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Biomedical subjects

C B Coulam

Publications and source records attributed to C B Coulam.

At least 19 recordsLinked to original sources
PubMed1995

Intracytoplasmic sperm injection facilitates fertilization even in the most severe forms of male infertility: pregnancy outcome correlates with maternal age and number of eggs available.

OBJECTIVE: To evaluate, in a prospective study, the fertilization and pregnancy rates after intracytoplasmic sperm injection (ICSI) in infertile couples with severe male infertility. DESIGN: Intracytoplasmic sperm injection was performed in 229 consecutive IVF cycles on 190 couples with rigorously defined severe male infertility or proven failure of fertilization in prior IVF cycles. Neither male nor female partners were chosen from a waiting list or on any other selective basis, including age, prior or anticipated ovarian response, or oocyte number or quality. There were no upper age limits, in no instance was donor sperm used for ICSI, and cycle cancellation rate was minimal. SETTING: Private genetics and fertility center in Fairfax, Virginia. MAIN OUTCOME MEASURES: Fertilization, transfer, and pregnancy rates were measured in ICSI-treated couples, and comparisons were made regarding both female age and strictly defined semen categories. RESULTS: Two hundred six cycles (90%) resulted in ETs, with initiation of 52 pregnancies (25% per transfer, 23% per cycle). Thirty-eight of 52 (18% per transfer) were clinical pregnancies with established gestational sacs or were ongoing or delivered. Pregnancies were achieved even in older women but were more readily established in younger women producing larger numbers of metaphase II oocytes. The severity of semen abnormalities had some small effect on fertilization rate, but only actual necrospermia was associated with markedly decreased frequency of embryo formation. Pregnancy per transfer was similar across groups. In some cases, pregnancy was initiated with fewer than 100 viable sperm in the ejaculate. CONCLUSIONS: Intracytoplasmic sperm injection is a very powerful new treatment for severe male infertility. Paradoxically, egg number and probably egg quality are now the main determinants of success in treating male infertility.

Adult↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

Very early (24-56 days from last menstrual period) embryonic heart rate in normal pregnancies.

To determine embryonic heart rate in early gestations, 426 ultrasonographic examinations from 24 to 56 days from onset of last menstrual period (LMP) were studied. All pregnancies had a subsequent successful outcome. Transvaginal ultrasonography was performed using an Acuson 128 10XP with a 5 MHz probe. Embryonic heart rate was determined by M-mode. No embryonic heart rate was observed prior to 34 days of gestation from onset of LMP (n = 65). At 35 days, two of 13 (15%) pregnancies had cardiac activity, and by 36 days 16 of 19 (82%) pregnancies had cardiac activity. By day 37 from onset of LMP all pregnancies demonstrated embryonic cardiac activity. From days 34 to 56, mean embryonic heart rate rose from 94 to 166 beats/min. We conclude that embryonic cardiac activity is first apparent at day 34 and should be visible by day 37 in normal pregnancies.

Female↗
PubMed1994

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%).

Abortion, Habitual↗
PubMed1994

Use of lymphocyte platelet binding assay for detecting a preimplantation factor: a quantitative assay.

PROBLEM: To evaluate the ability of the lymphocyte/platelet binding assay to identify a preimplantation factor (PIF). METHOD: Percentages of binding of lymphocytes by platelets in the presence of sera from 30 known pregnant and 30 nonpregnant individuals were compared using a novel lymphocyte/platelet binding assay. The assay is performed using a combination of a heat inactivated sera with donor O+lymphocytes, activated complement and an antibody against CD2 (T11, Ortho Pharmaceuticals). RESULTS: In nonpregnant females (23.6 +/- 6.5%) and males (17.7 +/- 4.7%) the percentage of lymphocytes bound by platelets was significantly different from pregnant women (56.1 +/- 15.9%) (P < 0.0001). Serial sampling of blood in five women undergoing IVF/ET who had normal pregnancies showed the detection of PIF by 4 days after transfer. The lymphocyte/platelet binding assay was not influenced by hCG, progesterone and estradiol. The interassay and intrassay variabilities were < 3%. CONCLUSIONS: The lymphocyte/platelet binding assay is a simple, reproducible, specific and cost efficient assay for measurement of PIF. Application of this assay will provide investigative and diagnostic tools for identifying and monitoring early pregnancy events.

Biological Assay↗
PubMed1994

Immunotherapy with intravenous immunoglobulin for treatment of recurrent pregnancy loss: American experience.

PROBLEM: Recurrent spontaneous abortion (RSA) is the cause of childlessness in 2-5% of reproducing couples. Immunological mechanisms have been proposed as an etiology in some cases of RSA. Various forms of immunotherapy have been attempted in individuals thought to have an immunologic mechanism associated with RSA. Intravenous immunoglobulin (IVIG) has been used in a pilot study to successfully treat women with RSA. METHOD: To evaluate the efficacy of IVIG in the prevention of RSA as prospective randomized, placebo-controlled clinical trial was undertaken. Women experiencing two or more consecutive RSAs receive either IVIG 500 mg/kg/month or placebo (albumin). RESULTS: To date 92 women have been enrolled in the study and 58 pregnancies have been achieved. The outcome of the 58 pregnancies include 20 deliveries, 9 ongoing pregnancies and 29 losses. Fourteen (49%) of the 29 pregnancy losses were blighted ova (empty gestational sacs) and 15 (51%) were intrauterine fetal deaths (IUFD's) occurring in the first trimester of pregnancy. Of 14 blighted ova, 8 were in women receiving IVIG and 6 were receiving placebo. Fifteen IUFD's occurred: 3 (20%) in women receiving IVIG and 12 (80%) placebo. Of 11 pregnancy losses occurring in women receiving IVIG, 8 (73%) were blighted ova and 3 (27%) were IUFD's. Eighteen losses occurred in women receiving placebo: 6 (33%) were blighted ova and 12 (67%) were IUFD's. CONCLUSIONS: These preliminary data suggest IVIG may be effective treatment for RSA. Analysis of data from the completed randomized placebo-controlled trial will test this suggestion.

Abortion, Habitual↗
PubMed1993

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.

Adult↗