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Biomedical subjects

C B Coulam

Publications and source records attributed to C B Coulam.

At least 37 records · Page 2Linked to original sources

Antiphospholipid antibodies associated with implantation failure after IVF/ET.

PURPOSE: Our purpose was to determine the specific antiphospholipid antibodies (APAs) that should be evaluated to identify individuals at risk for implantation failure associated with reproductive autoimmune failure syndrome (RAFS). METHODS: The prevalence of APAs among 312 women with implantation failure was compared with that of 100 fertile control women. To be included in the implantation failure group, each woman had to have had at least 12 embryos transferred without subsequent positive pregnancy test. Enzyme-linked immunoabsorbant assay was used to measure IgG, IgM, and IgA anticardiolipin, antiphosphatidyl ethanolamine, antiphosphatidyl inositol, antiphospatidic acid, anti-phosphatidyl glycerol, antiphosphatidyl choline, and antiphosphatidyl serine. RESULTS: When the values for each of the seven APAs in three isotypes were compared between women with implantation failure and the control population, all of the APAs tested had a significantly higher frequency among women with implantation failure. Positive APAs were detected in 69 (22%) of the 312 women with implantation failure compared with 5 (5%) of the 100 control women (P < 0.0001). Anticardiolipin antibodies were found in 13 (4%) of the 312 women with implantation failure and none of the controls. Fifty-six (18%) of the 312 with implantation failure were negative for anticardiolipin antibodies but had positive values of other APAs. CONCLUSIONS: A complete APA panel using seven isotypes is necessary for diagnosing implantation failure associated with RAFS. If only anticardiolipin antibody is measured, 4% (13/312) of the positive APAs are detected, and 81% (56/69) of women with implantation failure associated with RAFS will have the diagnosis missed.

Antibodies, Antiphospholipid↗

Comparison of ultrasonographic findings in spontaneous abortions with normal and abnormal karyotypes.

To determine whether ultrasonographic findings can predict the karyotype of spontaneous abortions, 137 pregnancies (54 spontaneous, 83 assisted ovulatory cycles) that subsequently aborted and had chromosome analysis performed on the products of conception were studied ultrasonographically. Transvaginal ultrasound was performed using an Acuson 128XP/10 with 7.5 MHz probe. The numbers of empty gestational sacs, small and normal for gestational size, embryonic poles and embryos with documented cardiac activity were calculated. The frequency of each of these findings in pregnancies with normal and abnormal karyotypes was compared. Of the 137 spontaneous abortions, 51 had normal chromosome analyses and 86 had abnormal karyotypes (68 aneuploidies and 18 polyploidies). Ultrasonographic findings in the 51 karyotypically normal pregnancies included 16 (31%) with empty gestational sacs, and 35 (69%) with embryonic poles, of which 24 (69%) were at least 1 week smaller than expected for gestational age and 11 (31%) were the expected size. Embryonic cardiac activity was documented in 22 (63%) of the 35 embryonic poles. Amongst 86 pregnancies with abnormal karyotypes, similar frequencies of ultrasound findings were found: 23 (27%) with empty gestational sacs, 42 (67%) with embryonic poles smaller than expected for gestational age, and 50 (79%) embryos lost after documentation of embryonic cardiac activity. No differences in the frequency of ultrasonographic findings of empty gestational sacs, small embryonic pole and embryonic cardiac activity were observed between karyotypically normal and abnormal spontaneous abortions. Ultrasonographic findings cannot predict the karyotype of spontaneous abortions.

Abortion, Spontaneous↗

Can luteal phase serum estradiol concentrations predict karyotypes of spontaneous abortions?

Low serum estradiol concentrations during pregnancy have been associated with spontaneous abortions. A large proportion of abortuses have chromosomal abnormalities. To determine whether serum estradiol during the luteal phase of conception cycles can predict the karyotype of spontaneous abortions, serum estradiol samples were drawn 11 days after embryo transfer from 52 women who subsequently had spontaneous abortions and chromosomal analysis was performed on the products of conception. The frequency of estradiol levels < 100 pg/ml was compared between normal and abnormal karyotypic spontaneous abortions. Chromosomal analyses among 52 spontaneous abortions revealed 14 (27%) to be normal and 38 (73%) abnormal. Among the 38 karyotypic abnormalities 30 were aneuploidy and eight were polyploidy. Serum estradiol levels were < 100 pg/ml in eight women (15%) and > 100 pg/ml in 44 women (85%). The frequencies of estradiol < 100 pg/ml in spontaneous abortions with normal (7%) and abnormal (18%) karyotypes were not significantly different. Thus, serum estradiol cannot predict the karyotype of spontaneous abortions.

Abortion, Spontaneous↗

Hypothesis: antiphospholipid antibodies associated with congenital anomalies?

Antiphospholipid antibodies have been associated with pregnancy loss. We now present a possible association between antiphospholipid antibodies, recurrent spontaneous abortion and congenital anomalies. L.M. is a 32-year-old woman, gravida 6, para 2023, whose obstetric history includes three spontaneous abortions and two infants with congenital anomalies including kidney atresia and oromandibular hypogenesis. The only normal offspring are twins born after receiving treatment of aspirin 80 mg daily during the pregnancy. Laboratory evaluation revealed the presence of circulating antiphospholipid antibodies. Antiphospholipid antibodies cause endothelial cell activation which has been proposed as a cause of congenital malformations. This case suggests the risk of not only recurrent spontaneous abortion but also congenital anomalies in the offspring of a women with antiphospholipid antibodies. The congenital anomalies are 'regional' and could result from embryonic vascular accidents as a result of antiphospholipid antibody interaction with endothelial cells. The only 'successful' pregnancy was with treatment with aspirin. If the associations illustrated in this obstetric history can be substantiated by population-based studies, it may be concluded that antiphospholipid antibodies are a risk factor for embryo teratogenicity as well as mortality.

Abortion, Habitual↗

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.

Abortion, Habitual↗

Embryonic origin of preimplantation factor (PIF): biological activity and partial characterization.

Preimplantation factor (PIF) is detected in the serum of women shortly after fertilization; its origin, however, has not been established. In this study, the embryonal origin of PIF was investigated and partial characterization of the factor was carried out. Culture media from viable human 2-8-cell stage embryos and mouse 2-cell-blastocyst stage embryos were analysed using the lymphocyte/platelet binding assay (LPBA). The assay was performed by combining culture media with donor O+ type blood-derived lymphocytes/platelets, complement and an antibody against CD2. Increased autorosette formation between lymphocytes and platelets (> 9%) was an indication for the presence of PIF. In addition, the effect of platelet-activating factor (PAF) and chaperonin 10 on PIF activity was determined. Partial purification of PIF was carried out using gel filtration and reverse-phase high purification liquid chromatography (HPLC), followed by mass spectrometry. Culture media of single human viable fertilized oocytes were negative for PIF; however, the 10-fold concentrated medium was positive for PIF. In medium in which five or more mouse embryos were cultured, PIF activity was observed starting at the morula stage and was higher by the blastocyst stage. Addition of PAF or chaperonin 10 to the PIF assay did not elicit a specific effect on PIF activity. Chromatographic data suggest that PIF activity is due to low molecular weight proteins. PIF appears to be a low molecular weight protein which is derived from viable preimplantation embryos. It is different from PAF or chaperonin 10. Its final characterization will be valuable for better understanding of maternal recognition of pregnancy and implantation.

Animals↗

Early (34-56 days from last menstrual period) ultrasonographic measurements in normal pregnancies.

To assess early embryonic growth and development, 361 pregnancies were studied from 34 to 56 days from last menstrual period. All pregnancies had a subsequent successful outcome. Transvaginal ultrasonography was performed using an Acuson 128 x P/10 with a 5-7.5 MHz probe. Gestational sac diameter, embryonic pole length and embryonic heart rates were measured. Embryonic heart rates were determined by M-mode. Gestational sac diameter, embryonic pole length and embryonic heart rate increased linearly relative to gestational age and to each other. Regression equations comparing gestational sac diameter and embryonic pole length as well as comparing embryonic heart rate with gestational sac diameter and embryonic pole length were constructed. To be normal, gestations that have (i) sac diameter of 20 mm and 30 mm should contain at least a 2 mm and 5 mm embryo with embryonic heart rates of at least 75 and 100 beats per min, respectively, and (ii) embryos measuring 2 mm, 5 mm, 10 mm and 15 mm should display embryonic heart rates of at least 75, 100, 120 and 130 beats per minute respectively.

Embryo, Mammalian↗

Development and validation of an assay for measuring preimplantation factor (PIF) of embryonal origin.

PROBLEM: Tests to determine presence of embryos prior to implantation are needed. METHODS: Sera from women after embryo transfer were tested for preimplantation factor (PIF) using the lymphocyte/platelet binding assay. Autorosettes were counted using blood type O+ donor lymphocytes and platelets incubated with blinded serum in the presence of antiCD2 antibody and rabbit complement. Human chorion gonadotropin (hCG) concentrations were determined 7 days later and compared with results of the lymphocyte/platelet assay. Implantation was confirmed by ultrasonographic evidence of presence of an intrauterine gestational sac. The roles of platelet activating factor (PAF) and chaperonin 10 in the observed phenomena were 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. Neither PAF nor chaparonin added to the tested sera controls influenced the percentage of lymphocyte/platelets rosettes. CONCLUSIONS: PIF is a likely candidate to be the next frontier of diagnosing the presence of viable preimplantation embryos in vivo.

Biological Factors↗

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.

Abortion, Habitual↗

Antiphospholipid antibody prevalence in patients with IVF failure.

Antiphospholipid antibodies (APAs) have been associated with reproductive wastage. The purpose of this study was to establish the prevalence of APAs in women who have had at least 12 embryos transferred during several in vitro fertilization (IVF) cycles without ensuing pregnancy. Sera from 42 women with IVF failure and 42 women who successfully conceived after IVF were tested for the presence of APAs by ELISA. Successful post-IVF pregnancy was determined by obtaining two consecutive rising beta-hCG levels followed by an ultrasound to confirm a viable conceptus. The sera were tested for three isotypes of antibody: IgA, IgG, and IgM against seven phospholipids: cardiolipin (CL), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidic Acid (PA), phosphatidyl-glycerol (PG), phosphatidylcholine (PC), and phosphatidyl-serine (PS). From the IVF failure group, 11/42 (26.2%) were positive for APAs. From the control group, 2/42 (4.8%) were found positive only for IgA against PE. The difference between IVF failure and successful IVF groups was significant (P = 0.01). These results suggest that antiphospholipid antibodies should be considered an important marker for increased risk of IVF failure. Patients who are involved with an IVF program should be tested for the presence of APAs prior to initiation of an IVF cycle.

Antibodies, Antiphospholipid↗

Laboratory evaluation of women experiencing reproductive failure.

Reproductive life table analysis indicates that the majority of reproductive failures result from post fertilization failures, whether before or after implantation. It is important to have a set of tests to clarify the diagnosis of the reproductive failure so that appropriate therapy can be instituted. To determine the frequency of abnormal immunologic tests among women experiencing reproductive failure, 108 patients were evaluated for the presence of antiphospholipid antibodies (APA); lupus anticoagulant (LA); thyroid-thyroglobulin and microsomal antibodies (TGT); embryotoxic factor (ETA); and systemic CD56+/CD16- cells. The frequency of abnormal results obtained from testing for APA, LA, TGT, ETA, and CD56+/CD16- cells among 108 patients with diagnoses of recurrent pregnancy loss (RPL)(n = 45), unexplained infertility (n = 45) including IVF failure (n = 10), endometriosis (n = 10), premature ovarian failure (n = 5), and polycystic ovaries (n = 3) were compared with 15 normal controls. Seventy of one hundred eight (65%) women experiencing reproductive failure had at least one positive test, compared to 1 of 15 (7%) controls (P = 0.0001). Presence of phospholipid antibodies was the most frequently abnormal result followed by elevated CD56+/CD 16 cells. The prevalence of a particular abnormal test varied among the diagnoses. The most frequent abnormal test among women with RPL was an increased percentage of CD56+/CD16- cells (40%), followed by APAs (29%), TGT (9%), and ETA (7%). The most frequent abnormal result among women with unexplained infertility was the presence of APAs (42%), followed by CD56+/CD16- cells (16%), ETA (16%), and TGT (9%). APA, CD56+/CD16- cells, ETA, and TGT are useful tools to assist in the diagnosis of reproductive failure.

Abortion, Habitual↗

Comparisons of pregnancy loss patterns after intracytoplasmic sperm injection and other assisted reproductive technologies.

OBJECTIVE: To compare outcome of pregnancies after intracytoplasmic sperm injection (ICSI) with those of other assisted reproductive technologies. DESIGN: Pregnancy outcomes after ICSI were followed prospectively and compared with pregnancy outcomes after IVF with fresh and frozen ETs and donor oocyte cycles. SETTING: A private tertiary referral center for genetics and infertility in Fairfax, Virginia. PATIENTS: One hundred thirty-six couples achieving pregnancy after undergoing ICSI, 71 after IVF, 35 donor oocyte recipients, and 19 after transfer of frozen-thawed embryos. INTERVENTIONS: In vitro fertilization and/or ET for all couples. Dilatation and curettage to obtain products of conception for chromosome analysis in 28 women experiencing spontaneous abortion. MAIN OUTCOME MEASURES: Pregnancy outcomes were classified as preclinical loss, clinical loss, and ongoing pregnancy. RESULTS: The mean frequency of preclinical pregnancy loss was 26% after ICSI, 28% after IVF, 3% after ET using donor oocytes, and 11% after frozen ET. The rate of clinical loss after ICSI (21%) was compared with IVF (18%), donor oocyte cycles (11%), and frozen ETs (21%). CONCLUSIONS: Intracytoplasmic sperm injection is not associated with an increase in pregnancy losses, clinical or preclinical, compared with conventional IVF.

Abortion, Spontaneous↗

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↗