Is the presence of deep infiltrative endometriosis underestimated in the surgical management of endometriosis?

OBJECTIVES: The aim of the study was to determine the presence of deep infiltrative endometriosis (DIE) in the surgical management of endometriosis. MATERIAL AND METHODS: Operation notes and histopathological reports of women with endometriosis were retrospectively analyzed in the Ege University Hospital between 2008 and 2018. A total of 191 women with suspicious of endometriosis but without clinical signs of DIE were enrolled in the study. Laparoscopic diagnosis of DIE was compared with histopathological reports. There was no histopathology before surgery. Endometriosis was suspected only based on symptoms. RESULTS: A total of 213 lesions that were thought to be DIE were removed from 191 women with endometriosis. Among these 213 lesions, 179 specimens were reported as endometriosis and 34 lesions as fibro-adipose tissue. Forty-nine right uterosacral ligaments were excised, and endometriosis was detected in 44 out of 49 specimens. Histopathological examination of 45 left uterosacral ligaments revealed endometriosis in 35 specimens. Finally, 25 endometriotic nodules were removed from the recto-vaginal space, and 22 of these were verified as endometriosis by a pathologist. The positive predictive value of laparoscopic visualization for DIE in the group suspected of endometriosis but without any clinical findings of DIE was 84%. CONCLUSIONS: Women with the suspicious of endometriosis, qualified to surgery, because of infertility or pain, should be prudently investigated to confirm or to exclude coexistence of DIE even if no preoperative sign of DIE was observed to provide complete resection. Otherwise, DIE continues to grow, causes pain postoperatively, and complicates subsequent surgery.

The Role of Ankaferd Blood Stopper and Oxytocin as Potential Therapeutic Agents in Endometriosis: A Rat Model.

To evaluate the potential effect of Ankaferd Blood Stopper (ABS) and oxytocin (OT) in an experimental endometriosis model, 18 female Sprague Dawley rats were used in this study. The animals were divided randomly into three groups after surgical induction of endometriosis: group 1: control group (isotonic NaCl, 1 mL/kg/day, intramuscular, n=6); group 2: OT group (OT, 80 U/kg/day, intramuscular, n=6); group 3: ABS group (ABS, 1.5 mL/kg/day, intraperitoneal, n=6). Each group was treated for four weeks (two times per week). Volumes of endometriotic explants were measured in biopsy samples for histopathological analysis. Vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1), and tumour necrosis factor (TNF-α) levels were measured in plasma and peritoneal fluid. Endometriotic explant volumes were significantly decreased after OT administration (P<0.0001). The epithelial score was significantly decreased in both treatment groups compared to the control group (P<0.05). TUNEL immunohistochemistry showed more apoptotic changes in the endometriosis foci (gland epithelium and surrounding tissue) in the OT group than in the control group (P<0.05). The levels of VEGF, MCP-1, and TNF-α were significantly reduced in the OT group (P<0.05), whereas no significant changes in protein levels were found in the ABS-applied group. The results indicate that OT has greater potential as a therapeutic agent in experimentally induced peritoneal endometriosis, where ABS, which is a VEGF modulator, appears to act through different mechanisms to show its palliative effects on a rat model of peritoneal endometriosis.

Determination of Isthmocele Using a Foley Catheter During Laparoscopic Repair of Cesarean Scar Defect.

STUDY OBJECTIVE: To demonstrate a new technique of isthmocele repair via laparoscopic surgery. DESIGN: Case report (Canadian Task Force classification III). The local Ethics Committee waived the requirement for approval. SETTING: Isthmocele localized at a low uterine segment is a defect of a previous caesarean scar due to poor myometrial healing after surgery [1]. This pouch accumulates menstrual bleeding, which can cause various disturbances and irregularities, including abnormal uterine bleeding, infertility, pelvic pain, and scar pregnancy [2-6]. Given the absence of a clearly defined surgical method in the literature, choosing the proper approach to treating isthmocele can be arduous. Laparoscopy provides a minimally invasive procedure in women with previous caesarean scar defects. INTERVENTION: A 28-year-old woman, gravida 2 para 2, presented with a complaint of prolonged postmenstrual bleeding for 5 years. She had undergone 2 cesarean deliveries. Transvaginal ultrasonography revealed a hypoechogenic area with menstrual blood in the anterior lower uterine segment. Magnetic resonance imaging showed an isthmocele localized at the anterior left lateral side of the uterus, with an estimated volume of approximately 12 cm3. After patient preparation, laparoscopy was performed. To repair the defect, the uterovesical peritoneal fold was incised and the bladder was mobilized from the lower uterine segment. During this surgery, differentiating the isthmocele from the abdomen can be challenging. Here we used a Foley catheter to identify the isthmocele. To do this, after mobilizing the bladder from the lower uterine segment, we inserted a Foley catheter into the uterine cavity through the cervical canal. We then filled the balloon of the catheter at the lower uterine segment under laparoscopic view, which allowed clear identification of the isthmocele pouch. The uterine defect was then incised. The isthmocele cavity was accessed, the margins of the pouch were debrided, and the edges were surgically reapproximated with continuous nonlocking single layer 2-0 polydioxanone sutures. We believed that single-layer suturing could provide for proper healing without necrosis due to suturation. During the procedure, the vesicouterine space was dissected without difficulty. A urine bag was collected with clear urine, and there was no gas leakage; thus, we considered a safety test for the bladder superfluous. Based on concerns about the possible increased risk of adhesions, we did not cover peritoneum over the suture. The patients experienced no associated complications, and she reported complete resolution of prolonged postmenstrual bleeding at a 3-month follow-up. CONCLUSION: Even though the literature is cloudy in this area, a laparoscopic approach to repairing an isthmocele is a safe and minimally invasive procedure. Our approach described here involves inserting a Foley catheter in the uterine cavity through the cervical canal, then filling the balloon in the lower uterine segment under laparoscopic view to identify the isthmocele.

Stem cells in endometrium and endometriosis.

Endometriosis is a common chronic gynecological disease that is classically defined by the presence of endometrial stromal and glandular tissues outside the uterine cavity. Pelvic pain and infertility are the nonspecific but the most common symptoms of the disease; however, no currently definitive treatment has been developed since its pathogenesis has not been completely understood. Currently, none of the proposed conventional theories can explain all aspects of endometriosis. Recent evidence supports the presence of endometrial stem/progenitor cells and their possible involvement in endometrial regeneration and differentiation. The stem cell theory is a new hypothesis which may clarify the underlying pathophysiologic mechanisms of endometriosis. However, this theory could not only account for an alternative pathogenic mechanism of endometriosis but could also be involved in all conventional theories. This article will review the evidence for the presence of endometrial stem/progenitor cells, their possible sources and their possible involvement in the pathogenesis of endometriosis.

Is there a relationship between age and side dominance of tubal ectopic pregnancies? --A preliminary report.

OBJECTIVES: To determine whether there exists a relationship between age and side dominance of tubal ectopic pregnancies. MATERIAL AND METHODS: One hundred twenty patients were retrospectively analyzed. The sides of the tubal ectopic pregnancies were recorded on the basis of laparoscopy or laparotomy findings. Five age groups were created: 20-24, 25-29, 30-34, 35-39, and > or = 40 years. RESULTS: Of the patients who were > 30 years of age, 46 (69%) and 21 (31%) had tubal ectopic pregnancies on the right and left sides, respectively (p = 0.002). In the 35-39 years of age group, 17 of 20 patients (85%) had tubal ectopic pregnancies on the right, and 3 of 20 patients (15%) on the left side (p = 0.002). In the 30-34 years of age group, 26 of 39 patients (67%) and 13 of 39 patients (33%) had tubal ectopic pregnancies on the right and left sides, respectively (p = 0.037). In the > or = 40 years of age group, 3 of 8 patients (37%) had tubal ectopic pregnancy on the right side, while 5 patients (63%) on the left side (p = 0.48). CONCLUSIONS: Patients who are between the age of 30-40 years have a right-sided dominance of tubal ectopic pregnancy however studies that involve larger numbers of subjects are needed to make definitive conclusions about women older than 40 years of age.

Effect of oxytocin treatment on explant size, plasma and peritoneal levels of MCP-1, VEGF, TNF-α and histopathological parameters in a rat endometriosis model.

OBJECTIVE: To determine the effects of oxytocin (OT) on surgically induced endometriosis in a rat model. STUDY DESIGN: Twelve female Sprague-Dawley rats were included. After the implantation and establishment of autologous endometrium onto the abdominal wall peritoneum, the rats were randomly divided into two groups, treated with intramuscular oxytocin (OT group, 160µgkg/day, n=6) or isotonic NaCl solution (control group, 1mLkg/day, n=6) for 28 days. To evaluate the therapeutic effects of OT, the explant volumes were calculated and the levels of vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1, and TNF-α were measured in plasma and peritoneal fluid. Endometriotic explants were examined histologically by semiquantitative analysis. RESULTS: After treatment, the mean endometriotic explant volume was decreased in the OT group (p=0.016). The histopathological score and VEGF immunoexpression of endometriotic explants were significantly lower in the OT group (p=0.007) than in controls (p=0.000). Inflammatory cytokine levels in plasma and peritoneal fluid were considerably decreased in the OT group. Moreover, TUNEL immunohistochemistry clearly demonstrated more apoptotic changes in the mononuclear cells of the OT group compared with controls. CONCLUSION: We suggest that oxytocin might be considered as a potential candidate therapeutic agent for endometriosis.

The effects of different hormone treatment on endothelial function in healthy postmenopausal women.

We aimed to compare the effects of different types of hormone treatment (HT) on endothelial function by means of brachial artery ultrasonographic examination in postmenopausal women. Sixty-two healthy postmenopausal women were included in this study. Subjects were assigned to one of the five groups receiving 6 months of treatment [estrogen (conjugated estrogen), estrogen (conjugated estrogen) plus progesterone (medroxyprogesterone acetate; MPA), raloxifene, tibolone or control]. Endothelial function was assessed by measurement of flow-mediated dilatation (FMD) and nitrate-dependent dilatation in the brachial artery. At the end of 6 months, FMD values were found to be significantly increased in women with HT use than the control group (p = 0.001). In subgroups, FMD increased significantly in the estrogen [12 ± 7 versus 25 ± 8, p = 0.001] and raloxifene groups [7 ± 5 versus 11 ± 3, p < 0.01] compared to tibolone and estrogen plus progesterone groups. In conclusion, endothelial function is impaired in postmenopausal women. Both estrogen and raloxifene regimens may improve endothelial functions in healthy postmenopausal women. The direct protective effects of these HT on the healthy endothelium may be more remarkable than the favorable effects on lipid profile.

Regression of endometrial implants by resveratrol in an experimentally induced endometriosis model in rats.

OBJECTIVE: To evaluate the effect of resveratrol on an experimentally induced endometriosis rat model. STUDY DESIGN: After endometriotic implants were surgically formed, rats were randomly divided into 2 groups as control group (saline treated, n = 6) and resveratrol group (10 mg/kg/d, n = 6). The inflammatory markers and histopathological changes were assessed at the end of the treatment period. Results Our results showed (1) significant reduction in the implant size (P < .0005); (2) significantly decreased levels of vascular endothelial growth factor (VEGF) in the peritoneal fluid and plasma (P < .005); and monocyte chemotactic protein 1 (MCP-1) in the peritoneal fluid (P < .05), (3) highly significant suppression of VEGF expression in the endometriotic tissue (P < .0005); and (4) considerable histological changes in the endometriotic foci following resveratrol treatment. CONCLUSION: Resveratrol appears to be effective on the development of endometriosis through its antiangiogenic and anti-inflammatory properties. Future studies with different doses of resveratrol might provide more comprehensive results regarding the treatment of endometriosis.

Identification of Y chromosome microdeletions in infertile Turkish men.

OBJECTIVE: The aim of this study was to determine the frequencies of Y chromosome microdeletions in infertile azoospermic and oligozoospermic Turkish men and in healthy control subjects. MATERIAL AND METHODS: Sixty-four azoospermic and 51 oligozoospermic patients infertile patients, and 70 healthy men who had a child without the aid of assisted reproductive technologies were included in this study. DNA was extracted from peripheral blood samples collected from the patients. Following multiplex PCR performed with 15 different primer sequences, Y chromosome AZFa, AZFb, AZFc and AZFd region microdeletions were determined by agarose gel electrophoresis. RESULTS: Y chromosome microdeletions were detected in 8 (12.5%) patients in the azoospermia group and 3 (5.9%) patients in the oligozoospermia group. The overall frequency of Y chromosome microdeletions in all infertile cases was 9.6%. Y chromosome microdeletions were not found in the healthy control group. Among the infertile cases, there were 4 (3.48%) AZFa, 2 (1.74%) AZFb, 3 (2.61%) AZFc and 7 (6.09%) AZFd region microdeletions. Y chromosome microdeletions were not found among healthy men in the control group. CONCLUSION: The presence of Y chromosome microdeletions among azoospermic and oligozoospermic infertile males suggests that routine genetic testing and genetic counseling prior to the use of assisted reproduction techniques are necessary.

Right endometrioma is related with more extensive obliteration of the Douglas pouch.

OBJECTIVE: To investigate that endometrioma is an asymmetric disease with left lateral predisposition as compared to other benign ovarian cyst and also, whether endometrioma side is related with endometriosis severity. METHODS: Operative and histopathologic findings of 340 women who underwent cystectomy for treatment of endometriotic (n = 239) and nonendometriotic ovarian cysts (n = 101) by laparoscopy (n = 268) or laparotomy (n = 72) between January 2005 and August 2009 were evaluated retrospectively. We compared left and right sided distribution of endometriotic and nonendometriotic ovarian cysts, and we also investigated the extent of endometriotic foci, obliteration of pouch of Douglas and endometriosis stage according to the revised American Fertility Society classification of endometriosis to assess whether endometrioma side is related with the severity of endometriosis. RESULTS: Of 239 women with endometriosis, endometrioma was found in the left ovary (n = 109), right ovary (n = 58) and bilaterally (n = 72). Of 101 control group women functional and dermoid cysts were found in the left ovary (n = 48), right ovary (n = 43) and bilaterally (n = 10). Among women with unilateral ovarian endometrioma (n = 167) a left cyst (63.3%) was found more frequently than a right cyst (34.7%) (P < 0.0001). In women with a left ovarian endometrioma pouch of Douglas was open in 99 (90.8%) cases. However, it was partially obliterated in 3 (2.8%) and completely obliterated in 7 (6.4%) cases. On the other hand, in women with a right endometrioma it was open in 44 (75.9%) cases and partially obliterated in 2 (3.4%) and completely obliterated in 12 (20.7%) cases. In women with a right endometrioma, the possibility of the pouch of Douglas obliteration is significantly higher than the women with a left endometrioma (P = 0.006). CONCLUSION: Moreover, we also showed that in women with a right endometrioma, incidence of the pouch of Douglas obliteration is higher and the endometriosis tends to be more severe compared to women with a left endometrioma. Our most relevant observation is obliteration of Douglas pouch which was found to be more extensive in women with right ovarian endometrioma. Our results showing left lateral predisposition of endometriomas are in agreement with the previous reports and highlight the retrograde menstruation theory for the pathogenesis of this enigmatic disorder.

Regulation of monocyte chemotactic protein-1 expression in human endometrial endothelial cells by sex steroids: a potential mechanism for leukocyte recruitment in endometriosis.

The main aim of this study is to describe the in vivo temporal and spatial expression of monocyte chemotactic protein 1 (MCP-1) in human endometrial endothelial cells (HEECs) and to compare the in vitro regulation of MCP-1 expression by sex steroids in HEECs from women with or without endometriosis. Eutopic endometrial tissues and endometriosis implants were grouped according to the menstrual cycle phase and were examined by immunohistochemistry for MCP-1 expression. No significant difference was observed for MCP-1 immunoreactivity in the endothelial cells of eutopic endometrium of women with endometriosis when compared to endometrium of women without endometriosis and to endometriosis implants. For in vitro studies, the purity of cultured HEECs (90%-95%) was confirmed by immunocytochemistry using endothelium-specific markers CD31 and CD146. The effects of estradiol (5 x 10(- 8) mol/L), progesterone (10(-7) mol/L), or both on MCP-1 messenger RNA (mRNA) and protein levels were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and enzyme-linked immunosorbent serologic assay (ELISA), respectively. Sex steroids did not have significant effect on MCP-1 mRNA and protein expression in HEECs from women without endometriosis. However, we observed that the sex steroid treatment stimulated MCP-1 mRNA and protein expression in HEECs from women with endometriosis (P < .05). We postulate that the stimulation of chemokine expression by sex steroids in the endometrial endothelial cells in women with endometriosis may play a central role in recruiting mononuclear cells, therefore contributing to the inflammatory aspect of endometriosis.

Incomplete androgen insensitivity (Reifenstein syndrome) - a case report.

We report a 20 year old case of partial androgen insensitivity syndrome, referred to our clinic with complaints concerning external genital organs and left undescended testicle. The phenotypically male case was first evaluated for secondary sex development. Axillary hair was scanty and no pubic hair was found. There was no breast development. In the gynecological examination, the clitoris was hypertrophic (4.6 cm) and a blind vagina with intact hymen was seen. Abdominopelvic ultrasonography revealed the absence of an uterus and adnexes which was supported by magnetic resonance imaging (MRI). There was a palpable mass in the left inguinal canal (cryptorchism), seen as atrophic tissue under the skin in MRI. Although the other testis was in the labioscrotal fold, it was atrophic. The Karyotype was 46 XY after genetic investigation.

Pulmonary embolus arising from sloughed off myoma in late puerperium.

Pulmonary embolus is a rare and serious complication of myoma uteri in the puerperium that resulted in late postpartum hysterectomy A 38-year-old, multiparous woman with a large myoma located on the left lateral wall of the uterus underwent emergency cesarean section due to fetal distres at 28 weeks. During the operation, a 15 cm sized intramural myoma was left without any intervention. On the 40(th) day postpartum the patient returned to the clinic with sepsis and pulmonary embolus because of obstruction of lochia drainage by the sloughed off myoma. The patient underwent hysterectomy and medical therapy for pulmonary embolus. We presented an unusual complication of uterine leiomyoma in the late postpartum period after cesarean section. Whatever the mode of sloughing off of the myoma, the results of the obstruction of lochia drainage may be devastating as in our case. To avoid these complications, clinicians must be aware of these symptoms and prompt intervention is essential.

Differential regulation of Akt phosphorylation in endometriosis.

Protein kinase B (PKB/Akt), a serine/threonine kinase, regulates the function of many cellular proteins involved in apoptosis and proliferation. It was postulated that there is a higher Akt activity in endometriosis compared with normal endometrium, and that oestrogen may be one of the factors responsible for the high Akt activation in endometriotic cells. Phospho-Akt (pAkt) concentrations in normal, eutopic and ectopic endometrial tissues were compared by immunohistochemistry, and a higher pAkt immunoreactivity was revealed in eutopic and ectopic endometrium compared with normal endometrium, in vivo. Higher Akt phosphorylation in stromal cells from eutopic endometrium was observed, when compared with normal, in vitro (P < 0.05). Akt phosphorylation was rapidly (2-10 min) stimulated when endometrial stromal cells from normal and endometriosis patients were treated with 17 beta-oestradiol. In endometrial stromal cells from the endometriosis group, ICI 182,780 (ICI, a specific oestrogen receptor antagonist) failed to antagonize the effect of oestradiol when combined with oestradiol, and revealed a stimulatory effect on Akt phosphorylation when given alone (P < 0.05). In conclusion, since Akt affects cell survival, it is suggested that increased Akt phosphorylation may be related to the altered apoptosis/proliferation harmony in endometriosis, and therefore Akt may play a critical role in the pathogenesis of endometriosis.

Expression of interleukin-8 and monocyte chemotactic protein 1 in women with endometriosis.

OBJECTIVE: To investigate the expression and localization of interleukin-8 (IL-8) and monocyte chemotactic protein 1 (MCP-1) in women with and without endometriosis. DESIGN: Comparative immunohistochemical study. SETTING: Academic medical center. PATIENT(S): Ectopic (n = 24) and homologous eutopic endometrium (n = 24) from women with endometriosis and endometrium from women without endometriosis (n = 27) were used for immunohistochemical analysis of IL-8 and MCP-1. INTERVENTION(S): Tissue sections were immunostained with antihuman IL-8 and MCP-1 antibodies. MAIN OUTCOME MEASURE(S): Microscopic evaluation to assess the presence and localization of IL-8 and MCP-1 throughout the menstrual cycle in both eutopic endometrial and endometriotic tissues of women with endometriosis and comparison with normal endometrium. RESULT(S): In normal endometrium, secretory phase samples expressed higher levels of epithelial IL-8 than in proliferative phase samples. Epithelial MCP-1 expression was similar in both proliferative and secretory phases. Proliferative phase samples showed higher epithelial IL-8 and MCP-1 expressions in eutopic endometrium of women with endometriosis compared with that of normal women. Immunoreactivities of both chemokines were significantly increased in the epithelial cells of ectopic endometrial tissues compared with those of normal endometrium. CONCLUSION(S): These findings suggest that IL-8 and MCP-1 may be involved in the pathogenesis of endometriosis.

Long-term use of gonadotropin-releasing hormone analogues before IVF in women with endometriosis.

PURPOSE OF REVIEW: To discuss the relationship between endometriosis and infertility, the impact of endometriosis on assisted reproductive techniques and also the benefits of prolonged use of gonadotropin-releasing hormone analogue before IVF in women with endometriosis. RECENT FINDINGS: The available evidence suggests that endometriosis is strongly associated with infertility. Many studies indicate lower pregnancy and implantation rates even in assisted reproductive cycles in women with endometriosis. It is well known that medical suppression of endometriosis does not appear to be warranted for endometriosis-associated infertility. Prolonged pretreatment with gonadotropin-releasing hormone analogue before IVF has been reported to improve clinical pregnancy rates in infertile women with endometriosis. SUMMARY: Based on the recently published data, infertile women with endometriosis may benefit from long-term pretreatment of gonadotropin-releasing hormone analogue prior to IVF.

The role of endometrium in endometriosis.

Endometriosis is defined as the presence of endometrial glands and stroma outside the uterus. Several theories have been proposed to explain the pathogenesis of this disease. According to Sampson's retrograde menstruation theory, endometrial cells are refluxed through the fallopian tubes during the menstruation and implant onto peritoneum or pelvic organs. Since retrograde menstruation is a very common phenomenon among women of reproductive age, there must be other factors that may contribute to the pathophysiology and/or pathogenesis of endometriosis. Genetic predisposition, environmental factors, and alterations in immune and endocrine functions are believed to play significant roles in the establishment and maintenance of endometriosis. Although the eutopic endometriums of women with and without endometriosis are histologically similar, studies revealed that there are many fundamental differences between these two tissues. Invasive properties, decreased apoptosis, alterations in expression of specific gene and proteins, and increased steroid and cytokine production have been identified in eutopic endometrium of women with endometriosis. Furthermore, significant biochemical differences exist even between ectopic and autologous eutopic endometrium. These differences can be explained by the direct effects of an inflammatory peritoneal environment.

Expression of interleukin-8 receptors in patients with adenomyosis.

OBJECTIVE: To investigate the expression of interleukin-8 (IL-8) receptors CXCR1 and CXCR2 in adenomyosis. DESIGN: Comparative immunohistochemical study. SETTING: Academic medical center. PATIENT(S): Thirty women who had undergone hysterectomy and were proved histopathologically to have adenomyosis, and 27 women without adenomyosis who had a hysterectomy for nonendometrial pathology such as leiomyomata or benign ovarian cysts. INTERVENTION(S): Tissue sections were immunostained with murine monoclonal anti-human CXCR1 and CXCR2 antibodies. MAIN OUTCOME MEASURE(S): Microscopic evaluation to assess the presence and localization of CXCR1 and CXCR2 throughout the menstrual cycle in both eutopic endometrial and adenomyotic tissues of women with adenomyosis and compare it with normal endometrium. RESULT(S): In eutopic endometrium of women with adenomyosis, proliferative phase samples showed higher epithelial CXCR1 and CXCR2 staining intensity compared with proliferative phase samples of normal endometrium. Adenomyosis foci expressed higher epithelial CXCR1 compared with the homologous eutopic endometrium and normal endometrium. On the other hand, adenomyosis foci and the homologous eutopic endometrium showed similar epithelial CXCR2 staining intensity, and this expression was higher than the normal controls. CONCLUSION(S): Intrinsic abnormalities concerning IL-8 and its receptor system may be present in the eutopic endometrium of women affected by adenomyosis. These findings suggest that IL-8 receptors may be involved in the pathogenesis and/or pathophysiology of adenomyosis.