Co-existence of Ovarian Teratomas With Other Gynecological Tumors.

INTRODUCTION: This study aims to investigate the co-existence of ovarian teratomas with other benign or malignant gynecological tumors in women who underwent gynecological surgery. METHODS: We retrospectively reviewed all women who underwent gynecological surgery over a 15-year period. Pre-operative, surgical, and histological records were obtained from women who presented with gynecological pathology, aiming to discover a possible link between ovarian teratomas and other gynecological tumors. RESULTS: Of the total patient sample, 288 (8.2%) had a mature teratoma, and 9 (0.3%) had an immature teratoma. The mean age was 38.0±13.3 years and 30.9±11.1 years, respectively. Women with mature teratoma showed a positive correlation with struma ovarii (SO, p=0.001). Moreover, we reported a positive linear relationship between struma ovarri and thecoma. Of the 288 women with a mature teratoma, 1 (0.3%) had co-existent endometrioid ovarian cancer, and 1 (0.3%) had borderline cancer. There were 14 women (4.9%) with a co-existent serous cystadenoma, 7 (2.4%) with a mucin cystadenoma, 1 (0.3%) with a thecoma, 4 (1.4%) with struma ovarii, 3 (1.0%) had Brenner cyst, 3 (1.0%) had ovarian fibroma, 2 had endometriosis (0.7%), and 8 (2.8%) had endometriomas. Of a total of nine women with immature teratomas, one (11.1%) had a serous cystadenoma. CONCLUSIONS: Ovarian teratomas may co-exist with other gynecological diseases. Our study reports various cases of the co-existence of several gynecological tumors with teratomas.

Anatomic Distribution of Benign Ovarian Tumors in Perimenopausal and Postmenopausal Women.

Introduction We aim to report the histotypes and reassess the anatomic distribution of benign ovarian tumors in perimenopausal and postmenopausal women. Methods Medical and pathology reports of women with histologically confirmed benign ovarian pathology were investigated. Data were collected, retrospectively between 2000 and 2020, and analyzed from perimenopausal and postmenopausal women with benign ovarian tumors, after bilateral salpingo-oophorectomy (BSO) with or without total abdominal hysterectomy (TAH). The ovarian masses histology and the distribution of locations were further evaluated. Results The total sample consisted of 1,355 women with benign ovarian tumors; 929 (68.6%) of the perimenopausal and 426 (31.4%) of the postmenopausal age. A dermoid cyst was prominent in the right ovary (52.8%), compared to the left side (41%) (p<0.01). Conversely, in patients with endometriomas and cysts of Morgagni, the observed proportion was more prominent in the left-sided ovary (61.8% vs 27%; p<0.001 and 52.3% vs 36.4%; p<0.01, respectively). Moreover, in the perimenopausal women, we mostly detected endometrioma (18.3%), dermoid cyst (15.5%) and cyst of Morgagni (4%) compared to postmenopausal women, where serous cysts (29.8%) and ovarian fibroids (8%) were the most common tumors. Conclusions Benign ovarian tumors are frequently seen in perimenopausal women and most histotypes present anatomical differences between the left and right ovaries. Serous cysts, followed by paraovarian, dermoid cysts and endometrioma present the commonest ovarian benign masses. Gynecologists should pay special attention to adnexal tumors in the postmenopausal period to choose the right operating setting for women at risk for ovarian cancer.

Influenza and Pertussis Vaccine Uptake during Pregnancy: Determinants Found through a Multi-Center Questionnaire Study of Pregnant Women and Healthcare Professionals.

The objective of this article is to assess the adherence of pregnant women to the national recommendations for influenza and pertussis vaccination and the reasons behind their non-adherence. This was a retrospective observational study conducted in a well-defined puerperant population of adequate healthcare standards from December 2018 to December 2019. The study was carried out with 1006 puerperants and 66 health care practitioners. Data were collected, including demographic-obstetric features of pregnant women, whether they received antenatal vaccination, the reasons for having been vaccinated or not as well as health professional's opinion regarding antenatal immunization. The uptake of influenza and pertussis vaccine during pregnancy was suboptimal with lack of recommendation of the vaccine by the healthcare providers being the main barrier. Factors positively associated with antenatal vaccination against influenza were higher level of maternal education and advanced maternal age while antenatal vaccination against pertussis was positively associated with higher level of maternal education. This large-scale retrospective study reveals the inadequacy of antenatal vaccination rates against pertussis and influenza in Crete, Greece. Results suggest that obstetricians' confidence in vaccination is of outmost importance for implementing immunization in pregnancy and any doubts on vaccine effectiveness and safety should be resolved. Routine antenatal vaccination counseling and pregnancy immunization campaigns are essential to improve vaccine uptake during pregnancy.

There is no significant correlation of adenomyosis with benign, premalignant and malignant gynecological pathologies. Retrospective study on 647 specimens.

OBJECTIVES: The aim of this study is to identify the prevalence of benign, premalignant and malignant gynecological pathologies in women with adenomyosis who underwent gynecological surgery. MATERIAL AND METHODS: The medical records collected between 1985 and 2020 were retrospectively reviewed. The pathology reports were studied from 647 cases where adenomyosis was presented. The estimated prevalence of benign, premalignant and malignant gynecological disorders in the general population was further evaluated. RESULTS: The mean age of women with adenomyosis was 54.1 ± 10.4 years old. Out of 647 patients, in 18.5% of the specimens we detected isolated adenomyosis and in 81.5% of cases a coexistence of one or more gynecological diseases, while in 84 out of 647 patients (13%) there was coexistence of adenomyosis with more than one gynecological condition (benign or malignancy). Among all cases, uterine leiomyomas were observed in 61.3% of patients, followed by endometrial polyps (11.9%), endometriosis (11.6%), endometrial hyperplasia (7.1%), endometrial cancer (3.6%), ovarian (1.4%) and cervical cancer (0.8%) (p < 0.001).Additionally, we found that women with a simultaneous co-existence of adenomyosis, leiomyomas and endometrial polyps or hyperplasia were younger (p < 0.01) in comparison to cases with malignancy. CONCLUSIONS: Adenomyosis presents a common benign but often progressing myometrial condition that it is underestimated in clinical practice. Even though some studies suggest a potential association with several gynecological pathologies, we did not confirm a significant difference of adenomyosis prevalence between benign, premalignant and malignant gynecological conditions compared with the general population. Further investigation is required to confirm our results.

Coexistence of cervical endometriosis with premalignant and malignant gynecological pathologies: report on a series of 27 cases.

Although cervical endometriosis represents a rare condition, there is evidence that implicates a complex interaction with other gynecological pathologies. This study aims to highlight this entity and further to explore the impact of oncological pathology of female genital tract on patients with cervical endometriosis. We retrospectively investigated the medical and pathological reports of 27 cases with cervical endometriosis, which were diagnosed by tissue biopsy. The results of the study show a relationship between CIN (cervical intraepithelial neoplasia) cases 19/27 (70percent) and cervical endometriosis. CIN I was more frequently found compared to patients with CIN II and CIN III. Furthermore, a high prevalence of HPV (human papilloma virus) was confirmed. Out of 27 patients, 2 cases with cervical (7.4percent), 2 with endometrial (7.4percent) and 3 with ovarian cancer (11.1percent) were detected. We confirmed the coexistence of more than one malignant gynecological pathology with cervical endometriosis in four cases (14.8percent). To conclude, cervical endometriosis is a rare disease co-existing considerably with premalignant and malignant gynecological conditions according to our data. Although the pathophysiology and genetics of cervical dysplasia is well delineated, further research is needed to establish the association between cervical endometriosis and gynecological premalignant and malignant pathology.

Cyclopia: The Face Predicts the Future.

The most extreme form of holoprosencephaly (HPE) is cyclopia and appears with a single characteristic midline diamond-shaped orbital structure and various facial, brain, and extrafacial features. We aimed to report a case of a cyclopic fetus diagnosed at the 22 weeks of the gestational age and further we reviewed the recent literature in order to highlight the etiopathogenesis and set goals for approaching such future pregnancies. Following the first-trimester assessment, in a 27-year-old pregnant woman, who underwent in vitro fertilization, the pregnancy was associated with a low risk for aneuploidies and a high risk for pre-eclampsia. On the anomaly scan, due to severe fetal brain maldevelopment and microcephale, HPE was suspected. Furthermore, three-dimensional ultrasound confirmed a common orbit in the midline of the face. Although the parents did not opt for amniocentesis and further postnatal management, parental karyotyping test did not detect any pathology. The pregnancy was terminated and the macroscopic examination of the aborted specimen revealed cyclopia, synophalmia, fussed eyelids with a proboscis on the upper midline of the face, and a malpositioned left ear. To conclude, cyclopia is not widely manifested, and different cyclo-pian disorders could still occur. Although this rare congenital abnormality is incompatible with life, the awareness of the spectrum of sonographic features and the appropriate genetic counseling can determine the outcome of current and forthcoming pregnancies.

[Corrigendum] Role of adenosine deaminase 2 gene variants in pediatric deficiency of adenosine deaminase 2: A structural biological approach.

Following the publication of the above article on modeling variants of adenosine deaminase 2 (ADA2), previously identified by Gibson et al [Kristen M. Gibson, Kimberly A. Morishita, Paul Dancey, Paul Moorehead, Britt Drögemöller, Xiaohua Han, Jinko Graham, Robert E. W. Hancock, Dirk Foell, Susanne Benseler, Rashid Luqmani, Rae S. M.Yeung, Susan Shenoi, Marek Bohm, Alan M. Rosenberg, Colin J. Ross, David A. Cabral and Kelly L. Brown: Identification of novel adenosine deaminase 2 gene variants and varied clinical phenotype in pediatric vasculitis. Arthritis Rheumatol 71: 1747­1755, 2019], (reference 18 in the article), Dr. Kelly L. Brown, corresponding author of the Gibson et al article, drew to the authors' attention possible discrepancies identified therein. Upon examining the matters raised by Dr. K. Brown, the authors wish to publish a corrigendum for this article, and the following textual changes are required to the main text. The authors noted that it was not accurate to have referred to the p.Gly47Arg mutation as being 'novel' when this mutation was being specifically referred to, so the word 'novel' should have been omitted from the sentence in the abstract starting on line 17: 'This led to suggestions that the mutations found may affect the formation/stability of the homodimer or may influence the activity of the enzyme (15)'. However, Gibson et al in their paper stated that ADA2 variant with the mutation Gly47Arg in sera from homozygous individuals was a dimer (18). Also, the word 'novel' should not have been included in the title of Fig. 3, and this should have appeared as follows: 'Figure 3. The DADA2­associated mutation G47R in the ADA2 structure', and also, for consistency, the titles of Figs. 4 and 5 should have been written as 'Figure 4. The DADA2­associated novel mutation R34W in the ADA2 structure' and 'Figure 5. The DADA2­associated novel mutation A357T in the ADA2 structure'. The authors would like to add that the p.Arg34Trp variant's association with DADA2 has been previously identified in a paper by Kaljas et al: Human adenosine deaminases ADA1 and ADA2 bind to different subsets of immune cells. Kaijas Y, Liu C, Skaldin M, Wu C, Zhou Q, Lu Y, Aksentijevich I and Zavialow AV: Cell Mol Life Sci 74: 550­570, 2017. In addition, the novel rare mutation identified by Gibson et al as Arg9Trp associated with DADA2 lies in the signal peptide [stated by the authors as Arg8Trp because Met#1 (ATG start codon) is not included in the protein numbering] and is not obviously included in the three­dimensional structure, and therefore the authors did not deal with it. So, the sentence in the Abstract starting on line 19 should have been written as follows: 'It was thus concluded that the Gly47Arg mutation affects the position and interaction of the dimer­associated HN1 helical structure'. All references of Arg8Trp in the text, when referred to the Gibson et al article, should be changed to Arg9Trp as referred therein so as not to cause confusion. Finally, in the legend for Fig. 2, 'His358' should have been written as 'His356' (line 3), and for the purposes of clarification, where 'at the next Asn352 (2)' was written at the end of the same sentence, this text should be changed to 'at the neighboring glycosylated Asn378 [Asn352 in (2)]'. Similarly, on p. 880, the sentence at the end of the penultimate paragraph of the Results section should have been written as follows: 'This disruption could be transmitted to the neighboring His356 coordinated to the metal ion or affect the confirmed glycosylation at the neighboring glycosylated Asn378 [Asn352 in (2)]'. The authors thank Dr. K. L. Brown for drawing these matters to their attention, and emphasize that the resultant corrections and clarifications do not alter either the results or the main conclusions reported in the paper. [the original article was published in Molecular Medicine Reports 21: 876­882, 2020; DOI: 10.3892/mmr.2019.10862].

Abdominal and perineal scar endometriosis: Retrospective study on 40 cases.

OBJECTIVE(S): Abdominal and perineal scar endometriosis usually develop in association with a prior surgical scar. The purpose of the study was to detect and review patients' characteristics of these women over a long period. STUDY DESIGN: We retrospectively review the clinical records of 860 women with endometriosis between 1989 and 2019. Data were collected and analyzed from medical and pathological reports of 40 patients with abdominal and perineal scar endometriosis. RESULTS: 26 patients (3,0 %) were detected in the abdominal wall endometriosis group (AWE) (mean age 36,5 ± 3,4 years) and 14(1,6 %) cases in the perineal endometriosis (PE) group (32,5 ± 2,4 years), respectively. We observed that 92,3 % of women with AWE had undergone at least 1 cesarean section. Moreover, the majority of patients presented with abdominal pain (77, 0 %) and sensation of a mass (96,2 %). 15,4 % of cases had concurrent pelvic endometriosis and the recurrent rate of the disease was 15,4 %. All cases with perineal scar endometriosis were multiparous and delivered vaginally with episiotomy. 92,8 % of patients presented with cyclical pain and swelling. 3 cases suffered from perineal endometriosis combined with pelvic endometriosis. There was a recurrence of perineal endometriosis in 2 women (14,2 %). Surgical excision was the standard treatment of this condition and tissue biopsy confirmed the diagnosis. CONCLUSIONS: Abdominal wall and perineal scar endometriosis are rare, multifactorial entities which are associated mainly with cesarean section and vaginal episiotomy. Clinicians should be aware of these conditions among all women of reproductive age presenting with cyclic or non-cyclic pain and swelling at the incision sites.

Endometriosis research in the -omics era.

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.

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

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 χ2 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 in utero 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.

Role of adenosine deaminase 2 gene variants in pediatric deficiency of adenosine deaminase 2: A structural biological approach.

Adenosine deaminase 2 (ADA2) belongs to the novel family of adenosine deaminase growth factors (ADGFs), which play an important role in tissue development. The deficiency of adenosine deaminase 2 (DADA2) is a recently recognized autosomal recessive autoinflammatory disease, characterized by various systemic vascular and inflammatory manifestations, which is associated with ADA2 mutations. Considering that a recent screening of an international registry of children with systemic primary vasculitis revealed novel and already known variants in ADA2, this study aimed to further investigate the functional significance of the rare variants detected, namely p.Gly47Arg, p.Gly47Ala, p.Arg8Trp, p.Leu351Gln and p.Ala357Thr, by using a structural biological approach. Three­dimensional models of the mutants were developed and their three­dimensional (3D) structures were subjected to detailed interaction and conformational analyses. This led to suggestions that the novel mutations found may affect the formation/stability of the homodimer or may influence the activity of the enzyme. It was thus concluded that the Arg8Trp and Gly47Arg mutations affect the position and interaction of the dimer­associated HN1 helical structure and therefore, dimer formation and stabilization, while Leu351Gln and Ala357Thr influence the metal coordination in the active site. These findings shed further light onto the structural consequences of the mutations under investigation.

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

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.

Role of FN1 and GREB1 gene polymorphisms in endometriosis.

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.

Defining the genetic profile of endometriosis.

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.

Keeping an Eye on Perimenopausal and Postmenopausal Endometriosis.

Introduction: 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. Material and Methods: 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 (p < 0.01). Results: Advanced endometriosis was more aggressive in the perimenopausal group (p < 0.05); in the same group, we observed a higher left-sided predisposition of endometriosis in comparison with the right side (p < 0.01). Endometrioma was the most common gynecological condition among patients with perimenopausal endometriosis in relation to the postmenopausal group (p < 0.001). Additionally, we found uterine leiomyomata more prominent in the perimenopausal group (p < 0.05). In contrast, adenomyosis was found higher in postmenopausal patients (p < 0.05); further, 24 cases with dry eye we observed. Conclusions: 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.

Clinical manifestations, evaluation and management of hyperprolactinemia in adolescent and young girls: a brief review.

Hyperprolactinemia (HPrl) is considered as a rare endocrinopathy in childhood. In children and adolescent girls, there are three major categories of HPrl causes; physiological, pathological and iatrogenic. Through hypogonadotropic hypogonadism, prolactin hypersecretion and production leads to the typical functional syndrome which is observed in female children and adolescents; delayed puberty, primary or secondary amenorrhea and/or galactorrhea. Regarding prolactinomas, clinical signs manifest with mass compression of the optic chiasm and anterior pituitary gland or prolactin hypersecretion. Targeted identification of HPrl is of significant importance for proper management and follow-up. The aim of this review is to focus on the evaluation of HPrl in adolescent and young girls. In addition, we aimed to summarize the current knowledge regarding the proper management of such cases.

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

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 case­control and genome­wide association studies (GWAS) detecting various endometriosis risk factors. In a recent study, we described a unique, three­generation 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.

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

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.

Endometriosis and in vitro fertilisation.

The aim of the present review was to discuss a matter of concern in the clinical field of obstetrics/gynecology, namely the potency of in vitro 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.

Association between ovarian cancer and advanced endometriosis.

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.