PubMed Health⌕ Search

Biomedical subjects

C W Burger

Publications and source records attributed to C W Burger.

At least 19 recordsLinked to original sources
PubMed2007

Molecular analysis of human endometrium: short-term tibolone signaling differs significantly from estrogen and estrogen + progestagen signaling.

Tibolone, a tissue-selective compound with a combination of estrogenic, progestagenic, and androgenic properties, is used as an alternative for estrogen or estrogen plus progesterone hormone therapy for the treatment of symptoms associated with menopause and osteoporosis. The current study compares the endometrial gene expression profiles after short-term (21 days) treatment with tibolone to the profiles after treatment with estradiol-only (E(2)) and E(2) + medroxyprogesterone acetate (E(2) + MPA) in healthy postmenopausal women undergoing hysterectomy for endometrial prolapse. The impact of E(2) treatment on endometrial gene expression (799 genes) was much higher than the effect of tibolone (173 genes) or E(2) + MPA treatment (174 genes). Furthermore, endometrial gene expression profiles after tibolone treatment show a weak similarity to the profiles after E(2) treatment (overlap 72 genes) and even less profile similarity to E(2) + MPA treatment (overlap 17 genes). Interestingly, 95 tibolone-specific genes were identified. Translation of profile similarity into biological processes and pathways showed that ER-mediated downstream processes, such as cell cycle and cell proliferation, are not affected by E2 + MPA, slightly by tibolone, but are significantly affected by E(2). In conclusion, tibolone treatment results in a tibolone-specific gene expression profile in the human endometrium, which shares only limited resemblance to E(2) and even less resemblance to E2 + MPA induced profiles.

Cluster Analysis↗
PubMed2006

Does subfertility explain the risk of poor perinatal outcome after IVF and ovarian hyperstimulation?

BACKGROUND: The primary objective of this study was to investigate whether subfertility explains poor perinatal outcome after assisted conception. A secondary objective was to test the hypothesis that ovarian hyperstimulation rather than the IVF procedure may influence the perinatal outcome. METHODS: Using data from a Dutch population-based historical cohort of women treated for subfertility, we compared perinatal outcome of singletons conceived after controlled ovarian hyperstimulation (COHS) and IVF (IVF + COHS; n = 2239) with perinatal outcome in subfertile women who conceived spontaneously (subfertile controls; n = 6343) and in women who only received COHS (COHS only; n = 84). Furthermore, we compared perinatal outcome of singletons conceived after the transfer of thawed embryos with (Stim + Cryo; n = 66) and without COHS (Stim - Cryo; n = 73). RESULTS: The odds ratios (ORs) for very low birthweight (<1500 g) and low birthweight (1500-2500 g) were 2.8 [95% confidence interval (95% CI) 1.9-3.9] and 1.6 (95% CI 1.2-1.8) in the IVF + COHS group compared with the subfertile control group. The ORs for very preterm birth (<32 weeks) and for preterm birth (32-37 weeks) were 2.0 (95% CI 1.4-2.9) and 1.5 (95% CI 1.3-1.8), respectively. Adjustment for confounders did not materially change these risk estimates. The difference in risk between the COHS-only group and the subfertile group was significant only for very low birthweight (OR 3.5; 95% CI 1.1-11.4), but the association became weaker after adjustment for maternal age and primiparity (OR 3.1; 95% CI 1.0-10.4). No significant difference in birthweight and preterm delivery was found between the group of children conceived after ovarian stimulation/ovulation induction and (Stim + Cryo) and the group of children conceived after embryo transfer of thawed embryos in a spontaneous cycle without ovarian stimulation/ovulation induction (Stim - Cryo). CONCLUSIONS: The poor perinatal outcome in this database could not be explained by subfertility and suggests that other factors may be important in the known association between assisted conception and poor perinatal outcome.

Adult↗
PubMed2006

Recurrent endometrial cancer: a retrospective study.

OBJECTIVE: The value of follow-up after treatment for endometrial cancer will be discussed. STUDY DESIGN: We evaluated our clinical experience, including mode of detection, of patients with recurrent endometrial cancer treated in the Erasmus Medical Centre in Rotterdam over a 20-year period. Clinical data and histopathological features from 64 patients were analyzed. Survival was analyzed with a Kaplan-Meier curve. RESULTS: Twenty-two patients had a local recurrence, 30 had a distant recurrence and 12 had simultaneous local and distant recurrent disease. Ninety-five percent of the local recurrences and 67% of the distant recurrences were detected within three years. Twenty-seven patients had a screen-detected recurrence, 34 had an interval screening recurrence and two had a chance finding recurrence. The overall survival rate at two years was 70% and at five years 53%. Patients with a screen-detected recurrence had a 5-year survival rate of 62%, while patients with interval screening and chance finding recurrences had a 5-year survival rate of 47%. CONCLUSION: A follow-up program in the first three years after primary treatment of endometrial cancer is useful in detecting recurrent disease. We have no reason to use a different program of follow-up in patients with low risk primary disease.

Aged↗
PubMed2006

Optimum number of oocytes for a successful first IVF treatment cycle.

Ovarian stimulation in IVF allows selection of embryos for transfer, but may have detrimental effects on oocyte and embryo quality and endometrial receptivity. This study investigated the optimal response to ovarian stimulation in terms of number of oocytes for achieving pregnancy in a first IVF cycle. Data from 7422 women who underwent their first IVF cycle for standard indications were analysed. All had been treated with exogenous gonadotrophins and gonadotrophin releasing hormone (GnRH) agonist co-treatment in a long down-regulation protocol between 1990 and 1995. Pregnancy rates in relation to the number of obtained oocytes were adjusted for age, fecundity, subfertility cause, gonadotrophin dosage, type of luteal support, and number of transferred embryos by multivariate analysis. Of the 7422 women who underwent oocyte retrieval, overall 85% had an embryo transfer and 24% conceived. The highest pregnancy rates per embryo transfer and per started cycle were observed when 13 oocytes were obtained (31 and 28%, respectively). This study supports the concept of an optimal range of oocytes obtained in response to ovarian stimulation for IVF, below and above which outcomes are compromised.

Adolescent↗
PubMed2006

The hormone replacement therapy drug tibolone acts very similar to medroxyprogesterone acetate in an estrogen-and progesterone-responsive endometrial cancer cell line.

Tibolone, a steroidogenic compound with both estrogenic and progestagenic properties, is used as an alternative for estrogen or estrogen plus progesterone hormone therapy for the treatment of symptoms associated with menopause and osteoporosis. We have evaluated whether the effect of tibolone on a human endometrial cell line is similar to, or comparable with, the effect of estradiol (E(2)), medroxyprogesterone acetate (MPA) or E(2) + MPA treatment. Using stable transfection techniques, the estrogen receptor (ER) expressing human endometrial cancer cell line, ECC1, was altered to also express both progesterone receptors (PRs). These cells were then used to assess growth regulation and expression profiling (Affymetrix U133plus2) under the influence of E(2) (1 nM), MPA (1 nM), E(2) + MPA or tibolone (100 nM). Growth assessment and comparison of profiles indicate that tibolone behaves predominantly like MPA. Furthermore, regulation of prereplication complex genes, such as the minichromosome maintenance genes, could be involved in the observed strong inhibition of growth by tibolone as well as MPA. In addition, in total, 15 genes were found to be specific for tibolone treatment. These genes were predominantly involved in regulation of the cell cycle and differentiation.

Cell Line, Tumor↗
PubMed2005

Effects of subfertility cause, smoking and body weight on the success rate of IVF.

BACKGROUND: We investigated the separate and combined effects of smoking and body mass index (BMI) on the success rate of IVF for couples with different causes of subfertility. METHODS: The success rate of IVF was examined in 8457 women. Detailed information on reproduction and lifestyle factors was combined with medical record data on IVF treatment. All IVF clinics in The Netherlands participated in this study. The main outcome measures were live birth rate per first cycle of IVF differentiated for the major predictive factors. RESULTS: For male subfertility the delivery rate per cycle was significantly lower than unexplained subfertility, OR of 0.70 (95% CI 0.57-0.86); for tubal pathology, the delivery rate was slightly lower, OR = 0.86 (95% CI 0.70-1.01). Smoking was associated with a significantly lower delivery rate was slightly lower; for OR = 0.72 (95% CI 0.61-0.84) and a significantly higher abortion rate compared to non-smoking delivery rates of 21.4% and 16.4%, respectively (P=0.02). Women with a BMI of > or = 27 kg/m2 had a significantly lower delivery rate, with an OR of 0.67 (95% CI 0.48-0.94), compared with normal weight women (BMI > or = 20 and <27 kg/m2). CONCLUSIONS: Both smoking and overweight unfavourably affect the live birth rate after IVF. The devastating impact of smoking on the live birth rate in IVF treatment is comparable with an increase in female age of >10 years from age 20 to 30 years. Subfertile couples may improve the outcome of IVF treatment by lifestyle changes.

Abortion, Spontaneous↗
PubMed2005

Primitive neuroectodermal tumor of the cervix uteri: a case report -- changing concepts in therapy.

BACKGROUND: Peripheral primitive neuroectodermal tumor (PNET) of the cervix uteri is extremely rare. Between 1987 and 2002, there have been eight cases described in the English literature. The treatment policies in these eight cases differed considerably, partly due to the rarity of the disease and to differing time periods of diagnosis and treatment. CASE: At the end of 2002, a 21-year-old woman presented with a PNET of the cervix uteri at our institute, the Erasmus Medical Center. For the appropriate treatment in this case, we reviewed the literature and decided that the treatment should be different from the local surgical treatment followed by additional treatments as most of the earlier reports describe. CONCLUSION: In view of the current knowledge of PNET belonging to the family of Ewing's sarcoma, and the improvement of treatment outcome in these tumors due to dose-intensive neo-adjuvant chemotherapy, patients with PNET of the cervix should be treated in accordance to the protocol for bony Ewing's sarcoma with multimodality therapy by means of induction chemotherapy, surgery, and consolidation chemotherapy.

Adult↗
PubMed2005

Tamoxifen treatment for breast cancer enforces a distinct gene-expression profile on the human endometrium: an exploratory study.

Tamoxifen treatment for breast cancer increases proliferation of the endometrium, resulting in an enhanced prevalence of endometrial pathologies, including endometrial cancer. An exploratory study was performed to begin to understand the molecular mechanism of tamoxifen action in the endometrium. Gene-expression profiles were generated of endometrial samples of tamoxifen users and compared with matched controls. The pathological classification of samples from both groups included atrophic/inactive endometrium and endometrial polyps. Unsupervised clustering revealed that samples of tamoxifen users were, irrespective of pathological classification, fairly similar and consequently form a subgroup distinct from the matched controls. Using SAM analysis (a statistical method to select genes differentially expressed between groups), 256 differentially expressed genes were selected between the tamoxifen and control groups. Upon comparing these genes with oestrogen-regulated genes, identified under similar circumstances, 95% of the differentially expressed genes turned out to be tamoxifen-specific. Finally, construction of a gene-expression network of the differentially expressed genes revealed that 69 genes centred around five well-known genes: TP53, RELA, MYC, epidermal growth factor receptor and beta-catenin. This could indicate that these well-known genes, and the pathways in which they function, are important for tamoxifen-controlled proliferation of the endometrium.

Antineoplastic Agents, Hormonal↗
PubMed2004

Molecular portrait of the progestagenic and estrogenic actions of tibolone: behavior of cellular networks in response to tibolone.

Tibolone is a synthetic steroid with estrogenic effects on brain, vagina, and bone without stimulating the endometrium. During tibolone treatment, it is thought that the progestagenic properties of tibolone stimulate cell differentiation, which effectively counterbalances the growth-stimulating effects of the estrogenic properties of tibolone. The objective of this study was to characterize the expression profile that reflects the endometrial responses to the separated estrogenic (growth-inducing) and progestagenic (growth-inhibiting) actions of tibolone, thus gaining insight into the counteracting effect of these properties of tibolone on the endometrium. The estrogenic action of tibolone was studied in the estrogen-responsive ECC1 cell line (expressing estrogen receptor alpha), and the progestagenic action was studied in the progesterone-responsive cell line Ishikawa PRAB-36 (expressing PRA and PRB). The data showed that the progestagenic and estrogenic effects of tibolone produce different expression profiles with a narrow overlap in genes; however, both properties modulate the same biological processes. The final genetic network analysis indicated that the estrogenic effect of tibolone is potentially counterbalanced by the progestagenic metabolite of tibolone via differential regulation of similar cellular processes. For example, both progestagenic and estrogenic properties stimulate proliferation, but they exert the opposite effect on apoptosis. The apoptosis network was stimulated by the progestagenic properties of tibolone; in contrast, the estrogenic effect of tibolone suppressed the apoptosis network. The current results indicate that this differential regulation is realized through modulation of a different group of genes and rarely via contraregulation of the same set of genes.

Adenocarcinoma↗
PubMed2004

[Methods and results of in-vitro fertilisation in the Netherlands in the years 1983-1994].

OBJECTIVE: To describe methods and results of in-vitro fertilisation (IVF) treatment during the first 12 years after the introduction of IVF treatment in the Netherlands. Design. Retrospective cohort study. METHOD: A nationwide study was conducted among women who had had their first IVF cycle stimulated with gonadotrophins in 12 IVF centres in the Netherlands in the period 1 January 1983 to 31 December 1994 (n = 8, 184). RESULTS: The subfertility diagnosis related to tubal factors decreased from 70% in 1987 to 25% in 1994. The subfertility diagnosis related to a male factor increased from 8.7% in 1987 to 35.5% in 1994. The mean age at first IVF treatment remained roughly constant. During the introduction of GnRH agonists there was an increase in gonadotrophin dosages, the number of retrieved oocytes, the number of high responders and/or women who experienced an ovarian hyperstimulation syndrome (OHSS). The percentage of deliveries with at least one baby born alive after the first IVF cycle increased from 6% in 1984 to 18% in 1994. The number of live births per 100 transferred embryos increased from 2.5 in 1985 to 12 in 1994. Furthermore, the mean numbers of embryos transferred after the first IVF cycle decreased from 3.2 in 1987 to 2.2 in 1994. The overall success rate - defined as the proportion of women who had at least one child born alive after one or more IVF cycles - for women who had their first IVF treatment between 1983 and 1994 was 37.1%. The percentage of triplets or quadruplets decreased from 8.7 in 1989 to 1.2 in 1994. The percentage of twin deliveries remained about 25. CONCLUSION: The introduction of GnRH agonists and the higher dosages of gonadotrophins led to a higher oocyte harvest. During the first years of IVF treatment there was an increase in the success rate after the first treatment cycle. The overall success rate remained constant after 1991. The risk of developing an OHSS increased whereas the rate of twin deliveries remained constant.

Adult↗
PubMed2004

Gene expression profiling in human endometrial cancer tissue samples: utility and diagnostic value.

OBJECTIVE: Recently, gene expression profiling techniques have been used on several human cancers to classify tumor subgroups with a specific biological behavior, which were previously undetected by the conventional histopathologic staging systems. In the current study, the clinical usefulness and prognostic value of gene expression profiling in human endometrial carcinomas were studied. METHODS: A macro cDNA array, containing cDNAs of 588 genes selected from different areas of cancer research, was used to generate gene expression profiles of tumor tissue samples. The gene expression profiles of 12 endometrial cancers, 3 benign (e.g. noncancer) endometrial tissue samples and 3 myometrial tissue samples, taken from human surgical specimen, were compared. RESULTS: The efficacy to generate a gene expression profile of these tissue samples was 77%. The RNA samples could be randomly taken from the tissue samples and were highly reproducible. Cluster analysis of gene expression profiles of the different samples showed that the benign endometrial and the myometrial samples clustered separately from the tumor samples, indicating that the gene expression profiles were tissue specific and not patient specific. Cluster analysis of the tumor samples revealed two distinct tumor clusters. Ranking of the tumors in the two clusters showed high similarity with the histopathologic classification [International Federation of Gynecology and Obstetrics (FIGO) grading]. CONCLUSION: Classification of endometrial tumors on basis of their gene expression profiles showed similarity with the FIGO grading system.

Adult↗
PubMed2003

Risk of benign gynaecological diseases and hormonal disorders according to responsiveness to ovarian stimulation in IVF: a follow-up study of 8714 women.

BACKGROUND: Over the past decade, attention has been focused increasingly on the long-term health effects of IVF in women. Assuming that hormonal changes due to stimulation regimens for IVF are strongest among 'high' responders, we evaluated whether responsiveness to ovarian stimulation in IVF is predictive of the risk of benign gynaecological disorders >12 months after the last IVF cycle. METHODS: A nationwide historical cohort study of women who underwent IVF treatment was conducted. After a median time of 4.6 years following the last IVF treatment cycle, 8714 cohort members completed a health survey questionnaire that inquired about reproductive variables and the occurrence and age at onset of specific medical conditions including uterine leiomyoma, surgically removed ovarian cysts and thyroid disorders. Detailed data on cause of subfertility and IVF treatment were collected from the medical records. Women were included in the 'high responders' group when on average >/=14 oocytes were retrieved per IVF cycle (n = 1562), in the 'normal responders' group when they had a mean number of 4-13 retrieved oocytes (n = 6033), and in the 'low responders' group when they had a mean number of 0-3 retrieved oocytes per cycle (n = 1119). RESULTS: Among women with a high response to ovarian stimulation, we found a borderline significantly decreased risk of uterine leiomyoma [relative risk (RR) = 0.6; 95% confidence interval (CI) 0.4-1.0] and surgically removed ovarian cysts (RR = 0.6; 95% CI 0.3-1.0) in comparison with 'normal responders'. After OHSS, the age-adjusted RRs were 1.8 (95% CI 0.9-3.8) for having surgically removed ovarian cysts and 1.0 (95% CI 0.4-2.2) for uterine leiomyoma (both not significant). CONCLUSIONS: Despite the small number of events observed, highly elevated risks of gynaecological disorders and hormonal diseases in women undergoing IVF treatment can be excluded based on the present data and this follow-up period. Women with a low response to ovarian stimulation tended to have higher risks of benign gynaecological diseases than high responders.

Cohort Studies↗
PubMed2003

Birth weight and age at menarche in patients with polycystic ovary syndrome or diminished ovarian reserve, in a retrospective cohort.

BACKGROUND: Few studies have investigated the association between subfertility in women and factors in early life such as birth weight and age at menarche, and most have produced contradictory results. In the present study, this association was investigated among women undergoing artificial reproductive techniques (ART), including IVF for reason of polycystic ovary syndrome (PCOS) or diminished ovarian reserve. Herein, PCOS included oligomenorrhoea and at least one additional symptom such as hyperandrogenism, hirsutism or polycystic ovaries on ultrasound. In most patients this was concomitant with elevated serum LH levels. Diminished ovarian reserve was defined as receiving a donated oocyte or having a low response to ovarian hyperstimulation. METHODS: Among a retrospective cohort of 26 428 women diagnosed with subfertility between 1980 and 1995, three study groups and one reference group were defined using data from medical records. Women were included in the first group if diagnosed as having PCOS (n = 265). In order to define diminished ovarian reserve capacity, two groups were selected: (i) women receiving a donated oocyte (n = 98); and (ii) women having a low response (three follicles or less) to ovarian hyperstimulation in both their first and second IVF cycles (n = 351). Women with tubal obstruction formed the reference group (n = 957). In a logistic regression model, the effect of birth weight and age at menarche was examined. Information on both variables was obtained from mailed questionnaires. RESULTS: Birth weight did not differ significantly between the study groups and the reference group. However, PCOS patients were significantly older at menarche [OR 3.31 (2.18-5.04)]. Women receiving a donated oocyte and low responders were significantly younger at menarche [OR 2.67 (1.35-5.29) and OR 2.01 (1.26-3.20) respectively]. CONCLUSION: The fetal origins hypothesis, the association between intrauterine growth retardation and disease in adult life, could not be confirmed, though a relationship between timing of menarche and PCOS and a diminished ovarian reserve was identified. Further investigation of the effect of birth weight on fertility outcome in a prospective setting is strongly advised.

Adult↗
PubMed2003

Progestogenic effects of tibolone on human endometrial cancer cells.

Tibolone, a synthetic steroid acting in a tissue-specific manner and used in hormone replacement therapy, is converted into three active metabolites: a Delta(4) isomer (exerting progestogenic and androgenic effects) and two hydroxy metabolites, 3 alpha-hydroxytibolone (3 alpha-OH-tibolone) and 3beta-OH-tibolone (exerting estrogenic effects). In the present study an endometrial carcinoma cell line (Ishikawa PRAB-36) was used to investigate the progestogenic properties of tibolone and its metabolites. This cell line contains progesterone receptors A and B, but lacks estrogen and androgen receptors. When tibolone was added to the cells, complete conversion into the progestogenic/androgenic Delta(4) isomer was observed within 6 d. Furthermore, when cells were cultured with tibolone or when the Delta(4) isomer or the established progestagen medroxyprogesterone acetate was added to the medium, marked inhibition of growth was observed. Interestingly, 3 beta-OH-tibolone also induces some inhibition of growth. These growth inhibitions were not observed in progesterone receptor-negative parental Ishikawa cells, and progestagen-induced growth inhibition of PRAB-36 cells could readily be reversed using the antiprogestagen Org-31489. Upon measuring the expression of two progesterone-regulated genes (fibronectin and IGF-binding protein-3), tibolone, the Delta(4) isomer and medroxyprogesterone acetate showed similar gene expression regulation. These results indicate that tibolone, the Delta(4) metabolite, and to some extent 3 beta-OH-tibolone exert progestogenic effects. Tibolone and most likely 3 beta-OH-tibolone are converted into the Delta(4) metabolite.

Cell Division↗
PubMed2001

Risk of cancer in the offspring of women who underwent ovarian stimulation for IVF.

BACKGROUND: Over the past decade attention has been increasingly focused on the long-term health effects of assisted reproductive technologies (ART), such as IVF, in both women and their offspring. To determine the risk of cancer in children conceived by IVF we used a large population-based historical cohort that was initially designed to examine the risk of gynaecological disorders in women who underwent IVF. METHODS: Children were included in the exposed group if they were conceived by IVF or other related fertility techniques (n=9484). The unexposed group consisted of 7532 children whose mothers were diagnosed with subfertility disorders but who were conceived naturally. All cohort members were asked to complete a mailed questionnaire that inquired about reproductive variables and cancer in the offspring (response rate 66.9%). RESULTS: During an average follow-up period of 6.0 years, 16 cancers were observed in the exposed and unexposed group combined, whereas 15.5 were expected [standardized incidence ratio (SIR) = 1.0; 95% confidence interval (95% CI) 0.6-1.7]. A direct comparison between children conceived after ART and naturally conceived children revealed no increased risk for childhood malignancies [risk ratio (RR) = 0.8; 95% CI 0.3-2.3]. CONCLUSIONS: Despite the small numbers of observed cancer cases, these findings demonstrate that children conceived by ART have no greatly increased risk of cancer during childhood compared with the general population and the internal reference group.

Adolescent↗