子宫内膜异位症合并不孕症的治疗策略

子宫内膜异位症（EMs）是妇科的常见病。单纯激素治疗并不能改善EMs合并不孕患者的生育结局。腹腔镜切除/剥除Ⅰ、Ⅱ期EMs病灶可增加不孕妇女的活产率。对于Ⅲ～Ⅳ期EMs合并不孕的首选治疗多数认为应采用手术+促性腺激素释放激素激动剂（GnRHa）,但也有一些异议。目前还没有证据表明哪一种腹腔镜下的手术技术可以获得更好的效果。荟萃分析发现EMs合并不孕患者与输卵管因素患者比较,助孕的总妊娠率下降约37%。有研究提示体外受精-胚胎移植（IVF-ET）前延长应用GnRHa可能会提高IVF的持续妊娠率和种植率。部分研究者认为,手术剥除卵巢内异囊肿会明显降低卵巢功能,而另一些作者则认为只要积累经验,注意保护卵巢组织,则手术对卵巢功能的影响不大。Ⅰ～Ⅱ期EMs术后可给予一定时间试孕,而Ⅲ～Ⅳ期EMs术后则应积极考虑助孕。对于助孕前是否应先行腹腔镜手术处理卵巢内异囊肿,目前存在争论。EMs复发,用药后助孕,特别是2次或以上的IVF,妊娠率明显优于再次手术。鉴于EMs对妊娠许多环节都有不利影响,助孕前先用药抑制EMs的活动无疑有利于助孕结果。     

Endometrial carcinoma using GnRH analogues therapy in endometriosis

Endometriosis affects a 10 % of women during their reproductive years. Unequoral statistics concerning the incidence of adenomyosis are not available although a combined occurrence of both diseases is found in a 20 % of cases. The risk that malignancy arises from endometrioid tissue typical for endometriosis is between a 0.3-1 %. 75 % of these malignancies are ovarian cancer in conjunction with pre-existing ovarian endometriosis; less frequently extraovarian malignancies are found. The development of malignancy of adenomyosis is very rarely reported. In this report we present the case of a 35 year old patient who suffered from both, endometriosis and adenomyosis and who underwent a therapy using GnRH analogues. After five months and before the completion of the therapy a hysterectomy with conservation of the ovaries was performed at the request of the patient (carcinophobia). The histology confirmed the diagnosis of adenomyosis and demonstrated the unexpected finding of an endometrium carcinoma. This latter arose from a complex atypical hyperplasia surrounded by hypoplastic endometrium. There is some evidence that suggests a slightly elevated risk of breast and ovarian cancer as well as haematological malignancies amongst patients with endometriosis. However, there does not appear to be an increased risk of endometrial carcinoma. Adipositas leads to an increased risk for the development of endometrial carcinoma due to the increased conversion of testosterone to estrone in fat. The peripheral synthesis of estrone is unaffected by GnRHa-therapy. A progesterone containing HRT should be added to a GnRHa-therapy in overweight patients to prevent the development of endometrial hyperplasia and/or carcinoma. In conclusion a careful indication has to be made for GnRHa-therapy in overweight patients and before and during the therapy high resolution ultrasound scan should be performed to evaluate the endometrium in those patients.     

Cellular localization of aromatase in human endometrium

The expression of aromatase was examined in human endometrium throughout the menstrual cycle, early pregnancy, and ovarian endometriosis with a specific monoclonal antiserum to human purified placental aromatase cytochrome P-450 (P-450AROM). Tissues were obtained from women undergoing hysterectomy, oophorectomy and/or intrauterine curettage. The day of the cycle was determined from the onset of the last menstrual period and confirmed by endometrial histology. In secretory endometrium, stronger immunoreactivity of aromatase was observed in epithelial gland than immunoreactivity of stroma, especially in mid and late secretory endometrium. In endometrium of early pregnancy, significant immunoreactivity was seen in both glandular cells and stromal cells. However, weak immunoreactivity was seen only in epithelial gland of ovarian endometriosis. There was no immunoreactivity in atrophic endometrium or late proliferative endometrium. These results show that the physiological action of endometrial aromatase is modulated by progesterone and equipped with the capacity for cyclic change throughout the menstrual cycle. The presence of aromatase in the ovarian endometriosis is of interest, since it is histologically different from normal cyclic endometrium, and this is consistent with the ability to synthesize estradiol. But the weak intensity in endometriosis probably means that only a small amount of estradiol was synthesized, which served to explain the poor response to GnRHa or danazol administered on ovarian cystic endometriosis.     

Synchronous ovarian and endometrial carcinoma: a strong link to endometriosis?

PURPOSE: To further study the clinicopathological features of synchronous ovarian and endometrial carcinomas. METHODS: We retrospectively studied all cases of synchronous ovarian and endometrial carcinomas diagnosed in our laboratory over the last 15-year period. The pathological findings were correlated with the clinical records of the patients. RESULTS: Seven cases of synchronous primary ovarian and endometrial carcinomas were retrieved. The most common presenting symptom was abnormal vaginal bleeding (5 cases, 71.4%). Five patients (71.4%) were postmenopausal and two (28.6%) were nulliparous. All seven patients had Stage I ovarian and endometrial carcinomas of endometrioid histology. Moreover, in all seven ovarian carcinomas endometriosis foci were observed, while atypical endometriosis was found in four of them. With the exception of one patient, who received adjuvant postoperative radiation, all remaining patients were treated with surgery alone. All patients were alive and free of disease at completion of the study. CONCLUSION: The correct classification of synchronous primary ovarian and endometrial carcinomas is often problematic because of the frequent confusion with their metastatic counterparts. Although the exact etiology remains unclear, endometriosis seems to be a major risk factor for their development.     

Case study of a pregnant woman with decidualized ovarian endometriosis whose preoperative findings suggested malignant transformation

BACKGROUND: Because both decidualization and malignant transformation of endometriosis are characterized by mural nodules on the wall of the cyst, the preoperative differential diagnosis is reportedly difficult. CASE: A 31-year-old woman was referred to our hospital at ten weeks of gestation. Sonographic examination revealed an intrauterine gestational sac and ovarian endometrial cyst. At 21 weeks of gestation, characteristic findings associated with malignant transformation of ovarian endometriosis were seen on color-flow Doppler sonography and contrast magnetic resonance imaging. Under the diagnosis of malignant transformation of ovarian endometriosis, right salpingo-oophorectomy was performed at 22 weeks' gestation. However, histopathologic examination revealed ovarian endometriosis with marked decidual changes but no evidence of malignancy. CONCLUSION: During pregnancy, intracystic vascularized excrescences of an endometrial cyst indicate not only malignant transformation but also decidualization. Thus, the preoperative differential diagnosis is reportedly difficult. However, the present findings of decidualization on magnetic resonance imaging seemed to be slightly different from those of malignant transformation, and therefore, might help distinguish decidualized endometriosis from malignant transformation preoperatively.     

Ovarian stimulation and endometriosis progression or recurrence: a systematic review

Available evidence on the impact of ovarian stimulation on the progression of endometriosis or its recurrence was systematically reviewed. Data from ovarian stimulation alone, or associated with intrauterine insemination (IUI) or IVF, were included. Sixteen studies were selected. Initial case reports (n = 11) documented some severe clinical complications. However, subsequent observational studies were more reassuring. Overall, five conclusions can be drawn: (i) IVF does not worsen endometriosis-related pain symptoms (moderate quality evidence); (ii) IVF does not increase the risk of endometriosis recurrence (moderate quality evidence); (iii) the impact of IVF on ovarian endometriomas, if present at all, is mild (low quality evidence); (iv) IUI may increase the risk of endometriosis recurrence (low quality evidence); (v) deep invasive endometriosis might progress with ovarian stimulation (very low quality evidence). In conclusion, available evidence is generally reassuring (at least for IVF) and does not justify aggressive clinical approaches such as prophylactic surgery before assisted reproductive technology treatment to prevent endometriosis progression or recurrence. However, further evidence is required before being able to reach definitive conclusions. In particular, the potential effects on deep invasive endometriosis and the possible synergistic effect of stimulation and pregnancy are two areas that need to be explored further.     

VEGF concentration in peritoneal fluid of patients with endometriosis

The theory of Sampson that endometrial cells and fragments desquamated during the menstrual period are transported through fallopian tubes into the peritoneal cavity where they implant, proliferate and develop into endometriotic lesions is generally accepted. There is increasing evidence that immunological mechanisms play a role in the pathogenesis and pathophysiology of endometriosis. Excessive endometrial angiogenesis is proposed as an important mechanism in the pathogenesis of endometriosis. Evidence is reviewed for the hypothesis that the endometrium of women with endometriosis has an increased capacity to proliferate, implant and grow in the peritoneal cavity. From the known angiogenic factors, vascular endothelial growth factor (VEGF) has emerged as a pivotally important regulator of normal angiogenesis and pathological neovascularization. In present study we evaluated the concentrations of VEGF in peritoneal fluid of patients with endometriosis and showed no correlation between AFS score and VEGF concentration in peritoneal and in ovarian endometriosis. Above results do not confirm former observations indicating the role of VEGF in endometriosis pathogenesis.     

Subacute focal endometritis. Association with cervical colonization with ureaplasma urealyticum, pelvic pathology and endometrial maturation

Subacute focal endometritis (SFE) has been associated with cervical Ureaplasma urealyticum colonization and is considered a significant indicator of pelvic adhesions or endometriosis. A retrospective analysis was performed comparing cervical isolation rates, endometrial maturation patterns and laparoscopic findings in 64 patients with SFE and in a control group of 70 unselected patients with no histologic evidence of SFE at endometrial biopsy. The data suggest that although the prevalence of pelvic damage of various types is high, SFE cannot be used as a reliable marker for pelvic adhesions or endometriosis; that SFE does not interfere with normal endometrial maturation; and that SFE is not invariably associated with cervical U urealyticum but may represent resolving infection. It is also possible that SFE represents endometrial autoimmunity either following mycoplasma infection or arising spontaneously.     

The effect of endometriosis on in vitro fertilization outcome

AIM: Endometriosis is a leading cause of pelvic pain and infertility. Implantation of endometrial cells to the peritoneal surface can lead to a spectrum of disease severity with the most severe causing extensive pelvic adhesions and anatomic distortion. Infertility can result from anatomic abnormalities as well proinflammatory cellular and immune factors. Treatment options for women seeking pregnancy include surgical removal and/or in vitro fertilization. The aim of this study was to review current literature on the pathogenesis of endometriosis and treatment options for infertility. METHODS: Recent published articles regarding infertility and endometriosis have been reviewed analyzing PubMed and Cochrane databases. RESULTS: In vitro fertilization (IVF) is a valid option for patients after surgical management has not restored fertility. IVF may be offered sooner to older patients or to those with more severe disease. It is unclear if prior surgical treatment has deleterious effects on IVF outcomes. It does appear, however, that surgical removal of endometriomas may lead to decreased ovarian reserve. This may not affect fertility outcomes. CONCLUSION: Endometriosis is a leading cause of pelvic pain and infertility. The most accepted theory of how endometriosis develops is the retrograde transplant theory by Sampson, but a constellation of numerous other factors are involved. The gold standard for diagnosis is operative; therefore, the true prevalence of this disease is uncertain. Many women with endometriosis will seek fertility treatment. In this case if endometriosis is found, it should be treated.     

Identifying the presence of antibodies against endometrial antigens. A preliminary study.

Serum and peritoneal fluid from women with and without evidence of endometriosis were tested for the presence of antibodies against endometrial tissue antigens with Western blot analysis. Serum antibodies against endometrial cytosolic antigens of molecular weight 45, 52, 58, 62 and 66 kd were present in samples obtained from women both with and without endometriosis. The patients with endometriosis had serum antibodies against 34-kd endometrial cytosolic antigen, which was not present in serum from fertile women without endometriosis. The peritoneal fluid from patients with endometriosis also reacted with 34-kd endometrial antigen but not the peritoneal fluid from control fertile women. There was no difference in the antigens detected with serum antibody when endometrium from fertile women without evidence of endometriosis and from women with endometriosis was used as a source of antigen. The presence of serum antibody against 34-kd endometrial antigen is specific to endometriosis. However, this antigen is expressed by endometrium of women both with or without endometriosis. Isolation and identification of this antigen may lead to development of a noninvasive aid for the diagnosis of endometriosis.     

卵巢子宫内膜异位症恶变过程中ER、PR蛋白表达的作用

目的探讨卵巢子宫内膜异位症恶变过程中ER和PR蛋白表达的作用。方法用免疫组化二步法检测ER和PR蛋白在卵巢子宫内膜异位症癌变组(30例),卵巢子宫内膜腺上皮不典型增生组(15例)和卵巢子宫内膜异位症组(30例)的表达。结果癌变组ER、PR的表达显著低于不典型增生组(P<0.05)及内异症组(P<0.01),不典型增生组与内异症组的表达无统计学差异(P>0.05);3组内异区的ER、PR表达无统计学差异;癌变组的癌变区、移行区的ER、PR表达明显低于内异区(P<0.01),而癌变组的癌变区和移行区两者表达无差别。癌变组的癌变区、移行区的ER、PR蛋白表达有相关性(P<0.05)。结论ER、PR表达缺失可能参与了内异症的恶变过程,内异症癌变失去了对性激素的依赖性。     

Non-invasive methods of diagnosis of endometriosis

PURPOSE OF REVIEW: Laparoscopy is the gold standard for the diagnosis of endometriosis but the need for visual evidence of the disease is a major stumbling-block for both effective clinical management of affected patients as well as for research into this common and debilitating reproductive disease. Laparoscopy is invasive and often causes a delay in diagnosis and treatment, especially in symptomatic teenagers and young women. Moreover, the visual inspection of the pelvis has major limitations, particularly for the diagnosis of retroperitoneal lesions. It is therefore not surprising that considerable efforts are being made to improve imaging techniques and to evaluate the diagnostic value of potential molecular markers of disease. RECENT FINDINGS: High-resolution transvaginal ultrasonography and, in selected cases, magnetic resonance imaging improve the diagnosis of retroperitoneal pelvic endometriosis as well as the identification of lesions that involve pelvic organs. A variety of serum and endometrial markers are being evaluated for their diagnostic potential, particularly in endometriosis associated infertility. The first gene profiling studies are showing positive results and proteomic technology is being applied to identify novel diagnostic protein expression patterns. SUMMARY: Current imaging techniques, such as transvaginal ultrasonography, are useful to screen the pelvis for the presence of retroperitoneal endometriosis but fail to diagnose peritoneal lesions, small ovarian endometriomas and adhesions. Postgenomic technologies and identification of novel serum and endometrial markers are likely to revolutionize future diagnosis of endometriosis.     

Endometriose und Nervenfasern

Nerve fibers could be detected in eutopic endometrium of patients with endometriosis and in ectopic endometriotic lesions such as peritoneal, deep infiltrating, and ovarian endometriotic lesions. The pathophysiological explanation for the occurrence of nerve fibers in endometrium and ectopic lesions is controversially discussed. There are two hypotheses: the occurrence of nerve fibers is induced by endometriosis or depends on pain mediators. Nerve fibers are only found in endometrium of patients with endometriosis and their presence is independent of the severity of pelvic pain. On the other hand, nerve fibers are found in endometrium of patients with chronic pelvic pain and with gynecological disorders like fibroids or endometriosis. It has to be clarified if the occurrence of endometrial nerve fibers can be used as a noninvasive test to diagnose endometriosis. However, endometriosis shows neuromodulatory properties. The nerve fiber invasion in endometriotic lesions may be a possible explanation for pain generation in endometriosis.     

Apoptosis expression in rats' endometrium after surgical induction of endometriosis

OBJECTIVES: Endometriosis is characterised as a presence of proliferating endometrial fragments growing outside uterus. Despite many investigations we still do not understand why in some women sheded endometrium implants itself into peritoneum and grows, and in the others does not. It is possible that apoptotic status of endometrial fragments implanted into peritoneum is responsible for endometriosis growth as well as the treatment results. Cellular apoptosis is characterised morphologically by cell shrinkage, nuclear pyknosis, chromatin condensation, and blebbing of the plasma membrane. MATERIAL AND METHODS: The study was performed on 28 mature Wistar rats. We studied endometria of rats after induction of endometriosis in peritoneal cavity. RESULTS: The only difference was found in endometrial glands. In animals with successful endometriosis implantation apoptosis indices in endometrial glands obtained during second laparotomy were lower than in the endometriosis free animals (p < 0.05).     

Endometrial release of soluble intercellular adhesion molecule 1 and endometriosis: relationship to the extent of the disease

OBJECTIVE: To relate endometrial release of the soluble form of intercellular adhesion molecule 1 with extent of endometriosis. METHODS: Samples of endometrium were collected from 23 women with endometriosis. Soluble intercellular adhesion molecule 1 was quantified in conditioned medium from 48-hour endometrial stromal cell cultures with use of a specific enzyme-linked immunosorbent assay. Levels were correlated with revised American Society for Reproductive Medicine classification score for adhesions, implants, and cysts and total score; number of endometriotic implants; cyst diameter; and presence or absence of pelvic pain symptoms and previous surgical procedures for endometriosis. RESULTS: Endometrial release of soluble intercellular adhesion molecule 1 directly correlated with number of implants (r = .64, P < .005) and score for implants (r = .61, P < .005). There was no significant correlation between levels of the soluble molecule and score for adhesions or total score. Soluble intercellular adhesion molecule 1 shed by endometrium did not correlate with the score for ovarian cysts, although an inverse relationship was found with ovarian cyst diameter (r = -0.52, P < .05). No differences were detected between women who had pelvic pain and those who did not and between those who had previous surgery for endometriosis and those who had not. CONCLUSION: The association between endometrial release of soluble intercellular adhesion molecule 1 and the number and score of endometriotic implants suggests that the molecule might be of value in evaluating spread potential of refluxed endometrium.     

Health technology assessment of surgical therapies for benign gynaecological disease

This chapter summarises the evidence of the benefits and harm of surgical therapies for benign gynaecological disease. We have limited the discussion in this chapter to three gynaecological conditions - menorrhagia, endometriosis and benign ovarian tumours - with a further section on the different surgical approaches for performing a hysterectomy for menorrhagia due to dysfunctional uterine bleeding and pelvic masses such as fibroids and benign adnexal masses. The currently available evidence suggests that there is little to choose between the four first-generation endometrial destruction techniques - laser ablation, transcervical resection of endometrium, vaporisation ablation and rollerball ablation - in terms of clinical efficacy and patient satisfaction. There is a paucity of evidence with regards to the comparison of the different second-generation endometrial-destruction techniques but current evidence suggests that bipolar radiofrequency ablation is more effective than thermal balloon ablation for treating menorrhagia. Overall, the second-generation techniques are at least as effective as first-generation methods but are easier to perform and can be done under local rather than general anaesthesia in some circumstances. Hysteroscopic endometrial ablation is an alternative to hysterectomy and should be offered to women with menorrhagia because of its high satisfaction rates, shorter operation time, shorter hospital stay, earlier recovery and reduced postoperative complications; hysterectomy remains the surgical option of choice for women with intractable menorrhagia despite repeated endometrial ablations and for those who do not wish under any circumstances to continue to have menstrual bleeding. The combined use of laparoscopic laser ablation, adhesiolysis and uterine nerve ablation has been shown to have a beneficial effect on pelvic pain associated with mild to moderate endometriosis. Current evidence also supports the use of laparoscopic treatment of minimal and mild endometriosis to improve the on-going pregnancy and live birth rate in infertile patients. The current available evidence suggests that the laparoscopic approach is superior to laparotomy for the surgical management of benign ovarian cysts. It results in less postoperative pain and a shorter postoperative hospital stay; it also costs less. With regards to the surgical approach for performing a hysterectomy for menorrhagia and benign pelvic masses, vaginal hysterectomy should be performed over laparoscopic and abdominal hysterectomy when possible. Where it is not possible to perform the hysterectomy vaginally, then laparoscopic hysterectomy can be employed instead of abdominal hysterectomy to avoid a laparotomy scar. There appears to be no significant advantage in performing a subtotal hysterectomy instead of the total removal of the uterine corpus and cervix.     

In vitro fertilization in patients with ovarian endometriomas

OBJECTIVE: The objective of the study was to establish whether operative treatment of recurrent ovarian endometriosis improves the prognosis of in vitro fertilization. METHODS AND MATERIAL: A retrospective analysis of one hundred endometriosis patients admitted to Tampere University Hospital for IVF treatment. Forty-five patients had an ovarian endometrioma during IVF treatment, 36 of the cases being recurrences after a previous operation. Fifty-five patients had ovarian endometriomas operated without recurrence. The patient groups with or without endometriosis did not differ in age, duration of infertility, sperm parameters, amount of gonadotropins required per oocyte and number of retrieved oocytes. RESULTS: The patients with ovarian endometriosis had more embryos (mean 3.9) than women without endometriomas (mean 2.8) (p<0.05) and the respective pregnancy rates per IVF cycle were 38% and 22%. Patients with endometriomas had a live birth rate of 27% compared with 20% in women with no endometriomas. CONCLUSIONS: The presence of a small endometrioma does not reduce the success of IVF treatment.     

Shortcomings and deficits in surgical treatment of gynecological cancers: a German problem only?

OBJECTIVES: The objective of this study was to assess the quality of preoperative diagnostic, primary surgical, and postoperative treatment of ovarian, endometrial, and cervical cancers in women in Hesse, Germany, in relation to current international recommendations. METHODS: Data on all diagnostic, surgical, and postoperative gynecological procedures undertaken in Hesse in 1997-2001 were collected in a standardized form and validated for clinical quality. Databases were generated for cases of endometrial, ovarian, and cervical cancer, and details of treatment were analyzed. RESULTS: There were 1119 cases of endometrial, 824 cases of ovarian, and 472 cases of cervical cancer. The malignancy remained undiagnosed until after surgery in 17.8% (199/1119) of endometrial cancers, 28.5% (245/824) of ovarian cancers, and 15.5% (73/472) of cervical cancers. There was evidence of suboptimal surgical treatment. Lymphadenectomy rates were low in endometrial and ovarian cancers (about 32%), and omentectomy rates in were low in ovarian cancer (about 50%). Furthermore, 10.7% (31/289) of patients with cervical cancer diagnosed before hospital admission did not undergo radical surgery. CONCLUSION: Discrepancies between guidelines and treatment of gynecological cancers in Hesse were striking, particularly for endometrial and ovarian cancer, and this situation may be mirrored internationally. The fact that many guidelines are not supported by results from clinical studies may be a factor in this apparently suboptimal treatment. Clinical collaborative trials are needed to provide the necessary evidence to support current recommendations and benchmarks of survey are required to facilitate future quality assessment.     

Relative expression of 1,25-dihydroxyvitamin D3 receptor, vitamin D 1 alpha-hydroxylase, vitamin D 24-hydroxylase, and vitamin D 25-hydroxylase in endometriosis and gynecologic cancers

The authors demonstrate expression of the vitamin D receptor (VDR) and its hydroxylases in the endometrium and ovaries of women with and without endometriosis and endometrial or ovarian cancer. Immunohistochemistry showed strong staining of the VDR in endometriosis and endometrial cancer, with the most intense staining in epithelial cells. The VDR mRNA was significantly increased in patients with endometrial and ovarian cancer compared to the control group. There was a significantly higher 1 alpha-hydroxylase expression in the endometrium of patients with endometriosis compared to healthy controls. The observed differences in VDR and 1 alpha -hydroxylase mRNA levels were maintained at the protein level. The authors found no differences in 25-OH vitamin D levels between the serum of patients with endometriosis (25.7 +/- 2.1 ng/mL, n = 46) and healthy controls (22.6 +/- 2.0 ng/mL, n = 33, P = .31). They hypothesize that vitamin D might influence the local activity of immune cells and cytokines thought to play important pathogenic roles in the development and maintenance of endometriosis.