PubMed Health⌕ Search

Biomedical subjects

Thomas M D'Hooghe

Publications and source records attributed to Thomas M D'Hooghe.

At least 19 recordsLinked to original sources
PubMed2006

Is the endometriosis recurrence rate increased after ovarian hyperstimulation?

OBJECTIVE: To test the hypothesis that the cumulative endometriosis recurrence rate (CERR) after fertility surgery for endometriosis stage III or IV is increased in women exposed to very high E(2) levels during ovarian hyperstimulation (OH) for IVF when compared with women exposed to less high E(2) levels during OH for intrauterine insemination (IUI). DESIGN: Retrospective cohort study including infertility patients with endometriosis stage III or IV. SETTING: Leuven University Fertility Center, between 1990 and 2001. PATIENT(S): Patients (n = 67) with endometriosis stage III (n = 45) or IV (n = 22) who underwent pelvic reconstructive surgery and subsequently started fertility treatment with either IVF only (n = 39), both IVF and IUI in different cycles (n = 11), or IUI only (n = 17). INTERVENTION(S): Life table analysis was used to calculate the CERR. MAIN OUTCOME MEASURE(S): The CERR based on histologic or cytologic proof of disease recurrence. RESULT(S): At 21 months after the start of OH the overall CERR was 31% and was significantly lower in patients treated with IVF only (7%) or women treated with both IVF and IUI in different cycles (43 %) than in those treated with IUI only (70%). At 36 months after the start of OH, the overall CERR was 63%. CONCLUSION(S): In contrast to our hypothesis, the results from this study showed that the CERR is lower after ovarian hyperstimulation for IVF than after lower-dose ovarian stimulation for IUI, suggesting that temporary exposure to very high E(2) levels in women during OH for IVF is not a major risk factor for endometriosis recurrence in women treated with assisted reproductive technology.

Adult↗
PubMed2006

ProteinChip technology is a useful method in the pathogenesis and diagnosis of endometriosis: a preliminary study.

OBJECTIVE: To test the feasibility of ProteinChip (Ciphergen Biosystems, Inc., Fremont, CA) technology as a proteomic tool in discovering and identifying proteins that are differentially expressed in endometrium, endometriotic tissue, and normal peritoneum from women with and without endometriosis. DESIGN: Differential analysis of protein expression in women with and without endometriosis. SETTING: University hospital. PATIENT(S): A total of nine patients during their secretory phase (days 20-22) were selected for this study on the basis of cycle phase and presence/or absence of endometriosis. INTERVENTION(S): Twelve tissues used in the study included six endometrial biopsies from women with mild endometriosis (n = 3) and a normal pelvis (n = 3) as well as paired samples of peritoneal endometriotic lesions (n = 3) and macroscopically normal peritoneum biopsies (n = 3) from three women with endometriosis. MAIN OUTCOME MEASURE(S): Numerous expression differences were observed in the above comparisons, representing both up-regulation and down-regulation in protein and peptide expression levels. RESULT(S): Endometrial expression for a number of proteins and peptides in the range of 2.8-12.3 kDa was 3-24 times lower in women with endometriosis than in those without endometriosis. When compared with normal peritoneum, endometriotic lesions showed an increased expression for a set of proteins and peptides in the range of 3-96 kDa, and especially an up-regulated cluster of proteins between 22 and 23 kDa, identified to be transgelin, a smooth muscle actin-binding protein. CONCLUSION(S): This preliminary study demonstrated that differential protein profiling by using ProteinChip array technology is feasible, reproducible, and may be developed into a powerful tool for endometriosis research.

Biomarkers↗
PubMed2006

Increased peritoneal and endometrial gene expression of biologically relevant cytokines and growth factors during the menstrual phase in women with endometriosis.

OBJECTIVE: To examine differential messenger RNA (mRNA) expression of relevant cytokines, metalloproteases, growth and adhesion factors in endometrium and peritoneum from women with endometriosis when compared with women without the disease during menstrual and luteal phases of the cycle. DESIGN: Patients with endometriosis were compared with control patients. SETTING: University hospital. PATIENT(S): A total of 35 patients (20 patients during the luteal phase and 15 patients during the menstrual phase) were selected for this study on the basis of cycle phase and presence or absence of endometriosis. INTERVENTION(S): In this study, endometriosis was laparoscopically and histologically confirmed in 24 women with endometriosis of revised American Society for Reproductive Medicine (ASRM) stage I-II (n = 12) and revised ASRM stage III-IV (n = 12), and the presence of a normal pelvis was documented by laparoscopy in 11 control patients. The macroscopically normal peritoneum tissues were collected from lateral wall left or right, near the colon ascendens or descendens. MAIN OUTCOME MEASURE(S): The expression levels were determined as ratios between the target molecules and beta-actin as housekeeping gene. RESULT(S): In women with endometriosis, peritoneal mRNA levels of matrix metalloproteinase (MMP)-3, transforming growth factor-beta, interleukin (IL)-6, and intercellular adhesion molecule-1 and endometrial mRNA levels of MMP-3, tumor necrosis factor (TNF)-alpha, and IL-8 were significantly higher during the menstrual phase when compared with luteal phase. During the menstrual phase of the cycle, both endometrial expression of TNF-alpha, IL-8, and MMP-3 mRNA levels and peritoneal expression of transforming growth factor-beta, IL-6, and intercellular adhesion molecule-1 mRNA levels were significantly higher in women with endometriosis when compared with controls. Immunohistochemical staining confirmed the presence of TNF-alpha in peritoneum and endometrium in both women with endometriosis and controls. CONCLUSION(S): Increased endometrial and peritoneal cytokine mRNA expression during menstruation may contribute to a pelvic inflammatory microenvironment favoring the development of endometriosis.

Biomarkers↗
PubMed2006

Endometriosis and assisted reproduction: the role for reproductive surgery?

PURPOSE OF REVIEW: The aim of this review paper is to discuss the relationship between endometriosis and assisted reproductive technology. More specifically, the following clinically relevant issues will be discussed. (1) Does the presence of endometriosis affect the outcome of assisted reproductive technology? (2) Does surgical treatment for endometriosis prior to or after assisted reproductive technology treatment affect the outcome of assisted reproductive technology? (3) Is assisted reproductive technology a risk factor for the recurrence of endometriosis after medical or surgical therapy? RECENT FINDINGS: The review is based on recently published review papers/meta-analyses or international guidelines as published by the European Society of Human Reproduction or the American Society of Reproductive Medicine, updated with a selective review of recent papers searching PubMed with the key words 'Endometriosis', 'Assisted Reproduction', 'IVF', 'IUI' and 'Reproductive Surgery'. SUMMARY: At the end of this review, a practical proposal for the clinical management of women with endometriosis-associated subfertility is proposed, based on our own experience.

Endometriosis↗
PubMed2006

Emerging drugs in endometriosis.

Endometriosis is a common, estrogen-dependent, gynaecological disease, defined as the presence of endometrial-like tissue outside the uterus. Although several medications are used for treatment of the disease, they are associated with high recurrence rates, considerable side effects and limited duration of application. Due to these limitations and to the impact of endometriosis on the quality of life of affected women, their environment and the society, there is a great need for new drugs able to abolish endometriosis and its symptoms. Studies in recent years investigating the (patho)physiological mechanisms involved in disease aetiology have fostered the development of novel therapeutic concepts for endometriosis, by targeting the hypothalamic-pituitary-gonadal axis, by selective modulation of estrogenic and progestogenic pathways, by inhibiting angiogenesis or by interfering with inflammatory and immunological factors. This article presents a brief summary of the currently available medications and an overview regarding the development of some of the most interesting and/or most promising novel drug candidates for endometriosis.

Endometriosis↗
PubMed2005

Tumour necrosis factor-alpha, interleukin-6 and interleukin-8 do not promote adhesion of human endometrial epithelial cells to mesothelial cells in a quantitative in vitro model.

BACKGROUND: A key factor in the pathogenesis of endometriosis is the endometrial-peritoneal adhesion. To study the pathogenesis of endometriosis, a quantitative in vitro assay (QIVA) was developed to measure in vitro adhesion between human endometrial epithelial cells and mesothelial cells using commercially available cell lines. Using the QIVA, the hypothesis was tested that tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-8 (IL-8) promote adhesion of endometrial epithelial cells to mesothelial cells. METHODS: Mesothelial cells were pre-treated with TNF-alpha, IL-6 or IL-8 in various concentrations (ranging from 0 to 1000 IU/ml) for 24 h. Confluent endometrial epithelial cells were labelled with [35S]methionine, added to the confluent mesothelial cells and incubated for 1 h. After incubation, non-adhering cells were removed and adherent cells were solubilized and their [35S]methionine radioactivity was counted to quantify the adherence of endometrial epithelial cells to mesothelial cells. RESULTS: The in vitro adhesion of human endometrial epithelial cells to human mesothelial cells was inhibited in a dose-dependent manner by TNF-alpha (P=0.0007), IL-6 (P<0.0001) and IL-8 (P=0.0004). CONCLUSIONS: Using a quantitative in vitro adhesion assay, we were unable to confirm our hypothesis that TNF-alpha, IL-6 and IL-8 promote the in vitro adhesion between endometrial epithelial cells and mesothelial cells.

Cell Adhesion↗
PubMed2005

Recombinant human TNFRSF1A (r-hTBP1) inhibits the development of endometriosis in baboons: a prospective, randomized, placebo- and drug-controlled study.

Endometriosis is associated with chronic inflammation, including an increased macrophage activity with increased secretion of cytokines, such as tumor necrosis factor (TNF) or TNF superfamily member 2, previously known as TNFalpha. In the present study, we tested the hypothesis that recombinant human TNFRSF1A (r-hTBP1) can inhibit the development of endometriotic lesions in the baboon, an established model for the study of endometriosis. Endometriosis was induced using intrapelvic injection of menstrual endometrium in 20 baboons with a normal pelvis. In the first part of the study, 14 baboons were randomly assigned to subcutaneous treatment with r-hTBP1, placebo, or GnRH antagonist (positive control). In the second part of the study, menstrual endometrium from 6 baboons was randomly incubated with either PBS or r-hTBP1 before intrapelvic seeding. Video laparoscopy was performed 25 days later to document the number, surface area, and estimated volume of endometriotic lesions and adhesions; to calculate the revised American Fertility Society (rAFS) score and stage; and to confirm the histological presence of endometriosis. In the first part, baboons treated with r-hTBP1 or with Antide (Bachem) had a lower endometriosis rAFS score, a lower surface area and estimated volume of peritoneal endometriotic lesions, and a lower histological confirmation rate compared with controls. Because of less adnexal and cul-de-sac adhesions, the number of baboons with endometriosis of stage II, III, or IV was lower among baboons treated with r-hTBP1 or Antide than among controls. In the second part, the surface area of endometriotic lesions was lower, and less severe endometriosis was observed in r-hTBP1-treated baboons. No hypoestrogenic effects were observed in baboons treated with r-hTBP1. In conclusion, r-hTBP1 can effectively inhibit the development of endometriosis without hypoestrogenic effects in baboons.

Animals↗
PubMed2005

New Belgian legislation regarding the limitation of transferable embryos in in vitro fertilization cycles does not significantly influence the pregnancy rate but reduces the multiple pregnancy rate in a threefold way in the Leuven University Fertility Center.

After the introduction of new Belgian legislation limiting the number of transferable embryos to prevent multiple pregnancies after assisted reproductive technology, the implantation rate per embryo remained stable at 26% and the clinical pregnancy rate per embryo transfer did not change significantly (37.5% before and 32.5% after legislation), whereas the multiple pregnancy rate per clinical pregnancy decreased threefold from 25.9% to 8.0%) in the Leuven University Fertility Center.

Academic Medical Centers↗
PubMed2004

Future directions in endometriosis research.

Endometriosis is an important gynecological disease, pathologically defined by the ectopic presence of both endometrial glands and stroma, and clinically associated with pelvic pain and infertility. Our current knowledge of the pathogenesis, pathophysiology of related infertility, and spontaneous evolution is still limited, although endometriosis has been described for many years. Future research in endometriosis needs to focus on pathogenesis studies in the baboon model and on the early interactions between endometrial and peritoneal cells in the pelvic cavity at the time of menstruation. Proteomic and genomic approaches are needed to detect potential differences between eutopic endometrium and myometrium in women with and without endometriosis. Immunomodulatory drugs inhibiting endometriosis-associated pelvic inflammation may offer new medical treatment for endometriosis in the future.

Animals↗
PubMed2003

Potential involvement of the immune system in the development of endometriosis.

This article presents an overview of immunological factors and their role in the development of endometriosis, with emphasis on inflammatory cytokines, growth and adhesion factors. Although retrograde menstruation is a common phenomenon among women of reproductive age, not all women who have retrograde menstruation develop endometriosis. The development of endometriosis is hypothesised to be a complex process, which may be facilitated by several factors, including the quantity and quality of endometrial cells in peritoneal fluid (PF), increased inflammatory activity in PF, increased endometrial-peritoneal adhesion and angiogenesis, reduced immune surveillance and clearance of endometrial cells, and increased production of autoantibodies against endometrial cells. Potential biomarkers like cytokines and autoantibodies upregulated during development of endometriosis may be useful in the development of a non-surgical diagnostic tool. Although endometriosis can be treated using hormonal suppression, there is need for non-hormonal drugs, which can inhibit the development of endometriosis and alleviate pain or infertility without inhibition of ovulation. New molecules that modulate immune function in endometriosis should be the targets for future research.

Endometriosis↗
PubMed2003

Application of the Fertilase-laser system versus the conventional mechanical method to immobilize spermatozoa for intracytoplasmic sperm injection. A randomized controlled trial.

A randomized controlled trial was set up to test the hypothesis that the fertilization rate of oocytes after intracytoplasmic sperm injection (ICSI) is higher after immobilization of the spermatozoa with the Fertilase-laser system technology than after immobilization of the spermatozoa with the conventional mechanical method. Metaphase II oocytes were injected with spermatozoa that were immobilized with the conventional mechanical method (group A, n=177) or with spermatozoa that were immobilized with the Fertilase-laser system technology (group B, n=179). The fertilization rate per successfully injected oocyte was comparable in group A (62.6%; 92/147) and in group B (56.3%; 89/158)(p=0.3). No difference could be observed in fertilization rates of oocytes injected with spermatozoa that were immobilized with the Fertilase-laser system technology compared to spermatozoa immobilized with the conventional mechanical method.

Adult↗
PubMed2003

Future directions in endometriosis research.

Future research in endometriosis must focus on pathogenesis studies in the baboon model, the early interactions between endometrial and peritoneal cells in the pelvic cavity at the time of menstruation, and potential differences between eutopic endometrium and myometrium in women with and without endometriosis. More integration is needed between the areas of epidemiology and genetics. Pelvic inflammation in women with endometriosis could be the target for new diagnostic and therapeutic approaches. Important questions remain regarding the relationship between endometriosis and environmental factors. Systemic and extrapelvic manifestations of endometriosis must be analyzed carefully, and better tools are needed to measure quality of life in women with chronic pain caused by endometriosis. Most current evidence supports a causal relationship between endometriosis and subfertility, and the spontaneous progressive nature of endometriosis has been demonstrated in 30% to 60% of patients. Recurrence of endometriosis after classic medical and surgical therapy is a major and underestimated problem, especially in women with advanced disease. Integrated clinical and research teams are needed that combine expert medical, surgical, and holistic care with state-of-the-art research expertise in immunology, endocrinology, and genetics to discover new diagnostic methods and medical treatments for endometriosis.

Animals↗
PubMed2003

Endometriosis and subfertility: is the relationship resolved?

There are many arguments to support the hypothesis that there is a causal relationship between the presence of endometriosis and subfertility. These arguments are reviewed in this article and include: (1) an increased prevalence of endometriosis in subfertile women compared with women of proven fertility; (2) a reduced monthly fecundity rate (MFR) in baboons with mild to severe (spontaneous or induced) endometriosis compared with those with minimal endometriosis or a normal pelvis; (3) a trend toward a reduced MFR in infertile women with minimal to mild endometriosis compared with women with unexplained infertility; (4) a dose-effect relationship: a negative correlation between the r-AFS stage of endometriosis and the monthly fecundity rate and crude pregnancy rate; (5) a reduced monthly fecundity rate and cumulative pregnancy rate after donor sperm insemination in women with minimal-mild endometriosis compared with those with a normal pelvis; (6) a reduced MFR after husband sperm insemination in women with minimal to mild endometriosis compared with those with a normal pelvis; (7) a reduced implantation rate per embryo after IVF in women with moderate to severe endometriosis compared with women with a normal pelvis; and (8) an increased monthly fecundity rate and cumulative pregnancy rate after surgical removal of minimal to mild endometriosis.

Animals↗
PubMed2003

Immunomodulators and aromatase inhibitors: are they the next generation of treatment for endometriosis?

PURPOSE OF REVIEW: This article will present an overview of current and new hormonal and non-hormonal medical treatment in the management of endometriosis, with special emphasis on immunomodulators and aromatase inhibitors. RECENT FINDINGS: Recent research shows a very promising role for new hormonal medication (aromatase inhibitors, estrogen and progesterone receptor modulators) and anti-inflammatory drugs (tumor necrosis factor-alpha inhibitors, matrix metalloproteinase inhibitors, cyclooxygenase-2 inhibitors) in the management of endometriosis. SUMMARY: The ideal drug in the treatment of endometriosis alleviates pain and cures sub-fertility without inhibition of ovulation or menstruation and without significant side effects or teratological effects. Such a drug would allow conception during treatment and would fundamentally change the management of endometriosis from a surgical approach to medical management. Although such a drug does not yet exist, promising research using tumor necrosis factor inhibitors indicates that this could become possible in the not too distant future. We strongly recommend testing new medication for the prevention or treatment of endometriosis in the baboon model, an established research model for fundamental and preclinical research in endometriosis.

Adjuvants, Immunologic↗
PubMed2003

Medical management of endometriosis: novel targets and approaches towards the development of future treatment regimes.

Endometriosis remains an enigmatic disease in women of reproductive age. Current treatment regimes used to manage the disease are primarily designed to induce a hypoestrogenic state which leads to a reduction in disease and associated symptoms. While these regimes have been used with great success, there are still drawbacks and limitations to these types of therapies. In this review, we address the shortcomings of current drugs used to medically manage endometriosis and offer potential target areas which may be attractive alternatives to current therapies. Emphasis is placed upon the promising research using tumor necrosis factor inhibitors in this context. Further, we discuss the advantages of such therapies and offer experimental approaches towards the development and testing of these regimes.

Adjuvants, Immunologic↗
PubMed2002

In-vitro adhesion of endometrium to autologous peritoneal membranes: effect of the cycle phase and the stage of endometriosis.

BACKGROUND: Endometrium can adhere to autologous peritoneum. This study was undertaken to determine the effect of the menstrual cycle phase and the presence and stage of endometriosis on in-vitro adhesion of endometrium onto autologous peritoneum. METHODS: This was performed in an academic medical research centre. Sixty-seven subfertile women with a visually normal pelvis (n = 18) and with biopsy-proven endometriosis (n = 49) were included. Endometrial and peritoneal biopsies were obtained at laparoscopy during menstrual, follicular and luteal phase. Endometrium was cultured in vitro with autologous peritoneum, followed by fixation, paraffin embedding, serial sectioning, hematoxylin-eosin and immunohistochemical staining. Endometrial-peritoneal adhesion was evaluated using light microscopy. RESULTS: Endometrial-peritoneal adhesion was observed in approximately 80% of the adhesion assays and was not affected by the phase of the cycle, or by the presence and stage of endometriosis. The continuity of the mesothelial layer was disrupted at the attachment sites. Epithelialization was observed along the edges to integrate the endometrial implant. After adhesion, histological changes were observed within and below the implant. CONCLUSIONS: Endometrium obtained during menstrual, follicular or luteal phase appears to have a similar potential to implant in vitro on autologous peritoneum, and this adhesion process is not affected by the stage of endometriosis.

Adult↗