Christel Meuleman

High prevalence of endometriosis in infertile women with normal ovulation and normospermic partners.

OBJECTIVE To determine the prevalence of histologically proven endometriosis in a subset of infertile women. DESIGN Retrospective case series with electronic file search and multivariable logistic regression analysis. SETTING Tertiary academic fertility center. PATIENT(S) Two hundred twenty-one infertile women without previous surgical diagnosis for infertility with regular cycles (variation, 21-35 days) whose partners have a normal semen analysis. INTERVENTION(S) Diagnostic laparoscopy and, if necessary, operative laparoscopy with CO(2) laser excision. MAIN OUTCOME MEASUREMENT(S) The prevalence of endometriosis and of fertility-reducing nonendometriotic tubal and/or uterine pathology. RESULT(S) The prevalence of endometriosis was 47% (104/221), including stage I (39%, 41/104), stage II (24%, 25/104), stage III (14%, 15/104), and stage IV (23%, 23/104) endometriosis, and was comparable in patients with (54%, 61/113) and without (40%, 43/108) pelvic pain. The prevalence of fertility-reducing nonendometriotic tubal and/or uterine pathology was 29% in all patients (15% in women with and 40% in women without endometriosis). A multivariate logistic regression model including pain, ultrasound data, age, duration of infertility, and type of fertility was not or not sufficiently reliable for the prediction of endometriosis according to the revised American Fertility Society (rAFS) classifications I-II and rAFS III-IV, respectively. CONCLUSION(S) Reproductive surgery is indicated in infertile women belonging to the study population, regardless of pain symptoms or transvaginal ultrasound results, since half of them have endometriosis and 40% of those without endometriosis have fertility-reducing pelvic pathology.

Coping Style and Depression Level Influence Outcome in In Vitro Fertilization

OBJECTIVE To examine the influence of depression levels and coping on IVF outcome in women, taking into account the cause of infertility. DESIGN Prospective clinical study. SETTING A university hospital. PATIENT(S) Ninety-eight women undergoing IVF treatment. INTERVENTION(S) Psychometric tests were administered at the first visit (day 3) of the investigated treatment cycle. MAIN OUTCOME MEASURE(S) Achievement of pregnancy. RESULTS The nonpregnant group reported increased expression of negative emotions. In the subgroup with a female indication for IVF, increased depressive symptomatology (correlated with increased expression of negative emotions) was associated with lower pregnancy rates (PRs), whereas in the subgroup with a male indication for IVF, increased depressive symptomatology (correlated with decreased expression of negative emotions) was associated with higher PRs. CONCLUSION(S) Expression of negative emotions predicts depression levels and outcome in IVF. The cause of infertility should be taken into account when investigating the relation between psychologic functioning and outcome in IVF.

Diagnosis of deep endometriosis by clinical examination during menstruation and plasma CA-125 concentration * †

OBJECTIVES To evaluate a clinical examination during menstruation and plasma CA-125 concentrations to diagnose deep endometriosis. DESIGN Prospective study in 61 women scheduled for a laparoscopy, a retrospective study in 140 women with deep endometriosis, and a clinical validation study in 16 women with painful pelvic nodularities during menstruation. SETTING University Hospital Gasthuisberg, a tertiary referral center. RESULTS In the retrospective study, deep endometriosis was detected by routine clinical examination in only 36% of women. Lesions infiltrating deeper than 15 mm were detected in 50%. In the prospective study pelvic nodularities were detected by routine clinical examination in 4 women but were detected in 22 by clinical examination during menstruation. The latter was highly reliable to diagnose deep endometriosis, cystic ovarian endometriosis, and cul-de-sac obliteration. CA-125 concentrations were higher during menstruation and correlated with deep endometriosis and with deep and cystic ovarian endometriosis. Nodularities at clinical examination or follicular phase CA-125 concentrations > 35 U/mL are useful to decide that a bowel preparation should be given, achieving a sensitivity of 87% and a specificity of 83%. In the clinical validation study, deep endometriosis was found in 14 of 16 women. CONCLUSION Clinical examination during menstruation can diagnose reliably deep endometriosis, cystic ovarian endometriosis, or cul-de-sac adhesions. This test, preferentially combined with a follicular phase CA-125 assay, should be used to decide whether a preparation for bowel surgery should be given.

Preimplantation genetic screening for aneuploidy of embryos after in vitro fertilization in women aged at least 35 years: a prospective randomized trial

OBJECTIVE To test the hypothesis that patients with advanced maternal age (AMA) have a higher implantation rate (IR) after embryo transfer of embryos with a normal chromosomal pattern for the chromosomes studied with preimplantation genetic screening (PGS) compared with patients who had an embryo transfer without PGS. DESIGN Prospective randomized controlled trial (RCT). SETTING Academic tertiary setting. PATIENT(S) Patients with AMA (> or =35 years). INTERVENTION(S) In an RCT, the clinical IR per embryo transferred was compared after embryo transfer on day 5 or 6 between the PGS group (analysis of chromosomes 13, 16, 18, 21, 22, X, and Y) and the Control group without PGS. MAIN OUTCOME MEASURE(S) No differences were observed between the PGS group and the Control group for the clinical IR (15.1%; 14.9%; rate ratio 1.01; exact confidence interval [CI], 0.25-5.27), the ongoing IR (at 12 weeks) (9.4%; 14.9%), and the live born rate per embryo transferred (9.4%; 14.9%; rate ratio 0.63; exact CI, 0.08-3.37). Fewer embryos were transferred in the PGS group (1.6 +/- 0.6) than in the Control group (2.0 +/- 0.6). A normal diploid status was observed in 30.3% of the embryos screened by PGS. CONCLUSION(S) In this RCT, the results did not confirm the hypothesis that PGS results in improved reproductive outcome in patients with AMA.

Evaluation of a panel of 28 biomarkers for the non-invasive diagnosis of endometriosis

BACKGROUND At present, the only way to conclusively diagnose endometriosis is laparoscopic inspection, preferably with histological confirmation. This contributes to the delay in the diagnosis of endometriosis which is 6-11 years. So far non-invasive diagnostic approaches such as ultrasound (US), MRI or blood tests do not have sufficient diagnostic power. Our aim was to develop and validate a non-invasive diagnostic test with a high sensitivity (80% or more) for symptomatic endometriosis patients, without US evidence of endometriosis, since this is the group most in need of a non-invasive test. METHODS A total of 28 inflammatory and non-inflammatory plasma biomarkers were measured in 353 EDTA plasma samples collected at surgery from 121 controls without endometriosis at laparoscopy and from 232 women with endometriosis (minimal-mild n = 148; moderate-severe n = 84), including 175 women without preoperative US evidence of endometriosis. Surgery was done during menstrual (n = 83), follicular (n = 135) and luteal (n = 135) phases of the menstrual cycle. For analysis, the data were randomly divided into an independent training (n = 235) and a test (n = 118) data set. Statistical analysis was done using univariate and multivariate (logistic regression and least squares support vector machines (LS-SVM) approaches in training- and test data set separately to validate our findings. RESULTS In the training set, two models of four biomarkers (Model 1: annexin V, VEGF, CA-125 and glycodelin; Model 2: annexin V, VEGF, CA-125 and sICAM-1) analysed in plasma, obtained during the menstrual phase, could predict US-negative endometriosis with a high sensitivity (81-90%) and an acceptable specificity (68-81%). The same two models predicted US-negative endometriosis in the independent validation test set with a high sensitivity (82%) and an acceptable specificity (63-75%). CONCLUSIONS In plasma samples obtained during menstruation, multivariate analysis of four biomarkers (annexin V, VEGF, CA-125 and sICAM-1/or glycodelin) enabled the diagnosis of endometriosis undetectable by US with a sensitivity of 81-90% and a specificity of 63-81% in independent training- and test data set. The next step is to apply these models for preoperative prediction of endometriosis in an independent set of patients with infertility and/or pain without US evidence of endometriosis, scheduled for laparoscopy.

Clinical outcome after radical excision of moderate-severe endometriosis with or without bowel resection and reanastomosis: a prospective cohort study.

Objective:To assess the clinical outcome of women requiring laparoscopic excision of moderate-severe endometriosis in women with and without bowel resection and reanastomosis. Methods:Two hundred three patients with laparoscopically excised moderate (n = 67) or severe (n = 136) endometriosis (rAFS: revised endometriosis classification of the American Fertility Society) were prospectively followed during a median of 20 months (1–45 months) using a CONSORT-inspired checklist. Patients completed the EHP30 Quality-of-Life Questionnaire and visual analogue scales (VAS) for dysmenorrhea, chronic pelvic pain, and deep dyspareunia and answered questions about postoperative complications, reinterventions/recurrences, and fertility outcome 1 month before and 6, 12, 18, and 24 months after surgery. Clinical outcome was compared between women with deeply infiltrative endometriosis undergoing CO2 laser ablative surgery with bowel resection (study group, 76/203; 37%) and without bowel resection (control group, 127/203; 63%). Results:Both groups were similar with respect to population characteristics and clinical outcome, except for mean rAFS score [higher in study group (73 ± 31) than in control group (48 ± 26)] and minor complication rate [higher in study group (11%) than in control group (1%)]. In both groups, mean VAS and EHP30 scores improved significantly and remained stable for 24 months after surgery, with a pregnancy rate of 51%. Within 1, 2, and 3 years follow-up, the cumulative reintervention rate was 1%, 7%, and 10%, respectively, and the cumulative endometriosis recurrence rate was 1%, 6%, and 8%, respectively. Conclusions:Clinical outcome after CO2 laser laparoscopic excision of moderate-severe endometriosis was comparable in women with or without bowel resection and reanastomosis, except for a higher minor complication rate occurring in women with bowel resection and reanastomosis (NCT00463398).

Endometriosis, recurrent miscarriage and implantation failure: is there an immunological link?

Endometriosis is more frequently diagnosed in patients with infertility than in a normal population. The goal of this paper is to give an overview of the clinical and fundamental evidence for a possible link between endometriosis and (recurrent) miscarriage or implantation failure after treatment with assisted reproductive technology. According to the literature, there is insufficient evidence for an association between endometriosis and (recurrent) miscarriage, but there is, however, epidemiological evidence to support the link between endometriosis and recurrent implantation failure after assisted reproduction. This can possibly be explained by alterations in humoral and cell-mediated immunity in women with endometriosis. Humoral immunological changes include increased formation of antibodies against endometrial antigens, anti-laminin-1 auto-antibodies and other auto-immune antibodies (e.g. antiphospholipid). Cell-mediated immunological changes include alterations in peritoneal and follicular fluid immune cells and cytokines. The possible negative effect of these immunological changes on folliculogenesis, ovulation, oocyte quality, early embryonic development and implantation in women with endometriosis suggests that infertility in endometriosis patients may be related to alterations within the follicle or oocyte, resulting in embryos with decreased ability to implant.

Increased frequency of chromosomal abnormalities in female partners of couples undergoing in vitro fertilization or intracytoplasmic sperm injection

OBJECTIVE To determine the prevalence of chromosomal abnormalities in female partners of couples undergoing IVF or intracytoplasmic sperm injection (ICSI). DESIGN Prospective study. SETTING Leuven University Fertility Center. PATIENT(S) Female candidates for IVF or ICSI. INTERVENTION(S) An initial cytogenetic study was performed on peripheral blood lymphocyte cultures using G- and R-banding. In all patients, > or =25 metaphases were examined. If a chromosomal aberration was detected, additional cytogenetic studies were performed for precise identification. MAIN OUTCOME MEASURE(S) Abnormal female karyotypes in comparison with the general female population. RESULT(S) Cytogenetic analysis was performed in 263 female partners of couples before entering an IVF or ICSI program. The prevalence of autosomal reciprocal balanced translocations was seven times higher in the study group (1.14%) than in the general population (0.16%). All abnormal karyotypes were found in the IVF group with male factor infertility. CONCLUSION(S) Chromosomal abnormalities are more frequent in the female partners of couples seeking fertility treatment. We recommend chromosomal analysis in women before starting IVF or ICSI treatment, even in the presence of male factor infertility.

Outcome after multidisciplinary CO2 laser laparoscopic excision of deep infiltrating colorectal endometriosis.

The aim of this retrospective cohort study was to evaluate clinical outcome after multidisciplinary laparoscopic excision of deep endometriosis. Patients (n = 56) were asked to complete questionnaires regarding quality of life (QOL), pain, fertility and sexuality to compare their status before and after surgery, and their medical files were analysed. Statistical analysis was performed with life table analysis, paired Wilcoxon and McNemar tests. Gynaecological pain, QOL and sexual activity improved significantly (P < 0.001; P < 0.0001 to P = 0.008 and P < 0.0001 to P = 0.0003 respectively) during a median follow-up 29 months after surgery. Post operative complications occurred in 11% but were directly related to surgery in only 5%. The cumulative recurrence rate of endometriosis was 2 and 7% at 1 and 4 years after surgery respectively. Cumulative pregnancy rate was 31 and 70% at 1 and 4 years after surgery respectively. In conclusion, multidisciplinary CO(2) laser laparoscopic excision of deep endometriosis with colorectal extension improves pain, QOL and sexuality with high fertility and low complication and recurrence rates.

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.