Papers by Christian Schneeberger
Molecular human reproduction, Jul 1, 2002
Steroid hormone receptor co-factors are abundantly expressed in the uterus in order to modify ste... more Steroid hormone receptor co-factors are abundantly expressed in the uterus in order to modify steroid hormone receptor action, either leading to activation or repression of transcription in the endometrium. However, the role of co-factors in remodelling of the human endometrium has not been established. We therefore endeavoured to evaluate the presence of the co-activator SRC (steroid receptor co-activator)-1 and the co-repressors N-CoR (nuclear receptor co-repressor) and steroid co-repressor SMRT (silencing mediator of retinod and thyroid) receptors in the human endometrium during the different phases of the menstrual cycle. By using a real-time RT-PCR assay, we showed that SRC-1, N-CoR and SMRT mRNA are expressed in human endometrium during all phases of the menstrual cycle, as well as in inactive endometrium. Moreover, endometrial expression of SRC-1 and N-CoR mRNA increased during menstruation when compared with the other phases of the menstrual cycle (P < 0.001). Immunohistochemistry demonstrated that SRC-1 and N-CoR stain positive in the glandular epithelium and stroma in menstrual phase endometrium. The staining was weak in proliferative and secretory endometrium and absent in inactive endometrium. Our results suggest that differential expression of endometrial steroid receptor co-factors probably play a role in the regulation of human endometrium remodelling.
American Journal of Obstetrics and Gynecology, Dec 1, 1998
Our purpose was to compare concentrations of messenger ribonucleic acid specific for the oxytocin... more Our purpose was to compare concentrations of messenger ribonucleic acid specific for the oxytocin receptor and for the vasopressin 1a receptor in myometrial and endometrial tissues of pregnant and nonpregnant women. Tissues from pregnant uteri were obtained from 95 women who were undergoing cesarean delivery between 26 and 42 weeks&#39; gestation. Tissues from nonpregnant uteri were obtained from 7 cycling women who were undergoing hysterectomy. The competitive reverse-transcription polymerase chain reaction method was used to determine messenger ribonucleic acid concentrations. A significant increase in oxytocin receptor messenger ribonucleic acid was found during the first half of pregnancy. Oxytocin receptor messenger ribonucleic acid concentrations were lower in tissues with spontaneous contractions than in quiescent tissues and were decreased in patients with advanced labor. Vasopressin 1a receptor messenger ribonucleic acid concentrations were high in tissues from both cycling and pregnant uteri but remained unchanged throughout gestation. The increase in oxytocin receptor protein concentrations seen in pregnancy is only partially controlled by messenger ribonucleic acid abundance. High concentrations of vasopressin 1a receptor messenger ribonucleic acid confirm the biologically active role of this receptor in both the cycling and the pregnant uterus.
Journal of Reproductive Immunology, 2008
TNF-alpha G308A, IL-6 G174C and IL-10 G1082A polymorphisms have recently been associated with pre... more TNF-alpha G308A, IL-6 G174C and IL-10 G1082A polymorphisms have recently been associated with preeclampsia (PE). The aim of this study was to clarify whether the occurrence of TNF-alpha, IL-6 and IL-10 polymorphisms is increased in women of our population with PE in a previous pregnancy. A retrospective, controlled, open, multicenter study was carried out in 107 women with a history of PE and 107 women with uncomplicated pregnancies. Smears from buccal gingival cells were analyzed for the polymorphisms of TNF-alpha, IL-6 and IL-10 by hybridization on microarrays. Statistical significance was calculated by the chi-quadrant test. Heterozygocity for the gene polymorphisms did not occur more often in preeclamptic women compared with controls (TNF-alpha: 29.0% versus 24.3%, p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.05; IL-6: 46.7% versus 51.4%, p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.05; or IL-10: 49.5% in each). Moreover, there was no significant difference between preeclamptics and controls with regard to homozygocity for TNF alpha (1.9% versus 3.7%, p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.05); IL-6 (17.8% versus 13.1%, p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.05); and IL-10 (30.8% versus 32.7%, p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.05). In contrast to the findings of some other investigators, gene polymorphisms do not seem to be important in our population for development of PE.
Journal of Ovarian Research, May 13, 2014
Background: Ovarian hyperstimulation syndrome (OHSS) is the most serious complication of IVF/ICSI... more Background: Ovarian hyperstimulation syndrome (OHSS) is the most serious complication of IVF/ICSI therapy. The pathophysiology and etiology of the disease is still not fully clarified. Methods: To assess whether polymorphisms of the VEGF/VEGF-receptor system contribute to the occurrence of ovarian hyperstimulation syndrome (OHSS), we performed a retrospective analysis of 116 OHSS patients, and 124 female controls. The following SNPs were genotyped: Rs2071559 (VEGFR2-604); rs2305948 (VEGFR2-1192); rs1870377 (VEGFR2-1719); rs2010963 (VEGF-405); and rs111458691 (VEGFR1-519). Odds ratios (ORs) were estimated with a 95% confidence interval (CI). Linkage disequilibrium (LD) analysis was performed in the three loci of the VEGFR2 gene. Result: We found an overrepresentation of the T allele of the VEGFR1-519 polymorphism in OHSS patients (P = 0.02, OR: 3.62, CI: 1.16-11.27). By genotype modeling, we found that polymorphism of VEGFR1-519 and VEGF-405 showed significant differences in patients and controls (p = 0.02, OR: 3.79 CI: 1.98-11.97 and p = 0.000005, OR: 0.29, CI: 0.17-0.50). LD analysis revealed significant linkage disequilibrium in VEGFR2. Conclusion: Polymorphisms in the VEGFR2 gene and in the VEGF gene are associated with the occurrence of OHSS. This strengthens the evidence for an important role of the VEGF/VEGF-receptor system in the occurrence of OHSS.
Biology of Reproduction, Jun 1, 1999
The mechanisms that ultimately regulate cervical ripening during parturition remain largely unkno... more The mechanisms that ultimately regulate cervical ripening during parturition remain largely unknown. A possible role for nitric oxide (NO) has recently emerged; however, the expression of NO synthase (NOS) within the human cervix in the ripening process has not been investigated. The purpose of this study was to identify cell types in the human cervix that contain NOS isoforms and to examine changes in their expression during the ripening process and the nonpregnant state. Inducible NOS (iNOS) immunoreactivity was observed in the epithelial cells and stromal spindle cells in 17 of 20 biopsies from cervices obtained within 10 min postpartum, but in only 4 of 12 nonpregnant controls (p ؍ 0.03). Endothelial NOS (eNOS) immunoreactivity was restricted to vascular endothelia in all sections, whereas neuronal NOS was not detectable. Inducible NOS activity in the postpartum group was 3.2 times that of the control group (p ؍ 0.0005), whereas constitutive NOS activity remained unchanged in both groups (p ؍ 0.222). Competitive reverse transcription-polymerase chain reaction revealed no differences in the expression of iNOS (p ؍ 0.443) or eNOS mRNA (p ؍ 0.409). The existence of iNOS in the human postpartum cervix suggests that increased production of NO, probably induced by cytokines, may be relevant to the process of natural cervical ripening in humans.
Placenta, Nov 1, 1998
Expression of endothelial nitric oxide synthase (eNOS) has been localized to the villous syncytio... more Expression of endothelial nitric oxide synthase (eNOS) has been localized to the villous syncytiotrophoblasts suggesting that NO release from these cells could prevent platelet adhesion and aggregation in the intervillous space. Hypoxia- or inflammation-dependent changes in the release of this vasoactive substance may result in thrombus formation and altered vascular resistance which occur in the placental bed of pre-eclamptic patients. To evaluate the influence of low-oxygen tension and inflammation on eNOS production in the trophoblast steady-state eNOS mRNA and protein levels were investigated in cytotrophoblastic BeWo and Jeg-3 cells cultured at 3.5 per cent oxygen and/or in the presence of the pro-inflammatory cytokines IL-1 and TNF-alpha. By RT-PCR and immunocytochemistry we demonstrate that BeWo cells produce eNOS mRNA and protein while eNOS polypeptide was undetectable in JEG-3 cells. In BeWo cells addition of both cytokines decreases eNOS mRNA and protein abundancies within 24 h of incubation while each substance alone had no effect. Compared to controls, the amount of eNOS transcripts was found to be elevated at low-oxygen tension, however, cNOS protein was downregulated after 24 h in the hypoxic environment, as shown by immunocytochemistry and Western blot analysis. Forskolin and methotrexate, which induce biochemical differentiation/ growth arrest in choriocarcinoma cells, stimulate eNOS mRNA and protein synthesis, but cannot overcome the decline of eNOS polypeptide levels during hypoxic incubation. It is speculated that acute hypoxia and inflammation impair eNOS/NO production of the trophoblast in vivo, which might contribute to pathological conditions of gestational diseases.
International Journal of Molecular Sciences, Dec 10, 2015
Like other RECQ helicases, WRN/RECQL2 plays a crucial role in DNA replication and the maintenance... more Like other RECQ helicases, WRN/RECQL2 plays a crucial role in DNA replication and the maintenance of genome stability. Inactivating mutations in RECQL2 lead to Werner syndrome, a rare autosomal disease associated with premature aging and an increased susceptibility to multiple cancer types. We analyzed the association of two coding single-nucleotide polymorphisms in WRN, Cys1367Arg (rs1346044), and Arg834Cys (rs3087425), with the risk, age at onset, and clinical subclasses of breast cancer in a hospital-based case-control study of an Austrian population of 272 breast cancer patients and 254 controls. Here we report that the rare homozygous CC genotype of rs1346044 was associated with an approximately twofold elevated breast cancer risk. Moreover, patients with the CC genotype exhibited a significantly increased risk of developing breast cancer under the age of 55 in both recessive and log-additive genetic models. CC patients developed breast cancer at a mean age of 55.2˘13.3 years and TT patients at 60.2˘14.7 years. Consistently, the risk of breast cancer was increased in pre-menopausal patients in the recessive model. These findings suggest that the CC genotype of WRN rs1346044 may contribute to an increased risk and a premature onset of breast cancer.
Cells
Estrogen receptor α (ERα), encoded by the ESR1 gene, is a key prognostic and predictive biomarker... more Estrogen receptor α (ERα), encoded by the ESR1 gene, is a key prognostic and predictive biomarker firmly established in routine diagnostics and as a therapeutic target of breast cancer, and it has a central function in breast cancer biology. Genetic variants at 6q25.1, containing the ESR1 gene, were found to be associated with breast cancer susceptibility. The rs2046210 and rs9383590 single nucleotide variants (SNVs) are located in the same putative enhancer region upstream of ESR1 and were separately identified as candidate causal variants responsible for these associations. Here, both SNVs were genotyped in a hospital-based case-control study of 409 female breast cancer patients and 422 female controls of a Central European (Austrian) study population. We analyzed the association of both SNVs with the risk, age at onset, clinically and molecularly relevant characteristics and prognosis of breast cancer. We also assessed the concordances between both SNVs and the associations of ea...
MHR: Basic science of reproductive medicine, 2018
Are increased sVCAM-1 and sICAM-1 levels associated with tumor necrosis factor-alpha-converting e... more Are increased sVCAM-1 and sICAM-1 levels associated with tumor necrosis factor-alpha-converting enzyme (TACE) activity in endometriosis? SUMMARY ANSWER: Here we provide the first functional evidence that induced TACE activity in human endometriotic epithelial cells is at least in part responsible for the enhanced release of sVCAM-1 from these cells. WHAT IS KNOWN ALREADY: We and others have shown that serum-soluble (s)VCAM-1 levels are significantly higher in women with endometriosis, compared to disease-free controls. Experimental evidence exists suggesting a role of sICAM-1 and sVCAM-1 in the pathogenesis of endometriosis. TACE was identified as the protease responsible for phorbol 12-myristate 13-acetate (PMA)-induced VCAM-1 release in murine endothelial cells. Additionally, it has recently been shown that TACE is upregulated in the endometrial luminal epithelium of the mid-secretory phase in infertile women.
International Journal of Molecular Sciences, 2015
Like other RECQ helicases, WRN/RECQL2 plays a crucial role in DNA replication and the maintenance... more Like other RECQ helicases, WRN/RECQL2 plays a crucial role in DNA replication and the maintenance of genome stability. Inactivating mutations in RECQL2 lead to Werner syndrome, a rare autosomal disease associated with premature aging and an increased susceptibility to multiple cancer types. We analyzed the association of two coding single-nucleotide polymorphisms in WRN, Cys1367Arg (rs1346044), and Arg834Cys (rs3087425), with the risk, age at onset, and clinical subclasses of breast cancer in a hospital-based case-control study of an Austrian population of 272 breast cancer patients and 254 controls. Here we report that the rare homozygous CC genotype of rs1346044 was associated with an approximately twofold elevated breast cancer risk. Moreover, patients with the CC genotype exhibited a significantly increased risk of developing breast cancer under the age of 55 in both recessive and log-additive genetic models. CC patients developed breast cancer at a mean age of 55.2˘13.3 years and TT patients at 60.2˘14.7 years. Consistently, the risk of breast cancer was increased in pre-menopausal patients in the recessive model. These findings suggest that the CC genotype of WRN rs1346044 may contribute to an increased risk and a premature onset of breast cancer.
LaboratoriumsMedizin, 2006
The number of reports investigating disease susceptibility based on the carriage of low-penetranc... more The number of reports investigating disease susceptibility based on the carriage of low-penetrance, high-frequency single nucleotide polymorphisms (SNPs) has increased over the last years. Evidence is accumulating defining specific individual variations in breast cancer susceptibility. Genetic variations of the estradiol and xenobiotic metabolisms, as well as genes involved in cell cycle control, have been described as significant contributors to breast cancer susceptibility with variations depending on ethnic background and co-factors such as smoking and family history of breast cancer. In sum, the highest level of evidence to date linking SNPs and breast cancer comes from nested case-control studies within the prospective Nurses' Health Study. These data establish seven SNPs – hPRB +331 G/A, AR CAG repeat, CYP 19 TTTA(10), CYP 1A1 Msp I, VDR FOK1, XRCC1 Arg194Trp, and XRCC2 Arg188His – as small, but significant risk factors for spontaneous, non-hereditary breast cancer. In add...
Clinical cancer research : an official journal of the American Association for Cancer Research, 1999
Estrogen receptor (ER), progesterone receptor (PR), the estrogen-inducible protein pS2, and plasm... more Estrogen receptor (ER), progesterone receptor (PR), the estrogen-inducible protein pS2, and plasminogen activator inhibitor-1 (PAI-1) are important prognostic factors in primary breast cancer. The protein concentrations of these factors in breast tumors have been well documented. However, few data about the mRNA expression of ER, PR, pS2, and PAI-1 in breast cancer are available, which is mostly due to the limitations of conventional techniques for mRNA analysis. We have described a competitive reverse transcription-PCR system for the simultaneous quantification of ER, PR, pS2, and PAI-1 mRNA in tumor samples. Here, we evaluated 100 tumor biopsies from breast cancer patients for the mRNA expression of ER, PR, pS2, and PAI-1. The results were analyzed for correlations with protein status and with clinical data. Significant correlations between mRNA expression levels and protein concentrations of all tested markers were found. In only a few cases was there an obvious discordance betwe...
Journal of Ovarian Research, 2014
Background: Ovarian hyperstimulation syndrome (OHSS) is the most serious complication of IVF/ICSI... more Background: Ovarian hyperstimulation syndrome (OHSS) is the most serious complication of IVF/ICSI therapy. The pathophysiology and etiology of the disease is still not fully clarified. Methods: To assess whether polymorphisms of the VEGF/VEGF-receptor system contribute to the occurrence of ovarian hyperstimulation syndrome (OHSS), we performed a retrospective analysis of 116 OHSS patients, and 124 female controls. The following SNPs were genotyped: Rs2071559 (VEGFR2-604); rs2305948 (VEGFR2-1192); rs1870377 (VEGFR2-1719); rs2010963 (VEGF-405); and rs111458691 (VEGFR1-519). Odds ratios (ORs) were estimated with a 95% confidence interval (CI). Linkage disequilibrium (LD) analysis was performed in the three loci of the VEGFR2 gene. Result: We found an overrepresentation of the T allele of the VEGFR1-519 polymorphism in OHSS patients (P = 0.02, OR: 3.62, CI: 1.16-11.27). By genotype modeling, we found that polymorphism of VEGFR1-519 and VEGF-405 showed significant differences in patients and controls (p = 0.02, OR: 3.79 CI: 1.98-11.97 and p = 0.000005, OR: 0.29, CI: 0.17-0.50). LD analysis revealed significant linkage disequilibrium in VEGFR2. Conclusion: Polymorphisms in the VEGFR2 gene and in the VEGF gene are associated with the occurrence of OHSS. This strengthens the evidence for an important role of the VEGF/VEGF-receptor system in the occurrence of OHSS.
Obstetrics & Gynecology, 2005
Genetic as well as hormonal factors are known to influence the development and clinical course of... more Genetic as well as hormonal factors are known to influence the development and clinical course of endometriosis. We aimed to investigate the association among 10 single nucleotide polymorphisms (SNPs) involved in the estrogen metabolism and endometriosis and to develop a multiple genetic model. METHODS: In a case-control study, we investigated the genotype frequencies of 10 estrogen metabolizing SNPs in 32 patients with endometriosis and 790 healthy controls using sequencing-on-chip-technology with solidphase polymerase chain reaction on oligonucleotide microarrays: catechol-O-methyltransferase, Val158Met G->A, 17--hydroxysteroid dehydrogenase type 1 (HSD17), vlV A->C, cytochrome P450 (CYP), 17 A2 allele T->C, CYP1A1 MspI RFLP T->C, CYP1A1 Ile462Val A->G, CYP19 Arg264Cys C->T, CYP19 C1558T C->T, CYP 1B1 Leu432Val, CYP1B1 Asn453Ser, and estrogen receptor alpha IVS1-401>C. Associations and 2-way interaction models between SNPs were calculated by stepwise logistic regression models. RESULTS: In a univariate model, HSD17 vlV A->C was associated with a significantly increased risk of endometriosis (P ؍ .004; odds ratio 3.9, 95% confidence interval 1.6-9.8). When all 2-way interactions of investigated SNPs were ascertained, no significant interactions among SNPs were observed. In a multivariate model, HSD17 vlV A->C was also significantly associated with endometriosis (P ؍ .002). CONCLUSION: We present data on multiple SNPs in patients with endometriosis indicating an association between HSD17 gene variation and the disease. Although not able to demonstrate interaction models of SNPs, we provide evidence of HSD17 vlV A->C as a low penetrance genetic marker of endometriosis.
Journal of Reproductive Immunology, 2008
TNF-alpha G308A, IL-6 G174C and IL-10 G1082A polymorphisms have recently been associated with pre... more TNF-alpha G308A, IL-6 G174C and IL-10 G1082A polymorphisms have recently been associated with preeclampsia (PE). The aim of this study was to clarify whether the occurrence of TNF-alpha, IL-6 and IL-10 polymorphisms is increased in women of our population with PE in a previous pregnancy. A retrospective, controlled, open, multicenter study was carried out in 107 women with a history of PE and 107 women with uncomplicated pregnancies. Smears from buccal gingival cells were analyzed for the polymorphisms of TNF-alpha, IL-6 and IL-10 by hybridization on microarrays. Statistical significance was calculated by the chi-quadrant test. Heterozygocity for the gene polymorphisms did not occur more often in preeclamptic women compared with controls (TNF-alpha: 29.0% versus 24.3%, p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.05; IL-6: 46.7% versus 51.4%, p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.05; or IL-10: 49.5% in each). Moreover, there was no significant difference between preeclamptics and controls with regard to homozygocity for TNF alpha (1.9% versus 3.7%, p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.05); IL-6 (17.8% versus 13.1%, p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.05); and IL-10 (30.8% versus 32.7%, p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.05). In contrast to the findings of some other investigators, gene polymorphisms do not seem to be important in our population for development of PE.
Human Reproduction, 2005
BACKGROUND: Lifestyle parameters, personal history and genetic factors are thought to affect the ... more BACKGROUND: Lifestyle parameters, personal history and genetic factors are thought to affect the timing of natural menopause in humans. Based on their biological function, estrogen-metabolizing gene polymorphisms have been regarded as candidate genes for early menopause. METHODS: In the present cross-sectional, multi-centre study, we analysed nine single nucleotide polymorphisms of six estrogen-metabolizing genes [three estrogen-synthesizing genes, i.e. 17-b-hydroxysteroid dehydrogenase type 1 (17-b HSD), cytochrome P-450 (CYP) 17 and CYP19; and three estrogen-inactivating genes, i.e. catechol-O-methyltransferase (COMT), CYP1A1 and CYP1B1 ] by sequencing-on-chip-technology in 1360 Caucasian women with natural menopause. Women's lifestyle parameters, reproductive and personal histories were ascertained. RESULTS: Carriage of at least one mutant allele of the CYP1B1-4 Asn453Ser A ! G polymorphism (P 5 0.004) and the number of full-term pregnancies (P < 0.001) were found to be independently associated with age at natural menopause. Women with at least one polymorphic allele of CYP1B1-4 experienced natural menopause earlier than non-carriers of the polymorphism [mean (SD) 48.6 (5.0) versus 49.4 (4.3) years]. Women with no, one, two and three or more full-term pregnancies experienced natural menopause at 48.5 (5.0), 48.8 (4.8), 49.5 (4.2) and 49.6 (4.6) years, respectively. CONCLUSION: We present the most comprehensive data on estrogen-metabolizing gene polymorphisms and timing of natural menopause to date. The number of full-term pregnancies and the CYP1B1-4 polymorphism are significant predictors of timing of natural menopause in Caucasian women.
Fertility and Sterility, 2002
To investigate the association between the 306-base pair insertion polymorphism in intron G of th... more To investigate the association between the 306-base pair insertion polymorphism in intron G of the progesterone receptor (PROGINS) and endometriosis. Case-control study. Tertiary care center. Ninety-five white women with surgically diagnosed and histologically confirmed endometriosis and 107 white women without endometriosis (controls). Determination of PROGINS was performed by polymerase chain reaction and gel electrophoresis. MAIN OUTCOIME MEASURE(S): Frequency and distribution of the PROGINS allele. Frequencies of the mutant allele T2 was 0.17 among women with endometriosis and 0.08 among controls (odds ratio, 2.41 [CI, 1.31-4.53]). Homozygosity for allele T2 was present in 3.2% of women with endometriosis and 0.9% of controls. PROGINS appears to be associated with endometriosis in white persons.
Fertility and Sterility, 2003
echogenic gray layers), and 5 patients exhibited a type C EP (homogenous, hyperechogenic endometr... more echogenic gray layers), and 5 patients exhibited a type C EP (homogenous, hyperechogenic endometrium). Endometrial thickness was measured in millimeters. Data were analyzed by Fisher's exact test, unpaired t test and/or logistic regression with Statview software. Clinical pregnancy was the primary outcome variable. Two-tailed pϽ0.05 was considered significant. Sample size was determined by study interval, and not power analysis. Results: Overall, clinical pregnancy was established in 64% of the 447 patients after transfer of embryos at the blastocyst or morula stage of development. Two hundred fifty-four of the 376 (68%) pattern A patients became pregnant versus 31 of the 66 (47%) of pattern B patients (P ϭ 0.0024). There was no statistically significant relationship between pattern A and B patients with regard to the variables of endometrial thickness (P ϭ 0.37), age (P ϭ 0.58), ART method (P ϭ 0.23) or number of embryos transferred (P ϭ 0.17). Excluding the 41 women who had only morula transferred, the difference in pregnancy between patterns A and B remained significant (P ϭ 0.013) for women who had a blastocyst transfer. Of the 5 women with pattern C endometrium, 3 became pregnant. If patients with B and C patterns were combined and compared to group A, as other investigators have suggested, there was still a significant difference between groups (P ϭ 0.0028). Conclusion: The presence of a B pattern endometrium on the day of hCG administration was associated with a significant reduction in clinical pregnancy in women undergoing blastocyst transfer. These results suggest that the endometrium may represent an obstacle to the establishment of pregnancy at ART for some patients. However, in patients with a B pattern, we would still proceed with embryo transfer rather than cryopreservation, since 47% of these patients achieved pregnancy. Based on these findings, further characterization of the endometrium defined as B pattern by ultrasound may identify barriers to implantation.
Biology of Reproduction, 1999
The mechanisms that ultimately regulate cervical ripening during parturition remain largely unkno... more The mechanisms that ultimately regulate cervical ripening during parturition remain largely unknown. A possible role for nitric oxide (NO) has recently emerged; however, the expression of NO synthase (NOS) within the human cervix in the ripening process has not been investigated. The purpose of this study was to identify cell types in the human cervix that contain NOS isoforms and to examine changes in their expression during the ripening process and the nonpregnant state. Inducible NOS (iNOS) immunoreactivity was observed in the epithelial cells and stromal spindle cells in 17 of 20 biopsies from cervices obtained within 10 min postpartum, but in only 4 of 12 nonpregnant controls (p ؍ 0.03). Endothelial NOS (eNOS) immunoreactivity was restricted to vascular endothelia in all sections, whereas neuronal NOS was not detectable. Inducible NOS activity in the postpartum group was 3.2 times that of the control group (p ؍ 0.0005), whereas constitutive NOS activity remained unchanged in both groups (p ؍ 0.222). Competitive reverse transcription-polymerase chain reaction revealed no differences in the expression of iNOS (p ؍ 0.443) or eNOS mRNA (p ؍ 0.409). The existence of iNOS in the human postpartum cervix suggests that increased production of NO, probably induced by cytokines, may be relevant to the process of natural cervical ripening in humans.
American Journal of Obstetrics and Gynecology, 1998
Our purpose was to compare concentrations of messenger ribonucleic acid specific for the oxytocin... more Our purpose was to compare concentrations of messenger ribonucleic acid specific for the oxytocin receptor and for the vasopressin 1a receptor in myometrial and endometrial tissues of pregnant and nonpregnant women. Tissues from pregnant uteri were obtained from 95 women who were undergoing cesarean delivery between 26 and 42 weeks&#39; gestation. Tissues from nonpregnant uteri were obtained from 7 cycling women who were undergoing hysterectomy. The competitive reverse-transcription polymerase chain reaction method was used to determine messenger ribonucleic acid concentrations. A significant increase in oxytocin receptor messenger ribonucleic acid was found during the first half of pregnancy. Oxytocin receptor messenger ribonucleic acid concentrations were lower in tissues with spontaneous contractions than in quiescent tissues and were decreased in patients with advanced labor. Vasopressin 1a receptor messenger ribonucleic acid concentrations were high in tissues from both cycling and pregnant uteri but remained unchanged throughout gestation. The increase in oxytocin receptor protein concentrations seen in pregnancy is only partially controlled by messenger ribonucleic acid abundance. High concentrations of vasopressin 1a receptor messenger ribonucleic acid confirm the biologically active role of this receptor in both the cycling and the pregnant uterus.
Uploads
Papers by Christian Schneeberger