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C B Coulam

Publications and source records attributed to C B Coulam.

At least 55 records · Page 3Linked to original sources

Recent advances in reproductive genetic technologies.

New possibilities for the diagnosis and treatment of reproductive and genetic disorders are becoming available as a result of a series of recent technical advances. Intracytoplasmic sperm injection (ICSI) allows treatment of numerous infertile men whose sperm cannot penetrate the egg to initiate fertilization. Molecular genetic testing provides clients of reproductive age with additional information that permits prevention of genetic diseases such as fragile X syndrome, the leading cause of inherited mental retardation. Preimplantation genetic testing (PGT) offers couples who carry genetic disorders the prospect of having children with a greatly decreased risk of initiating a pregnancy involving an affected individual. Flow-cytometric sperm separation offers a new, effective approach for prevention of X-linked genetic disorders. Two major causes of recurrent pregnancy loss (RPL) involve recurrent trisomies and immunological disorders. Of the latter, 70% of studied populations of patients can attain live births with simple treatment protocols. Maternal serum assays involving multiple markers reduce both false positives and false negatives in detection of trisomies. Despite these advances in research, many safe and effective methods of diagnosis and treatment remain under-utilized in the clinical arena.

Abortion, Habitual↗

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.

Adult↗

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.

Adult↗

Uterine receptivity in an oocyte donation programme.

Oocyte donation is a useful model for the assessment of potential factors affecting implantation since embryos generated are from younger oocytes than in in-vitro fertilization programmes and are therefore expected to have higher and more consistent implantation rates. Transvaginal sonographic measurement of endometrial thickness, echogenic pattern and uterine artery impedance, measured as pulsatility index (PI) and resistance index (RI), were retrospectively compared in 99 recipient women following 117 fresh embryo transfers that resulted in 51 conception cycles and 66 non-conception cycles. The prevalence of a multilayered echogenic pattern was significantly greater (91.2%) in conception than in non-conception (44.4%) cycles. No differences in endometrial thickness, PI or RI were observed between conception and non-conception cycles. However, no pregnancy occurred when the PI was > or = 3.4 (sensitivity 100%). The number of days or cumulative dose of oestrogen intake and the serum oestradiol concentration prior to progesterone administration were not different in the multilayered pattern versus other echogenic pattern groups. The data show that it may be beneficial to await achievement of a PI < 3.4 and a multilayered pattern endometrium prior to embryo transfer in an oocyte donation programme.

Adult↗

Predictive factors in recurrent spontaneous aborters--a multicenter study.

PROBLEM: Compare data from several centers relating to success rates in recurrent spontaneous miscarriage and assess the significance of indicators of subsequent pregnancy loss. METHOD: Data from 777 couples with unexplained recurrent spontaneous abortion from independent studies at seven centers were analyzed using logistic regression analysis. The following covariates were considered: age of patient, number of previous spontaneous abortions, length of previous abortions history, sub-fertility index (defined as the product of the number of spontaneous abortions and the abortion history), whether a patient was a primary or secondary aborter, and whether a patient had received leukocyte immunotherapy. RESULTS: There was a highly significant difference between the seven centers in success rates in the subsequent pregnancy and a highly significant association between success rate and each of the following covariates: the number of previous abortions, the length of the previous abortion history and the sub-fertility index. In particular, for each increase of 10 units in the value of the sub-fertility index, up to a value of 30, the odds in favor of a successful pregnancy decreased by a factor of 0.6, i.e., 40%. There was, however, little evidence of an association between the success rate in the subsequent pregnancy and age, parity, or immunization with cells from the husband. CONCLUSIONS: The sub-fertility index may be a useful measure of likelihood of success in a subsequent pregnancy.

Abortion, Habitual↗

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.

Abortion, Habitual↗

Preimplantation factor (PIF) predicts subsequent pregnancy loss.

PROBLEM: To evaluate the ability of preimplantation factor (PIF) measured in the lymphocyte/platelet binding assay (LPBA) to predict subsequent spontaneous abortion. METHOD: Serum from 57 women experiencing first trimester pregnancy losses were studied using the LPBA (46 women conceived after in vitro fertilization and embryo transfer for treatment of infertility and 11 with a history of unexplained recurrent spontaneous abortion conceived spontaneously). The assay employs a combination of heat inactivated sera with donor O+ lymphocytes and platelets, complement and an antibody against CD2. Chromosome analysis was performed on 32 of the abortuses. Results of PIF assay were compared between karyotypically normal and abnormal abortuses. RESULTS: PIF assay was negative in all 57 women at the time of abortion. Among 12 karyotypically normal abortuses only 1 woman (8%) had an initial positive PIF, 11 (92%) had negative PIF. Serial PIF assays were performed on 15 women. PIF assay became negative a minimum of two weeks prior to demonstration of intrauterine demise at a time when hCG concentrations remained elevated. A trend to subnormal was seen in women with normal when compared to those with abnormal abortus karyotype, but the numbers were too small to reach statistical significance (P = 0.09). CONCLUSION: Measurement of PIF throughout the first trimester of pregnancy predicts subsequent pregnancy loss.

Abortion, Habitual↗

Reciprocal alteration in circulating TJ6+ CD19+ and TJ6+ CD56+ leukocytes in early pregnancy predicts success or miscarriage.

PROBLEM: TJ6 is a cytokine whose membrane form is regularly expressed on the B lymphocytes of women during pregnancy. In a previous study we have shown that pregnancies that end in a spontaneous abortion are characterized by an increase in natural killer (NK) cells and that NK cells in these pregnancies also expressed TJ6, whereas NK cells from pregnancies that terminate normally neither increase in number nor do they express significant amounts of the cytokine. METHODS: To evaluate the ability of TJ6 to predict pregnancy outcome, 61 blood samples from pregnant women were studied. Blood samples were drawn between 5 and 12 weeks of gestation and analyzed for lymphocyte expression of TJ6 using Cytoron Absolute flow cytometry and two-color fluorescence. The percentage of CD19+ (B) cells and CD56+ (NK) cells that expressed TJ6 was calculated, and this percentage was correlated with subsequent pregnancy outcome classified as successful (viable birth) or unsuccessful (abortion, stillbirth). TJ6 CD19 and TJ6 CD56 was determined in 32 blood samples from women with successful pregnancy outcomes and 29 samples from women with unsuccessful pregnancy outcome. RESULTS: The mean TJ6 CD19 expression for successful pregnancies was 10.6% and for unsuccessful pregnancies was 5.1% (P < 0.03). The mean TJ6 CD56+ percentage of circulating cells that express TJ6 expression for successful pregnancies was 3.3% and for unsuccessful pregnancies was 10.4% (P = 0.02). All unsuccessful pregnancies had less than 90% of circulating CD19 cells express TJ6 and/or greater than 50% of circulating CD56 cells express TJ6. Use of the expression of TJ6 on CD19 and CD56 cells during the first trimester predicts viable pregnancy with a sensitivity of 100%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 100%. CONCLUSIONS: The work now being reported validates the hypothesis that expression of TJ6 on NK cells obtained from pregnant women predicts the outcome of pregnancy. In addition we show that this prognosticator can be reliably demonstrated early in the first trimester.

Abortion, Spontaneous↗

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.

Abortion, Habitual↗

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.

Abortion, Habitual↗

Systemic CD56+ cells can predict pregnancy outcome.

PROBLEM: To evaluate differences in circulating CD56+ cells between successful and unsuccessful pregnancies, 114 pregnant women were studied prospectively. METHOD: Seventy women had a history of infertility (INF) and 44 had two or more previous spontaneous abortions (RSA). Among the infertile women, 12 were donor egg recipients (DER) and 15 underwent intracytoplasmic sperm injection (ICSI) for treatment of male factor infertility. Nineteen women were carrying multiple gestations (MG) and 55 had singleton gestations (SG). Thirteen additional women were receiving intravenous immunoglobulin (IVIg). RESULTS: The percentage of CD56+ cells was determined in 310 blood samples from 114 pregnant women by flow cytometry. The prevalence of women with persistent elevation of percent of 56+ cells (> 12%) was 58% among DER, 73% among ICSI, 37% among MG, 22% among SG, 18% among RSA, and 39% among INF. Thirteen women with SG received IVIG, 10 had CD56+ cells greater than 12% and all 13 experienced live births. Women with percentage CD56+ cells persistently greater than 12% who were not DER, not ICSI, not receiving IVIg, and not carrying MG had a live birth rate of 11%. Women with greater than 12% CD56+ cells had normal karyotype in 78% of concepti studied in contrast to women less than 12% CD56+ cells who had 68% abnormal karyotypes (P = 0.04). CONCLUSION: Elevated CD56+ cells in pregnant women who are not DER, not ICSI, not receiving IVIg, and not carrying MG predicts loss of a karyotypically normal conceptus with a specificity of 87% and positive predictive value of 78%. While the specificity value of this test is high in both infertile and RSA populations, the sensitivity is 86% in RSA and only 54% in INF suggesting this test does not identify all losses among INF. It may identify a subset of pregnancies at risk for loss of a karyotypically normal embryo that may respond to treatment with IVIg.

Abortion, Habitual↗

A novel bioassay for detection of preimplantation factor (PIF).

PROBLEM: To identify the presence of vital preimplantation embryos in vivo in humans, a newly observed phenomenon based on autorosette formation between lymphocytes and platelets, when treated with pregnant sera, was used as a marker. METHOD: Serum samples were obtained from 65 patients on the fourth day after embryo transfer (ET). Sera from 10 healthy males and 47 nonpregnant women were used as controls. The preimplantation factor (PIF) was detected by using blood group O+ donor lymphocytes and platelets incubated with blinded serum in the presence of anti-CD2 antibody and rabbit complement. Human chorion gonadotropin (hCG) concentrations were determined 7 days later and compared with results of the lymphocyte-platelets assay. Implantation was confirmed by ultrasonographic evidence of presence of an intrauterine gestational sac. The role of platelet activating factor (PAF) in the observed phenomena was studied experimentally. RESULTS: Significantly more lymphocyte-platelet rosette formations were observed when sera from women who successfully implanted were compared to sera from women who failed to implant. This assay yielded a specificity of 95%, sensitivity of 88%, positive predictive value of 94%, and negative predictability of 90%. PAF added directly to the cell suspension and tested sera controls did not influence the percentage of lymphocyte/platelets rosettes. CONCLUSION: The application of PIF assay will enable the identification and study of early pregnancy events before the implantation occur. PAF by itself is not responsible for the rosette formation.

Biological Assay↗

Immunotherapy for recurrent spontaneous abortion.

Recurrent pregnancy loss is a healthcare concern. Safe and effective treatments are necessary. Since women experiencing recurrent pregnancy loss are a heterogeneous population, specific markers are necessary to identify those who will respond to various treatments. The presence of antiphospholipid antibodies identifies women with recurrent pregnancy loss who are most likely to respond to heparin and aspirin treatment. An elevated concentration of NK cells in maternal blood and a loss of karyotypically normal embryos after detection of cardiac activity on ultrasonographic examination identify women who are most likely to respond to IVIg treatment. An obstetric history of recurrent primary abortion with an absence of maternal antipaternal lymphocytotoxic antibodies and anti-phospholipid antibodies predicts women who are most likely to respond to allogeneic leukocyte immunization. However, the treatment effect is low, with a livebirth rate of 60% which represents an enhancement over no treatment in the range of 8-10%. The difference in livebirth rates between women receiving IVIg therapy as compared to placebo was 28%. Women experiencing recurrent spontaneous abortion who have high, as opposed to low levels of leukocyte antibody do not respond to leukocyte immunization therapy. They do, however, respond to treatment with IVIg--the overall success rate of IVIg being 70%. It is important to be able to identify women likely to respond to various forms of immunotherapy. Chromosomal abnormalities are evident in 60% of recurrent aborters. Women experiencing recurrent aneuploidy in their abortus would not be expected to respond to immunotherapy. At the present time, the only way to identify such women is to have the results of chromosome analysis of previous pregnancy losses available. Having access to this information will require a change in current obstetric practice regarding obtaining karyotyping of all pregnancy losses. The cost-effectiveness of chromosome studies from abortuses is apparent when costs of evaluation and treatment are considered.

Abortion, Habitual↗

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.

Adult↗

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.

Abortion, Habitual↗

Ultrasonographic predictors of implantation after assisted reproduction.

OBJECTIVE: To assess the utility of endometrial thickness, echogenic endometrial pattern, and uterine artery impedance measured as pulsativity index in predicting implantation. DESIGN: Prospective case-controlled study of infertile patients undergoing assisted reproductive technologies (ARTs). PATIENTS: Four hundred five women undergoing ARTs were studied: 100 women after ET of thawed embryos in natural cycles (frozen ET), 107 women after standardized IVF-ET, 99 women receiving donor oocytes after controlled endometrial development with estrogen and P, and 99 women undergoing IUI with various ovarian stimulation regimens (none, 16; GnRH, 7; clomiphene citrate [CC], 29; hMG, 47). INTERVENTIONS: Transvaginal ultrasonographic examination performed on the day of hCG administration during stimulated cycles; on E2 day 15 during controlled endometrial cycles; and on the day of ovulation during natural, CC, and GnRH pump cycles. MAIN OUTCOME MEASURE: The endometrial thickness, echogenic pattern, and pulsativity index results in 170 conception cycles were compared with 235 nonconception cycles. RESULTS: When conception and nonconception cycles were compared, no difference in mean endometrial thickness and significant differences in the frequency of nonmultilayered pattern and pulsativity index > 3.3 were observed. Forty-seven percent of nonconception and 9% of conception cycles were associated with at least one of these factors. CONCLUSION: Ultrasonic measurements of pulsativity index, resistance index, and echogenic pattern are useful in predicting implantation after assisted reproduction.

Case-Control Studies↗

Intravenous immunoglobulin for in-vitro fertilization failure.

The aim of this study was to determine the effectiveness of intravenous (i.v.) immunoglobulin (Ig) for treatment of individuals experiencing failure after in-vitro fertilization (IVF) and embryo transfer. A total of 29 women with unexplained infertility who failed to become pregnant after IVF/embryo transfer were divided into two groups based on performance in previous IVF cycles: 16 women had fertilization of > or = 50% of oocytes retrieved and/or produced > or = 3 embryos each cycle and 13 had fertilization of < 50% of oocytes retrieved and/or produced < 3 embryos each cycle. Each woman had received at least 12 transferred embryos (95th percentile for successful IVF patients) or had experienced two or more biochemical pregnancies without ultrasonic confirmation of implantation during previous IVF/embryo transfer attempts. All women received i.v. Ig 500 mg/kg prior to the next embryo transfer. Only one of the 13 (8%) women with suboptimal fertilization and embryo yield became pregnant in the treatment cycle. Of 16 women who had previously had fertilization of at least 50% of oocytes retrieved and produced at least three embryos, nine (56%) became pregnant in the treatment cycle. The difference in pregnancy rates between the two groups is significant (P = 0.02). Intravenous Ig is useful in the treatment of unexplained IVF failure in women who have oocyte fertilization rates > or = 50% and generate at least three embryos per cycle.

Adult↗