Pre- and post-surgical management of endometriosis

The efficacy of medical and surgical treatment of endometriosis-associated infertility and pelvic pain is a source of questions and controversies. Complete resolution of endometriosis is not yet possible, but therapy has essentially three main objectives: (1) to reduce pain, (2) to increase the possibility of pregnancy, and (3) to delay recurrence for as long as possible. It could be concluded that a consensus will probably never be reached on minimal and mild endometriosis. In cases of moderate and severe endometriosis-associated infertility, the combined approach (operative laparoscopy with gonadotropin-releasing hormone agonist) must be considered as first-line treatment. The mean pregnancy rate of 50% reported in the literature following surgery provides scientific proof that operative treatment should first be undertaken to give our patients the best chance of conceiving naturally. In cases of rectovaginal adenomyotic nodule, surgery must be considered as first-line therapy, medical therapy being relatively inefficacious.     

Surgical management of endometriosis

The efficacy of medical and surgical treatment of endometriosis-associated infertility and pelvic pain is a source of ongoing controversy. Complete resolution of endometriosis is not yet possible and current therapy has three main objectives: (1) to reduce pain; (2) to increase the possibility of pregnancy; and (3) to delay recurrence for as long as possible. It is possible that a consensus will never be reached on the optimal treatment of minimal and mild endometriosis. In case of moderate and severe endometriosis-associated infertility, the combined approach (operative laparoscopy with a gonadotropin-releasing hormone (GnRH) agonist) should be considered as 'first-line' treatment. The mean pregnancy rate of 50% reported in the literature following surgery provides scientific proof that operative treatment should first be undertaken to give our patients the best chance of conceiving naturally. In case of rectovaginal adenomyotic nodules, surgery must be considered as first-line therapy, medical therapy being relatively in-efficacious.     

Surgical management of endometriosis

Surgical management of endometriosis has assumed a prominent role in treating endometriosis-associated infertility and pain. Given the relative lack of prospective, randomized, controlled studies, firm conclusions regarding optimal treatment are difficult. With respect to infertility, the available data generally support surgical management as effective for all stages of disease. Ovarian suppression is usually ineffective and should not be used for endometriosis-associated infertility except in highly selected cases. The management of endometriosis-associated pain usually needs to be multifaceted with surgery being an important, but not the only, component. Except for selected young women responding to ovarian suppression, most patients should have diagnostic laparoscopy with concurrent surgical therapy. The decision to operate depends on clinical judgment, surgeon skill, and individual patient needs. A comprehensive long-term management plan incorporating various treatment modalities should be developed to optimize each patient's management with respect to pain, pelvic masses, and reproductive goals. More studies using sophisticated designs and statistical methods and basic science initiatives in endocrinology, immunology, and genetics are increasingly giving us better insight into endometriosis. With improved knowledge of this complex medical condition, more refined conclusions regarding optimal treatment approaches will become possible and enable clinicians to obtain better outcomes for their patients.     

Advances in treatment options of endometriosis

Endometriosis, defined as the presence of endometrial tissue outside the uterus, is a challenging condition associated with substantial morbidity. Management of endometriosis must be individualized according to the desired treatment outcome, whether it is relief of pain, improvement of fertility, or the prevention of recurrence. For alleviation of endometriosis-associated pain, medical treatment is generally successful, with no medical agent being more efficacious than another in spite of significantly differing side-effect profiles. Surgical therapy has also been demonstrated to reduce pain scores in comparison with expectant management, although conservative surgery has been frequently associated with recurrence. The efficacy of combination therapies still remains to be clarified. For treatment of endometriosis-associated infertility, suppressive medical treatment has been proven to be detrimental to fertility and should be discouraged, while surgery is probably efficacious for all stages. Controlled ovarian hyperstimulation with intrauterine insemination is recommended in early-stage and surgically corrected endometriosis. Combined surgery with GnRH analog treatment has been proposed to be first-line therapy, followed by IVF as second-line therapy in advanced cases. More rigorously designed randomized clinical trials focusing on the endocrinological, immunological, and genetic aspects of endometriosis are necessary to refine conclusions regarding the etiopathogenesis and therapeutic innovations of this perplexing disease.     

Endometriosis and fertility

Endometriosis is a chronic inflammatory condition of reproductive age which can lead to infertility and chronic pelvic pain. The pathophysiology of endometriosis-associated infertility is not well understood and it appears to be multi-factorial; mechanical, inflammatory, hormonal, genetic and environmental processes can disturb each step of the normal reproductive physiology; folliculogenesis, ovulation, sperm function, gamete transport, fertilization and implantation. Medical management has limited role for women with endometriosis wishing to conceive. The ongoing pregnancy rate for infertile women with milder forms of the disease is improved by surgery. Surgical management for symptoms associated with severe disease and endometrioma in infertile women needs careful consideration of possible benefits and associated risks. Endometriosis-associated infertility is a recognised indication for assisted conception treatment.     

Surgical Outcomes in Patients With Endometriosis: A Systematic Review

ObjectiveAmong women treated surgically for endometriosis-associated pain, comprehensive data are lacking on the proportions of patients who experience little or no symptom relief, develop recurrent symptoms, or require further surgical treatment for endometriosis. The aim of this study was to assess the efficacy of surgical procedures used to treat endometriosis-associated pain.MethodsMedline and Embase were searched on October 13, 2016. Articles referring to women undergoing surgery for the treatment of endometriosis-associated pain were screened by two independent investigators. For each included treatment arm, data were extracted for the proportion of patients reporting partial or no improvement after surgery for endometriosis-associated pain, pain recurrence, or requirement for further surgery.ResultsA total of 38 studies were included. Most studies did not report relevant outcomes to evaluate pain (71.1%) and recurrent surgery (68.4%). Of the women who underwent lesion excision, 11.8% reported no improvement in pain, and 22.6% underwent further surgery. Postoperative pain, recurrent pain, and adverse events were reported by 34.3%, 28.7%, and 14.8%, respectively, of patients who underwent excision or ablation of endometriosis combined with pelvic denervation and in 25.0%, 15.8%, and 8.1% of women who underwent lesion excision alone. Of the patients who were treated surgically for deep endometriosis affecting the bowel and/or bladder, 7.0% experienced recurrent symptoms, and 4.1% underwent further surgery.ConclusionThis review supports the findings of previous studies and highlights the need for standardized reporting and more detailed follow-up after surgery for endometriosis-associated pain.     

应用腹腔镜诊断和治疗子宫内膜异位症及不孕症的疗效

目的观察应用腹腔镜诊断和治疗盆腔子宫内膜异位症(内异症)及不孕症的疗效.方法对 314例经腹腔镜诊断为盆腔内异症的患者,按1985年美国生育学会修订的内异症分期标准(r-AFS)进行分期,其中Ⅰ期58例,Ⅱ期173例,Ⅲ期68例,Ⅳ期15例;并于腹腔镜下进行卵巢异位内膜病灶切除和粘连分解、盆腔腹膜异位内膜病灶内凝固术及清除腹腔液等手术治疗.术后随访36周,对妊娠者随访到妊娠20周.比较不同r-AFS分期患者术后累计妊娠率和流产率.结果 314例患者术后36周内妊娠共254例,分别为Ⅰ期50例(86.2%,50/58),Ⅱ期141例(81.5%,141/173),Ⅲ期52例(76.5%,52/68)和Ⅳ期11例(73.3%,11/15).经统计学检验,各期患者累计妊娠率比较,差异无统计学意义(P>0.05);术后24周内的妊娠率(93.7%,238/254)高于术后25～36周(6.3%,16/254;P<0.01).254例妊娠患者中,流产12例,流产率与分期无关(P>0.05);妊娠12周内流产率(83.3%,10/12)高于妊娠12周后(16.7%,2/12; P<0.05).结论应用腹腔镜可检查、诊断各期内异症及其引起不孕症的盆腔因素;腹腔镜手术治疗可提高内异症患者的妊娠率.在腹腔镜下清除腹腔液及进行腹腔异位内膜病灶内凝固术,可较完全地破坏盆腔腹膜异位内膜病灶,对各期特别是Ⅰ、Ⅱ期内异症患者生育力的恢复,有重要作用.     

Endometriosis and Mechanisms of Pelvic Pain

Endometriosis remains an enigmatic disorder in that the cause, the natural history, and the precise mechanisms by which it causes pain are not completely understood. The pain symptoms most commonly attributed to endometriosis are dysmenorrhea, dyspareunia, and chronic pelvic pain. Pain may be due to nociceptive, inflammatory, or neuropathic mechanisms, and there is evidence that all 3 of these mechanisms are relevant to endometriosis-associated pelvic pain. It is proposed that the clinically observed inconsistencies of the relationships of endometriosis severity and the presence or severity of pain are likely due to variable roles of different pain mechanisms in endometriosis. A better understanding of the roles of nociceptive, inflammatory, and neuropathic pain in endometriosis is likely to improve the treatment of women with endometriosis-associated pelvic pain.     

Endometriosis-associated infertility diagnosis based on saliva microRNA signatures

Research questionCan a saliva-based miRNA signature for endometriosis-associated infertility be designed and validated by analysing the human miRNome?DesignThe prospective ENDOmiARN study (NCT04728152) included 200 saliva samples obtained between January 2021 and June 2021 from women with pelvic pain suggestive of endometriosis. All patients underwent either laparoscopy, magnetic resonance imaging, or both. Patients diagnosed with endometriosis were allocated to one of two groups according to their fertility status. Data analysis consisted of identifying a set of miRNA biomarkers using next-generation sequencing, and development of a saliva-based miRNA signature of infertility among patients with endometriosis based on a random forest model.ResultsAmong the 153 patients diagnosed with endometriosis, 24% (n = 36) were infertile and 76% (n = 117) were fertile. Small RNA-sequencing of the 153 saliva samples yielded approximately 3712 M raw sequencing reads (from ～13.7 M to ～39.3 M reads/sample). Of the 2561 known miRNAs, the feature selection method generated a signature of 34 miRNAs linked to endometriosis-associated infertility. After validation, the most accurate signature model had a sensitivity, specificity and area under the curve of 100%.ConclusionA saliva-based miRNA signature for endometriosis-associated infertility is reported. Although the results still require external validation before using the signature in routine practice, this non-invasive tool is likely to have a major effect on care provided to women with endometriosis.     

子宫内膜异位症与慢性盆腔痛

慢性盆腔痛是子宫内膜异位症（内异症）的常见症状。内异症相关疼痛的机制复杂,可采取药物（首选口服避孕药联合非甾体类抗炎药）、手术以及手术联合药物抑制卵巢功能的治疗,现多主张采取长期综合个体化治疗。     

Does Helica treatment of early endometriosis confer short- and long-term benefits in terms of pain relief and sub-fertility?

Early-stage endometriosis is a known contributing factor for chronic pelvic pain and sub-fertility. To determine whether Helica Thermal Coagulation is an effective short- and long-term treatment for endometriosis-associated chronic pelvic pain and sub-fertility. Thirty six patients were followed up from 6 weeks to 1 year post-Helica treatment of early endometriosis. Pain relief was assessed subjectively. Eight of the women suffered from sub-fertility in addition to pelvic pain, while three patients suffered from sub-fertility alone. Ninety-three percent were pain free at 6 weeks, 75 % were pain free at 6 months and 37.5 % remained pain free at 1-year follow-up. Of those who continued to have pain at 1-year follow-up, three had repeated Helica treatment, two had hysterectomy and bilateral salpingoopherectomy, and the rest were commenced on different hormonal treatment to control endometriosis. Ten women (62 %) conceived within 1 year of treatment. Helica coagulation seems to be an effective way of treating early endometriosis-associated pelvic pain and sub-fertility. However, its effects only seem to be short term, with a decline in symptom relief and pregnancy rate over the 12-month post-operative period. Larger RCT are required.     

Gonadotrophin-releasing hormone analogues and endometriosis: current strategies and new insights

Background: Endometriosis is an estrogen-dependent chronic inflammatory disease affecting 5% to 10% of women in reproductive age and has been reported also in adolescents. Its main clinical presentations are chronic pelvic pain and infertility. Objective: To provide a comprehensive review of the recently published data concerning the mechanism of action of gonadotrophin-releasing hormone analogues (GnRHas) as well as to analyze their role in the management of endometriosis-associated pain and infertility in addition to its value in adolescent cases. Furthermore, to provide practical recommendations and new insights based on the best available information. Methods: Systematic search was performed of the Cochrane Library and Medical Literature Analysis and Retrieval System Online database looking for the different trials, reviews and various guidelines relating to GnRHas usage in the management of endometriosis-associated pain, infertility and in adolescent cases. Results: From a pathophysiological perspective, there is a growing scientific evidence that GnRHas exert its therapeutic effects by their classical pituitary downregulation and via a direct effect on the endometrial cells themselves. Accordingly, they represent an important medical option for the management of different aspects of this enigmatic disease. Conclusion: GnRHas have a valuable strategic role in treatment of endometriosis-associated pain and infertility as well as in adolescents above 16 years.     

An evidence-based medicine approach to the treatment of endometriosis-associated chronic pelvic pain: placebo-controlled studies

OBJECTIVE: Use an evidence-based medicine (EBM) approach to evaluate the evidence regarding efficacy of treatment of endometriosis-associated chronic pelvic pain (CPP) in placebo-controlled randomized clinical trials (RCT). DESIGN: Review of six randomized, controlled trials (Canadian Task Force classification I). SETTING: University of Rochester School of Medicine and Dentistry. Patients. Three hundred eighty-one women with endometriosis enrolled in placebo-controlled randomized clinical trials. Intervention. A MEDLINE search of published medical articles from January 1976, to January 1998. MEASUREMENTS AND MAIN RESULTS: Six placebo-controlled randomized clinical trials were found that addressed the treatment of pelvic pain associated with endometriosis and met validity criteria; one was a study of surgical treatment, two of medical therapies, and three of combined surgical and medical treatments. They clearly show that laparoscopic surgery and medical treatment with medroxyprogesterone acetate, danazol, or nafarelin are more effective than placebo. Evidence for efficacy of leuprolide acetate is weaker. At 6 months, absolute decreases in pain scores are quite similar with surgical or medical treatment. Medical therapy after surgical treatment significantly reduced pain, but six months after it was stopped there was no difference between women treated and not treated postoperatively. CONCLUSIONS: Although either surgical or medical treatment of endometriosis in women with CPP is clearly indicated, pain relief of 6 or more months' duration can be expected in only 40 to 70% of women with endometriosis-associated CPP.     

Endometriosis-associated infertility

This review summarizes the recent literature examining the relationship between endometriosis and infertility. It is clear that the advanced stage of the disease and the mechanical disruption of the pelvic anatomy may cause infertility. The link between early stage endometriosis and infertility remains a source of controversy. Management plans must be individualized contingent upon the stage of disease, the age of the patient and the duration of infertility. The preponderance of data suggests that ablative therapy at the time of laparoscopy is as good as, or superior to expectant or medical therapy. With the exception of IVF/ET, ovarian suppression with GnRH agonists is not warranted in endometriosis-associated infertility. Controlled ovarian hyperstimulation with IUI is appropriate therapy in women with minimal-to-mild and surgically corrected endometriosis.     

Endometriosis related infertility

From the literature, the crucial knowledge were drawn among endometriosis related infertility. Endometriosis is an important factor of infertility in minimal or light stages and a major one in mild or moderate stages. Thus, a laparoscopy must be performed to confirm endometriosis when suggestive clinical or biological signs exist. In absence of them, laparoscopy can be delayed after intra-uterine inseminations (IUI). The first line treatment is laparoscopic surgery. Its efficacy is proven. It is useless to prescribe a post-operative medical treatment (GnRH analogues). Surgery leads to 25 to 40% of deliveries. It is dependant on age, infertility duration, tubo-ovarian adhesion and tubes involvement. But, surgery can be avoided and the patient is directly referred to In Vitro Fertilization (IVF) when the lesions extension is so important that surgery exposes to complications or when there is a permanent other indication for IVF (severe male infertility). When infertility persists 6 to 12 months after surgery and without patent recurrence, ovulation stimulations and IUI are performed as the second line treatment. After IUI failure, or in case of recurrence, IVF must be applied. A second surgery is not recommended. The IVF results are not impaired by the presence of endometriosis and even of endometriomas. Thus, it is useless to operate again endometriosis before IVF. In opposition, in severe stages or in cases of recurrence, a pre-IVF medical treatment (GnRH analogues) improves the results. IVF do not increased the risk of endometriosis acute growth. In case of infertility and pain, infertility is considered as the first target. But medical treatment can be prescribed between the IVF attempts.     

Prevalence of Endometriosis and Peritoneal Pockets in Women with Infertility and/or Pelvic Pain

ObjectiveTo evaluate the prevalence of endometriosis and peritoneal pockets and to analyze whether these pockets are associated with pain.MethodsAnalysis of prospectively registered data of all women undergoing laparoscopy for infertility or pelvic pain between 1988 and 2011 at KU Leuven University Hospital.ResultsOf 4497 women, 191 had 238 pockets, with a prevalence of 4.7% in women with infertility only, 4.9% in women with infertility and pelvic pain, and 3.5% in women with pelvic pain only (P = 0.045 for all infertility vs. pelvic pain only). Prevalence did not vary by age. Pockets were associated with endometriosis (P < 0.0001), which was found in 77% of women with pockets. Among women with infertility only, the prevalence of endometriosis was higher in women with pockets (P = 0.0001) than in women without. The prevalence of endometriosis was similar in women with infertility and pelvic pain or pelvic pain only. Pelvic pain as an indication for surgery was associated simultaneously (through logistic regression) with endometriosis (P < 0.0001) and pockets (P = 0.040). Pelvic pain severity was associated simultaneously with pockets (P = 0.0026) and the severity of subtle (P = 0.001), typical (P = 0.030), cystic ovarian (P = 0.051), and deep endometriosis (P < 0.0001). Pelvic pain severity was not associated with endometriosis in the pockets or the diameter or location of pockets.ConclusionsThe prevalence of pockets was low, at between 3.5% and 5%. Women with infertility only and pockets had more endometriosis than women without. Severe pelvic pain and pelvic pain as an indication for surgery were associated with the presence of pockets as well as the presence and severity of endometriosis.     

腹腔镜下子宫内膜异位症生育指数在子宫内膜异位症合并不孕中的应用研究

目的:探讨腹腔镜下子宫内膜异位症生育指数(EFI)对子宫内膜异位症(EMT)合并不孕患者的生育力评估的临床价值。方法:回顾性分析在我院进行腹腔镜手术治疗的EMT合并不孕、随访资料完整的118例患者的临床资料进行EFI评分,随访术后妊娠情况。结果:118例患者术后3年累积妊娠率为46.6%;术后第1、2、3年的妊娠率分别为28.8%、14.4%和3.4%,组间比较差异有统计学意义(P<0.05)。EFI评分9～10分、5～8分、≤4分者的术后3年累积妊娠率分别为76.2%、47.4%、10.5%,术后3年累积妊娠率与EFI评分、术后使用促排卵药物治疗呈正相关(tau-b=0.367,0.439;P<0.01);与美国生育协会修订的EMT分期(r-AFS)标准及使用促性腺激素释放激素激动剂(GnRH-a)无相关性(tau-b=0.006,0.076;P>0.05)。不同临床类型的术后3年累积妊娠率间两两比较,差异均无统计学意义(P>0.05)。结论:腹腔镜下EFI评分用于评估EMT合并不孕患者的生育力,指导后续治疗有重要的参考意义,可根据EFI评分,综合评估患者的生育状况,选择个体化的后续治疗方案;EMT合并不孕患者不建议长期期待以提高患者的妊娠率。     

腹腔镜子宫骶神经切断术治疗子宫内膜异位症疼痛的多中心前瞻性对照研究

目的:研究、评价腹腔镜子宫骶神经切断术(LUNA)治疗子宫内膜异位症疼痛的安全性和有效性。方法:应用多中心随机对照的前瞻性研究方法,收集82例中、重度痛经患者的临床资料,分析比较同时行LUNA对子宫内膜异位症保守手术后各种疼痛缓解率的影响,并评价手术的安全性。结果:71例患者纳入分析,LUNA组51例,对照组20例。LUNA组术后痛经缓解率90.2%,高于对照组的60.0%(P=0.02);LUNA组性交痛术后缓解率85.7%,高于对照组的50.0%(P=0.048);LUNA组慢性盆腔痛(CPP)缓解率100%,高于对照组的71.4%(P=0.041),差异均有统计学意义。手术安全性:LUNA组患者手术时间延长,术后肛门排气时间延长,但两组术中出血量、术后体温、住院时间、总住院费用以及手术费用均无统计学差异。所有研究对象均无手术并发症发生。结论:内异症保守手术同时行LUNA手术,术后2年内能有效的缓解内异症的各种疼痛。     

A randomized study comparing triptorelin or expectant management following conservative laparoscopic surgery for symptomatic stage III-IV endometriosis

OBJECTIVE: To investigate the role of adjuvant treatment with gonadotropin-releasing-hormone agonist (GnRHa) following conservative surgical treatment of endometriosis. STUDY DESIGN: Sixty patients in the reproductive age (mean age 28.6 years), with symptomatic stages III and IV endometriosis following laparoscopic surgery and without previous hormonal treatment were enrolled in a prospective, randomized, controlled trial to compare the effects of 3-month treatment with triptorelin depot-3.75 i.m. (30 patients) versus expectant management using placebo injection (30 patients). RESULTS: Six patients (one in triptorelin group and five in placebo group) were lost at follow-up, the remaining 54 were suitable for analysis. Pelvic pain persistence or recurrence, endometrioma relapses and pregnancy rate were evaluated during a 5-year follow-up. The results of 29 cases treated with triptorelin and 25 that received placebo did not show significant differences in pain recurrence (P=1, RR=0.94, 95% CI=0.57-1.55), endometrioma relapse (P=0.67, RR=1.29, 95% CI=0.66-2.50), and pregnancy rate in infertile women (P=0.80, RR=0.81, 95% CI=0.37-1.80). Curves of time of pain recurrence and pregnancy during 5-year follow-up did not show significant differences between the two groups (P=0.79 and P=0.51, respectively, using Mantel-Haenzsel logrank test). CONCLUSION: Triptorelin treatment after operative laparoscopy for stage III/IV endometriosis does not appear to be superior to expectant management in terms of prevention of symptoms recurrence and endometrioma relapse, and has no influence on pregnancy rate in endometriosis-associated infertility.     

Comparison of 2 therapeutic strategies in severe endometriosis, in young women consulting for sterility or pain. II. In the case of infertility, value of ovarian stimulation with intrauterine insemination after surgery

AIM OF THE STUDY: Define the best medico surgical strategy in infertile women with stage III-IV endometriosis. MATERIAL AND METHODS: Two groups, A (N26) and B (N 37), treated for infertility associated or not with pelvic pain, due to stage AFS III or IV endometriosis, were compared. They had similar surgical procedure: operative laparoscopy including resection of endometriotic lesions, more particularly endometriomas and rectovaginal septum nodules. Associated medical strategy was different: group A, operative laparoscopy without preoperative treatment and in 40% a second laparoscopy taking place after 2-3 months of LHRH analogues; no post operative treatment; group B, operative laparoscopy taking place after ovarian blockage with 3-6 weeks of Diane (Androcur + ethinyl estradiol), then 2-3 months of analogue postoperative treatment immediately followed by ovarian stimulation (OS) + intrauterine insemination (IUI) in women more than 30 years old with operative tubes (N 22), no treatment for six months in similar cases less than 30 (N 5), and IVF in women with damaged tubes (N 5) or after OS + IUI failure (N 4). One patient refused two patients with high FSH level had oocyte donation. RESULTS: Two years evolutive pregnancy rate was significantly higher (p < 0.01) in group B (59%) versus group A (23%) and was higher after OS + IUI (68%) than after IVF (55%) or without any treatment in women < 30 (43%). The difference is equally significant by age (p < 0.05), for endometriomas (p < 0.01) and for recurrences (p < 0.01). CONCLUSION: Similar results obtained for pelvic pain (see chapter I) suggest that both strategies are similarly successful in treating endometriosis. These results confirm the interest of an ART after surgery for stage III-IV endometriosis and show that OS + IUI, a less costly than IVF technique, can be used successfully in selected cases with operative tubes.