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Biomedical subjects

S A Carson

Publications and source records attributed to S A Carson.

At least 37 records · Page 2Linked to original sources

Prospective study showing that antisperm antibodies are not associated with pregnancy losses.

OBJECTIVE: To obtain prospective data on the relationship between presence of antisperm antibodies in maternal sera and first trimester pregnancy losses. DESIGN: First trimester sera obtained from diabetic and nondiabetic women recruited within 21 days of conception were analyzed using the indirect immunobead test for immunoglobulin (Ig)G, IgA, and IgM antisperm antibodies. Regional binding also was considered: sperm head, midpiece, and sperm tail. Results were correlated with pregnancy outcome. SETTING: Five university centers. PATIENTS: One hundred eleven women who experienced pregnancy loss (55 diabetic; 56 nondiabetic) were matched 2:1 with 104 diabetic and 116 nondiabetic women (controls) who subsequently had a normal liveborn infant. INTERVENTION: None. MAIN OUTCOME MEASURE: Pregnancy outcome (spontaneous abortion, liveborn) correlated with presence or absence of antisperm antibodies. RESULTS: Analyzing samples without knowledge of clinical status, no differences were observed with respect to IgG, IgA, and IgM binding when a positive test was defined as 50% of sperm showing antibody binding. Likewise, no association was found for IgG and IgM antisperm antibodies at 20% binding. The only positive finding was observed for IgA antisperm antibodies at 20% binding (Fisher's Exact test). This one positive finding merely could reflect multiple comparisons. No significant differences between groups were observed when analysis was stratified according to location of antibody binding (head, midpiece, tail tip, entire sperm). When the sample was stratified into those having and not having a prior loss, a relationship between antisperm antibodies and pregnancy loss still was not evident. CONCLUSION: Further work is necessary to determine whether IgA antisperm antibodies truly are associated with pregnancy loss or whether antisperm antibodies play any role in repetitive aborters. Findings in this study suggest that antisperm antibodies do not play a major role in pregnancy loss.

Abortion, Spontaneous↗

Single serum progesterone as a screen for ectopic pregnancy: exchanging specificity and sensitivity to obtain optimal test performance.

OBJECTIVE: To investigate the diagnostic accuracy of screening serum P in diagnosis of ectopic pregnancy (EP) and to identify a cutoff value that provides the best compromise between test sensitivity and specificity. DESIGN: Retrospective analysis. SETTING: University hospital. INTERVENTIONS: Observation only. PATIENTS: First trimester pregnant women at risk for EP. MAIN OUTCOME MEASURE: Single P measurements were obtained from 3,674 pregnancies with outcomes defined as EP, viable intrauterine pregnancy (IUP), and spontaneous abortion (SAB). Diagnostic accuracy of the test was analyzed by generating receiver operating characteristic (ROC) curves, which quantify the ability of the test to distinguish EP and SAB from IUP. RESULTS: Diagnostic accuracy for EP versus IUP was 88.7% +/- 0.1% (mean +/- SEM); for SAB versus IUP, 93.8% +/- 0.4%; and for SAB + EP versus IUP, 92.8% +/- 0.4%. Diagnostic accuracy for SAB versus EP was only 39.4% +/- 0.2%. In the interval of 15.0 to 19.9 ng/mL (47.7 to 63.3 nmol/L), P missed 5.3% of the EPs and incorrectly included 84.3% of the viable IUPs; in the interval of 20.0 to 24.9 ng/mL (63.6 to 79.2 nmol/L), sensitivity improved in that only 3.5% of the EPs were missed but 88.8% of viable IUPs were included incorrectly. A cutoff value of > or = 17.5 ng/mL (55.7 nmol/L), the median point of the 15.0 to 19.9 ng/mL (47.7 to 63.3 nmol/L) interval, missed only 35 of 423 (8.3%) total EPs in the study. CONCLUSION: Analysis of ROC curves demonstrates that single serum P has high diagnostic accuracy for differentiating accidents of pregnancy (SAB and EP) from viable IUP, both individually (SAB versus IUP and EP versus IUP) and collectively (SAB + EP versus IUP); it cannot efficiently discriminate SAB versus EP. We conclude that for P > or = 17.5 ng/mL (55.7 nmol/L), patients thought to be at risk for EP may be followed reasonably without ultrasound or further invasive diagnostic studies.

Abortion, Spontaneous↗

Ovarian hyperstimulation augments adrenal dehydroepiandrosterone sulfate secretion.

OBJECTIVE: To determine if factor(s) secreted by the ovaries during hyperstimulation potentiate basal and ACTH-stimulated adrenal androgen secretion. DESIGN: Retrospective and prospective and prospective clinical study. SETTING: University tertiary care center infertility clinic. PARTICIPANTS: Two hundred thirteen hyperstimulation cycles in endocrinologically normal women were identified from 92 patients with ovulatory infertility, aged 25 to 45 years. Further, seven endocrinologically normal infertile women, aged 22 to 37 years, who were undergoing empiric ovarian hyperstimulation for infertility were identified and studied. INTERVENTIONS: In the previously performed cycles, basal and peak serum DHEAS and cortisol (F) levels were assayed and compared with each other and to the extant E2 levels. Additionally, at the baseline and the peak of ovarian hyperstimulation cycles, a standard ACTH test was performed and serum was assayed for DHEAS, DHEA, and F. MAIN OUTCOME MEASURE: Basal and ACTH-stimulated serum DHEAS, DHEA (prospective part only), and F concentrations. Where applicable, mean peak values were generated and compared between the baseline and the peak of stimulation with or without a correction for intrapatient variability in F secretion. RESULTS: Basal serum DHEAS levels rose with ovarian hyperstimulation independent of F. Post-ACTH mean peak value concentrations rose with ovarian hyperstimulation for DHEAS but not DHEA or F. CONCLUSIONS: Ovarian hyperstimulation potentiates basal and ACTH perturbed adrenal DHEAS secretion. This implies the existence of a humoral ovarian factor(s) that mediate this ovarian-adrenal cross-talk.

Adrenocorticotropic Hormone↗

Ectopic pregnancy: new advances in diagnosis and treatment.

Recent reports affirm that ectopic pregnancy has become a medical rather than a surgical disease. Early diagnosis is the key to effective nonsurgical treatment. Diagnostic algorithms using serum progesterone, serial beta-human chorionic gonadotropin measurements, ultrasound, and office curettage now make definitive diagnosis possible without laparoscopy. Laparoscopic salpingostomy, the surgical gold standard, is an effective therapy but carries surgical complications and is expensive. Systemic variable dose methotrexate produces outcomes close to laparoscopic salpingostomy in similar patients. Single dose systemic methotrexate and intratubal methotrexate appear to be less effective. In many cases, ectopic pregnancies do not meet suitable medical criteria and still require surgery. The challenge today is identifying patients at risk and bringing them into the system during the early first trimester when treatment is simple.

Female↗

Flow cytometry provides rapid and highly accurate detection of antisperm antibodies.

OBJECTIVE: Immunobead testing (IBT), the current standard for antisperm antibody detection, is time consuming and somewhat subjective. To overcome these limitations and maintain accuracy, we studied an immunofluorescent assay using flow cytometry. DESIGN: A validation study comparing flow cytometry to IBT in the detection of serum antisperm antibodies. SETTING: Flow cytometry laboratory. PATIENTS: Sera from 37 men after vasectomy (test) and sera from 35 fertile men (control). MAIN OUTCOME MEASURE: Test serum with and without immunoglobulin (Ig)G, IgA, and IgM antisperm antibodies as defined by IBT were analyzed by flow cytometry. Sensitivity and specificity of flow cytometry was calculated by defining the IBT as the true result. RESULTS: Flow cytometry identified 22 of 22 sera that were IgG positive (100% sensitivity), 12 of 14 sera that were IgA positive (86% sensitivity), and 4 of 4 sera that were IgM positive (100% sensitivity). Overall, 22 of 37 men were positive for antisperm antibodies. The flow cytometry correctly identified 71 of 71 negative sera (100% specificity). Fluorescence intensity values from the 37 study patients significantly correlated with immunobead binding to the head region and to the entire (more than one) region. CONCLUSIONS: Detection of IgG, IgA, and IgM antisperm antibodies by flow cytometry is highly sensitive and specific. In addition, flow cytometry is able to assess thousands of sperm rapidly and accurately, reducing sampling error and technical time.

Antibodies↗

Basal follicle stimulating hormone (FSH) predicts response to controlled ovarian hyperstimulation (COH)-intrauterine insemination (IUI) therapy.

PURPOSE: This work investigates the relationship of basal follicle stimulating hormone (FSH) measurements and age to ovarian responsiveness and pregnancy occurrence following controlled ovarian hyperstimulation and intrauterine insemination (COH-IUI). METHOD: Basal FSH was measured retrospectively in sera from infertility patients obtained on cycle day 2, 3, or 4 of a COH-IUI treatment cycle. Basal FSH was then correlated with COH response parameters and treatment outcome in ovulatory (n = 98) and anovulatory (n = 33) patients. Clinical data were collected from retrospective chart review. In the ovulatory group, increasing basal FSH was associated with fewer follicles (P = 0.01) and lower peak estradiol (P = 0.0001). RESULTS: No age related effects were detected in the anovulatory group. Also, there were no pregnancies in this group when basal FSH was > 22.1 mIU/ml. Increasing age in the ovulatory group was associated with fewer follicles (P = 0.0001), lower peak estradiol (P = 0.0001), and fewer pregnancies (P = 0.04). In the anovulatory group, basal FSH did not correlate with follicle numbers or peak estradiol, although more ampoules of hMG were used for stimulation (P = 0.03). CONCLUSIONS: Increasing basal FSH and patient age both correlated inversely with ovarian responsiveness to COH in ovulatory patients. Basal FSH can be used in clinically to identify patients undergoing COH who are unlikely to respond to superovulatory drugs and unlikely to become pregnant.

Adult↗

Embryo survival after pronuclear microinjection and trophectoderm biopsy.

OBJECTIVE: Our purpose was to compare murine embryo development after pronuclear microinjection of a gene construct, followed by trophectoderm biopsy at the blastocyst state, with development after a single micromanipulation, and with cultured controls. STUDY DESIGN: alpha-Myosin heavy-chain gene sequence was microinjected into the murine embryo pronucleus and cultured to blastocyst. After trophectoderm biopsy the embryos were allowed to re-expand. Re-expanded embryos were transferred to pseudopregnant females; implantation and live birth rates were recorded. In this study group the rates were compared with three control groups of embryos simultaneously cultured after (1) pronuclear microinjection only, (2) trophectoderm biopsy only, and (3) non-micromanipulated, culture only. RESULTS: A total of 1222 embryos were divided among the four groups. In the study group 472 embryos underwent pronuclear microinjection and trophectoderm biopsy. Of these, 203 (43%) reached the blastocyst stage and underwent biopsy; 183 (38.8%) re-expanded after biopsy. Of 275 pronuclear microinjected only (control 1) embryos, 113 (41.1%) reached the blastocyst stage. Of 336 embryos 148 (44.0%) reached the blastocyst stage and underwent trophectoderm biopsy only (control 2); 129 (39.2%) survived biopsy. The cultured only group (control 3) consisted of 139 pronuclear embryos; 67 (48.2%) developed to the blastocyst stage. CONCLUSIONS: Murine embryos can survive two micro-manipulations, pronuclear microinjection followed by trophectoderm micro-biopsy. Although there is minimal effect of these procedures on embryonic development in vitro, the live birth rate is tenuous.

Animals↗

Intrauterine insemination in fertile women delivers larger number of sperm to the peritoneal fluid than intracervical insemination.

Randomized IUI or intracervical insemination of eight fertile women with 50 x 10(6) sperm was performed to determine whether IUI delivers more spermatozoa to the peritoneal cavity. After IUI (n = 4), 2,053 to 29,450 sperm were recovered in the PF at laparoscopy. No sperm were found in the PF after intracervical insemination (n = 4). After IUI, CM contained 1.0 x 10(6) to 57.0 x 10(6) sperm/mL; after intracervical insemination, 0 to 1.2 x 10(3) sperm/mL were seen. One therapeutic mechanism for IUI is delivery of larger sperm numbers to the fertilization site by rapid (4 hours) transport. In addition, there is greater retrograde colonization of CM that may result in sustained release of sperm.

Cervix Uteri↗

Trophectoderm microbiopsy in murine blastocysts: comparison of four methods.

PURPOSE: This study compares four trophectoderm microbiopsy techniques for removal of blastomeres from murine blastocysts: (1) aspiration, trophectoderm pipetted through the zona; (2) incision, trophectoderm excised with a microrazor; (3) slit/excision, the zona slit and herniating trophectoderm excised; and (4) hatch/excision, trophectoderm cells excised after spontaneous hatching. RESULTS: Murine blastocysts were comparatively biopsied using one of four methods and contrasted to zona slit and nonmicromanipulated controls. Operative cellular injury was assessed by uptake of fluorescein isothiocyanate (FITC). Postoperative embryonic viability was assessed by blastocoele reexpansion and hatching inner cell mass development and trophectoderm plating. All techniques yielded cells available for genetic analysis. CONCLUSIONS: The slit/excision technique and hatch/excision techniques exhibited lower operative injury and the higher postoperative viability than aspiration or incision. The slit/excision and the hatch/excision techniques, though requiring two operative steps, appear to be the least damaging of the four methods. Therefore, they should be most applicable to human blastocysts obtained either by extended culture in vitro or by uterine lavage.

Animals↗

Predicting pregnancy survival from a single first trimester vaginal ultrasonogram.

This retrospective study evaluates early first trimester FHR, gestational SACD, and CRL measurements as means to predict ultimate pregnancy outcome. Outcomes of 274 pregnancies were monitored a single time by transvaginal ultrasonography with measurements recorded between 5.0 and 9.0 weeks' gestation. The measurements were then correlated with the pregnancy outcomes. FHR (P < 0.0001), gestational SACD (P = 0.0002), and CRL (P = 0.0059) each correlated positively with a successful pregnancy outcome. Measurements from a single transvaginal ultrasonogram can be used to predict a successful pregnancy outcome in the early first trimester.

Anthropometry↗

Serum progesterone and uterine curettage in differential diagnosis of ectopic pregnancy.

The implementation of a serum P less than 5.0 ng/mL is important because it resolves the differential diagnosis of EP by enabling timely uterine curettage. Curettage with examination of curettings or documentation of falling hCG can be used to prevent unnecessary laparoscopies in patients undergoing spontaneous abortions and can make possible definitive diagnosis and medical treatment of EP completely eschewing anesthesia and surgery.

Curettage↗

Superovulation fails to increase human blastocyst yield after uterine lavage.

Uterine lavage affords the potential for non-invasive human blastocyst recovery, with obvious potential for preimplantation genetic diagnosis. In an effort to duplicate in women the multiple blastocyst recovery per cycle that can be achieved in several other species, we initiated a programme in which fertile women underwent superovulation, followed by lavage and embryo collection. We superovulated 15 fertile women, aged 21-40, in 29 cycles using one of four regimens. Insemination was by either intercourse or artificial intracervical donor insemination with cryopreserved sperm from men of proven fertility. In 28 of 29 cycles, the uterus was lavaged daily for 1, 2, or 3 days between 5 and 10 days after human chorionic gonadotropin (hCG) administration or luteinizing hormone (LH) surge. Almost total fluid volume was recovered in every lavage. There were no retained pregnancies and no complications. Surprisingly, only two morulae, one blastocyst, and four unfertilized ova were recovered. Thus, alterations in ovulation induction, insemination timing, or lavage techniques must be contemplated in order to increase the blastocyst yield and thus fulfil the potential of uterine lavage for preimplantation diagnosis.

Adult↗

Low human chorionic somatomammotropin fails to predict spontaneous resolution of unruptured ectopic pregnancies.

Early diagnosis of EP allows conservative medical and surgical therapy but also commits a proportion of patients whose EP would spontaneously resolve to therapeutic intervention. This prospective study examined the feasibility of not treating those EPs whose hCS level was low. However, three of eight subjects with EP required therapy. Thus, a single hCS alone cannot be used to identify which EPs required no therapy.

Abortion, Spontaneous↗

Feasibility of semen collection and cryopreservation during chemotherapy.

Collection and cryopreservation of semen was undertaken in a 40-year-old man undergoing combination cyclophosphamide-doxorubicin-vincristine-prednisone chemotherapy for diffuse large cell lymphoma. Semen samples worthy of cryopreservation could be obtained through 39 days of therapy, with azoospermia observed after 70 days. Although pregnancy has not been attempted in the current case, reports by others suggest that normal outcomes can be expected with thawed semen collected during chemotherapy.

Adult↗

Methotrexate treatment of unruptured ectopic pregnancy: a report of 100 cases.

In an ongoing clinical trial, 100 patients with an unruptured ectopic pregnancy of 3.5 cm or less in greatest dimension were treated with an outpatient protocol of methotrexate and citrovorum factor chemotherapy. Methotrexate and citrovorum were given on alternating days until the hCG titer had decreased by 15% on 2 consecutive days. The patients ranged in age from 16-40 years, gravidity from 1-8, and parity from 0-5. Twenty-three patients had a previous ectopic pregnancy. Of the 100 patients, 96 (96%) received methotrexate/citrovorum as primary therapy and four (4%) were treated for persistent hCG titers after a conservative surgical procedure. The tubal pregnancies of patient nos. 1-50 were confirmed by laparoscopy, whereas patient nos. 51-100 were diagnosed according to a nonlaparoscopic algorithm. Four patients of 100 failed medical therapy and required surgery. Of these, one had an ectopic pregnancy with cardiac activity, one ruptured after intercourse, and the remaining two cases had no specific identifiable risk factors. Of the ectopic pregnancies with cardiac activity, 80% were successfully treated. Five patients (5%) had methotrexate-related side effects, all after the fourth dose, but none required treatment for these side effects. Hysterosalpingograms done on 58 patients subsequently demonstrated tubal patency in 84.5% on the involved side. To date, 37 pregnancies have occurred in this group, of which 31 (89.2%) were intrauterine and four (10.8%) were recurrent ectopic pregnancies. We conclude that methotrexate/citrovorum is safe, effective, and helps to preserve reproductive performance when used as primary therapy for unruptured ectopic pregnancy and for treatment of persistent disease following a conservative surgical procedure.

Adolescent↗