collected material. SETTING: Private practice at the Genetics and IVF Institute, Fairfax, Virginia and Grupo de Reproducción AGY Asociados, México City, México. PATIENTS: Women with (n = 94) and without (n = 130) a history of recurrent spontaneous abortion who had a spontaneous abortion between January 1, 1992 and November 1, 1994. INTERVENTION: Chromosomal analysis performed on products of conception using standard G-banding technique. MAIN OUTCOME MEASURE: The percentage of chromosomal abnormalities among products of conception from women with and without recurrent spontaneous abortion was compared. RESULTS: Among products of conception from women with recurrent spontaneous abortion, 57% (54/94) had abnormal and 43% (40/94) had normal chromosome analyses. Products of conception from women without recurrent spontaneous abortion had abnormal chromosome analyses in 57% (74/130) and normal results in 43% (56/130). CONCLUSIONS: No differences in frequency of abnormal karyotype were observed in products of conception from women with recurrent spontaneous abortion compared with women without recurrent spontaneous abortion.

Intravenous immunoglobulin for treatment of recurrent pregnancy loss.

PROBLEM: Efficacy of immunotherapy for treatment of recurrent spontaneous abortion (SA) has been controversial. The low treatment effect of white blood cell immunization lead to investigations of alternative treatments including intravenous (i.v.) immunoglobulin (Ig). To evaluate the efficacy of IVIg for treatment of recurrent SA, a prospective, randomized, double blinded, placebo-controlled trial was performed. METHODS: Ninety-five women experiencing two or more consecutive spontaneous abortions, with no known cause were randomized and received either IVIg 500 mg/kg/month or placebo (albumin). RESULTS: Of 95 women participating in the study, 47 received IVIg and 48 received placebo. Medication was discontinued in 34 women who failed to conceive within four cycles. The remaining 61 women achieved pregnancy. Pregnancy outcomes included 29 deliveries and 32 recurrent SA. Among women delivering live births 18 (62%) received IVIg and 11 (38%) received placebo. By contrast, 21 (66%) women experiencing recurrent SAs received placebo and 11 (34%) received IVIg. Among 61 women who conceived, 29 received IVIg and 32 received placebo. Of the 29 women who conceived and received IVIg, 18 (62%) delivered live births and 11 (38%) experienced recurrent SA. Of 32 women who conceived and received placebo 11 (34%) delivered live births and 21 (66%) had recurrent SA. The difference in live birth rates between women receiving IVIg and placebo was significant (P = 0.04, odds ratio 3.1). CONCLUSION: IVIg is effective in enhancing the percentage of live births among women experiencing unexplained recurrent SA.

Prevalence of embryotoxic factor in sera from women with unexplained recurrent abortion.

PROBLEM: The presence of embryotoxic factors in sera from women with recurrent spontaneous abortion (RSA) has been proposed as a basis for classification of unexplained RSA. To determine the prevalence of circulating embryotoxins among women with idiopathic RSA, sera from 160 women were studied using the mouse blastocyst assay. METHODS: Two-cell embryos were collected from superovulated mated (CB6F1/J mice and cultured in media supplemented with fetal bovine serum (FBS) or 10% serum at 37 degrees C with 5% CO2 and high humidity. Each assay was run in triplicate using three mice with at least five embryos from each mouse. Results were determined by calculating the average percentage atresia for each mouse. FBS, known to support embryo proliferation, was used to control in each assay. RESULTS: The prevalence of embryotoxic factors among women experiencing RSA was 24.4% (39/160). There is no correlation found between the presence of embryotoxicity and phospholipid antibodies, lupus anticoagulant, and thyroglobulin/microsomal antibodies. CONCLUSION: The embryotoxicity assay can serve as a basis for a new approach for classification of unexplained recurrent spontaneous abortion.

Serum progesterone at the time of human chorionic gonadotrophin does not predict pregnancy in in-vitro fertilization and embryo transfer.

Controversy exists as to whether the serum concentration of progesterone on the day of human chorionic gonadotrophin (HCG) administration following ovarian stimulation for in-vitro fertilization (IVF) and embryo transfer can be used to predict the likelihood of success. This retrospective study was undertaken to answer this question by analysing a large population of IVF and embryo transfer cycles (n = 756). In addition to the concentration of progesterone on the day of HCG administration, all variables known to impact on IVF and embryo transfer success (such as patient age), indication for IVF and embryo transfer, number of oocytes retrieved and the number of embryos generated and transferred were examined. There was a significant increase in the number of oocytes retrieved with increasing progesterone concentration at the time of HCG administration. However, there was no correlation of progesterone concentration at HCG administration with pregnancy and implantation rates. It is concluded that previous reports associating a slight elevation of progesterone in gonadotrophin-releasing hormone agonist ovarian stimulation cycles for IVF and embryo transfer may be misleading because of a small sample size or the presence of confounding variables that affect IVF and embryo transfer success.

Effect of seminal plasma on implantation rates.

The objective of this study was to evaluate the effect of seminal plasma on implantation rates. A prospective randomized placebo-controlled clinical trial was designed, and carried out at the Center for Reproduction and Transplantation Immunology. Eighty-seven women experiencing unexplained infertility and/or recurrent spontaneous abortion were recruited into the study and were randomized into groups using vaginal capsules containing seminal plasma or placebo (lubrication jelly). Implantation rates documented by the appearance of an intrauterine gestational sac visible on transvaginal ultrasonographic examination by the 6th week of gestation were compared between women receiving either seminal plasma or placebo. The results obtained from this study demonstrated that, of the 87 women participating in the study, 23 (26%) did not achieve pregnancy within 1 year. Nine of these infertile women received seminal plasma and 14 received placebo. Implantation rates were higher among women receiving seminal plasma (35/44, 80%) compared to placebo (29/43, 67%). The conclusions drawn from this study suggest that vaginal capsules containing seminal plasma appear to enhance implantation. They, therefore, may be useful in the treatment of couples undergoing assisted reproductive technologies or with unexplained infertility.

Validation of an embryotoxicity assay.

PROBLEM: Culture of mouse blastocysts has served as a tool for identifying various embryotoxic factors in human serum. While inactivated, sera from recurrently aborting women inhibit mouse blastocyst development in vitro. Variation in results from individual serum samples has limited the usefulness of this assay in establishing a new classification of idiopathic recurrent spontaneous abortion (RSA). METHOD: Two-cell embryos were collected from superovulated mated CB6F1/J mice and cultured in Ham's F-10 media supplemented with 10% fetal bovine serum (FBS) or tested human serum at 37 degrees C with 5% CO2 and high humidity. Each sample was assayed in triplicate using three mice with at least five embryos from the same mouse per dish. Development was evaluated at 72 h and the frequency of atretic embryos was recorded. RESULTS: Intrasample (interassay) variation yielded a coefficient of variation of 9%. When repeated, samples from a given individual were evaluated and the coefficient of variation was 8.7%. Interoperator variability was 4% interassay and 2% intrassay. Atresia of embryos was 23% when incubated with FBS (N = 122), 21% in FC (N = 122), and in the sera of patients with RSA 34.6% (N = 95). Results of percentage of atresia from the fertile control group had a nonparametric distribution. Using 2.2 multiples of the median to determine the 95% confidence interval, a threshold at 44.0% of atresia was established. CONCLUSIONS: The critical step in maintaining low variability in this bioassay is to control mouse variability by averaging the percentage atresia from different mice as embryo donors for each tested serum. A subgroup of 24% (23/95) RSA patients who displayed embryotoxic activity was identified with a specificity of 95% and positive predictive value of 83%, P = 0.001.

Comparison of pulsatility indices on the day of oocyte retrieval and embryo transfer.

Transvaginal ultrasonography with colour blood flow imaging and analysis of impedance to uterine arterial blood flow has been used to provide an index of uterine receptivity for implantation after IVF/embryo transfer. A mean uterine arterial pulsatility index (PI) > 3.0 at the time of embryo transfer predicted 35% of failures to become pregnant. Cryopreserving embryos in non-receptive cycles and transferring them in receptive cycles would be expected to improve pregnancy rates. Earlier decisions regarding embryo cryopreservation can be made if receptive cycles can be predicted at the time of oocyte retrieval rather than at embryo transfer. To assess differences in uterine artery impedance, PI were measured serially in 107 women on both the day of oocyte retrieval and the day of embryo transfer. Mean PI on the day of oocyte retrieval was 2.52 +/- 0.59, and on the day of embryo transfer was 2.78 +/- 0.45. No significant difference was observed when PI determined on the day of oocyte retrieval were compared with PI on the day of embryo transfer. These data suggest that the PI measurement done on the day of oocyte retrieval could substitute for the measurement done on the day of embryo transfer. This would allow prediction of non-receptive endometria earlier in the cycle. Further studies are needed to evaluate whether cryopreservation of embryos and transfer when the uterus is more receptive will increase the implantation rates.

Endocrine factors associated with recurrent spontaneous abortion.

The role of endocrine factors as a cause of recurrent spontaneous abortion is controversial. Diabetes mellitus and thyroid disease do not represent a significant risk factor for recurrent pregnancy loss. Luteal-phase defect has been questioned because there are no accurate methods for diagnosis and no convincing evidence of correction with treatment exists. The corpus luteum is an unusual endocrine gland, highly diverse in function and important for successful reproduction in all mammalian species. Much controversy exists about the luteal function in humans and how defects in luteal function affects reproduction. Disagreement has been due to lack of accurate diagnosis and controlled studies to determine whether correction of the luteal-phase defect is worthwhile when treating female reproductive problems. The donor egg recipient model from assisted reproductive technology programs has shown that corpus luteum function can be replaced by estrogen and progesterone administration. The mechanism by which these steroids stimulate a uterus to be receptive to implantation of the embryo is not known. Several proteins produced by the endometrium are candidate markers for uterine receptivity. Further work needs to be done to correlate these markers with subsequent pregnancy outcome. A noninvasive marker for uterine receptivity is ultrasonographic evaluation of the endometrium. Although the sensitivity of this test is high (100%), its specificity is low (only 20% to 60%).

Incidence of antiphospholipid antibodies in patients with monoclonal gammopathy of undetermined significance.

The incidence of antiphospholipid antibodies in patients with monoclonal gammopathy of undetermined significance (MGUS) was studied. Antiphospholipid antibodies were measured in the sera of 93 patients (49 women, 44 men; mean age 70 [+/- 21] years) with MGUS by using an enzyme-linked immunosorbent assay (ELISA). The phospholipids tested were cardiolipin (CL), phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidylglycerol (PG), phosphatidic acid (PA), phosphatidylcholine (PC), and phosphatidylethanolamine (PE). Positive results were defined as a value higher than the number of multiples of the mean per phospholipid, which included 76 of 80 (95%; 20 age-matched) control individuals. The immunoglobulin-G (IgG) or IgM antiphospholipid antibodies isotype varied among the patients, as did the phospholipid specificity. For IgG, PI was found elevated in 32% of the MGUS samples, whereas the other phospholipid antigens ranged from 9% to 15%. The percentage of patients with IgM antiphospholipid antibodies was higher. The authors observed PS, PI, PA, and PC as positive in 45%, 35%, 25%, and 25% of patients, respectively. Of the 12 sera studied for IgA isotype, three (25%) were positive for PS, six (50%) for CL, and none for PE. Patients with MGUS manifested a significantly higher (P < .01) incidence of antiphospholipid antibodies in their blood than did the control persons. No difference in the incidence of antiphospholipid antibodies was seen between younger and older (age-matched) control patients. No correlation was found between serum levels of immunoglobulins and optical density reading of the blank plates used as ELISA controls.

Ultrasonographic findings of pregnancy losses after treatment for recurrent pregnancy loss: intravenous immunoglobulin versus placebo.

OBJECTIVE: To describe the ultrasonographic findings of pregnancies that terminated in repeat abortion in women participating in an ongoing randomized placebo-controlled clinical trial evaluating the efficacy of intravenous (IV) immunoglobulin (Ig) in the treatment of recurrent spontaneous abortion (SA). DESIGN: A prospective descriptive study of ultrasonographic findings of pregnancies from 27 women experiencing repeated recurrent SAs after entry into a clinical trial. SETTING: Clinical practice at the Genetics & IVF Institute in Fairfax, Virginia. PATIENTS: Women experiencing two or more consecutive recurrent SAs received either 500 mg/kg per mo IV Ig or placebo (albumin). To date 90 women have been enrolled in the clinical trial and 52 have achieved pregnancy. The outcome of the 52 pregnancies include 16 deliveries, 9 ongoing pregnancies, and 27 losses. INTERVENTIONS: Ultrasonographic examinations performed in 27 women experiencing pregnancy loss are the subject of this study. MAIN OUTCOME MEASURES: The frequency of ultrasonographic findings of empty gestation sac (blighted ovum) and intrauterine fetal demise (IUFD) is compared between patients receiving IV Ig and placebo. RESULTS: Ultrasonographic findings of the 27 pregnancies losses included 11 blighted ova and 16 IUFDs. Of 11 blighted ova, 8 (73%) were in women receiving IV Ig and 3 (27%) were receiving placebo. Sixteen IUFDs were observed: 3 (19%) in women receiving IV Ig and 13 (81%) in women receiving placebo. Of 11 pregnancy losses occurring in women receiving IV Ig, 8 (73%) were blighted ova, 3 (27%) were IUFDs. Sixteen pregnancy losses occurred in women receiving placebo: 3 (19%) were blighted ova and 13 (81%) were IUFDs. The differences in frequency of blighted ova between IV Ig- and placebo-treated women was significant. CONCLUSION: IV Ig is not effective in preventing blighted ova and may be effective in preventing IUFDs.

Colour Doppler ultrasound guidance for transcervical wire tuboplasty.

To evaluate the usefulness of high-resolution ultrasound with colour Doppler mapping system in performing transcervical wire tuboplasty, 13 infertile women with bilateral proximal tubal obstruction demonstrated by X-ray or colour Doppler ultrasound hysterosalpingography and chromoperturbation at laparoscopy were treated by transcervical wire tuboplasty utilizing colour Doppler mapping ultrasound guidance. A co-axial catheter was used to introduce a 0.016-in. flexible wire to the occluded portion. Transcervical wire catheterization was accomplished in 25 of 26 tubes (96%), resulting in patency in 24 of 25 tubes (96%). At the end of the procedure all patients had at least one tube patent (100%). Five (38%) women achieved pregnancies within 1 year after the procedure. High-resolution ultrasound with colour Doppler mapping system is an efficacious way to perform transcervical wire tuboplasty, avoiding the risk of radiation and allergic reaction.

Early diagnosis of ectopic pregnancy using receiver-operator characteristic curves of serum progesterone concentrations.

The objective was to assess the usefulness of serum progesterone concentrations in the differentiation of intra-uterine (viable and non-viable) and extra-uterine pregnancies. Progesterone concentrations were prospectively measured at 4, 5 and 6 weeks gestation in 338 pregnancies which resulted in 242 viable births, 81 abortions and 15 ectopic pregnancies. Progesterone threshold analysis was performed using receiver-operator characteristic curves. The progesterone threshold value for ectopic pregnancy at 4 weeks was 5 ng/ml, at 5 weeks 10 ng/ml and at 6 weeks 20 ng/ml. A significant difference was observed between all intra-uterine versus ectopic pregnancies (P = 0.0005), but not between viable versus non-viable intra-uterine pregnancies (P = 0.37). The differences were most clearly defined at 4 weeks and decreased with increasing gestation. We conclude that serum progesterone and gestational age taken together can differentiate intra-uterine from extra-uterine pregnancies with a very high sensitivity and specificity at 4 weeks gestation, a time when ectopic pregnancies are not evident on ultrasound examination.

Current status of immunologic recurrent pregnancy loss.

Normal mammalian pregnancy is confronted with a great number of self (autoimmune) and foreign (alloimmune) antigens that modulate the immune system of the mother. When maternal immune response is affected, recurrent pregnancy loss can result. Recurrent pregnancy loss affects 2% to 5% of reproducing couples. Half of these failures can be explained by genetic, hormonal, infectious, and anatomic factors. Eighty percent of the unexplained failures are proposed to have an immunologic cause. HLA typing, mixed lymphocytotoxic antibody tests, mixed lymphocyte culture reactions, lupus anticoagulant tests, and antiphospholipid antibody determination are methods used to study and differentiate between auto- and alloimmune response. Experimental therapies, including leukocyte immunization, seminal plasma suppositories, intravenous immunoglobulin, aspirin and prednisone, and heparin, have been tried to manage this condition. Results of randomized placebo-controlled clinical trials will aid in the choice of treatment for recurrent pregnancy loss. New assays to diagnose auto- and alloimmune factors in recurrent pregnancy loss are being investigated.