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Biomedical subjects

Christel Meuleman

Publications and source records attributed to Christel Meuleman.

12 recordsLinked to original sources

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↗

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↗

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↗

No difference in cycle pregnancy rate and in cumulative live-birth rate between women with surgically treated minimal to mild endometriosis and women with unexplained infertility after controlled ovarian hyperstimulation and intrauterine insemination.

OBJECTIVE: The association between infertility and minimal to mild endometriosis is controversial and poorly understood. The clinical pregnancy rate (PR) per cycle after controlled ovarian hyperstimulation (COH) with or without intrauterine insemination (IUI) is reportedly lower in women with surgically untreated minimal to mild endometriosis than in women with unexplained infertility. It is possible that prior laparoscopic removal of endometriosis has a positive effect on the clinical PR after COH and IUI. Therefore, we tested the hypothesis that after COH and IUI the PR per cycle and the cumulative live-birth rate (CLBR) are equal or higher in women with recently surgically treated minimal to mild endometriosis when compared with women with unexplained infertility. DESIGN: A retrospective, controlled cohort study. SETTING: Leuven University Fertility Centre, a tertiary academic referral center. PATIENT(S): One hundred seven women treated during 259 cycles with COH and IUI including patients with endometriosis (n = 58, 137 cycles) and unexplained infertility (n = 49, 122 cycles). All patients with endometriosis had minimal (n = 41, 100 cycles) or mild (n = 17, 37 cycles) disease that had been laparoscopically removed within 7 months before the onset of treatment with COH and IUI. INTERVENTION(S): Controlled ovarian hyperstimulation using clomiphene citrate (23 cycles) or gonadotrophins (236 cycles) in combination with IUI. MAIN OUTCOME MEASURE(S): Clinical PR per cycle and CLBR within four cycles of treatment with COH and IUI. RESULT(S): The clinical PR per cycle was comparable in women with minimal or mild endometriosis (21% or 18.9%, respectively) and in women with unexplained infertility (20.5%). The CLBR within four cycles of COH and IUI was also comparable in women with minimal endometriosis, mild endometriosis, and unexplained infertility (70.2%, 68.2 %, 66.5%, respectively). CONCLUSION(S): The data from our study suggest that COH and IUI shortly after laparoscopic excision of endometriosis is as effective as COH and IUI in patients with unexplained subfertility.

Adult↗

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↗

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↗

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↗

Isolated teratozoospermia and intrauterine insemination.

OBJECTIVE: This study tests the hypothesis that IUI treatment in cases with isolated teratozoospermia (<10% normal forms using strict criteria, normal motility and normal count), results in a lower cumulative live birth rate compared to cases with normozoospermia. DESIGN: A retrospective cohort study. SETTING: An academic fertility center. PATIENT(S): Eight hundred seventy-two IUI cycles in 440 couples were analyzed. INTERVENTION(S): Couples (n = 440) were classified in three groups: normozoospermia (n = 213), isolated teratozoospermia (n = 104), and male factor infertility (n = 123). MAIN OUTCOME MEASURE(S): Live birth rate per cycle and cumulative live birth rate (CLBR). RESULT(S): The three groups were similar with regard to female age, female infertility factors, and ovarian response after hormonal stimulation. The overall CLBR after four cycles was 41.5%, and was significantly increased in the normozoospermic group (52.8%) when compared to the isolated teratozoospermia group (33.4%) and the male factor infertility group (31.4%). CONCLUSION(S): This study documents for the first time that the CLBR after four IUI cycles is significantly and similarly reduced in couples with isolated teratozoospermia as in couples with other sperm defects, when compared to couples with normozoospermia. As with couples with male factor infertility, couples with isolated teratozoospermia should be counseled about other treatment options such as IVF, as the CLBR after three IVF cycles is 70%-80% in our program.

Adult↗

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↗

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↗

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↗

A prospective randomized study: day 2 versus day 5 embryo transfer.

BACKGROUND: This randomized controlled study was performed in an unselected IVF/ICSI population to test the hypothesis that blastocyst transfers result in higher clinical pregnancy rates (CPR) per oocyte retrieval when compared with day 2 transfers. METHODS: Blind randomization for transfer on day 2 (group 1) or day 5/6 (group 2) was performed before stimulation. Oocytes and embryos were cultured in sequential media in 5.5% CO(2), 5% O(2), 89.5% N(2) and 90% humidity. A maximum of two embryos was transferred. RESULTS: The two groups were similar for age, IVF indication, number of treatment cycles, rate of ICSI/IVF, number of fertilized oocytes and number of embryos transferred. The CPR/oocyte retrieval was comparable in group 1 (32%) and in group 2 (44%), while the CPR/embryo transfer was significantly higher (P < 0.01) in group 2 (60%) than in group 1 (35%). Similarly, the implantation rate per embryo transferred was significantly higher (P < 0.03) in group 2 (46%) than in group 1 (29%). The cryo-augmented delivery rate/oocyte retrieval was comparable in group 2 (36.3%) and in group 1 (28.6%). CONCLUSION: This randomized study in an unselected population showed a significantly higher CPR/embryo transfer and a tendency toward a higher CPR/oocyte retrieval in patients receiving blastocysts when compared with day 2 transfers.

Adult↗