Publications by authors named "Ioannis Matalliotakis"

57 Publications

Demetra Application: An integrated genotype analysis web server for clinical genomics in endometriosis.

Int J Mol Med 2021 Jun 28;47(6). Epub 2021 Apr 28.

Laboratory of Genetics, Department of Biotechnology, Agricultural University of Athens, 11855 Athens, Greece.

Demetra Application is a holistic integrated and scalable bioinformatics web‑based tool designed to assist medical experts and researchers in the process of diagnosing endometriosis. The application identifies the most prominent gene variants and single nucleotide polymorphisms (SNPs) causing endometriosis using the genomic data provided for the patient by a medical expert. The present study analyzed >28.000 endometriosis‑related publications using data mining and semantic techniques aimed towards extracting the endometriosis‑related genes and SNPs. The extracted knowledge was filtered, evaluated, annotated, classified, and stored in the Demetra Application Database (DAD). Moreover, an updated gene regulatory network with the genes implements in endometriosis was established. This was followed by the design and development of the Demetra Application, in which the generated datasets and results were included. The application was tested and presented herein with whole‑exome sequencing data from seven related patients with endometriosis. Endometriosis‑related SNPs and variants identified in genome‑wide association studies (GWAS), whole‑genome (WGS), whole‑exome (WES), or targeted sequencing information were classified, annotated and analyzed in a consolidated patient profile with clinical significance information. Probable genes associated with the patient's genomic profile were visualized using several graphs, including chromosome ideograms, statistic bars and regulatory networks through data mining studies with relative publications, in an effort to obtain a representative number of the most credible candidate genes and biological pathways associated with endometriosis. An evaluation analysis was performed on seven patients from a three‑generation family with endometriosis. All the recognized gene variants that were previously considered to be associated with endometriosis were properly identified in the output profile per patient, and by comparing the results, novel findings emerged. This novel and accessible webserver tool of endometriosis to assist medical experts in the clinical genomics and precision medicine procedure is available at http://geneticslab.aua.gr/.
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http://dx.doi.org/10.3892/ijmm.2021.4948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083807PMC
June 2021

Endometriosis research in the -omics era.

Gene 2020 May 9;741:144545. Epub 2020 Mar 9.

Section of Molecular Pathology and Human Genetics, Department of Internal Medicine School of Medicine, University of Crete, Heraklion, Greece. Electronic address:

Endometriosis is a pathological condition extensively studied, but its pathogenesis is not completely understood, since its pathophysiology stems from a broad spectrum of environmental influences and genetic factors. Moreover, the nature of this condition is heterogeneous and includes different anatomical entities. Scientists actively pursue discovery of novel biomarkers in the hope of better identifying susceptible individuals in early stages of the disease. High-throughput technologies have substantially revolutionized medical research and, as a first step, the advent of genotyping arrays led to large-scale genome-wide association studies (GWAS) and enabled the assessment of global transcript levels, thus giving rise to integrative genetics. In this framework, comprehensive studies have been conducted at multiple biological levels by using the "omics" platforms, thus allowing to re-examine endometriosis at a greater degree of molecular resolution. -Omics technologies can detect and analyze hundreds of markers in the same experiment and their increasing use in the field of gynecology comes from an urgent need to find new diagnostic and therapeutic tools that improve the diagnosis of endometriosis and the efficacy of assisted reproductive techniques. Proteomics and metabolomics have been introduced recently into the every day methodology of researchers collaborating with gynecologists and, importantly, multi-omics approach is advantageous to gain insight of the total information that underlies endometriosis, compared to studies of any single -omics type. In this review, we expect to present multiple studies based on the high-throughput-omics technologies and to shed light in all considerable advantages that they may confer to a proper management of endometriosis.
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http://dx.doi.org/10.1016/j.gene.2020.144545DOI Listing
May 2020

Epidemiological aspects of the outcomes from the treatment of endometriosis: Experience from two different geographical areas.

Exp Ther Med 2020 Feb 5;19(2):1079-1083. Epub 2019 Dec 5.

Section of Molecular Pathology and Human Genetics, Department of Internal Medicine, School of Medicine, University of Crete, 71003 Heraklion, Greece.

The purpose of the present study was two-fold: First to review the epidemiological aspects of the experience on the surgical outcomes via laparotomy or laparoscopy, as regards endometriosis from two different academic institutions and, second, to illustrate potential differences in two different geographical areas, New Haven (US) and Greece. This retrospective study included 1,200 patients (15-80 years of age) treated via laparotomy or laparoscopy, at two different institutions, for endometriosis, between 1990 and 2017. Data were collected and analyzed from medical and pathological reports. The statistical methods used included the Student's t-test and χ test, as well as the Mann-Whitney U test. A total of 600 women from Yale University and 600 women from Greece participated in this study. Endometrioma was confirmed in 359 (29.9%) cases. Women were compatible in terms of the site of endometriomas. Left-sided cysts were observed (P<0.001) significantly more often compared with right-sided cysts in both groups. The two groups of patients had similar rates of endometriosis stages. A statistically significant positive association (P<0.001) was found for the co-existence of benign gynecological tumors (apart from endometrioma), endometriosis-associated ovarian cancer and for post-menopausal endometriosis in women with endometriosis from Greece. Moreover, similar results were observed as regards endometriosis following exposure to diethylstilbestrol (DES), non-Hodgkin's lymphoma, endometriosis-associated Lyme disease, human immuno-deficiency virus (HIV), melanoma and endometriosis in adolescents, between the two groups. To conclude, the two populations exhibited similar results as regards the surgical outcomes of endometriosis laparoscopic or open surgery. Endometriosis represents a multifactorial entity that depends on complex interactions of hormonal, genetic, immunological and environmental factors. Gynecologists should be aware that there is an association between endometriosis and cancerous diseases. It is thus suggested that the presence of comorbidities in women with endometriosis.
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http://dx.doi.org/10.3892/etm.2019.8296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966115PMC
February 2020

Role of FN1 and GREB1 gene polymorphisms in endometriosis.

Mol Med Rep 2019 Jul 15;20(1):111-116. Epub 2019 May 15.

Section of Molecular Pathology and Human Genetics, Department of Internal Medicine, School of Medicine, University of Crete, 71003 Heraklion, Greece.

Endometriosis is a complex gynecological disorder, affecting up to 10% of women of childbearing age, characterized by the presence of functional endometrial tissue at ectopic positions generally within the peritoneum. It is a heritable condition influenced by multiple genetic, epigenetic and environmental factors, with an overall heritability estimated at approximately 50%. The aim of the present study was to evaluate the association of rs1250248 and rs11674184 single nucleotide polymorphisms (SNPs), mapping to fibronectin 1 (FN1) and growth regulation by estrogen in breast cancer 1 (GREB1) genetic loci, respectively, with the risk of endometriosis. A total of 166 women with endometriosis (stages I-IV) who were hospitalized for the condition, diagnosed by laparoscopic intervention and histologically confirmed, and 168 normal controls were recruited and genotyped. Genotyping of the rs1250248 and rs11674184 SNPs was performed with TaqMan primer/probe sets. A significant association was detected with the A allele, as well as the AA and AG genotypes of rs1250248 (FN1) in patients with endometriosis, as well as in patients with stage I and II of the disease only. The rs11674184 SNP of the GREB1 gene was not found to be associated with an increased susceptibility to endometriosis either for all patients (stages I-IV) or for subgroups of stage I and II or III and IV of the disease only. Our results demonstrated a genetic association between the rs1250248 (FN1) SNP and endometriosis at both the genotypic and allelic level. However, although rs11674184 of GREB1 constitutes one of the most consistently associated SNPs with endometriosis in European ancestry populations, it was not found to be associated with endometriosis in this study.
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http://dx.doi.org/10.3892/mmr.2019.10247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6580018PMC
July 2019

Retrospective evaluation of pathological results among women with ovarian endometriomas versus teratomas.

Mol Clin Oncol 2019 Jun 15;10(6):592-596. Epub 2019 Apr 15.

Department of Obstetrics and Gynecology, Venizeleio and Pananio General Hospital of Heraklion, Heraklion 71409, Greece.

The coexistence of endometrioma with dermoid cyst of the ovaries is an unusual entity, although they are both common and benign gynecological tumors. The present study aimed to investigate the association between ovarian dermoid cyst (teratoma) and endometrioma. We retrospectively, included 315 women with endometrioma and 172 with ovarian teratoma. Data were collected from medical and pathological reports from two different areas between 1995 and 2018. The mean age of cases with endometrioma was similar (35.8±7.2 years) to patients with ovarian teratoma (34.2±6.8 years). Considering the types of dermoid cysts, the observed proportion of mature type was 168/172 (98%), the immature type was 4/172 (2%) and struma ovarii was14/172 (8.1%) respectively. Endometrioma was significantly more frequent in the left ovary [174/266 (65.4%)] than in the right ovary [92/266 (34.6%)], P<0.001. By contrast, ovarian teratoma were predominant in the right ovary, 98/172 (60.6%), compared to the left side, 56/172 (32.5%), P<0.001. Regarding the size of the masses, we detected an inverse distribution between the two groups. Thirteen women were detected with ovarian teratoma and endometriosis, with 6 cases being in the same ovary. Our results indicate a left lateral predispostion of endometrioma and a right of ovarian teratoma and suggest that the pathogenesis between these conditions is different. The coexistence of endometriosis with dermoid cyst of the ovary, presents a challenge to the physicians and the investigators. Further research is required to establish the relationship between endometriosis and ovarian teratoma.
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http://dx.doi.org/10.3892/mco.2019.1844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488942PMC
June 2019

Defining the genetic profile of endometriosis.

Exp Ther Med 2019 May 6;17(5):3267-3281. Epub 2019 Mar 6.

Section of Molecular Pathology and Human Genetics, Department of Internal Medicine, School of Medicine, University of Crete, Heraklion 71003, Greece.

Endometriosis is a pathological condition which has been extensively studied, since its pathophysiology stems from a broad spectrum of environmental influences and genetic factors. Familial studies aim at defining inheritance trends, while linkage analysis studies focus on the identification of genetic sites related to endometriosis susceptibility. Genetic association studies take into account candidate genes and single nucleotide polymorphisms, and hence target at unraveling the association between disease severity and genetic variation. The common goal of various types of studies is, through genetic mapping methods, the timely identification of therapeutic strategies for disease symptoms, including pelvic pain and infertility, as well as efficient counselling. While genome-wide association studies (GWAS) play a primary role in depicting genetic contributions to disease development, they entail a certain bias as regards the case-control nature of their design and the reproducibility of the results. Nevertheless, genetic-oriented studies and the implementation of the results through clinical tests, hold a considerable advantage in proper disease management. In this review article, we present information about gene-gene and gene-environment interactions involved in endometriosis and discuss the effectiveness of GWAS in identitying novel potential therapeutic targets in an attempt to develop novel therapeutic strategies for a better management and treatment of patients with endometriosis.
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http://dx.doi.org/10.3892/etm.2019.7346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447774PMC
May 2019

Keeping an Eye on Perimenopausal and Postmenopausal Endometriosis.

Diseases 2019 Mar 12;7(1). Epub 2019 Mar 12.

Section of Molecular Pathology and Human Genetics, Department of Internal Medicine, School of Medicine, University of Crete, 71003 Heraklion, Greece.

: We aimed to describe and review the epidemiological aspect of the disease pattern of a series of perimenopausal and postmenopausal women with a histology confirmation of endometriosis. : We retrospectively examined the clinical records of 184 perimenopausal and 46 postmenopausal women with endometriosis. Data were collected and analyzed from 1100 patients' charts with confirmed endometriosis and involved cases from two different geographical areas, New Haven (US) and Greece. The statistical methods included ײ and the Mann-Whitney U test. In the perimenopausal group (age 45⁻54 years), there were 184 patients (16.7%) and the postmenopausal group (55⁻80 years) had 46 (4.2%). The average age of diagnosis was (49 ± 2.3) and (61.2 ± 5.1), respectively ( < 0.01). : Advanced endometriosis was more aggressive in the perimenopausal group ( < 0.05); in the same group, we observed a higher left-sided predisposition of endometriosis in comparison with the right side ( < 0.01). Endometrioma was the most common gynecological condition among patients with perimenopausal endometriosis in relation to the postmenopausal group ( < 0.001). Additionally, we found uterine leiomyomata more prominent in the perimenopausal group ( < 0.05). In contrast, adenomyosis was found higher in postmenopausal patients ( < 0.05); further, 24 cases with dry eye we observed. : Postmenopausal endometriosis is an important underestimated condition. Although the reported situation is not common, various clinicopathological characteristics were observed in both groups. Clinicians should be aware that there is a correlation between endometriosis and endometriosis-associated ovarian cancer in perimenopausal and postmenopausal age.
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http://dx.doi.org/10.3390/diseases7010029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6473414PMC
March 2019

Whole exome sequencing identifies hemizygous deletions in the UGT2B28 and USP17L2 genes in a three‑generation family with endometriosis.

Mol Med Rep 2019 Mar 3;19(3):1716-1720. Epub 2019 Jan 3.

Section of Molecular Pathology and Human Genetics, Department of Internal Medicine, University of Crete, Heraklion 710 03, Crete, Greece.

Endometriosis is an enigmatic condition with an unknown etiology and a poorly understood pathogenesis. It is considered to appear from the interplay of many genetic and environmental factors, affecting up to 10% of women and represents a major cause of pain and infertility. The familial association of endometriosis, as demonstrated through monozygotic twin and family studies suggests a genetic contribution to the disease, with further case‑control and genome‑wide association studies (GWAS) detecting various endometriosis risk factors. In a recent study, we described a unique, three‑generation family of Cretan origin (Greece) with 7 females with surgically confirmed endometriosis (grandmother, 3 daughters and 3 granddaughters). All the affected members of this family displayed a variety of clinical manifestations and complications. In the present study, to further analyze the genetic variants conferring the risk of developing endometriosis, whole exome sequencing (WES) was performed, using the AmpliSeq technology on the Ion Proton platform. An initial analysis of 64 variants that were detected across the 14 genes previously confirmed to be associated with endometriosis, did not identify any deleterious exonic variants in these genes. However, further analysis revealed 2 hemizygous deletions in the grandmother that segregate in several of her affected offspring. The first deletion was found in the UGT2B28 locus, spanning 7 informative sequence variants across at least 14 kb. The second deletion, located in USP17L2, spans 3 informative variants across at least 2 kb. On the whole, the findings of the presents study implicate 2 additional genes in the pathogenesis of endometriosis, apart from those already identified by GWAS.
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http://dx.doi.org/10.3892/mmr.2019.9818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390005PMC
March 2019

Co-existence of endometriosis with 13 non-gynecological co-morbidities: Mutation analysis by whole exome sequencing.

Mol Med Rep 2018 Dec 1;18(6):5053-5057. Epub 2018 Oct 1.

Section of Molecular Pathology and Human Genetics, Department of Internal Medicine, School of Medicine, University of Crete, Heraklion 71003, Greece.

Endometriosis is an enigmatic condition with an unknown etiology and poorly understood pathogenesis and women with endometriosis represent a high-risk population group for a large category of chronic conditions. The study focused on a 67-year-old woman who presented with a 40-year history of familial endometriosis associated with various non-gynecological co-morbidities, thus representing a unique case from a cohort of 1,000 patients with endometriosis. Her family history included infertile members suffering from endometriosis. Thirteen non-gynecological co-morbidities were documented throughout the years, including five autoimmune diseases (i.e., systemic lupus erythematosus, ankylosing spondylitis, multiple sclerosis, bronchial asthma and Crohn's disease), urinary bladder diverticulum, osteoporosis, multinodular goiter, cardiovascular diseases, gastroesophageal reflux disease, malignant tumor of urinary bladder, Barrett's esophagus and bilateral cataract. In order to understand the potential role of gene mutations in the development of all those co-morbidities, whole exome sequencing was performed and the presence of various disease-associated, potentially causal missense variants, were observed. These findings are in accordance with the previously suggested common underlying etiologic pathway for some, but not all, autoimmune disorders. This unusual case provides novel insights demonstrating that endometriosis can coexist with various chronic autoimmune diseases and other conditions, including non-gynecological malignancies, which possibly share a common genetic cause, a fact that should be taken into consideration seriously by clinicians.
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http://dx.doi.org/10.3892/mmr.2018.9521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6236265PMC
December 2018

Endometriosis and fertilisation.

Exp Ther Med 2018 Aug 13;16(2):1043-1051. Epub 2018 Jun 13.

Section of Molecular Pathology and Human Genetics, Department of Internal Medicine, School of Medicine, University of Crete, Heraklion 71003, Crete, Greece.

The aim of the present review was to discuss a matter of concern in the clinical field of obstetrics/gynecology, namely the potency of fertilization (IVF) in the management of endometriosis-associated infertility. Endometriosis is a medical condition affecting one tenth of women in their fertile years, and accounts for up to 50% of infertile women. Thus, such high prevalence has established the necessity for investigating the effectiveness of available techniques in eradicating the disease and constraining infertility as well as the accompanying pain symptoms of endometriosis. The underlying mechanisms connecting endometriosis with low fecundity have been extensively studied, both in terms of genetic alterations and epigenetic events that contribute to the manifestation of an infertility phenotype in women with the disease. Several studies have dealt with the impact of IVF in pregnancy rates (PRs) on patients with endometriosis, particularly regarding women who wish to conceive. Results retrieved from studies and meta-analyses depict a diverse pattern of IVF success, underlining the involvement of individual parameters in the configuration of the final outcome. The ultimate decision on undergoing IVF treatment should be based on objective criteria and clinicians' experience, customized according to patients' individual needs.
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http://dx.doi.org/10.3892/etm.2018.6307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090275PMC
August 2018

Association between ovarian cancer and advanced endometriosis.

Oncol Lett 2018 May 16;15(5):7689-7692. Epub 2018 Mar 16.

Department of Obstetrics and Gynecology, Venizeleio General Hospital, 71409 Heraklion, Crete, Greece.

We retrospectively analyzed clinicopathological data in two different countries over the past years on the association between ovarian endometriosis and ovarian carcinoma. Medical and pathological reports were evaluated from 1,000 patients with endometriosis from two different geographical areas. The prevalence and women characteristics of cases were analyzed. Endometriosis-associated ovarian cancer was present in 20 (2%) cases, among the study subjects. The observed prevalence was 12 (60%) for endometrioid carcinoma, 4 (20%) for clear cell ovarian carcinoma, 2 (10%) for serous and 2 (10%) for mucinous adenocarcinoma. A higher proportion of endometrioid carcinoma cases were noted in comparison with other types (P<0.001). We found only 3/20 (15%) postmenopausal cases. In all cases, we reported advanced stage of endometriosis (stage III or IV). Left-sided endometrioid carcinoma were notably more common than right-sided ones (P<0.001). In the majority of cases, malignant transformation of endometriosis was observed in endometrioid carcinoma or clear cell carcinoma of the ovary. Further research is required to establish the relationship between endometriosis and ovarian cancer.
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http://dx.doi.org/10.3892/ol.2018.8287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5920362PMC
May 2018

Co-existence of benign gynecological tumors with endometriosis in a group of 1,000 women.

Oncol Lett 2018 Feb 20;15(2):1529-1532. Epub 2017 Nov 20.

Department of Obstetrics and Gynecology, Venizeleio General Hospital, 71409 Heraklion, Crete, Greece.

The purpose of this study was two-fold, first to investigate the association between endometriosis and the risk of benign gynecologic tumors and, secondly, to evaluate the distribution of endometrioma and ovarian cysts in women with endometriosis. The medical and pathological reports of 1,000 women with endometriosis were retrospectively reviewed. The incidence of ovarian cysts, uterine leiomyomas and adenomyosis, as well as the side of ovarian cysts were further compared. A total of 295 cases of endometriomas, 172 cases of adenomyosis, 173 cases of ovarian cysts and 89 cases of uterine leiomyomas were confirmed histologically in patients with endometriosis. Serous cysts represented the most frequent diagnosis (n=81, 8.1%) in women with ovarian cysts, followed by dermoid cysts (n=15, 1.2%). In women with unilateral endometriomas, the observed proportion of left-sided cysts was found in 65.6% (164 of 250), significantly higher compared with right-sided cysts (86 out of 250, 34.4%) (P<0.001). Moreover, patients with other ovarian cysts were recognized as left-sided in 60% (96 out of 160) of cases, significantly higher compared with right-sided cysts (64 out of 160, 40%) (P<0.01). On the whole, the current study indicates that endometriosis may be associated with an increased risk of benign gynecological tumors, such as ovarian cysts, adenomyosis and leiomyomas. The results of this study confirm a left lateral predisposition of endometriomas and ovarian cysts.
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http://dx.doi.org/10.3892/ol.2017.7449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774344PMC
February 2018

The role of IL‑16 gene polymorphisms in endometriosis.

Int J Mol Med 2018 Mar 9;41(3):1469-1476. Epub 2018 Jan 9.

Section of Molecular Pathology and Human Genetics, Department of Internal Medicine, School of Medicine, University of Crete, 71003 Heraklion, Crete, Greece.

Endometriosis is one of the most common gynecological diseases affecting up to 10% of the female population of childbearing age and a major cause of pain and infertility. It is influenced by multiple genetic, epigenetic and environmental factors. Interleukin‑16 (IL‑16) is a proinflammatory cytokine playing a pivotal role in many inflammatory and autoimmune diseases as well as in the pathogenesis of endometriosis. The aim of the present study was to evaluate the association of two IL‑16 gene single nucleotide polymorphisms (SNPs), rs4072111 and rs11556218, with the risk of endometriosis in women from Greece as well as to gain insight about the structural consequences of these two exonic SNPs regarding development of the disease. A total of 159 women with endometriosis (stages I‑IV) hospitalized for endometriosis, diagnosed by laparoscopic intervention and histologically confirmed, and 146 normal controls were recruited and genotyped. Subjects were genotyped using a polymerase chain reaction restriction fragment length polymorphism (PCR‑RFLP) strategy. A significant association was detected regarding the GG and GT genotype as well as 'G' allele of rs11556218 in patients with endometriosis. The rs4072111 SNP of the IL‑16 gene was not found to be associated with an increased susceptibility to endometriosis either for all patients (stages I‑IV) or for stage III and IV of the disease only. Our results demonstrated that rs11556218 is associated with endometriosis in Greek women, probably by resulting in the aberrant expression of IL‑16, as suggested by the bioinformatics analysis conducted on the SNP‑derived protein sequences, which indicated a possible association between mutation and functional modification of Pro‑IL‑16.
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http://dx.doi.org/10.3892/ijmm.2018.3368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819913PMC
March 2018

The role of gene polymorphisms in endometriosis.

Mol Med Rep 2017 Nov 29;16(5):5881-5886. Epub 2017 Aug 29.

Section of Molecular Pathology and Human Genetics, Department of Internal Medicine, School of Medicine, University of Crete, Heraklion 710 03, Greece.

Endometriosis is a benign gynecologic disorder, affecting up to 10% of women, characterized by the presence of functional endometrial tissue at ectopic positions generally within the peritoneum. It is a heritable condition influenced by multiple genetic and environmental factors, with an overall heritability estimated at approximately 50%. In this study, we investigated whether single nucleotide polymorphisms (SNPs) rs7521902, rs10859871 and rs11031006, mapping to WNT4, VEZT and FSHB genetic loci, respectively, are associated with risk for endometriosis in a Greek population. This study included 166 women with histologically confirmed endometriosis diagnosed through surgery and 150 normal controls. Genotyping of the rs7521902, rs10859871 and rs11031006 SNPs was performed with Taqman primer/probe sets. A significant association was detected with the AC genotype of rs7521902 (WNT4) in patients with stage III and IV disease only. Evidence for association with endometriosis was also found for the AC genotype of the rs10859871 of VEZT. Notably, a significant difference in the distribution of the AG genotype and the minor allele A of FSHB rs11031006 SNP was found between the endometriosis patients and controls. We found a genetic association between rs11031006 (FSHB) SNP and endometriosis. WNT4 and VEZT genes constitute the most consistently associated genes with endometriosis. In the present study, an association of rs7521902 (WNT4) and rs10859871 (VEZT) was confirmed in women with endometriosis at the genotypic but not the allelic level.
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http://dx.doi.org/10.3892/mmr.2017.7398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865763PMC
November 2017

Genetic association study in a three-generation family with seven members with endometriosis.

Mol Med Rep 2017 Nov 23;16(5):6077-6080. Epub 2017 Aug 23.

Section of Molecular Pathology and Human Genetics, Department of Internal Medicine, School of Medicine University of Crete, Heraklion 71003, Greece.

The aim of this study was to investigate whether five single nucleotide polymorphisms (SNPs), associated with endometriosis, may confer new insight towards a genotype‑phenotype association with endometriosis. We studied a three-generation family with seven women who had endometriosis. Blood specimens were obtained from all the affected female family members. The entire family was genotyped for five SNPs mapped to WNT4, VEZT, FSHB and IL-16 genetic loci. We further evaluated the members of the family with endometriosis and described all obstetric and gynecological complications caused by the disease in these seven women. The five SNPs analyzed did not reveal any genotype-phenotype correlation with the disease. The members of the family with endometriosis showed a variety of clinical manifestations and complications. None of the five genetic markers examined correlated genotype with phenotype in the case of the Greek three-generation family examined. Therefore, we conclude that more gene polymorphisms must be investigated in the members of this family to gain insight regarding a genotype‑phenotype correlation in endometriosis and the potential development of a personalized care for the patients based on these data.
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http://dx.doi.org/10.3892/mmr.2017.7337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865811PMC
November 2017

Extra pelvic endometriosis: Retrospective analysis on 200 cases in two different countries.

Eur J Obstet Gynecol Reprod Biol 2017 Oct 18;217:34-37. Epub 2017 Aug 18.

Department of Obstetrics & Gynecology and Reproductive Sciences Yale University School of Medicine, USA. Electronic address:

Objective(s): The purpose of the study was to review patients' characteristics and the location of extrapelvic endometriosis.

Study Design: Out of 1000 women with endometriosis during a 20year period, we found 200 cases with extra pelvic endometriosis. Medical reports were evaluated and the diagnosis was confirmed on the pathological specimen. This study involved cases from two different geographical areas, New Haven and Crete. The age, parity, symptoms, previous surgeries, diagnostic modalities, histopathological evaluation and location of endometriotic implants found in other areas were recorded and analyzed from the patient's charts.

Main Outcome Measure(s): Statistical methods included x and Mann-Whitney U test s measuring incidence of right-VS left sided endometriosis.

Results: 200 patients with extrapelvic endometriosis and 800 patients with pelvic endometriosis were included in the study. The gastrointestinal tract represents the most common location of extrapelvic endometriosis with 104/200(52%) cases (p<0, 01), followed by the urinary system with70/200(35%) cases. We observed the Left-sided ureter being involved in 49/200(24, 5%) cases, significantly higher compare with the right-sided ureter 21/100(10, 5%) (p <0, 01). All women had similar characteristics involving age, weight, main complaints, age of menarche, endometriosis stages, gravid and family history of endometriosis.

Conclusion(s): The gastrointestinal tract and the urinary system are the most common sites of the extrapelvic endometriosis, which was obvious in both countries. Moreover, we observed that there are no significant differences in demographic variants, menstrual and reproductive characteristics in women with extrapelvic and pelvic endometriosis.
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http://dx.doi.org/10.1016/j.ejogrb.2017.08.019DOI Listing
October 2017

Endometriosis in Adolescent and Young Girls: Report on a Series of 55 Cases.

J Pediatr Adolesc Gynecol 2017 Oct 27;30(5):568-570. Epub 2017 May 27.

Department of Obstetrics and Gynecology and Reproductive Sciences Yale University School of Medicine, New Haven, Connecticut.

Study Objective: The aim of this retrospective study was to evaluate endometriosis in adolescent and young girls and further to review the menstrual, reproductive characteristics, and risk factors.

Design And Setting: We reviewed the medical records of adolescent and young girls with endometriosis from 2 different countries. Data were collected and analyzed from charts of 900 patients with endometriosis.

Participants And Interventions: Fifty-five female adolescents aged between 13 and 21 years (mean age 18.3 years) participated in our series. This study was conducted in the Obstetric and Gynecology Department of Venizeleio General Hospital of Crete and involved all patients diagnosed with endometriosis between 1996 and 2016.

Main Outcome Measures: Statistical methods included χ and Mann-Whitney U test.

Results: Of 900 patients with endometriosis we found 55 female adolescents (6.1%). The mean age was 18.3 ± 2.3 years, significantly younger compared with the advanced endometriosis patients (32.7 ± 7.2; P < .001). Regarding the menstrual reproductive and others characteristics, we observed several differences in adolescent young girls compared with the advanced age endometriosis group. The factors associated with an increased risk for young women include age at menarche, dysmenorrhea, history of asthma, and a positive family history of endometriosis. Additionally, we report on 16 of 55 (32%) adolescent women with endometriosis and congenital malformations (P < .01) and 5 patients who were diagnosed with dry eye syndrome.

Conclusion: There is an association between endometriosis in adolescent and young women and risk factors including early menarche, early onset of dysmenorrhea, history of asthma, previous surgical procedures, obstructive genital anomalies, and family history of endometriosis.
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http://dx.doi.org/10.1016/j.jpag.2017.05.007DOI Listing
October 2017

Peritoneal fluid concentrations of β-chemokines in endometriosis.

Eur J Obstet Gynecol Reprod Biol 2013 Jul 7;169(1):103-7. Epub 2013 Mar 7.

Department of Neonatology, University of Crete, Greece.

Objective: To examine whether the levels of MCP-1, RANTES and MCP-3 in the peritoneal fluid correlate with endometriosis.

Study Design: Patients with endometriosis were compared with controls.

Setting: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.

Subjects: This study involved 95 women of reproductive age who were undergoing laparoscopy for evaluation of infertility or for pelvic pain. They were divided into an endometriosis group (n=54) and a control group (n=41).

Interventions: Peritoneal fluid samples were obtained and β-chemokines (MCP-1, RANTES and MCP-3) were measured using ELISA.

Statistical Analysis: Mean and median values were used to present values. Due to the non-normality of chemokines, a log transformation was applied. Differences were examined using independent samples t-test. One-way ANOVA and Tukey HSD multiple comparison post hoc tests were applied. A significance level at 0.05 was set.

Results: The levels of MCP-1 are higher (p for log values=0.024) in the control group (mean=687.6, SD=467.7 pg/ml) than those of the endometriosis group (mean=570.4, SD=633.1 pg/ml). The same is true for the median values of MCP-1 (control median=568.5, endometriosis median=384.7 pg/ml). MCP-3 and RANTES do not differ significantly (MCP-3 p=0.787, RANTES p=0.153). The levels of MCP-1 in patients with stage II endometriosis are significantly lower in comparison with stage III (p=0.048) and stage IV (p=0.033) endometriosis.

Conclusions: A decrease in the concentrations of MCP-1 in stage I endometriosis has been observed, which is even larger in stage II, in contrast to stage III and stage IV endometriosis, which exhibit concentrations similar to the controls.
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http://dx.doi.org/10.1016/j.ejogrb.2013.02.010DOI Listing
July 2013

History of endometriosis may adversely affect the outcome in menopausal recipients of sibling oocytes.

Reprod Biomed Online 2012 Nov 8;25(5):543-8. Epub 2012 Aug 8.

Iakentro, Fertility Centre, Thessaloniki, Greece.

Due to the known adverse effect of endometriosis on gamete quality, it has always been difficult to demonstrate a direct effect of endometriosis on implantation. In order to eliminate these confounding effects, this prospective comparative study studied a population of menopausal recipients with and without endometriosis sharing sibling oocytes coming from the same donor. The aim was to understand the impact of endometriosis on implantation, pregnancy and live birth rates in menopausal recipients. A total of 240 menopausal recipients of donated sibling oocytes, were divided in two groups. Group I consisted of 120 recipients diagnosed with endometriosis and group II consisted of 120 controls. The implantation and pregnancy rates were significantly lower in the endometriosis group compared with the control group (23.81% versus 31.48%, P=0.019; 45.00% versus 58.33%, P=0.039, respectively). In oocyte donation cycles, a recipient's history of endometriosis might have a negative impact on implantation, pregnancy and live birth rates, even in menopausal women. Infertility in endometriosis may be due to poor oocyte quality or embryos with decreased ability to implant due to impaired fertilization. There are no conclusive data on the impact of endometriosis on implantation. The already-known adverse effect of endometriosis on gamete quality makes it more difficult to demonstrate a direct effect of endometriosis on implantation. In order to eliminate these confounding effects we studied a population of menopausal recipients with and without endometriosis sharing sibling oocytes coming from the same oocyte donor. The oocyte donation model was used in an attempt to understand whether the endometrium, the oocytes or both are affected by endometriosis. The aim of the present study was to understand the impact of endometriosis on implantation, pregnancy and live birth rates in menopausal recipients. A total of 240 menopausal recipients of donated sibling oocytes were divided into two groups. Group I consisted of 120 recipients diagnosed with endometriosis and group II consisted of 120 controls. The pregnancy and implantation rates were significantly lower in the endometriosis group compared to the control group (45.00% versus 58.33%, P=0.039) and (23.81% versus 31.48%, P=0.019) respectively. In oocyte donation cycles, a recipient's history of endometriosis might have a negative impact on implantation, pregnancy and live birth rates, even in menopausal women.
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http://dx.doi.org/10.1016/j.rbmo.2012.07.020DOI Listing
November 2012

Molecular response of the human diaphragm on different modes of mechanical ventilation.

Respiration 2013 3;85(3):228-35. Epub 2012 Aug 3.

Departments of Anaesthesia, University Hospital of Heraklion, Medical School, University of Crete, Heraklion, Greece.

Background: The mechanical stress that the human diaphragm is exposed to during mechanical ventilation affects a variety of processes, including signal transduction, gene expression, and angiogenesis.

Objectives: The study aim was to assess the change in the production of major angiogenic regulators [vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF2), and transforming growth factor beta 1 (TGFB1)] on the human diaphragm before and after contraction/relaxation cycles during mechanical ventilation.

Methods: This observational study investigates the diaphragmatic mRNA expression of VEGF, FGF2, and TGFB1 in surgical patients receiving general anesthesia with controlled mechanical ventilation (CMV) with muscle relaxation (group A, n = 13), CMV without muscle relaxation (group B, n = 10), and pressure support of spontaneous breathing (group C, n = 9). Diaphragmatic samples were obtained from each patient at two time points: 30 min after the induction of anesthesia (t1) and 90 min after the first specimen collection (t2).

Results: No significant changes in the mRNA expression of VEGF, FGF2, and TGFB1 were documented in groups A and C between time points t1 and t2. In contrast, in group B, the mRNA levels of the above angiogenic factors were increased in time point t2 compared to t1, a finding which was statistically significant (pVEGF = 0.003, pFGF2 = 0.028, pTGFB1 = 0.001).

Conclusions: These findings suggest that the molecular response of the human diaphragm before and after application of diverse modes of mechanical ventilation is different. Angiogenesis via the expression of VEGF, FGF2, and TGFB1 was only promoted in CMV without muscle relaxation, and this may have important clinical implications.
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http://dx.doi.org/10.1159/000338841DOI Listing
September 2013

Cryptic sperm defects may be the cause for total fertilization failure in oocyte donor cycles.

Reprod Biomed Online 2012 Feb 30;24(2):148-52. Epub 2011 Oct 30.

Iakentro, Fertility Centre, Thessaloniki, Greece.

In conventional IVF cycles with total fertilization failure, rescue intracytoplasmic sperm injection (ICSI) performed 24h after insemination has yielded poor results. However, when ICSI is used, total fertilization failure is a rare event. The aim of the present study is to investigate the degree of sperm contribution to fertilization failures using the egg-sharing model in oocyte donor cycles. The study included only the oocyte donor cycles of sibling oocytes with total fertilization failure in at least one of the matched recipients. Oocytes from 49 oocyte donor cycles were equally shared among 98 recipients undergoing conventional IVF. Due to total fertilization failure in half of the recipients, rescue ICSI was carried out. Compared with the conventional IVF only group, the rescue ICSI group had a lower pregnancy rate (30.61% versus 71.43%), clinical pregnancy rate (28.57% versus 67.35%) and ongoing pregnancy rate (28.57% versus 63.27%) (all P<0.01). Cryptic sperm defects in apparently normal spermatozoa may be the cause of total fertilization failure, indicating the need for simple routine tests to detect them.
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http://dx.doi.org/10.1016/j.rbmo.2011.10.011DOI Listing
February 2012

Changes in metabolic profile and adipoinsular axis in morbidly obese premenopausal females treated with restrictive bariatric surgery.

World J Surg 2011 Sep;35(9):2022-30

Bariatric Unit, Department of Surgical Oncology, P.O. Box 1352, Heraklion, 71110, Crete, Greece.

Background: The aim of the present study was to evaluate the effects of surgically induced weight loss on the metabolic profile and adipocytokine levels in premenopausal morbidly obese females.

Methods: Twenty premenopausal morbidly obese (MO) women with a median age of 34 years (range: 24-48 years) and a median body mass index (BMI) of 41.47 kg/m(2) (range: 38.0-56.73 kg/m(2)) were studied (13 women underwent gastric banding and 7 women underwent sleeve gastrectomy). In addition, 20 lean premenopausal women with a median age of 32 years (range: 22-44 years) and a median BMI of 20.0 kg/m(2) (range: 18.5-24.7 kg/m(2)) were also studied. Anthropometric measurements and metabolic parameters were analyzed in each patient, along with changes in leptin, adiponectin, resistin, and interleukin-6 (IL-6) before surgery, 6 months after surgery, and 12 months after surgery. Comparisons with the reference normal-weight subjects were also performed.

Results: Both weight and BMI were found to be significantly decreased postoperatively. A 54.5% loss of excess BMI was observed 12 months after surgery, and was associated with significant improvement in all anthropometric and metabolic parameters. Twelve months after surgery we also observed decreased levels of serum leptin, resistin, and IL-6; increased levels of serum adiponectin; and a remarkable improvement in metabolic syndrome markers. Furthermore, postoperative serum resistin and IL-6 levels were found to reach those of normal-weight volunteers.

Conclusions: The results of this study suggest that weight loss through restrictive bariatric surgery results in a significant reduction in leptin, resistin, and IL-6 levels, and an increase in adiponectin levels, in addition to improving insulin sensitivity and glucose and lipid homeostasis in young morbidly obese female patients. These changes were significantly correlated with the magnitude of weight loss.
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http://dx.doi.org/10.1007/s00268-011-1165-9DOI Listing
September 2011

Ampicillin/sulbactam versus cefuroxime as antimicrobial prophylaxis for cesarean delivery: a randomized study.

BMC Infect Dis 2010 Nov 30;10:341. Epub 2010 Nov 30.

Department of Obtsterics and Gynecology, University General Hospital of Heraclion, Heracleion, Greece.

Background: The efficacy and safety of a single dose of ampicillin/sulbactam compared to a single dose of cefuroxime at cord clamp for prevention of post-cesarean infectious morbidity has not been assessed.

Methods: Women scheduled for cesarean delivery were randomized to receive a single dose of either 3 g of ampicillin-sulbactam or 1.5 g of cefuroxime intravenously, after umbilical cord clamping. An evaluation for development of postoperative infections and risk factor analysis was performed.

Results: One hundred and seventy-six patients (median age 28 yrs, IQR: 24-32) were enrolled in the study during the period July 2004-July 2005. Eighty-five (48.3%) received cefuroxime prophylaxis and 91 (51.7%) ampicillin/sulbactam. Postoperative infection developed in 5 of 86 (5.9%) patients that received cefuroxime compared to 8 of 91 (8.8%) patients that received ampicillin/sulbactam (p=0.6). In univariate analyses 6 or more vaginal examinations prior to the operation (p=0.004), membrane rupture for more than 6 hours (p=0.08) and blood loss greater than 500 ml (p=0.018) were associated with developing a postoperative surgical site infection (SSI). In logistic regression having 6 or more vaginal examinations was the most significant risk factor for a postoperative SSI (OR 6.8, 95% CI: 1.4-33.4, p=0.019). Regular prenatal follow-up was associated with a protective effect (OR 0.04, 95% CI: 0.005-0.36, p=0.004).

Conclusions: Ampicillin/sulbactam was as safe and effective as cefuroxime when administered for the prevention of infections following cesarean delivery.

Trial Registration: Clinicaltrials.gov identifier: NCT01138852.
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http://dx.doi.org/10.1186/1471-2334-10-341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3009979PMC
November 2010

Different HLA-DR expression in endometriotic and adenomyotic lesions: correlation with transvaginal ultrasonography findings.

Arch Gynecol Obstet 2010 May 8;281(5):851-6. Epub 2009 Jul 8.

Department of Radiology, NIMITS Hospital, and 2nd Department of Obstetrics and Gynecology, University of Athens, Medical School Attikon, Athens, Greece.

Objective: Human leukocyte antigen-DR (HLA-DR) has been implicated in eutopic and ectopic glandular epithelial cells in endometriosis. We investigated the expression of HLA-DR in endometriotic and adenomyotic tissues within the stromal and glandular cells. Moreover, we correlate the HLA-DR expression according the transvaginal ultrasonography findings.

Methods: We studied operative and pathologic reports of 113 women who underwent laparoscopic or laparotomy treatment of endometrioma or adenomyosis. Tissues from 51 women with endometrioma and 62 women with adenomyosis were retrospectively evaluated. The distribution and intensity of the HLA-DR immunostaining was assessed using electron microscopy. Pathologic finding of the uterine junction zone and the size of endometrioma were evaluated with the laparoscopic results and the ultrasound findings.

Results: In adenomyosis tissues, the percentage of HLA-DR cells expression was significantly higher in stromal cells (83.9%) compared to glandular cells (25.8%), (p<0.001). The number of HLA-DR-positive endometriotic glandular cells was significantly higher than the total glandular adenomyotic cells (p<0.005). HLA-DR-positive cells was significantly different between stromal (p<0.016) and glandular cells (p<0.044) in each side of endometrioma. Finally, HLA-DR-positive percentage cells were significantly more frequent in the secretory phase than the proliferative in stromal and glandular cells in both groups.

Conclusion: HLA-DR antigen expression in endometrium and adenomyotic tissues. However, HLA-DR expression is distributed preferentially in glandular epithelial cells in endometrioma and in the adenomyotic stroma. In both groups the HLA-DR expression was significantly higher in the secretory phase than the proliferative or glandular and stroma cells. Larger perspective studies are needed to establish the expression of HLA antigens in immune reactions which occur in adenomyosis and endometriosis.
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http://dx.doi.org/10.1007/s00404-009-1168-zDOI Listing
May 2010

ABO and Rh blood groups distribution in patients with endometriosis.

Arch Gynecol Obstet 2009 Dec 20;280(6):917-9. Epub 2009 Mar 20.

Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, USA.

Background: The aim of this investigation was twofold: first, to demonstrate an association between endometriosis, ABO blood groups and Rhesus factor and, second, to show potential correlation of ABO blood group and stages of endometriosis.

Methods: Two hundred and thirty-one women with endometriosis and 166 infertile women without endometriosis were studied retrospectively at the Yale University Hospital. All the cases were diagnosed by laparoscopy and in all of them ABO blood groups and Rhesus factor were determined by standard techniques. Women with endometriosis were divided into two groups according to the stage: Group 1 included 124 cases with stages I and II, and Group 2, 107 women with stages III and IV. Statistical methods included chi(2) and odds ratios (95% CI).

Results: The identified distribution of ABO and Rh blood groups in women with endometriosis differed significantly from that of the women without endometriosis [chi(2) = 26.27, (P < 0.001); chi(2) = 18.71, (P < 0.001), respectively]. The blood group A was more predominant in women with endometriosis, while blood group O was less predominant. The overall risk of women with endometriosis and A blood group was 2.89 (95%CI, 1.85-4.52). No significant difference was detected in ABO and Rh blood groups in women with endometriosis according to the severity of disease.

Conclusion: Women with endometriosis have a 2.9-fold increased risk in the A blood group distribution. The role of blood groups in the development of endometriosis remains to be determined.
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http://dx.doi.org/10.1007/s00404-009-1031-2DOI Listing
December 2009

Endometriosis related to family history of malignancies in the Yale series.

Surg Oncol 2010 Mar 18;19(1):33-7. Epub 2009 Mar 18.

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.

Objective: Recent studies reported that endometriosis could behave as a neoplasmatic process. The purpose of this study is to investigate the family risk of ovarian, colon and prostate cancer in women with endometriosis.

Study Design: A search of medical records at the Yale New Haven Hospital from 1996 to 2002 identified 348 women with endometriosis and 179 women without endometriosis. All the cases were diagnosed by laparoscopy. Demographic characteristics were evaluated in women with positive or negative family history of cancers in women with endometriosis.

Results: The overall risk of patients with endometriosis and positive family history of cancers was 7.7 (95% confidence interval 3.8-15.7) (chi(2)=39.8, P<0.001). Significant excess was observed for ovarian cancer in first- and second-degree relatives (OR=10.5, 95% CI (2.5-44.2), chi(2)=14.3, P<0.001), colon cancer (OR=7.5, 95% CI (2.7-21.1), chi(2)=18.2, P<0.001) and prostate cancer (OR=4.5, 95% CI (14-15.3), chi(2)=6.1, P<0.001). We found similar results in first- and second-degree relatives with ovarian and colon cancer. Moreover, we found similar results regarding the demographic characteristics in women with positive family history of cancers and in women with negative history.

Conclusions: These data suggest a familial association of endometriosis with ovarian, colon and prostate cancers. This evidence could support the genetics and molecular similarities between endometriosis and cancer. Future studies will be important to determine a clear genetic link between endometriosis and cancer.
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http://dx.doi.org/10.1016/j.suronc.2009.02.012DOI Listing
March 2010

Impact of body mass index on IVF and ICSI outcome: a retrospective study.

Reprod Biomed Online 2008 Jun;16(6):778-83

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut, USA.

A group of 140 women with a body mass index (BMI) < or = 24 kg/m(2) undergoing 291 cycles was compared with a group of 138 women with a BMI >24 kg/m(2) in 291 cycles, with respect to duration of ovarian stimulation and dose of gonadotrophin, number of oocytes collected, cleavage and implantation rate, clinical pregnancy, miscarriage and delivery rates. Patients with a BMI > 24 kg/m(2) demonstrated a significant decrease in the number of follicles after stimulation (P = 0.01), a comparative increase in the number ampoules of gonadotrophin used (P = 0.03) and a lower number of eggs collected (P = 0.05). The mean number of embryos on days 1, 2 and 3 was significantly lower in the group with BMI > 24 kg/m(2) (P < 0.001). No significant difference was found in clinical pregnancy and miscarriage rates between the two groups. In spite of the lower response in women with BMI > 24 kg/m(2), the delivery rate per retrieval was not different (24.6 versus 24.8%). These results indicate a lower stimulation response in women with elevated BMI, but no adverse effect on IVF outcome. In relation to wellbeing, however, it is recommended that patients with a high BMI reduce their weight before IVF treatment.
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http://dx.doi.org/10.1016/s1472-6483(10)60142-3DOI Listing
June 2008

The familial risk of breast cancer in women with endometriosis from Yale series.

Surg Oncol 2008 Dec 5;17(4):289-93. Epub 2008 May 5.

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, CT, USA.

Objective: Few studies examining the association of endometriosis with the risk of breast cancer. Our goal was to investigate the familial risk of breast cancer in women with endometriosis.

Design: Retrospective study.

Setting: University-based endometriosis referral center.

Patients: Three hundred fifty-two women with endometriosis and 180 infertile women without endometriosis were studied using laparoscopy between August 1996 and February 2002. The endometriosis group was further subdivided into a group of women with 94 positive and 268 negative family histories of breast cancer.

Main Outcome Measure(s): The overall risk of familial breast cancer among first- and second-degree relatives in patients with endometriosis and the association between potential risk factors was estimated by chi(2) and by crude adjusted odds ratios (95% CI).

Results: Positive family history of breast cancer was detected in (26.7%) 94/352 of endometriosis group and in (5%) 9/180 of controls. The relative risk of women with endometriosis and positive family history of breast cancer was (OR=6.9 (95% CI, 3.4-14.1), chi(2)=34.6, P<0.001). Endometriosis was associated with the risk of first-degree relatives of breast cancer (OR=5.69 (95% CI, 2.4-13.3), P<0.001). Moreover, endometriosis was significantly associated with the risk of breast cancer in mothers (OR=6.3 (95% CI, 2.2-17.8), P<0.001) and in maternal aunts (OR=5.9 (95% CI, 1.3-72.9), P<0.001). The two groups are similar in age, race height, main complaints, age of menarche, cycle length, days of flow, estimated blood loss, stage of endometriosis and the presence of endometrioma.

Conclusion(s): This study found an elevated risk associated with family history of breast cancer among women with endometriosis. A familial clustering interaction with a familial history of breast cancer in women with endometriosis is possible, but should be investigated further.
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http://dx.doi.org/10.1016/j.suronc.2008.01.002DOI Listing
December 2008

Familial aggregation of endometriosis in the Yale Series.

Arch Gynecol Obstet 2008 Dec 1;278(6):507-11. Epub 2008 May 1.

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut, USA.

Objective: To investigate the familial aggregation and the risk of endometriosis among the female relatives of women with endometriosis. We also compared the epidemiologic characteristics of women with and without family history of endometriosis.

Patient(s): A total of 485 women with endometriosis and 197 infertile women without endometriosis underwent surgical investigation between August 1996 and February 2002.

Main Outcome Measure(s): The relative risk of endometriosis in a first-degree relative and the association between potential risk factors was estimated by chi2 and by crude adjusted odds ratios (95% CI).

Results: Endometriosis was identified in 9.5% of first-degree relatives of women with endometriosis versus only 1% of controls. The odds ratio for endometriosis in a first-degree relative was 10.21 (95% CI 2.45-42.5; P<0.001). In 3.9% of cases women with endometriosis reported that their mother had been diagnosed with endometriosis and 5.6% of cases that at least one sister had been diagnosed. Compared to the control group the odds ratio for the mother having endometriosis (7.99, 95% CI 1.06-60.1) or at least one sister having (11.55, 95% CI 1.56-85.59) were significantly elevated. Among women with endometriosis who reported a family history of endometriosis, and women with endometriosis who did not report a family history of endometriosis, there were no differences in demographic characteristics, body habitus, or menstrual parameters.

Conclusion(s): Women with endometriosis have a tenfold increased risk of endometriosis in their first-degree relatives.
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http://dx.doi.org/10.1007/s00404-008-0644-1DOI Listing
December 2008

Increased rate of endometriosis and spontaneous abortion in an in vitro fertilization program: no correlation with epidemiological factors.

Gynecol Endocrinol 2008 Apr;24(4):194-8

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut, USA.

Background: There are conflicting data concerning endometriosis and spontaneous abortion (SAB). The aim of the present study was to evaluate if there was any association between endometriosis and SAB. Moreover, we investigated risk factors in women with endometriosis and SAB.

Methods: The medical files of 457 married women with endometriosis and 200 infertile women without endometriosis were studied retrospectively. All cases were diagnosed by laparoscopy. Data concerning demographic variables and menstrual characteristics were recorded from 226 women with endometriosis, which were divided into two groups. Group 1 included 126 cases with endometriosis and SAB, and Group 2 comprised 100 parous women with endometriosis and without SAB. Statistical comparisons between groups were made using the chi(2) test and odds ratios (OR) and 95% confidence intervals (CI).

Results: The proportion of SAB was significantly higher in women with endometriosis than in infertile women without endometriosis (126/457 (27.6%) vs. 36/200 (18.0% ); OR = 1.7, 95% CI 1.1 = 2.6; p = 0.01). The frequency of nulligravid women was significantly higher in women with endometriosis than in the control group (OR = 1.9, 95% CI 1.4 - 2.81; p = 0.001). Mean age, age at onset of endometriosis, race, height, weight, body mass index, medical history of allergies, and family histories of endometriosis and cancer were similar in women with endometriosis and SAB and in parous women with endometriosis but without SAB. Moreover, the two groups were similar in age at menarche, length of cycle, duration and amount of flow, and the severity of disease. The incidence of infertility was significantly higher in women with SAB (p < 0.001).

Conclusion: These data suggest but do not prove that the risk of SAB is increased in women with endometriosis. The epidemiological risk factors of endometriosis are not associated with an increase in the abortion rate.
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http://dx.doi.org/10.1080/09513590801948341DOI Listing
April 2008