Search

Endometriosis is a benign, estrogen-dependent gynecological condition with an uncertain exact pathogenetic mechanism. The aim of this study was to evaluate the potential differential expression of Insulin Growth Factor 1 (IGF-1) isoforms in deeply infiltrating endometriotic (DIE) lesions, in ovarian endometriomas, and in the eutopic endometrium of the same endometriosis patients and to compare their expression with that in the eutopic endometrium of women without endometriosis. A total of 39 patients were included: 28 with endometriosis, of whom 15 had endometriomas only, 7 had DIE nodules only, and 6 had both DIE and endometriomas, and 11 without endometriosis served as controls. We noticed a similar pattern of expression between IGF-1Ea and IGF-1Ec, which differed from that of the IGF-1Eb isoform, possibly implying differential biological actions of different isoforms in DIE subtypes. We observed a tendency of lower expression of IGF-1Ea and IGF-1Ec in endometriomas without DIE compared to endometriomas with concurrent DIE or in DIE nodules. In conclusion, differential expression of IGF-1 isoforms may indicate that DIE with its associated ovarian lesions and simple ovarian endometriosis should be considered as two forms of the disease developing under different molecular pathways.

Pathogenesis of endometriosis involves growth factors, which are synthesized locally. Insulin-like growth factor-1 (IGF-1) prevents apoptosis and has mitogenic action on endometrial cells. The IGF-1 gene undergoes alternative splicing and results in three isoforms (IGF-1Ea, IGF-1Eb, and IGF-1Ec or MGF). We analyzed the mRNA expression of IGF-1 isoforms in tissue samples of eutopic endometrium and endometriotic cyst obtained during laparoscopy from women with endometriosis. We documented that all three IGF-1 isoforms are expressed in both eutopic endometrium and ovarian endometrioma. Furthermore, we documented a significant decrease in all IGF-1 isoform expression in endometriotic cyst compared to endometrium of women with endometriosis. The reduction may correlate with the disease status and presence of fibrotic inactive tissue found in late stages of the disease.

The peritoneal fluid of women with endometriosis contains an increased insulin-like growth factor 1 (IGF-1) bioavailability, which is produced by limited hydrolysis of urokinase-type plasminogen activator (uPA) on IGF-binding protein 3 (IGFBP-3). Recently, IGF-1 was shown to inhibit apoptosis of endometrial-like cells in vitro, suggesting that a microenvironment of increased IGF-1 bioavailability can optimize the survival of endometrial cells grown ectopically. Here the expression of mRNA of IGFBP-3 and uPA in tissue biopsies from eutopic endometrium and endometriotic lesions obtained at laparoscopy from women with endometriosis have been analyzed, and it is documented that both IGFBP-3 and uPA mRNA expression are increased from 3- to 10-fold in endometriotic lesions versus eutopic endometrium. Consequently, the necessary components (uPA and IGFBP-3 expression) of endocrine/autocrine/paracrine enhancement of local IGF bioavailability mediated by uPA hydrolysis of the IGFBP-3 were present in endometriotic lesions. These data possibly explain the origin of the increased content of uPA activity, IGF-1 bioavailability, and NH(2)-truncated forms of IGFBP-3 in the peritoneal fluid of women with endometriosis.

Objective: To investigate possible correlation(s) between mutations of BrCA1, BrCA2, and p53 genes versus soluble HLA expression in familial endometriosis., Design: Mutation analysis., Setting: University teaching departments and hospital., Patient(s): A family with seven women in two generations with familial endometriosis., Intervention(s): Mutation analysis of BrCA1, BrCA2, and p53 genes., Main Outcome Measure(s): A point mutation of the BrCA1 gene appears to inhibit soluble HLA secretion., Result(s): Among the three genes examined, only the BrCA1 gene showed a T to A mutation at position 3232 that correlates with total abolishment of both class I and class II antigen release., Conclusion(s): A possible correlation between a BrCA1 mutation and soluble HLA expression appears to exist. The mutation is not stage dependent and seemingly influences the secretion of both class I and class II antigens that are totally absent from the serum of only one family member.

Endometriosis is a benign, estrogen-dependent gynecological condition with an uncertain exact pathogenetic mechanism. The aim of this study was to evaluate the potential differential expression of Insulin Growth Factor 1 (IGF-1) isoforms in deeply infiltrating endometriotic (DIE) lesions, in ovarian endometriomas, and in the eutopic endometrium of the same endometriosis patients and to compare their expression with that in the eutopic endometrium of women without endometriosis. A total of 39 patients were included: 28 with endometriosis, of whom 15 had endometriomas only, 7 had DIE nodules only, and 6 had both DIE and endometriomas, and 11 without endometriosis served as controls. We noticed a similar pattern of expression between IGF-1Ea and IGF-1Ec, which differed from that of the IGF-1Eb isoform, possibly implying differential biological actions of different isoforms in DIE subtypes. We observed a tendency of lower expression of IGF-1Ea and IGF-1Ec in endometriomas without DIE compared to endometriomas with concurrent DIE or in DIE nodules. In conclusion, differential expression of IGF-1 isoforms may indicate that DIE with its associated ovarian lesions and simple ovarian endometriosis should be considered as two forms of the disease developing under different molecular pathways. [ABSTRACT FROM AUTHOR]

The aim of this study is to assess the value of laparoscopy for couples diagnosed with mild male factor infertility and at least three previous failed In-Vitro Fertilization (IVF) attempts. A total of 169 couples were included in this prospective cohort study. Patients were presented with the option of being subjected to laparoscopic investigation for correction of previously unidentified endometriosis or pelvic adhesions. The outcome measures were Live Birth/Ongoing Pregnancy, clinical pregnancy and positive hCG rate. One-hundred and one of them opted for, whereas 68 opted against laparoscopic investigation. All patients proceeded with a single ICSI cycle. Following laparoscopic investigation, 43 patients were diagnosed with endometriosis, 22 with adhesions, while for 36 patients laparoscopic investigation provided no further diagnosis. No statistically significant differences were observed regarding baseline hormonal levels and other characteristics between the two groups and the three subgroups. When compared to the no-laparoscopy group, women subjected to laparoscopy presented with a higher clinical pregnancy and ongoing pregnancy/live birth rate. Following endometriosis correction, a marginally non-statistically significant trend was observed regarding a decrease in poor-quality blastocysts (p = 0.056). A statistically significant higher clinical pregnancy (p = 0.03) and ongoing pregnancy/live birth rate was observed in the endometriosis group when compared to male factor infertility only (p = 0.04). Laparoscopic identification and correction of undiagnosed endometriosis in couples initially diagnosed with male infertility and at least 3 failed previous IVF attempts, appears to be a promising approach efficiently addressing infertility for these patients while avoiding IVF overuse. [ABSTRACT FROM AUTHOR]

The present study aims to explore the effectiveness of laparoscopic surgery on women presenting with infertility, of unidentified aetiology according to the standard infertility investigation, and recurrent failed In Vitro Fertilization (IVF) attempts. Identifying and correcting possible underlying pathologies by laparoscopy may subsequently enable natural conception in an effort to address infertility and avoid IVF overuse. One-hundred and seven (107) women with unidentified aetiology of infertility and recurrent failed IVF attempts met the inclusion criteria. Laparoscopic surgery was performed as the endpoint of the patients' diagnostic journey, aiming to identify a possible underlying factor as the cause of infertility. Sixty-two (62) out of 107 patients (57.94%) that underwent laparoscopy were diagnosed with endometriosis, 25 out of the 107 patients (23.3%) were diagnosed with periadnixal and pelvic adhesions, and 20 cases (18.69%) presented with no pathology and remained unexplained. Following identification and correction of endometriosis and pelvic adhesions, patients were invited to conceive naturally. For the patients that laparoscopic investigation failed to reveal any pathology they were categorized as unexplained infertility and were subjected to a single IVF cycle. Natural conception success rate within the first postoperative year was the primary outcome. Within the first postoperative year, 30 out of 62 patients (48.38%) diagnosed with endometriosis following laparoscopic investigation achieved a natural conception, and 28 out of them (93.4%) reported live-births. Additionally, 11 out of 25 patients (44%) diagnosed with periadnixal and pelvic adhesions achieved natural conception within the first operative year. Regarding the group of unexplained infertility patients, only four out of the 20 patients (20%) achieved clinical pregnancy in the first post-operative IVF cycle. In conclusion, laparoscopy appears to be a promising approach, addressing infertility, providing significant diagnostic findings, while avoiding IVF overuse regarding patients of unidentified infertility presenting with recurrent failed IVF attempts. [ABSTRACT FROM AUTHOR]

The transcription of the insulinlike growth factor 1 (igf-1) gene generates three mRNA isoforms, namely IGF-1Ea, IGF-1Eb and IGF- 1Ec (or MGF [mechano growth factor]). Herein, we analyzed the expression of IGF-1 isoforms in eutopic and ectopic endometrium (red lesions and endometriotic cysts) of women with endometriosis, and we characterized the actions of a synthetic MGF E-peptide on KLE cells. Our data documented that all three igf-1 gene transcripts are expressed in the stromal cells of the eutopic and ectopic endometrium; however, endometriotic cysts contained significantly lower IGF-1 isoform expression, both at the mRNA and protein level, as was shown using semiquantitative PCR and immunohistochemical methods. In addition, the glandular cells of the eutopic endometrium did not express any of the IGF-1 isoforms; however, the glandular cells of the ectopic endometrium (red lesions) did express the IGF-1Ec at mRNA and protein level. Furthermore, synthetic MGF E-peptide, which comprised the last 24 amino acids of the MGF, stimulated the growth of the KLE cells. Experimental silencing of the type 1 IGF receptor (IGF-1R) and insulin receptor expression of KLE cells (siRNA knock-out methods) did not alter the mitogenic action of the synthetic MGF E-peptide, revealing that MGF E-peptide stimulates the growth of KLE cells via an IGF-1R-independent and insulin receptor-independent mechanism. These data suggest that the IGF-1Ec transcript might generate, apart from mature IGF-1 peptide, another posttranslational bioactive product that may have an important role in endometriosis pathophysiology. [ABSTRACT FROM AUTHOR]