Thomas D’Hooghe

Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries

OBJECTIVE To assess the impact of endometriosis on health-related quality of life (HRQoL) and work productivity. DESIGN Multicenter cross-sectional study with prospective recruitment. SETTING Sixteen clinical centers in ten countries. PATIENT(S) A total of 1,418 premenopausal women, aged 18-45 years, without a previous surgical diagnosis of endometriosis, having laparoscopy to investigate symptoms or to be sterilized. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Diagnostic delay, HRQoL, and work productivity. RESULT(S) There was a delay of 6.7 years, principally in primary care, between onset of symptoms and a surgical diagnosis of endometriosis, which was longer in centers where women received predominantly state-funded health care (8.3 vs. 5.5 years). Delay was positively associated with the number of pelvic symptoms (chronic pelvic pain, dysmenorrhoea, dyspareunia, and heavy periods) and a higher body mass index. Physical HRQoL was significantly reduced in affected women compared with those with similar symptoms and no endometriosis. Each affected woman lost on average 10.8 hours (SD 12.2) of work weekly, mainly owing to reduced effectiveness while working. Loss of work productivity translated into significant costs per woman/week, from US

Single-cell paired-end genome sequencing reveals structural variation per cell cycle

4 in Nigeria to US

World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project: III. Fluid biospecimen collection, processing, and storage in endometriosis research

456 in Italy. CONCLUSION(S) Endometriosis impairs HRQoL and work productivity across countries and ethnicities, yet women continue to experience diagnostic delays in primary care. A higher index of suspicion is needed to expedite specialist assessment of symptomatic women. Future research should seek to clarify pain mechanisms in relation to endometriosis severity.

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

The nature and pace of genome mutation is largely unknown. Because standard methods sequence DNA from populations of cells, the genetic composition of individual cells is lost, de novo mutations in cells are concealed within the bulk signal and per cell cycle mutation rates and mechanisms remain elusive. Although single-cell genome analyses could resolve these problems, such analyses are error-prone because of whole-genome amplification (WGA) artefacts and are limited in the types of DNA mutation that can be discerned. We developed methods for paired-end sequence analysis of single-cell WGA products that enable (i) detecting multiple classes of DNA mutation, (ii) distinguishing DNA copy number changes from allelic WGA-amplification artefacts by the discovery of matching aberrantly mapping read pairs among the surfeit of paired-end WGA and mapping artefacts and (iii) delineating the break points and architecture of structural variants. By applying the methods, we capture DNA copy number changes acquired over one cell cycle in breast cancer cells and in blastomeres derived from a human zygote after in vitro fertilization. Furthermore, we were able to discover and fine-map a heritable inter-chromosomal rearrangement t(1;16)(p36;p12) by sequencing a single blastomere. The methods will expedite applications in basic genome research and provide a stepping stone to novel approaches for clinical genetic diagnosis.

Serial laparoscopies over 30 months show that endometriosis in captive baboons (Papio anubis, Papio cynocephalus) is a progressive disease

Objective To harmonize standard operating procedures (SOPs) and standardize the recording of associated data for collection, processing, and storage of human tissues relevant to endometriosis. Design An international collaboration involving 34 clinical/academic centers and three industry collaborators from 16 countries on five continents. Setting In 2013, two workshops were conducted followed by global consultation, bringing together 54 leaders in endometriosis research and sample processing from around the world. Patient(s) None. Intervention(s) Consensus SOPs were based on: 1) systematic comparison of SOPs from 24 global centers collecting tissue samples from women with and without endometriosis on a medium or large scale (publication on >100 cases); 2) literature evidence where available, or consultation with laboratory experts otherwise; and 3) several global consultation rounds. Main Outcome Measure(s) Standard recommended and minimum required SOPs for tissue collection, processing, and storage in endometriosis research. Result(s) We developed “recommended standard” and “minimum required” SOPs for the collection, processing, and storage of ectopic and eutopic endometrium, peritoneum, and myometrium, and a biospecimen data collection form necessary for interpretation of sample-derived results. Conclusion(s) The EPHect SOPs allow endometriosis research centers to decrease variability in tissue-based results, facilitating between-center comparisons and collaborations. The procedures are also relevant to research into other gynecologic conditions involving endometrium, myometrium, and peritoneum. The consensus SOPs are based on the best available evidence; areas with limited evidence are identified as requiring further pilot studies. The SOPs will be reviewed based on investigator feedback and through systematic triannual follow-up. Updated versions will be made available at: http://endometriosisfoundation.org/ephect.

Evolution of spontaneous endometriosis in the baboon (Papio anubis, Papio cynocephalus) over a 12-month period*

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.

Reasons for dropout in infertility treatment.

OBJECTIVE To test the hypothesis that spontaneous endometriosis is a progressive disease in baboons. DESIGN AND SETTING Prospective cohort study, Institute of Primate Research, Nairobi, Kenya. PARTICIPANTS Twelve baboons with histologically proven spontaneous endometriosis. INTERVENTIONS Fifty-four serial laparoscopies (4.2 +/- 1.9 per animal, range 1 to 7) were performed after 1 to 3 months (n = 2), 4 to 6 months (n = 1), 7 to 9 months (n = 6), 10 to 12 months (n = 17), 13 to 15 months (n = 7), 16 to 18 months (n = 1), 19 to 21 months (n = 8), 22 to 24 months (n = 8), 25 to 27 months (n = 2), and 30 to 32 months (n = 2). MAIN OUTCOME MEASURE During each laparoscopy the pelvis was examined for the presence of endometriosis. The number, size, and type of endometriotic implants were noted on a pelvic map and both endometriosis score and stage were calculated. Remodeling was defined as a change in laparoscopic appearance (typical, subtle, suspicious) of an individual endometriotic lesion. Data were analyzed by a signed rank test. RESULTS Endometriosis was progressive as shown by the significant increase in the number and surface of lesions and in endometriosis scores after 24 months. The total number of endometriotic lesions after 24 months consisted of 69% new (and mostly subtle) implants, 10% remodeled lesions, and 21% unchanged implants. CONCLUSIONS This study demonstrated that endometriosis in captive baboons undergoing repeated laparoscopies is a dynamic and moderately progressive disease with periods of development and regression and active remodeling between different types of lesions.

The cycle pregnancy rate is normal in baboons with stage I endometriosis but decreased in primates with stage II and stage III-IV disease.

To document the spontaneous evolution of endometriosis, a repeat laparoscopy was performed in 11 baboons after 10 and/or 12 months. The mean number of endometriotic lesions had increased significantly after 10 months (P less than 0.02) because of a high proportion of new lesions (82%). These implants were mainly subtle (67%) and localized on the uterine peritoneum (58%). Progression of endometriosis did not go beyond revised AFS stage I. Additionally, repeat laparoscopy in 10 baboons with an initially normal pelvis showed an endometriosis incidence of 70% after 10 to 12 months. Remodeling of the lesions was apparent in both groups after 12 months. These results suggest that endometriosis is moderately progressive in the baboon. It is possible that multiple laparoscopies could favor the development of endometriosis.

Deoxyribonucleic acid methyltransferases and methyl-CpG-binding domain proteins in human endometrium and endometriosis.

Background: The objective of this study was to explore the reasons why couples discontinue fertility treatment. Methods: A retrospective exploratory study was performed at the Leuven University Fertility Centre, a university hospital-based fertility center. Women who discontinued treatment between September 2000 and December 2001 were contacted in 2004–2005 by telephone for a standardized interview which covered 9 dropout reasons. For each reason, its importance on the decision to stop treatment was measured on an 11-point Likert scale. Results: On average, psychological burden (x = 5.96) had the highest impact on the decision to stop treatment followed by physical burden (x = 4.48) and female age (x = 3.64). Perceived lack of staff expertise (x = 1.84), negative impact on social contacts (x = 2.12) and financial burden (x = 2.16) had the lowest impact on the decision to stop treatment. Longer duration of infertility was significantly positively correlated with a higher rating of physical burden as a reason to discontinue treatment (r = 0.48; p < 0.05). Discussion: On average, psychological burden appears to be most frequently named as the number one reason to discontinue infertility treatment, whereas financial burden had the lowest impact. Longer duration of infertility is associated with more externalizing reasons to discontinue treatment.

Clinical outcome after laparoscopic radical excision of endometriosis and laparoscopic segmental bowel resection.

OBJECTIVES To test the hypothesis that fertility is reduced in baboons with endometriosis. DESIGN Prospective controlled follow-up study. SETTING Institute of Primate Research, Nairobi Kenya. SUBJECTS Seventy-one baboons, including 34 controls (normal pelvis) and 37 animals with histologically proven endometriosis (16 spontaneous and 21 induced). Baboons with endometriosis had minimal (n = 9), mild (n = 14), moderate (n = 7), or severe (n = 7) disease. INTERVENTIONS Seventy-one baboons were mated during 286 cycles. MAIN OUTCOME MEASURES Cycle fecundity rate, cycle pregnancy rate, cycle abortion rate. RESULTS Cycle pregnancy rate (excluding spontaneous abortions) was 15% (44/286) and was comparable between controls (19%, 20/104) and baboons with endometriosis (13%, 24/182). The cycle pregnancy rates were 24%, 10%, 7.5%, and 12.5% in animals with minimal, mild, moderate, and severe endometriosis, respectively. The cycle pregnancy rate was significantly lower in baboons with stage III-IV endometriosis (9%, 6/64) and with stage II disease (10%, 7/73) than in animals with stage I endometriosis (24%, 11/45) or in controls with a normal pelvis (19%). CONCLUSION The normal cycle pregnancy rate in baboons with stage I endometriosis and the decreased cycle pregnancy rate in baboons with stage II and stage III-IV disease suggest that fertility decreases with the stage of endometriosis in baboons.