ESHRE guideline for the diagnosis and treatment of endometriosis
Stephen Kennedy1,10,
Agneta Bergqvist2,
Charles Chapron3,
Thomas DHooghe4,
Gerard Dunselman5,
Robert Greb6,
Lone Hummelshoj7,
Andrew Prentice8,
Ertan Saridogan9 on behalf of the ESHRE Special Interest Group for Endometriosis and Endometrium Guideline Development Group*
1 University of Oxford, Oxford, UK, 2 Karolinska Institutet, Stockholm, Sweden, 3 Clinique Universitaire Baudelocque, Paris, France, 4 Leuven University, Leuven, Belgium, 5 Maastricht University, Maastricht, The Netherlands, 6 Muenster University Hospital, Muenster, Germany, 7 Endometriose Foreningen, Denmark, 8 University of Cambridge, Cambridge, UK and 9 University College Hospital, London, UK
10 To whom correspondence should be addressed at: Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK. E-mail: skennedy{at}molbiol.ox.ac.uk
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Abstract
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The objective was to develop recommendations for the diagnosis and treatment of endometriosis and its associated symptoms. A working group was convened comprised of practising gynaecologists and experts in evidence-based medicine from Europe, as well as an endometriosis self-help group representative. After reviewing existing evidence-based guidelines and systematic reviews, the expert panel met on three occasions for a day during which the guideline was developed and refined. Recommendations based solely on the clinical experience of the panel were avoided as much as possible. The entire ESHRE Special Interest Group for Endometriosis and Endometrium was given the opportunity to comment on the draft guideline, after which it was available for comment on the ESHRE website for 3 months. The working group then ratified the guideline by unanimous or near-unanimous voting; finally, it was approved by the ESHRE Executive Committee. The guideline will be updated regularly, and will be made available at http://www.endometriosis.org/guidelines.html with hyperlinks to the supporting evidence, and the relevant references and abstracts. For women presenting with symptoms suggestive of endometriosis, a definitive diagnosis of most forms of endometriosis requires visual inspection of the pelvis at laparoscopy as the gold standard investigation. However, pain symptoms suggestive of the disease can be treated without a definitive diagnosis using a therapeutic trial of a hormonal drug to reduce menstrual flow. In women with laparoscopically confirmed disease, suppression of ovarian function for 6 months reduces endometriosis-associated pain; all hormonal drugs studied are equally effective although their side-effects and cost profiles differ. Ablation of endometriotic lesions reduces endometriosis-associated pain and the smallest effect is seen in patients with minimal disease; there is no evidence that also performing laparoscopic uterine nerve ablation (LUNA) is necessary. In minimalmild endometriosis, suppression of ovarian function to improve fertility is not effective, but ablation of endometriotic lesions plus adhesiolysis is effective compared to diagnostic laparoscopy alone. There is insufficient evidence available to determine whether surgical excision of moderatesevere endometriosis enhances pregnancy rates. IVF is appropriate treatment especially if there are coexisting causes of infertility and/or other treatments have failed, but IVF pregnancy rates are lower in women with endometriosis than in those with tubal infertility. The management of severe/deeply infiltrating endometriosis is complex and referral to a centre with the necessary expertise is strongly recommended. Patient self-help groups can provide invaluable counselling, support and advice.
Key words:
diagnosis/endometriosis/ESHRE guidelines/treatment
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Introduction
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Endometriosis is defined as the presence of endometrial-like tissue outside the uterus, which induces a chronic, inflammatory reaction. The condition is predominantly found in women of reproductive age, from all ethnic and social groups. The associated symptoms can impact on general physical, mental and social well-being. Therefore, it is vital to take careful note of the womans complaints, and to give her time to express her concerns and anxieties as in other chronic diseases. Some women, however, have no symptoms at all.
Treatment must be individualized, taking the clinical problem in its entirety into account, including the impact of the disease and the effect of its treatment on quality of life. Pain symptoms may persist despite seemingly adequate medical and/or surgical treatment of the disease. In such circumstances, a multi-disciplinary approach involving a pain clinic and counselling should be considered early in the treatment plan. It is also important to involve the woman in all decisions; to be flexible in diagnostic and therapeutic thinking; to maintain a good relationship with the woman, and to seek advice where appropriate from more experienced colleagues or refer the woman to a centre with the necessary expertise to offer all available treatments in a multi-disciplinary context, including advanced laparoscopic surgery and laparotomy.
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Sources
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The guideline was commissioned by the ESHRE Special Interest Group (SIG) on Endometriosis and Endometrium, and developed by a working group. No systematic attempt was made to search the published literature independently of the following sources:
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Recommendations
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The highest level of available evidence was used to form all the recommendations contained in this guideline. The evidence was graded using standard criteria shown in Table I.
This scale, which was developed to apply to studies about the effectiveness of health-care interventions, is only a guide to the validity and relevance of evidence. Other questions may be more appropriately addressed by different study designs: for example, a question about the predictive power of an investigation is best answered with observational data.
Recommendations were based on, and linked to, the supporting evidence, or, where necessary, the informal consensus of the working group. The strength of evidence corresponding to each level of recommendation is shown in Table II. Regarding diagnostic tests specifically, a recommendation based on the existence of a well-conducted systematic review was assessed as grade A.
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Localization and appearance of endometriosis
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The most commonly affected sites are the pelvic organs and peritoneum, although other parts of the body such as the lungs are occasionally affected. The extent of the disease varies from a few, small lesions on otherwise normal pelvic organs to large, ovarian endometriotic cysts (endometriomas) and/or extensive fibrosis and adhesion formation causing marked distortion of pelvic anatomy. Disease severity is assessed by simply describing the findings at surgery or quantitatively, using a classification system such as the one developed by the American Society for Reproductive Medicine (ASRM) (1997)
. There is no correlation between such systems and the type or severity of pain symptoms.
Endometriosis typically appears as superficial powder-burn or gunshot lesions on the ovaries, serosal surfaces and peritoneum black, dark-brown, or bluish puckered lesions, nodules or small cysts containing old haemorrhage surrounded by a variable extent of fibrosis. Atypical or subtle lesions are also common, including red implants (petechial, vesicular, polypoid, haemorrhagic, red flame-like) and serous or clear vesicles. Other appearances include white plaques or scarring and yellow-brown peritoneal discoloration of the peritoneum.
Endometriomas usually contain thick fluid like tar; such cysts are often densely adherent to the peritoneum of the ovarian fossa and the surrounding fibrosis may involve the tubes and bowel. Deeply infiltrating endometriotic nodules extend >5 mm beneath the peritoneum and may involve the uterosacral ligaments, vagina, bowel, bladder or ureters. The depth of infiltration is related to the type and severity of symptoms (Koninckx et al., 1991
; Porpora et al., 1999
; Chapron et al., 2003a
).
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Symptoms
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Establishing the diagnosis of endometriosis on the basis of symptoms alone can be difficult because the presentation is so variable and there is considerable overlap with other conditions such as irritable bowel syndrome and pelvic inflammatory disease. As a result there is often a delay of several years between symptom onset and a definitive diagnosis (Hadfield et al., 1996
; Arruda et al., 2003
; Husby et al., 2003
).
The following symptoms can be caused by endometriosis based on clinical and patient experience: severe dysmenorrhoea; deep dyspareunia; chronic pelvic pain; ovulation pain; cyclical or perimenstrual symptoms (e.g. bowel or bladder associated) with or without abnormal bleeding; infertility; and chronic fatigue. However, the predictive value of any one symptom or set of symptoms remains uncertain as each of these symptoms can have other causes, and a significant proportion of affected women are asymptomatic.
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Clinical signs
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Finding pelvic tenderness, a fixed retroverted uterus, tender uterosacral ligaments or enlarged ovaries on examination is suggestive of endometriosis. The diagnosis is more certain if deeply infiltrating nodules are found on the uterosacral ligaments or in the pouch of Douglas, and/or visible lesions are seen in the vagina or on the cervix. The findings may, however, be normal.
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Diagnosis
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Histology
Investigations
Ultrasound
Magnetic resonance imaging
Blood tests
Investigations to assess disease extent
Assessment of ovarian cysts
Laparoscopy
Empirical treatment of pain symptoms without a definitive diagnosis
Treatment of endometriosis-associated pain in confirmed disease
Non-steroidal anti-inflammatory drugs
It is important to note that NSAIDs have significant side-effects, including gastric ulceration and an anti-ovulatory effect when taken at mid-cycle. Other analgesics may be effective but there is insufficient evidence to make recommendations.
Hormonal treatment
The levonorgestrel intrauterine system (LNG-IUS) may be effective at reducing endometriosis-associated pain (Vercellini et al., 1999a
), but there is insufficient evidence to make recommendations.
Duration of GnRH agonist treatment
Surgical treatment
There are no data to justify hormonal treatment prior to surgery to improve the success of surgery (Muzii et al., 1996
).
There are no data supporting the use of uterine suspension but, in certain cases, there may be a role for pre-sacral neurectomy (Soysal et al., 2003
).
Post-operative treatment
Hormone replacement therapy
Treatment of endometriosis-associated infertility in confirmed disease
Treatment of endometriotic lesions
The recommendation above is based upon a systematic review and meta-analysis of two, similar but contradictory RCTs comparing laparoscopic surgery (± adhesiolysis) with diagnostic laparoscopy alone. Nevertheless, some members of the working group questioned the strength of the evidence because: (i) small numbers were treated in one of the studies (Parazzini, 1999
); (ii) although in the other, larger study (Marcoux et al., 1997
) there was a significantly higher monthly fecundity rate in the treated compared to the control group, patients were apparently not blinded to whether they were treated or not.
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Assisted reproduction in endometriosis Intrauterine insemination
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IVF
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The recommendation above is based on a systematic review but the working group noted that endometriosis does not adversely affect pregnancy rates in some large databases (e.g. SART and HFEA) (Templeton et al., 1996
).
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Coping with disease Complementary therapies
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Patient support groups
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Notes
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* The manuscript was prepared by the first author; all other authors contributed equally and are listed in alphabetical order. Guideline Development Group: Agneta Bergqvist, Karolinska Institutet, Stockholm (Chair), Charles Chapron, Clinique Universitaire Baudelocque, Paris (Working party), Gerard Dunselman, Maastricht University (Working party), Robert Greb, Muenster University Hospital (Working party), Thomas DHooghe, Leuven University (Vice-Chair), Lone Hummelshoj, Endometriose Foreningen, Denmark (Working party), Stephen Kennedy, University of Oxford (Report writer), Philippe Koninckx, Leuven University and University of Oxford (Contributor), Roberto Matorras, País Vasco University (Contributor), Michael Mueller, University of Berne (Contributor), Andrew Prentice, University of Cambridge (Working party), Ertan Saridogan, University College Hospital, London (Working party), Juan Garcia-Velasco, Instituto Valenciano de Infertilidad, Madrid (Contributor). 
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References
|
---|
Abbott JA, Hawe J, Clayton RD and Garry R (2003) The effects and effectiveness of laparoscopic excision of endometriosis: a prospective study with 25 year follow-up. Hum Reprod 18,19221927.[Abstract/Free Full Text]
Adamson GD, Hurd SJ, Pasta DJ and Rodriguez BD (1993) Laparoscopic endometriosis treatment: is it better? Fertil Steril 59,3544.[ISI][Medline]
American, Society for Reproductive Medicine (1997) Revised classification of endometriosis: 1996. Fertil Steril 67,817821.[CrossRef][ISI][Medline]
Ang, WC, Alvey CM, Marran S, Kennedy SH and Golding S. A systematic review of the accuracy of magnetic resonance imaging (MRI) in the diagnosis of endometriosis. (Submitted for publication.)
Arruda MS, Petta CA, Abrao MS and Benetti-Pinto CL (2003) Time elapsed from onset of symptoms to diagnosis of endometriosis in a cohort study of Brazilian women. Hum Reprod 18,49.
Barnhart K, Dunsmoor-Su R and Coutifaris C (2002) Effect of endometriosis on in vitro fertilization. Fertil Steril 77,11481155.[CrossRef][ISI][Medline]
Beral V and Million Women Study Collaborators (2003) Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet 362,419427.[CrossRef][ISI][Medline]
Beretta P, Franchi M, Ghezzi F, Busacca M, Zupi E and Bolis P (1998) Randomized clinical trial of two laparoscopic treatments of endometriomas: cystectomy versus drainage and coagulation. Fertil Steril 70,11761180.[CrossRef][ISI][Medline]
Bianchi S, Busacca M, Agnoli B, Candiani M, Calia C and Vignali M (1999) Effects of 3 month therapy with danazol after laparoscopic surgery for stage III/IV endometriosis: a randomized study. Hum Reprod 14,13351337.[Abstract/Free Full Text]
Busacca M, Somigliana E, Bianchi S, De Marinis S, Calia C, Candiani M and Vignali M (2001) Post-operative GnRH analogue treatment after conservative surgery for symptomatic endometriosis stage IIIIV: a randomized controlled trial. Hum Reprod 16,23992402.[Abstract/Free Full Text]
Chapron C, Vercellini P, Barakat H, Vieira M and Dubuisson JB (2002) Management of ovarian endometriomas. Hum Reprod Update 8,67.
Chapron C, Fauconnier A, Dubuisson JB, Barakat H, Vieira M and Breart G (2003a) Deep infiltrating endometriosis: relation between severity of dysmenorrhoea and extent of disease. Hum Reprod 18,760766.[Abstract/Free Full Text]
Chapron C, Fauconnier A, Vieira M, Barakat H, Dousset B, Pansini V, Vacher-Lavenu MC and Dubuisson JB (2003b) Anatomical distribution of deeply infiltrating endometriosis: surgical implications and proposition for a classification. Hum Reprod 18,157161.[Abstract/Free Full Text]
DHooghe TM, Debrock S, Hill JA and Meuleman C (2003) Endometriosis and subfertility: is the relationship resolved? Semin Reprod Med 21,243254.[CrossRef][ISI][Medline]
Fedele L, Bianchi S, Zanconato G, Bettoni G and Gotsch F (2004) Long-term follow-up after conservative surgery for rectovaginal endometriosis. Am J Obstet Gynecol 190,10201024.[CrossRef][ISI][Medline]
Guzick DS, Silliman NP, Adamson GD, Buttram-VC J, Canis M, Malinak LR and Schenken RS (1997) Prediction of pregnancy in infertile women based on the American Society for Reproductive Medicines revised classification of endometriosis. Fertil Steril 67,822829.[CrossRef][ISI][Medline]
Hadfield R, Mardon H, Barlow D and Kennedy S (1996) Delay in the diagnosis of endometriosis: a survey of women from the USA and the UK. Hum Reprod 11,878880.[Abstract]
Hornstein MD, Yuzpe AA, Burry KA, Heinrichs LR, Buttram-VL J and Orwoll ES (1995) Prospective randomized double-blind trial of 3 versus 6 months of nafarelin therapy for endometriosis associated pelvic pain. Fertil Steril 63,955962.[ISI][Medline]
Hornstein MD, Hemmings R, Yuzpe AA and Heinrichs WL (1997) Use of nafarelin versus placebo after reductive laparoscopic surgery for endometriosis. Fertil Steril 68,860864.[CrossRef][ISI][Medline]
Hughes E, Fedorkow D, Collins J and Vandekerckhove P (2004) Ovulation suppression for endometriosis (Cochrane Review). In The Cochrane Library, Issue 3. John Wiley & Sons Ltd, Chichester, UK.
Husby GK, Haugen RS and Moen MH (2003) Diagnostic delay in women with pain and endometriosis. Acta Obstet Gynecol Scand 82,649653.[CrossRef][ISI][Medline]
Jacobson TZ, Barlow DH, Garry R and Koninckx P (2004a) Laparoscopic surgery for pelvic pain associated with endometriosis (Cochrane Review). In The Cochrane Library, Issue 3. John Wiley & Sons Ltd, Chichester, UK.
Jacobson TZ, Barlow DH, Koninckx PR, Olive D and Farquhar C (2004b) Laparoscopic surgery for subfertility associated with endometriosis (Cochrane Review). In The Cochrane Library, Issue 3. John Wiley & Sons Ltd, Chichester, UK.
Kauppila A and Ronnberg L (1985) Naproxen sodium in dysmenorrhea secondary to endometriosis. Obstet Gynecol 65,379383.[Abstract]
Kauppila A, Puolakka J and Ylikorkala O (1979) Prostaglandin biosynthesis inhibitors and endometriosis. Prostaglandins 18,655661.[CrossRef][Medline]
Koninckx PR, Meuleman C, Demeyere S, Lesaffre E and Cornillie FJ (1991) Suggestive evidence that pelvic endometriosis is a progressive disease, whereas deeply infiltrating endometriosis is associated with pelvic pain. Fertil Steril 55,759765.[ISI][Medline]
Koninckx PR, Oosterlynck D, DHooghe T and Meuleman C (1994) Deeply infiltrating endometriosis is a disease whereas mild endometriosis could be considered a non-disease. Ann NY Acad Sci 734,333341.[Abstract]
Koninckx PR, Meuleman C, Oosterlynck D and Cornillie FJ (1996) Diagnosis of deep endometriosis by clinical examination during menstruation and plasma CA-125 concentration. Fertil Steril 65,280287.[ISI][Medline]
Lefebvre G, Allaire C, Jeffrey J, Vilos G, Arneja J, Birch C and Fortier M (2002) SOGC clinical guidelines. Hysterectomy. J Obstet Gynaecol Can 24,3761.[Medline]
Marcoux S, Maheux R and Berube S (1997) Laparoscopic surgery in infertile women with minimal or mild endometriosis. Canadian Collaborative Group on Endometriosis. New Engl J Med 337,217222.[Abstract/Free Full Text]
Matorras R, Elorriaga MA, Pijoan JI, Ramon O and Rodriguez-Escudero FJ (2002) Recurrence of endometriosis in women with bilateral adnexectomy (with or without total hysterectomy) who received hormone replacement therapy. Fertil Steril 77,303308.[CrossRef][ISI][Medline]
Mol BW, Bayram N, Lijmer JG, Wiegerinck MA, Bongers MY, van-der VF and Bossuyt PM (1998) The performance of CA-125 measurement in the detection of endometriosis: a meta-analysis. Fertil Steril 70,11011108.[CrossRef][ISI][Medline]
Moore J, Copley S, Morris J, Lindsell D, Golding S and Kennedy S (2002) A systematic review of the accuracy of ultrasound in the diagnosis of endometriosis. Ultrasound Obstet Gynecol 20,630634.[CrossRef][ISI][Medline]
Moore J, Kennedy SH and Prentice A (2004) Modern combined oral contraceptives for pain associated with endometriosis (Cochrane Review). In The Cochrane Library, Issue 3. John Wiley & Sons Ltd, Chichester, UK.
Morgante G, Ditto A, La MA and De LV (1999) Low-dose danazol after combined surgical and medical therapy reduces the incidence of pelvic pain in women with moderate and severe endometriosis. Hum Reprod 14,23712374.[Abstract/Free Full Text]
Muzii L, Marana R, Caruana P and Mancuso S (1996) The impact of preoperative gonadotropin-releasing hormone agonist treatment on laparoscopic excision of ovarian endometriotic cysts. Fertil Steril 65,12351237.[ISI][Medline]
Muzii L, Marana R, Caruana P, Catalano GF, Margutti F and Panici PB (2000) Postoperative administration of monophasic combined oral contraceptives after laparoscopic treatment of ovarian endometriomas: a prospective, randomized trial. Am J Obstet Gynecol 183,588592.[CrossRef][ISI][Medline]
Namnoum AB, Hickman TN, Goodman SB, Gehlbach DL and Rock JA (1995) Incidence of symptom recurrence after hysterectomy for endometriosis. Fertil Steril 64,898902.[ISI][Medline]
Osuga Y, Koga K, Tsutsumi O, Yano T, Maruyama M, Kugu K, Momoeda M and Taketani Y (2002) Role of laparoscopy in the treatment of endometriosis-associated infertility. Gynecol Obstet Invest 53(Suppl 1), 3339.[CrossRef][ISI][Medline]
Parazzini F (1999) Ablation of lesions or no treatment in minimalmild endometriosis in infertile women: a randomized trial. Gruppo Italiano per lo Studio dellEndometriosi. Hum Reprod 14,13321334.[Abstract/Free Full Text]
Parazzini F, Fedele L, Busacca M, Falsetti L, Pellegrini S, Venturini PL and Stella M (1994) Postsurgical medical treatment of advanced endometriosis: results of a randomized clinical trial. Am J Obstet Gynecol 171,12051207.[ISI][Medline]
Porpora MG, Koninckx PR, Piazze J, Natili M, Colagrande S and Cosmi EV (1999) Correlation between endometriosis and pelvic pain. J Am Assoc Gynecol Laparosc 6,429434.[ISI][Medline]
Prentice A, Deary AJ and Bland E (2004a) Progestagens and anti-progestagens for pain associated with endometriosis. In The Cochrane Library, Issue 3. John Wiley & Sons Ltd, Chichester, UK.
Prentice A, Deary AJ, Goldbeck WS, Farquhar C and Smith SK (2004b) Gonadotrophin-releasing hormone analogues for pain associated with endometriosis. In The Cochrane Library, Issue 3. John Wiley & Sons Ltd, Chichester, UK.
Proctor ML and Murphy PA (2004) Herbal and dietary therapies for primary and secondary dysmenorrhoea (Cochrane Review). In The Cochrane Library, Issue 3. John Wiley & Sons Ltd, Chichester, UK.
Proctor ML, Smith CA, Farquhar CM and Stones RW (2004) Transcutaneous electrical nerve stimulation and acupuncture for primary dysmenorrhoea (Cochrane Review). In The Cochrane Library, Issue 3. John Wiley & Sons Ltd, Chichester, UK.
Redwine DB and Wright JT (2001) Laparoscopic treatment of complete obliteration of the cul-de-sac associated with endometriosis: long-term follow-up of en bloc resection. Fertil Steril 76,358365.[CrossRef][ISI][Medline]
Rickes D, Nickel I, Kropf S and Kleinstein J (2002) Increased pregnancy rates after ultralong postoperative therapy with gonadotropin-releasing hormone analogs in patients with endometriosis. Fertil Steril 78,757762.[CrossRef][ISI][Medline]
Selak V, Farquhar C, Prentice A and Singla A (2004) Danazol for pelvic pain associated with endometriosis (Cochrane Review). In The Cochrane Library, Issue 3. John Wiley & Sons Ltd, Chichester, UK.
Soysal ME, Soysal S, Gurses E and Ozer S (2003) Laparoscopic presacral neurolysis for endometriosis-related pelvic pain. Hum Reprod 18, 588592.[Abstract/Free Full Text]
Surrey ES and Hornstein MD (2002) Prolonged GnRH agonist and add-back therapy for symptomatic endometriosis: long-term follow-up. Obstet Gynecol 99,709719.[Abstract/Free Full Text]
Surrey ES, Silverberg KM, Surrey MW and Schoolcraft WB (2002) Effect of prolonged gonadotropin-releasing hormone agonist therapy on the outcome of in vitro fertilizationembryo transfer in patients with endometriosis. Fertil Steril 78,699704.[CrossRef][ISI][Medline]
Telimaa S, Ronnberg L and Kauppila A (1987) Placebo-controlled comparison of danazol and high-dose medroxyprogesterone acetate in the treatment of endometriosis after conservative surgery. Gynecol Endocrinol 1,363371.[Medline]
Templeton A, Morris JK and Parslow W (1996) Factors that affect outcome of in-vitro fertilisation treatment. Lancet 348,14021406.[CrossRef][ISI][Medline]
Tummon IS, Asher LJ, Martin JS and Tulandi T (1997) Randomized controlled trial of superovulation and insemination for infertility associated with minimal or mild endometriosis. Fertil Steril 68,812.[CrossRef][ISI][Medline]
Vercellini P, Aimi G, Panazza S, De GO, Pesole A and Crosignani PG (1999a) A levonorgestrel-releasing intrauterine system for the treatment of dysmenorrhea associated with endometriosis: a pilot study. Fertil Steril 72,505508.[CrossRef][ISI][Medline]
Vercellini P, Crosignani PG, Fadini R, Radici E, Belloni C and Sismondi P (1999b) A gonadotrophin-releasing hormone agonist compared with expectant management after conservative surgery for symptomatic endometriosis. Br J Obstet Gynaecol 106,672677.[ISI][Medline]
Vercellini P, Aimi G, Busacca M, Apolone G, Uglietti A and Crosignani PG (2003a) Laparoscopic uterosacral ligament resection for dysmenorrhea associated with endometriosis: results of a randomized, controlled trial. Fertil Steril 80,310319.[CrossRef][ISI][Medline]
Vercellini P, Chapron C, De Giorgi O, Consonni D, Frontino G and Crosignani PG (2003b) Coagulation or excision of ovarian endometriomas? Am J Obstet Gynecol 188,606610.[CrossRef][ISI][Medline]
Ylikorkala O and Viinikka L (1983) Prostaglandins and endometriosis. Acta Obstet Gynecol Scand Suppl 113,105107.[Medline]
Submitted on April 25, 2005;
accepted on April 29, 2005.