ORIGINAL ARTICLE: FERTILITY PRESERVATION Uterus-sparing operative treatment for adenomyosis Grigoris F. Grimbizis, M.D., Ph.D., Themistoklis Mikos, M.D., M.Sc., Ph.D., and Basil Tarlatzis, M.D., Ph.D. 1st Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Thessaloniki, Greece Objective: To review systematically the literature on uterus-sparing surgical treatment options for adenomyosis. Design: Systematic literature review. Setting: Tertiary academic center. Patient(s): Women with histologically proven adenomyosis treated with uterus-sparing surgical techniques. Intervention(s): Conservative uterine-sparing surgery for adenomyosis classified as (1) complete excision of adenomyosis, (2) cytoreductive surgery or incomplete removal of the lesion, or (3) nonexcisional techniques, with studies selected if women with adenomyosis were treated surgically without performing hysterectomy. Main Outcome Measure(s): The cure rate after interventional strategies, the rate of symptom (dysmenorrhea and menorrhagia) control, and pregnancy rate in each group of intervention. Result(s): A quality assessment tool was used to assess the scientific value of each study. In total, 64 studies dealing with 1,049 patients were identified. After complete excision, the dysmenorrhea reduction, menorrhagia control, and pregnancy rate were 82.0%, 68.8%, and 60.5%, respectively. After partial excision, the dysmenorrhea reduction, menorrhagia control, and pregnancy rate were 81.8%, 50.0%, and 46.9%, respectively. Conclusion(s): Uterine-sparing operative treatment of adenomyosis and its variants appear to be feasible and efficacious. Welldesigned, comparative studies are urgently needed to answer the multiple questions arising from this intriguing intervention. (Fertil SterilÒ 2013;-:-–-. Ó2013 by American Society Use your smartphone for Reproductive Medicine.) to scan this QR code Key Words: Adenomyoma, adenomyosis, cytoreductive surgery, juvenile cystic adenomyoma, and connect to the uterus-sparing surgery Discuss: You can discuss this article with its authors and with other ASRM members at http:// fertstertforum.com/grimbizisgf-uterus-sparing-surgery-adenomyosis/ I n 1860, von Rokitansky was one of the first to describe a condition characterized by the heterotopic occurrence of islands of endometrium scattered throughout the myometrium (1, 2), specified by Frankl in 1932 as ‘‘adenomyosis interna’’ (3). Quite a few reports since the beginning of the previous century have outlined the feasibility of uterine-sparing surgery in women with postoperatively proven adenomyosis causing subfertility (2). The term ‘‘hysteroplasty’’ has been proposed to describe the conservative operation in which childbearing function is preserved in young women with extensive adenomyosis (4). During the last decades, there is an increasing trend of getting pregnant at a later age. Adenomyosis, a disease mostly diagnosed between 30 and 45 years of age, increasingly complicates the fertility potential of women in this age group (5). Minimal access surgery techniques and organpreserving surgery is a parallel trend that characterizes modern gynecology (6). Thus, the need for uterus- Received May 27, 2013; revised and accepted October 15, 2013. G.F.G. has nothing to disclose. T.M. has nothing to disclose. B.T. received unrestricted research grants, travel grants, and honoraria from Merck Sharp and Dohme and Merck Serono, and travel grants and honoraria from IBSA and Ferring. Reprint requests: Grigoris F. Grimbizis, M.D., Ph.D., Assistant Professor in Obstetrics and Gynecology, 1st Department of Obstetrics and Gynecology, Aristotle University of Tsimiski 51 Str., Thessaloniki, Thessaloniki, Greece 54623 (E-mail: [email protected]). Fertility and Sterility® Vol. -, No. -, - 2013 0015-0282/$36.00 Copyright ©2013 American Society for Reproductive Medicine, Published by Elsevier Inc. http://dx.doi.org/10.1016/j.fertnstert.2013.10.025 VOL. - NO. - / - 2013 discussion forum for this article now.* * Download a free QR code scanner by searching for “QR scanner” in your smartphone’s app store or app marketplace. preserving surgery in women with symptomatic adenomyosis warrants a conservative operative management of the disease. Adenomyosis is defined as the presence of endometrial tissue (glands and stroma) within the myometrium; heterotopic endometrial tissue foci are associated with a variable degree of smooth muscle cell hyperplasia. Adenomyosis can either be diffuse or localized (focal), depending on the extend of myometrial invasion. Moreover, adenomyotic lesions may have a histologic spectrum from mostly solid to mostly cystic (7). Adenomyosis is enigmatic in terms of etiology, diagnosis, and clinical significance. Regarding the etiology of the disease, the current trend in thought is that adenomyosis or adenomyoma results as a down-growth and invagination of the endometrial 1 ORIGINAL ARTICLE: FERTILITY PRESERVATION basalis into the adjacent myometrium after disruption of the normally intact boundary between them. The incidence of adenomyosis is increased after uterine surgery (i.e., myomectomy), cesarean delivery, postpartum endometritis, pregnancy, uterine trauma, and endometrial interventions (i.e., endometrial ablation, dilation and curettage, or dilation and evacuation of products of conception). Uterine manipulations appear to be a crucial factor predisposing the invasion of endometrial cells in the myometrium (8). A dysfunction at the endometrial-myometrial junction is speculated that might be the causative factor of adenomyosis, a condition that could theoretically link the disease to endometriosis as well (9). There is no consensus on the appropriate management of symptomatic adenomyosis in women seeking fertility. This is because [1] the causative relationship between adenomyosis and subfertility has not been fully confirmed, and [2] the incidence of subfertility in women with adenomyosis has not been defined (10). The concept of conservative, uterine-sparing surgery for adenomyosis is increasing as fertility preservation and quality-of-life improvement can be achieved in this group of patients (11). Nevertheless, conservative surgery has not become the standard treatment for adenomyosis. This is mainly because adenomyotic tissue invades the uterine muscle layer in a way that make the borders of the lesion unclear, so complete excision of the affected area remains inaccurate (11). Moreover, the excision of adenomyotic tissue is always accompanied by excision of myometrium, so it is partly destructive for the uterine wall: the advantages of removing an affected area must be balanced against the disadvantages of leaving a possibly defective uterine wall. Hence, there is a recognized difficulty in establishing the state-of-the-art conservative surgical technique for uterine-sparing management of adenomyosis, and operative options include nonstandardized cytoreductive approaches (12). Additionally, initial experience with simple excision of adenomyotic lesions and covering or simply closing the myometrium was reported to be disappointing because this group of patients had quick recurrences and soon needed hysterectomy (13). Our study is a systematic review of the literature about uterus-sparing surgical treatment options for adenomyosis [1] aiming to review and categorize the available proposals of surgical uterus-sparing techniques (open or laparoscopic) for the treatment of symptomatic adenomyosis, and [2] to assess the effect of each type of surgical treatment on symptoms and future fertility, according to the best available data in the literature. could be classified into the following clinical/histologic variants: 1. Diffuse adenomyosis. The extensive form of the disease, characterized by foci of endometrial mucosa (glands and stroma) scattered throughout the uterine musculature (14). 2. Focal adenomyosis. A restricted area of hypertrophic and distorted endometrium and myometrium, usually embedded within the myometrium (14, 15). The histologic characteristics of focal adenomyosis may differ from patient to patient, from almost solid to only cystic (adenomyotic cysts); thus, this form could be subdivided to: a. Adenomyoma. Any disease that infiltrates a restricted area of the myometrium with more or less clear borders and with mainly solid characteristics. Practically, the term adenomyoma seems to be used for grossly circumscribed adenomyotic masses (15, 16). b. Cystic adenomyosis. An extreme form of adenomyosis characterized mainly by the presence of a single adenomyotic cyst within myometrium (8). I. In women younger than 30 years old, focal cystic adenomyosis is described as juvenile cystic adenomyosis (JCA). For this variant, Takeuchi et al. (17) proposed the following diagnostic criteria: age less than 30 years, cystic lesion >1 cm clearly independent of the endometrium, and severe dysmenorrhea. 3. Polypoid adenomyomas. Circumscribed endometrial masses composed of predominantly endometrioid glands and a stromal component predominantly of smooth muscle (15). a. Typical polypoid adenomyomas. Polypoid adenomyomas without architectural or cellular atypia (15). b. Atypical polypoid adenomyomas. A rare variant of polypoid adenomyomas characterized by atypical endometrial glands, often squamous metaplasia, and a cellular smooth muscle stroma (18). 4. Other forms. a. Adenomyomas of the endocervical type. Rare forms of adenomyomatous polyps in the uterine cervix that contain epithelial component of endocervical type. These lesions are important because they must be differentiated from adenoma malignum (19). b. Retroperitoneal adenomyomas. Adenomyotic nodules that are thought to arise from metaplasia of m€ ullerian remnants beneath the peritoneum and in the area of upper rectovaginal septum (7). MATERIALS AND METHODS Clinical/histologic classification of adenomyosis Classification of Uterine-Sparing Techniques Until now, a clear classification of adenomyosis has not existed. This is further complicated by the histologic diversity, and the differences in the extent and location of the disease. However, categorization of the patients is necessary to evaluate the results of surgical treatment. Thus, taking into account the histologic characteristics and the extent of the myometrial invasion, adenomyosis For most cases of adenomyosis, the lesion presents with a minor or major degree of myometrial infiltration. In these cases, removal of healthy myometrium happens inevitably during excision of the lesion. It seems sound to stipulate that any classification of the currently available surgical techniques regarding the excision of adenomyosis should be based on the extent of removal of adjacent healthy myometrium and 2 VOL. - NO. - / - 2013 Fertility and Sterility® the preservation of the integrity (and subsequently the functionality) of the uterine wall. Accordingly, one could classify the currently available uterine preserving surgical options for adenomyosis as following: 1. Complete excision of adenomyosis. a. Adenomyomectomy. Preferably used in cases of localized adenomyosis (adenomyoma) but also in selected cases of more diffuse adenomyosis with reconstruction of the uterine wall. This includes the complete removal of all clinically recognizable non-microscopic lesions. The integrity of uterine wall is maintained (20). b. Cystectomy. Used in cases of cystic focal adenomyosis, including the entire removal of the adenomyotic cyst (17, 21). 2. Cytoreductive surgery/partial adenomyomectomy. Used in cases of diffuse adenomyosis, including the partial removal of the clinically recognizable non-microscopic lesions because complete removal of the lesion would lead to the concomitant excision of critical amount of healthy myometrium, which could lead to ‘‘functional’’ hysterectomy (13, 22). 3. Nonexcisional techniques. Used in interventions where removal of adenomyotic tissue is not included (22–24). Selection Criteria Studies were selected if women with adenomyosis were treated surgically without performing a hysterectomy. For the constellation of systematic review that examines the outcome of conservative surgical methods of treatment of adenomyosis, we included randomized trials, cohort studies, case-control studies, case series, and case reports. Both prospective and retrospective studies were included. Studies were excluded if the outcome was not clearly stated. NonEnglish studies, duplicate publications, and studies published only in abstract form were excluded. Special issues of ambiguity were the mode of final diagnosis of adenomyosis before the intervention, the control of the disease, and the reproductive outcome. Definitive diagnosis of adenomyosis is made with a biopsy (14). Preoperative diagnosis of adenomyosis has been performed with ultrasound and/or magnetic resonance imaging (MRI); however, MRI seems to exhibit higher sensitivity and specificity compared with other diagnostic modalities (25, 26). In our review, all articles where histology was not obtained were excluded. The control of the disease was evaluated by the reduction of pain, menorrhagia, or symptoms. There was no restriction on the modality of how the outcome was reported, whether it was in a form of a questionnaire or was clinician of patient reported. The reproductive outcome was measured by the number and type of conceptions in patients who wished to become pregnant, the pregnancy outcome, and the number of babies taken home. the titles and abstracts from the electronic searches were examined by two reviewers (T.M. and G.G.), and full manuscripts of all articles that met the selection criteria were retrieved. Second, full manuscripts were examined to make final inclusion or exclusion decisions. Any disagreement in the inclusion/exclusion stage was resolved by arbitration from a third reviewer (B.C.T.). All selected articles were assessed for the following: study design, adequate description of patient characteristics, completeness of information in the data sets, preoperative or intraoperative diagnosis of adenomyosis, use of validated assessment method of symptoms, pain, and bleeding, rates and types of intraoperative complications, rates of recurrence of adenomyosis and need for further interventions, and postinterventional rates of conception and full-term pregnancy. Data Extraction Two assessors (T.M. and G.G.) independently reviewed the titles and abstracts of all identified citations. From full text articles and using a standardized data collection form, the reviewers independently extracted data regarding the study design, the number of patients, the characteristics of the participants, the modality of the initial diagnosis, the primary intervention, the duration of follow-up observation, the postoperative outcomes in terms of symptom reduction, the pain reduction, the uterine volume reduction, and the reproductive outcome. The reproductive outcome after the primary intervention was recorded in terms of the number wishing to conceive, the number of natural conceptions or conceptions after assisted reproduction techniques (ART), and the number of terminations of pregnancies (TOP), miscarriages, ongoing pregnancies, preterm and full-term deliveries, including the mode of delivery. Quality Assessment of Studies All of the studies were evaluated and consequently ranked to ascertain the specific power of each, based on certain criteria. This was performed solely to assist the reader in assessing objectively the scientific value of each study. These criteria are reported and explained in Supplemental Table 1 (available online). The criteria were selected and modified from already proposed quality assessment tools (Newcastle-Ottawa Quality Assessment Scale) for clinical studies. Each criterion could be graded either as 0 (study not meeting the criterion) or 1 (study meeting the criterion). Each study was then graded with a score ranging from 0 (poorest performance, minimum total score) to 9 (best performance, maximum total score), depending on the fulfillment of the criteria. Studies that scored 5 or more the trials with powerful evidence in their results; they were selected for further analysis. Studied that scored less than 4 were trials with poor evidence; they were not included in subsequent analysis. Statistical Analysis Study Selection Studies were included in the systematic review after a twostage process (Supplemental Fig. 1, available online). First, VOL. - NO. - / - 2013 Statistical analyses were performed to establish the cure rate after interventional strategies, the rate or recurrence of symptoms, the hysterectomy rate, and the pregnancy and the 3 ORIGINAL ARTICLE: FERTILITY PRESERVATION delivery rate in each intervention group. For analysis, the log rates were pooled, weighting each study by the inverse of its variance, and the summary estimates were calculated. The statistical analysis was performed using Microsoft Excel and MedCalc 11.4.4 (MedCalc Software). RESULTS Currently Available Methods of Uterine-Sparing Surgical Treatment Adenomyomectomy for diffuse or focal adenomyosis, cytoreductive surgery (partial adenomyomectomy), or a variety of nonexcisional techniques has been described thoroughly in the literature for the uterine-sparing surgical treatment of adenomyosis. The described proposals, classified according to the radicality of the excision of the adenomyotic tissue are shown in Table 1. Complete Excision of Adenomyosis/ Adenomyomectomy Classic technique. An adenomyomectomy (open or laparoscopic) includes the same steps as myomectomy (open or laparoscopic). This technique involves [1] recognition of the lesion's location and borders by inspection and/or palpation, [2] longitudinal incision of the uterine wall along the adenomyoma (Fig. 1Aa), [3] sharp and blunt dissection of the lesion with scissors, graspers, and/or diathermy in a fashion similar to the removal of a fibroid (Fig. 1Ab), [4] suturing of the uterine wall in a seromuscular layer (16, 27) or in two or more layers (4, 10) (Fig. 1Ad), and suturing of the endometrial cavity with absorbable suture when necessary. In cases of laparoscopic adenomyomectomy (Fig. 1Ac), the adenomyotic mass is removed with the use of a morcellator (16). In cases where intraoperative recognition of the adenomyotic lesion is arduous, the use of ultrasound guidance has been proposed, either in the form of hydroultrasonographic monitoring or in the form of transtrocar ultrasonography (28, 29). Modification in wall reconstruction: U-shaped suturing. In this laparoscopic modification, after removal of adenomyomatous tissue, the wall's cavelike wound is approximated by Ushape sutures at the muscle layer; the seromuscular layer is closed by figure-eight sutures (30). Modification in wall reconstruction: overlapping flaps. In this laparoscopic modification, a transverse incision is made in the adenomyotic tissue, and the lesion is excised with a monopolar needle. The remaining seromuscular layers are overlapped and sutured to counteract the lost muscle layer of the uterus (Fig. 1Ba–d) (31). Triple-flap method. This laparotomy technique involves [1] extraperitonealization of the uterus and rubber tourniquet placement for hemostasis; [2] bisection of the uterus in the midline and in the sagittal plane with a scalpel until the uterine cavity is reached (Fig. 1Ca); [3] opening of the endometrial cavity to permit the introduction of the index finger to guide during excision of adenomyotic tissues; [4] use of Martin TABLE 1 Classification of uterine sparing surgical techniques and of their variants. Surgical category Complete excision Techniques Adenomyomectomy Described variant 1. Classic technique (Hyams 1952; Grimbizis et al., 2008; Wang et al. 2009)/plus intraoperative ultrasound guidance (Nabeshima et al. 2003; Nabeshima et al. 2008) Modifications: U-shaped suturing (Sun et al. 2011) Overlapping flaps (Tacheshi et al. 2006) 2. Triple flap method (Osada et al. 2011) Cystectomy Classic technique Partial excision (cytoreductive surgery) Partial adenomyomectomy 1. Classic technique (Fujishita et al. 2004) 2. Transverse H incision (Fujishita et al. 2004) 3. Wedge resection of the uterus (Sun et al. 2011) 4. Asymmetric dissection of the uterus (Nishida et al. 2010) Nonexcisional techniques Combined with excisional Uterine artery ligation together with adenomyomectomy (Kang et al. 2009) 1. Uterine artery ligation (Wang et al. 2002) 2. Electrocoagulation of myometrium (Wood, 1998; Philips, 1996) 1. Endometrial resection (Wood, 1998; Fernandez et al. 2007; Kumar et al. 2007; Maia et al. 2007) 2. Endometrial ablation (Preuthhupan et al. 2010) 3. Hysteroscopic cystectomy 1. High-frequency ultrasound (HIFU) (Yang et al. 2009) 2. Alcohol instillation for cystic adenomyosis (Furman et al. 2007) 3. Endometrial nonhysteroscopic ablation Radiofrequency (Ryo et al. 2006) Microwave (Kanaoka et al. 2004) Balloon (Chan et al. 2001) Nonexcisional only Hysteroscopic Others Grimbizis. Uterus sparing surgery for adenomyosis. Fertil Steril 2013. 4 VOL. - NO. - / - 2013 Fertility and Sterility® forceps to grasp adenomyotic tissues and to excise them from surrounding myometrium, leaving a myometrial thickness of 1 cm from serosa above and endometrium below (Fig. 1Cb); [5] closure of the endometrium with 3–0 Vicryl (Fig. 1Cc); and [6] closure of the flaps of the uterine wall approximating the myometrium and serosa of the one side of the bisected uterus in the anteroposterior plane with interrupted 2–0 Vicryl (Fig. 1Cd), while the contralateral side of the uterine wall is brought over the reconstructed first side in such a way as to cover it (Fig. 1Ce) (20). Cytoreductive Surgery/Partial Adenomyomectomy Classic technique: excision of diffused adenomyosis. Cytoreductive surgery for adenomyosis includes the following steps: [1] a vertical or transverse incision is applied in the middle of the anterior or the posterior uterine wall; [2] Ford T clamps (or an equivalent instrument) are applied to the wound edges so as myometrium of the subserous layer, which is rarely affected by adenomyosis (up to 10 mm), can be preserved; [3] the uterine wall is inspected for clinically recognizable non-microscopic adenomyotic lesions (coarse, white trabeculations), which are excised piece by piece with as much of the adjacent normal myometrium as possible being preserved; [4] if adenomyosis is extended to the contralateral wall of the uterus as well, the incision is extended over the top of the uterus and down toward the urinary bladder of the pouch of Douglas. Closure of myometrium is performed in one or more layers and closure of the serosa in one layer with interrupted sutures. Attention is taken to not leave any uterine defect that could increase the risk of hematoma (12). Transverse H incision technique. In this laparotomy modification, mainly described for anterior uterine wall adenomyosis, ligation of the uterine cervix throughout the broad ligament and vasoconstricting agents are used to minimize blood loss. A vertical incision is made in the uterine wall, and two transverse incisions are applied perpendicularly to the initial incision along the upper and lower edges of the uterus (H incision). A 5-mm thickness of the uterine serosa is resected from the uterine myometrium along the vertical incision. This resection is extended, and the uterine serosa is widely opened bilaterally at the area under the H incision. Then, slices of adenomyotic tissue are removed, using manual palpation to define the borders of healthy myometrium. Chromopertubation test using indigo-carmine allows assessment of endometrial perforation. As above, closure of myometrium is performed in one or more layers and closure of the serosa in one layer with interrupted sutures (12). Wedge resection of the uterine wall. In this technique (open or laparoscopic), the part of the seromuscular layer where adenomyosis is located is removed by wedge resection of the uterine wall. The operation is completed with traditional closure of the uterine wounds as described in the classic technique of partial adenomyomectomy (30). Asymmetric dissection of uterus. In this laparotomy technique, the uterus is dissected longitudinally with a surgical VOL. - NO. - / - 2013 electric knife in an asymmetrical fashion to divide the inside from the outside, preserving both the uterine cavity and bilateral uterine arteries. From this incision, the myometrium is dissected diagonally, as if hollowing out the uterine cavity. With a transverse incision, the uterine cavity is then opened; the index finger is inserted into the cavity, and adenomyotic lesions are excised using a loop electrode to a thickness of 5 mm of the inner myometrium. The procedure continues with excision of adenomyosis to a thickness of 5 mm of the serosal myometrium. Then the endometrial cavity is closed, and the uterine flaps are rejoined in layers (muscle and serosa) (13). Laparoscopically assisted vaginal excision. In this technique, the surgeon initially confirms that the uterus is free of any adhesions. A laparoscopic bilateral uterosacral ligament removal is performed, and a posterior colpotomy follows. Through the vaginal incision, the uterus is extracted, and under direct manipulation the surgeon removes adenomyotic fragments verified by touch using monopolar cautery. The residual myometrium is closed in two layers. The advantages of this method are comparable to open adenomyomectomy because of excising adenomyotic tissue distinguished by touch and knotting manually with adequate tension (32). Nonexcisional Techniques The following groups of nonexcisional techniques have been described in the literature for the uterine-sparing management of adenomyosis. 1. Combination of excisional and nonexcisional techniques. Kang et al. (33) described a technique of performing laparoscopic resection of diffuse adenomyosis after laparoscopic uterine artery occlusion. 2. Laparoscopic nonexcisional techniques. These techniques include laparoscopic electrocoagulation of the myometrium (22, 23, 34) and laparoscopic uterine artery ligation (24). 3. Hysteroscopic nonexcisional techniques. These techniques include operative hysteroscopy (35), rollerball endometrial ablation (36), transcervical resection of the endometrium (37, 38), and endomyometrial resection (22). 4. Other techniques. These techniques include ablation of focal adenomyosis with high frequency ultrasound (HIFU) (39), alcohol instillation under ultrasound guidance for the treatment of cystic adenomyosis (40), radiofrequency ablation of focal adenomyosis (41), microwave endometrial ablation (42), and balloon thermoablation (43) for diffuse adenomyosis. Synopsis of the Literature that Deals with UterineSparing Treatment of Adenomyosis In total, 64 studies dealing with 1,049 patients treated with uterine-sparing surgical methods for adenomyosis were analyzed. Complete excision of adenomyosis was described in 20 studies (488 patients) (Supplemental Table 2); of these, 9 studies (469 patients) scored R5 during quality assessment (4, 10, 11, 16, 20, 30, 31, 44–56) (Table 2). Partial 5 ORIGINAL ARTICLE: FERTILITY PRESERVATION FIGURE 1 Grimbizis. Uterus sparing surgery for adenomyosis. Fertil Steril 2013. excision of adenomyosis was described in 11 studies (128 patients) (Supplemental Table 3); of these, 3 studies (83 patients) scored R5 during quality assessment (10, 12, 13, 22, 30, 32, 57–61). Complete excision of cystic adenomyomas was described in 22 studies (38 patients) (see Supplemental Table 4); of these, 2 studies (13 6 patients) scored R5 during quality assessment (8, 17, 21, 28, 29, 62–77)(Table 2). Nonexcisional methods for adenomyosis were applied in 15 studies (395 patients) (see Supplemental Table 5); of these, 4 studies (342 patients) scored R5 during quality assessment (22–24, 33, 35–43, 78)(Table 2). VOL. - NO. - / - 2013 Fertility and Sterility® FIGURE 1 Continued (A) Complete adenomyomectomy classic technique: (a) Longitudinal incision along the adenomyoma. (b) Sharp and blunt dissection with scissors, graspers and/or diathermy. (c) Suturing of the endometrial cavity. (d) Suturing of the uterine wall. (B) Complete adenomyomectomy classic technique with overlapping flaps: (a) Transverse incision. (b) The lesion is excised with monopolar needle. (c, d) The remaining seromuscular layers are overlapped and sutured to counteract the lost muscle layer of the uterus. (C) Complete adenomyomectomy with triple flap technique: (a) Bisection of the uterus in the midline and in the sagittal plane. (b) Opening of the endometrial cavity and excision of adenomyotic tissues leaving a myometrial thickness of 1 cm. (c) Closure of the endometrium. (d) Closure of the flaps approximating the myometrium and serosa of the one side of the bisected uterus in the anteroposterior plane. (e) The contralateral side of the uterine wall is brought over the reconstructed first side in such a way as to cover it. Grimbizis. Uterus sparing surgery for adenomyosis. Fertil Steril 2013. Results after complete excision of adenomyosis/adenomyomectomy. In 9 studies, 469 patients were treated with complete excision of adenomyosis/adenomyomectomy (Supplemental Table 2, available online). Overall, the mean patient age was 37.5 years old (1.5 years), and the mean VOL. - NO. - / - 2013 follow-up period was 25.1 months (7.0 months). The mean reduction of pain was 82.0% (5.4%), and the mean reduction of bleeding was 68.8% (14.8%) (see Table 3). After excluding the studies where fertility preservation was not the primary outcome, 147 out of 341 patients wishing to 7 Uterus sparing surgical treatment of adenomyosis: quality assessment of the relevant studies. Author, year Complete adenomyomectomy Dai et al. 2012 Study design No. of patients Modality of initial diagnosis/definition of extent of the disease Pro 1 38 1 U/S Osada et al. 2011 Pro 1 104 1 U/S, MRI Wang et al. 2009 Pro 1 165 1 U/S Takeuchi et al. 2006 Pro 1 14 0 MRI Al Jama et al. 2011 Retro 0 18 0 U/S, MRI Focal adenomyosis (adenomyoma) Diffuse/focal adenomyosis Representativeness of the cases Ascertainment of exposure/detailed surgical technique 1 Consecutive 1 Surgical records 1 Consecutive 1 Surgical records 1 Consecutive 1 Surgical records 1 Consecutive 1 Surgical records Focal adenomyosis (adenomyoma) 1 Consecutive 1 Surgical records Focal adenomyosis (adenomyoma) Focal adenomyosis (adenomyoma) Koo et al. 2011 Retro 0 18 0 U/S Focal adenomyosis (adenomyoma) 1 Consecutive 1 Surgical records Sun et al. 2011 Retro 0 40 0 NA Focal adenomyosis (adenomyoma) 0 Consecutive 1 Surgical records Grimbizis et al. 2008 Retro 0 6 0 U/S Focal adenomyosis (adenomyoma) 1 Consecutive 1 Surgical records Fedele et al. 1993 Retro 0 18 1 Histology Focal adenomyosis (adenomyoma) 0 Consecutive 1 Surgical records Focal adenomyosis (adenomyoma) Diffuse adenomyosis 0 1 Consecutive 1 Surgical records Partial excision of adenomyosis/partial adenomyomectomy Sun et al. 2011 Retro 0 13 0 NA Consecutive 1 Surgical records VOL. - NO. - / - 2013 Nishida et al. 2010 Retro 0 44 1 MRI Wang et al. 2009 Retro 0 28 1 U/S Diffuse adenomyosis 1 Consecutive 1 Surgical records Fujishita et al. 2004 Retro 0 11 0 U/S, MRI Diffuse adenomyosis 1 Consecutive 1 Surgical records Diffuse/focal adenomyosis 0 Wood, 1998 Retro 0 25 1 NA Grimbizis. Uterus sparing surgery for adenomyosis. Fertil Steril 2013. NA 0 Surgical records Open excision/classic technique Open excision/triple flap technique Open or lap excision/classic technique Lap excision/uterine wall reconstruction with overlapping flaps Open or lap excision/classic technique Open or lap excision/classic technique Open or lap complete excision/classic technique with additional U-shape suturing Lap excision/classic technique Open excision/classic technique Lap partial excision/classic reconstruction Open excisiona/asymmetric dissection of uterus Open excisiona/classic technique Open partial excision/modified H incision Lap excisiona/classic technique Follow up/adequate length Outcome evaluation Adequacy of follow-up of cohorts Statistical analysis Total grade 1 Structured questionnaire 1 24/12 1 Yes 1 Yes 1 9 1 Structured questionnaire 1 24/12 1 Yes 1 Yes 1 9 1 Structured questionnaire 1 24/12 1 Yes 1 Yes 1 9 1 Structured questionnaire 1 NA 0 No 0 Yes 1 6 1 Self 0 36/12 1 Yes 1 Yes 1 6 report 1 Structured questionnaire 1 9/12 0 Yes 1 Yes 1 6 1 Self 0 27/12 1 Yes 1 Yes 1 5 report 1 Structured questionnaire 1 13/12 0 Yes 1 No 0 5 1 Self 0 53/12 1 Yes 1 No 0 4 0 20/12 0 Yes 1 Yes 1 4 report 1 Self report 1 Structured questionnaire 1 12/12 0 Yes 1 No 0 6 1 Structured questionnaire 1 36/12 1 Yes 1 Yes 1 8 1 Self 0 36/12 1 Yes 1 Yes 1 6 0 24/12 1 Yes 1 No 0 4 report 1 Self report ORIGINAL ARTICLE: FERTILITY PRESERVATION 8 TABLE 2 VOL. - NO. - / - 2013 TABLE 2 Continued. Author, year Study design No. of patients Modality of initial diagnosis/definition of extent of the disease Representativeness of the cases Ascertainment of exposure/detailed surgical technique Follow up/adequate length Outcome evaluation Adequacy of follow-up of cohorts Statistical analysis Total grade Cystic adenomyomas and juvenile cystic adenomyomas Takeuchi et al. 2010 Kriplani et al. 2011 Nonexcisional techniques Kang et al. 2009 Retro Retro 1 0 9 4 0 0 U/S, MRI U/S, MRI JCA JCA 1 1 Consecutive Consecutive 1 1 Surgical records Lap Surgical records Lap Laparoscopic partial resection of adenomyosis þ UAO Laparoscopic uterine artery ligation Myometrial electrocoagulation Laparoscopic bipolar coagulation Rollerball endometrial ablation TCRE Mirena Retro 0 37 1 U/S Diffuse/focal adenomyosis 1 Consecutive 1 Surgical records Wang et al. 2002 Pro 1 20 0 U/S, MRI 0 Consecutive 1 Surgical records Wood, 1998 Retro 0 11 0 NA 0 NA 0 Philips et al. 1996 Pro 1 10 0 MRI 0 NA 0 Surgical records Surgical records Preutthupan et al. 2010 Retro 0 190 1 U/S Unclear description of lesion Diffuse/focal adenomyosis Unclear description of lesion Diffuse/focal adenomyosis 1 Consecutive 1 Surgical records Maia et al. 2003 Retro 0 95 1 U/S 0 Consecutive 1 Surgical records Wood, 1998 Retro 0 18 0 NA 0 NA 0 Surgical records Unclear description of lesion Diffuse/focal adenomyosis 1 Structured questionnaire 1 35/12 1 Yes 1 Yes 1 8 1 Structured questionnaire 1 18/12 0 Yes 1 No 0 5 1 Structured questionnaire 1 12/12 0 Yes 1 Yes 1 7 1 Structured questionnaire 1 8/12 0 Yes 1 Yes 1 6 1 Self report 0 24/12 1 Yes 1 No 0 3 1 Self report 0 25/12 1 Yes 1 No 0 4 1 Self report 0 60/12 1 Yes 1 Yes 1 7 1 Self report 0 12/12 0 Yes 1 Yes 1 5 1 Self report 0 24/12 1 Yes 1 No 0 3 excision/classic technique excision/classic technique Endomyometrial resection Note: HIFU ¼ high-intensity focal ultrasound; HSG ¼ hysterosalpingogram; Lap ¼ Laparoscopic; MEA ¼ microwave endometrial ablation; MRI ¼ magnetic resonance imaging; NA ¼ not applicable; Pro ¼ prospective, Retro ¼ retrospective; TCRE ¼ transcervical endometrial resection, UAO ¼ uterine artery occlusion; U/S ¼ ultrasound. a Unclear description of the radicality of adenomyotic tissue excision. Grimbizis. Uterus sparing surgery for adenomyosis. Fertil Steril 2013. Fertility and Sterility® 9 Postoperative results, pregnancy rates, and pregnancy outcomes after uterus-sparing surgery for adenomyosis. Author, year Reduction No. of of symptoms patients (%) Complete adenomyomectomy Dai et al. 2012 38 Osada et al. 2011 104 Wang PH et al. 2009 Surgical group Reduction of pain (%) Reduction of bleeding (%) Patients wishing to conceive (n, %) Natural Conceptions (n, %) Conceptions after ART (n, %) Total Conceptions (n, %) Miscarriages (n, %) Ongoing pregnancy (n, %) Preterm (n, %) Full-term (n, %) Total deliveries (n, %) NA NA >80% VAS: 10–1.6 >80% VAS: 10–2.8 — 26 — 4 — 12 — 16 — 2 — — — — — 14 — 14 Recurrence 7 No uterine rupture VNRS-6: 3.8–1.1 VNRS: 6: 3.9–0.7 NA Adenomyoma relapse 49.0% Adenomyoma relapse 28.1% VD 1 51 NA Surgicalmedical Takeuchi et al. 2006 Al Jama et al. 2011 Koo et al. 2011 114 NA 14 NA 18 NA 18 NA Sun et al. 2011 40 NA Grimbizis et al. 6 2008 Subtotal (Symptoms) Subtotal 341 (Fertility outcome) Partial adenomyomectomy Nishida 44 et al. 2010 Cure — Scale: 3.08–1.2 27 20 (74.1%) — 20 3 (11.1%) — 2 (7.4%) 15 (55.6%) 17 Scale: 3.68–0.9 44 35 (79.5%) — 35 3 (6.8%) — 5 (11.4%) 27 (61.4%) 32 VAS: 10–2.5 8 2 — 2 — 1 — 1 2 NA NA 18 8 — 8 2 — — 6 6 NRS: 8.1–1.3 MVJ: 4.3–3.2 — — — — — — — — — 40% 24 8 5 — — 3 3 Cure — — — — — — — 91.2% Cure 82.00 VAS: 9.4–0.8 NA VNRS-6: 4.9–1.8 NA Wang PH et al. 2009 Fujishita et al. 2004 (modified) 28 6 55% Fujishita et al. 2004 (classic) 5 18% VOL. - NO. - / - 2013 Subtotal 56.11 (symptoms) Subtotal 34 (fertility outcome) Complete adenomyomectomy (JCA) Takeuchi 9 NA et al. 2010 Kriplani 4 Cure et al. 2011 NA 81.78 Improve — NA 28 NA 4 NA — Grimbizis. Uterus sparing surgery for adenomyosis. Fertil Steril 2013. — 72/147 (48.98) — 17/147 (11.56) 89/147 (60.54) — — — 13 2 — 2 — — — 13 (46.4%) 15/89 (16.85) — 1/89 (1.13) 7/89 (7.87) 66/89 (74.16) — — — — — 1 — 1 2 — — — — — 4 (14.3%) — 74/89 (83.15) 9 (32.1%) — 9 Report of 2 incidental pregnancies; recurrence 3 GnRH-a 6/12 C/S 1, Recurrence 1; endometrium perforation 1 Recurrence 4; endometrium perforation 2 50.00 32/34 (94.12) Pain score: 10–2 Pain score: 9.75–0.25 — 5/11 (45.5%) C/S 6/18; TAH 3 GnRH therapy; uterine scar dehiscence U/S relapse rate 15.0% None 68.79 147/341 (43.11) NA 3/13 (23.1%) Comment 15/32 (46.88) 0/32 (0.00) 15/32 (46.88) 4/15 (26.67) 1/15 (6.67) 0/15 (0.00) 10/15 (66.67) 11/15 (73.33) NA 3 3 — 3 — — — 3 3 NA — — — — — — — — — V/D 2; C/S 1 None ORIGINAL ARTICLE: FERTILITY PRESERVATION 10 TABLE 3 VOL. - NO. - / - 2013 TABLE 3 Continued. Author, year Reduction No. of of symptoms patients (%) Subtotal (symptoms) Nonexcisional techniques Kang 37 et al. 2009 86.13 Reduction of pain (%) 84.62 NA Median Pain score 8/11–4/11 Pain score 2.4–1.1 (53% red) Patients wishing to conceive (n, %) Natural Conceptions (n, %) Conceptions after ART (n, %) Total Conceptions (n, %) Miscarriages (n, %) Ongoing pregnancy (n, %) Preterm (n, %) Full-term (n, %) Total deliveries (n, %) Median PBAC: 158–59 — — — — — — — — — PBAC: 516–263 (49% red) — — — — — — — — — — — — — — — — — — Reduction of bleeding (%) — Wang et al. 2002 20 NA Preutthupan et al. 2010 190 NA NA Maia et al. 2003 (Mirena) 53 NA NA 20% — — — — — — — — — Maia, 2003 (no Mirena) Subtotal (symptoms) Total (fertility outcome) 42 NA NA 90% — — — — — — — — — — 54.62 384 Comment Reduced/healed: 165 (86.8%) Hysterectomy 2; reduction of volume (%): 224.6–91.6 (59.2) Hysterectomy 3; 45% dissatisfied; reduction of volume (%): 268–217 (12%) Hysterectomy 3; GnRH pretreatment Repeat TCRE 4; hysterectomy 4 None 73.68 182/384 (47.39) 90/182 (49.45) 17/182 (9.34) 107/182 19/107 (58.79) (17.76) 2/107 (1.87) 7/107 (6.54) 79/107 (73.83) 88/107 (82.24) Note: C/S ¼ cesarean section; MVJ ¼ Mansfield-Voda-Jorgensen menstrual bleeding scale; NA ¼ not applicable; NRS ¼ numerical rating scale; PBAC ¼ pictorial blood loss assessment chart; TAH ¼ total abdominal hysterectomy; TCRE ¼ transcervical endometrial resection; U/S¼ ultrasound; VAS ¼ Visual Analogue Score; VD ¼ vaginal delivery; VNRS ¼ verbal numeric rating scale. Grimbizis. Uterus sparing surgery for adenomyosis. Fertil Steril 2013. Fertility and Sterility® 11 ORIGINAL ARTICLE: FERTILITY PRESERVATION conceive (43.1%) were found; these patients achieved 89 conceptions (pregnancy rate: 60.5%) and delivered 74 babies (delivery rate: 83.1%) (see Table 3). Results after partial excision of adenomyosis/cytoreductive surgery. In 3 studies, 83 patients underwent open or laparoscopic partial excision of adenomyosis/adenomyomas (Supplemental Table 3, available online). All were retrospective cohort studies; the mean age of patients was 35.4 years (1.9 years), and the mean follow-up period was 24.1 months (13.3 months). In this group of patients, the mean reduction of pain was 81.8% (0.0), and the mean reduction of bleeding was 50.0% (0.0) (see Table 3). After excluding the studies where fertility preservation was not the primary outcome, there were 32 out of 34 patients wishing to conceive (94.1%), who achieved 15 conceptions (46.9%) and gave birth to 11 babies (73.3%) (see Table 3). Results after complete excision of cystic adenomyomas (including juvenile cystic adenomyomas). In 2 studies [13 patients, mean age 23.1 (3.2) years, follow-up period 29.8 (8.2) months], there was a reported 86.1% (9.6%) reduction of symptoms and 84.6% (7.2%) reduction of pain after excision of cystic adenomyomas (see Table 3; Supplemental Table 4, available online). Out of three patients wishing to conceive, there were three conceptions and three deliveries (see Table 3). Results after nonexcisional techniques. In 4 studies [342 patients, mean age 42.03 (1.65) years, follow-up period 38.43 (24.17) months], there was a reported 54.6% (1.2%) reduction of pain and 73.7% (23.6%) reduction of bleeding (see Table 3; Supplemental Table 5, available online). Out of 9 patients wishing to conceive, there were 5 (55.6%) conceptions and 1 delivery (50.0%). DISCUSSION Uterine-sparing treatment of adenomyosis appears to be feasible and efficacious. The reduction of dysmenorrhea after conservative surgery ranges from 54.6% (nonexcisional techniques) to 84.6% (complete adenomyomectomy). The reduction of menorrhagia ranges from 50.00% (partial adenomyomectomy) to 68.8% or even 73.68% (nonexcisional techniques). The pregnancy rate ranges from 46.9% (partial adenomyomectomy) to 60.5% (complete adenomyomectomy). Comments on Quality of Data The main problem of an attempt to systematically review these procedures is that there are few good quality studies. In an effort to qualify the data of each study, a 9-item quality assessment tool was created. This tool was based on the Newcastle-Ottawa Quality Assessment scale. Based on this tool, data from only 17 out of the 64 studies were used to calculate the results after uterus-sparing surgery for adenomyosis, in terms of dysmenorrhea reduction, menorrhagia reduction, and pregnancy outcome. In fact, a small number of prospective studies deal with the conservative surgical treatment of adenomyosis, and there has been no uniform design and/or outcome, so the feasibility of pooling the results may be suboptimal. Overall, the quality of the results may be 12 inferior, especially regarding therapies such as partial excision of adenomyosis (no prospective studies identified, small number of patients), the complete excision of cystic adenomyomas (one prospective study, but the total number of patients was very small for eliciting secure results), and the nonexcisional techniques (three prospective studies, but the treatments were totally different, so the results cannot be combined). On the other hand, for the treatment of adenomyosis with complete excision of the lesion, we found four prospective studies and a total of 8 studies scoring R5 after applying the assessment tool. In this subgroup, the investigators reported the use of surgical techniques based on the same operative principles, so a total of 469 treated patients accumulated, which offered good quality data for further analysis. In this subgroup of patients, both treatment and fertility rates appear to be increased (dysmenorrhea control: 82.0%; menorrhagia control: 68.8%; pregnancy rate: 60.5%). Comments on the Control of Symptoms In terms of dysmenorrhoea control, the main contemporary techniques applied for the uterine-sparing techniques for the treatment of adenomyosis appear to yield comparable clinical results. After complete excision of adenomyosis, partial excision of adenomyosis, and complete excision of cystic adenomyomas, the reduction of dysmenorrhoea was found to be 82.0%, 81.8%, and 84.6%, respectively (P ¼ not statistically significant). It seems that the excision of the bulk of adenomyosis controls the pain even if some amount of residual lesion has been left, as happens in cases of cytoreductive surgery. However, all the series included are studies where specially designed cytoreductive techniques were applied, such as the triple flap Osada technique (20), and these results could not be generalized across all the techniques used for the conservative surgery (such as the ‘‘wedge’’ resection technique, represented in this review by only a few case reports). In terms of menorrhagia control, the results differed after partial excision of adenomyosis (50.00% reduction) and complete excision of adenomyosis (68.79% reduction). With nonexcisional techniques, the control of menorrhagia appears to be better compared with the partial excision techniques, and to be comparable to that of the complete excision techniques (73.7%). Nonexcisional techniques is an heterogeneous group of operations including many cases of hysteroscopic ablation. In these cases, the control of bleeding is achieved through the destruction/excision of endometrium, resulting in loss of the fertility of the patient; in addition, in the group of nonexcisional techniques, control of symptoms is achieved indirectly and without treatment of the primary disease. Furthermore, it seems that, especially after partial excision of adenomyosis, the residual lesion adjacent to the endometrium continues to cause bleeding symptoms. This is an implication for clinical practice: in cases of diffuse adenomyosis with menorrhagia, cytoreductive partial excision of the lesion is less effective compared with complete excision techniques or nonexcisional techniques where fertility may be lost. VOL. - NO. - / - 2013 Fertility and Sterility® Comments on Fertility after Treatment Complications Overall, there was a restriction in the design of the studies included in this review regarding the fertility potential after uterine-sparing surgery for adenomyosis. Most of the studies were not primarily designed to address this issue, as the study populations were mainly women with adenomyosis but not necessarily and subfertility. On the other hand, uterussparing surgery for adenomyosis involves techniques that modify the anatomy of the uterus (i.e., pelvic adhesions, uterine deformities, intrauterine adhesions, or reduced uterine capacity). These deformities may contribute to a declined postoperative pregnancy rate (13). Nevertheless, not only was fertility finally preserved, but any subfertility related to adenomyosis appears largely to be treated after cytoreductive surgery, considering that the crude delivery rate appears to be higher than 70%. In view of the fact that pregnancy rates after surgical treatment of fibroids appear to be 50%, the postoperative fertility outcome after excision of adenomyosis should be considered satisfactory (79). Nevertheless, although the existing evidence for the burden on clinical pregnancy and delivery rate caused by intramural fibroids is based on comparative studies (the common odds ratio [95% confidence interval] is 0.8 [0.6–0.9] and 0.7 [0.5–0.8], respectively), research of similar design (prospective, controlled) for the burden on fertility caused by adenomyosis is lacking (79). According to the findings of this review, the conception rates do not appear to be statistically significantly different between partial excision of adenomyosis (46.8%) and complete excision of adenomyosis (60.5%) (P¼ .22). These results are in agreement with analogous research published in the literature about the role of treatment of adenomyosis in subfertility (80). Similar results have been accumulated about the delivery rate after partial (73.3%) and complete (83.1%) excision of adenomyosis (P¼ .58), and the miscarriage rate after partial (26.7%) and complete (16.9%) excision of adenomyosis (P¼ .58). No comment upon the achievement of pregnancy after nonexcisional techniques can be made because of the lack of reliable data. It appears that there is a trend for increased fertility after surgery for adenomyosis in the complete excision group, but more data are needed to elicit safe results for clinical practice. Adenomyosis and uterine rupture. A spontaneous uterine rupture during pregnancy in gravid uteri complicated by adenomyosis has been recorded in isolated case reports, even with no prior cytoreductive surgery (2). Furthermore, there is a recognized risk of uterine rupture during pregnancy or labor after conservative surgery for adenomyosis (32). However, the risk of rupture accompanies all types of uterine surgery: the incidence of symptomatic uterine rupture during vaginal birth after cesarean delivery (VBAC) or laparoscopic myomectomy is reported to be 0.27% and 1.0%, respectively (27, 81). After adenomyomectomy, it is speculated that subsequent uterine scars may conceal dense residual adenomyotic foci, and as a consequence the tensile strength of the uterus may decline leading to possible rupture of pregnant uterus (82). Wang et al. (48) described this risk as being as high as one out of eight women experiencing uterine rupture in pregnancy/labor after cytoreductive surgery for adenomyosis. Moreover, there are some studies where alternative operative procedures are proposed for the adequate healing of uterine wound after this type of intervention to prevent major complications such as uterine rupture during labor (11). Pregnancy Issues Intervention to conception time. In most of the studies that dealt with pregnancy after surgery for adenomyosis, attempts for conception were permitted at least 3 months after the intervention (13, 62). Implication to ART methods. It has been reported that ART methods show increased pregnancy rates compared with natural cycles after an operative intervention for adenomyosis (30). Moreover, a single-embryo transfer policy ensures less risk of uterine rupture, because a twin pregnancy generates uterine activity at an earlier gestational age, which may lead to this devastating event (32). Although the data dealing with this issue are still scarce, our results do not support the use of a particular technique to increase the conception rates after ART methods in women with adenomyosis. VOL. - NO. - / - 2013 Adenomyosis and delivery. Although most of the reported deliveries have been completed by cesarean delivery, there have been a few reports vaginal deliveries being allowed. Sporadic reports have outlined the risk of severe atonic postpartum hemorrhage in women with known adenomyosis, which can necessitate a peripartum hysterectomy (2). Because of the absence of data and experience, an elective caesarian delivery after adenomyomectomy seem preferable for patient safety, especially in nonorganized centers. General Comments Conservative surgical intervention: first-line approach for adenomyosis. This study shows that conservative surgical intervention is quite likely to improve symptoms from diffuse adenomyosis, and in cases of focal adenomyosis there is a good possibility of permanent treatment. So it is sound to select the appropriate treatment for the right patient: in cases of focal adenomyosis, laparoscopic excision appears to be the first-line approach; in women with diffuse adenomyosis who are interested in a future pregnancy, aggressive excision of the lesion with secure restoration of the uterine wall thickness might offer the best results. It is of outmost important to preoperatively [1] ensure the definite diagnosis of adenomyosis, and [2] assess the location and the size of each adenomyotic focus. Magnetic resonance imaging assists in the achievement of both of these preoperative goals and helps the surgeon to remove completely each focus of adenomyosis (26, 51). Preoperative and postoperative use of GnRH agonist therapy. The role of combination approach to adenomyosis with cytoreductive surgery and administering a gonadotropinreleasing hormone (GnRH) agonist in the management of patients wishing to preserve their uterus is not clear. It is hypothesized have a synergistic effect because during 13 ORIGINAL ARTICLE: FERTILITY PRESERVATION cytoreductive surgery the affected tissues with relatively poor blood supply are removed and the response of the remaining adenomyosis to hormone treatment is therefore enhanced (83). The advantages of preoperative use of GnRH-agonist therapy include the reduction of uterine vascularity, the correction of anemia, and the reduction of operative bleeding (facilitates laparoscopy rather than laparotomy) (12). The disadvantages of preoperative use of GnRH-agonist therapy are that normal size uteri recognizing adenomyotic tissues after GnRH treatment is difficult, assessing the demarcation between adenomyosis and normal myometrium is difficult, the risk of endometrial perforation is increased, and removing a large amount of adenomyotic lesions becomes difficult (an adverse effect of GnRH-agonist therapy) (12). Laparotomy or Laparoscopy 4. 5. 6. 7. 8. 9. 10. 11. 12. Traditionally, laparotomy has been used for the surgical treatment of adenomyosis because of the extension of the disease within the myometrium and the difficulty in suturing the remaining uterine wedges after the excision. The main advantage of laparotomy remains the ability of the surgeon to palpate and recognize the adenomyotic lesions intraoperatively. However, when the adenomyotic lesion can be clearly outlined via MRI, laparoscopy is feasible either for ablation of the adenomyotic foci or for excision of adenomyomas, whereas laparoscopic suturing presents no more difficulty compared with suturing after myomectomy (16, 51). 16. Which Technique is Better? 17. There is no strong evidence to indicate a technique that secures the best clinical and reproductive performance. Each investigator describes the theoretical advantages of his or her technique, but in practice the results show no statistically significant clinical differences. Mainly, most of the modifications aim [1] to maximize the amount of adenomyosis excised during surgery by offering an increased area where surgical manipulations can be performed, and [2] to empower the uterine wall integrity so that a future pregnancy can be sustained without uterine rupture. 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Laparoscopic excision of myometrial adenomyomas in patients with adenomyosis uteri and main symptoms of severe dysmenorrhea and hypermenorrhea. J Am Assoc Gynecol Laparosc 2004;11:86–9. Wei S, Feng R, Cui Q, Luo Y, Zhang S. Uterine adenomyoma with lymphoid infiltration simulating lymphoma. Gynecol Oncol 2004;95:409–11. VOL. - NO. - / - 2013 53. 54. 55. 56. 57. 58. 59. 60. 61. 62. 63. 64. 65. 66. 67. 68. 69. 70. 71. 72. 73. 74. 75. 76. 77. Ozaki T, Takahashi K, Okada M, Kurioka H, Miyazaki K. Live birth after conservative surgery for severe adenomyosis following magnetic resonance imaging and gonadotropin-releasing hormone agonist therapy. Int J Fertil Womens Med 1999;44:260–4. Kataoka ML, Togashi K, Konishi I, Hatabu H, Morikawa K, Kojima N, et al. MRI of adenomyotic cyst of the uterus. J Comput Assist Tomogr 1998;22: 555. Hofmann GE, Acosta AA, Gaddy NE. Hysterosalpingographic diagnosis of uterine adenomyoma. Obstet Gynecol 1989;73:885–7. Honore LH, Cumming DC, Dunlop DL, Scott JZ. Uterine adenomyoma associated with infertility. A report of three cases. J Reprod Med 1988;33:331–5. Lin J, Sun C, Zheng H. Gonadotropin-releasing hormone agonists and laparoscopy in the treatment of adenomyosis with infertility. Chin Med J (Engl) 2000;113:442–5. Huang WH, Yang TS, Yuan CC. Successful pregnancy after treatment of deep adenomyosis with cytoreductive surgery and subsequent gonadotropin-releasing hormone agonist: a case report. Zhonghua Yi Xue Za Zhi (Taipei) 1998;61:726–9. Kammerer-Doak DN, Magrina JF, Nemiro JS, Lidner TK. Benign gynecologic conditions associated with a CA-125 level > 1,000 U/mL: a case report. J Reprod Med 1996;41:179–82. Van Praagh I. Conservative surgical treatment for adenomyosis uteri in young women: local excision and metroplasty. Can Med Assoc J 1965;93: 1174–5. Naidu PM, Chacko S, Krishna S. Pregnancy following fundectomy for adenomyosis: report of a case. J Obstet Gynaecol Br Emp 1958;65:994–5. Kriplani A, Mahey R, Agarwal N, Bhatla N, Yadav R, Singh MK. Laparoscopic management of juvenile cystic adenomyoma: four cases. J Minim Invasive Gynecol 2011;18:343–8. Acien P, Bataller A, Fernandez F, Acien MI, Rodríguez JM, Mayol MJ. New cases of accessory and cavitated uterine masses (ACUM): a significant cause of severe dysmenorrhea and recurrent pelvic pain in young women. Hum Reprod 2012;27:683–94. Chun SS, Hong DG, Seong WJ, Choi MH, Lee TH. Juvenile cystic adenomyoma in a 19-year-old woman: a case report with a proposal for new diagnostic criteria. J Laparoendosc Adv Surg Tech A 2011;21:771–4. Acien P, Acien M, Fernandez F, Jose Mayol M, Aranda I. The cavitated accessory uterine mass: a m€ ullerian anomaly in women with an otherwise normal uterus. Obstet Gynecol 2010;116:1101–9. Akar ME, Leezer KH, Yalcinkaya TM. Robot-assisted laparoscopic management of a case with juvenile cystic adenomyoma. Fertil Steril 2010;94: e55–6. Liang YJ, Hao Q, Wu YZ, Wu B. Uterus-like mass in the left broad ligament misdiagnosed as a malformation of the uterus: a case report of a rare condition and review of the literature. Fertil Steril 2010;93:1347.e13–6. Ball E, Ganji M, Janik G, Koh C. Laparoscopic resection of cystic adenomyosis in a teenager with arcuate uterus. Gynecol Surg 2009;6:367–70. Ho ML, Ratts V, Merritt D. Adenomyotic cyst in an adolescent girl. J Pediatr Adolesc Gynecol 2009;22:e33–8. Dogan E, Gode F, Saatli B, Seçil M. Juvenile cystic adenomyosis mimicking uterine malformation: a case report. Arch Gynecol Obstet 2008;278:593–5. Kamio M, Taguchi S, Oki T, Tsuji T, Iwamoto I, Yoshinaga M, et al. Isolated adenomyotic cyst associated with severe dysmenorrhea. J Obstet Gynecol Res 2007;33:388–91. Takeda A, Sakai K, Mitsui T, Nakamura H. Laparoscopic management of juvenile cystic adenomyoma of the uterus: report of two cases and review of the literature. J Minim Invasive Gynecol 2007;14:370–4. Potter DA, Schenken RS. Noncommunicating accessory uterine cavity. Fertil Steril 1998;70:1165–6. Tamura M, Fukaya T, Takaya R, Ip CW, Yajima A. Juvenile adenomyotic cyst of the corpus uteri with dysmenorrhea. Tohoku J Exp Med 1996;178:339–44. Ors F, Lev-Toaff A, Bergin D. Cystic adenomyoma: transvaginal ultrasound and MRI findings. Anatol Clin Investig 2009;3:68–70. Iribarne C, Plaza J, De la Fuente P, Garrido C, Garzon A, Olaizola JI. Intramyometrial cystic adenomyosis. J Clin Ultrasound 1994;22:348–50. Parulekar SV. Cystic degeneration in an adenomyoma (a case report). J Postgrad Med 1990;36:46–7. 15 ORIGINAL ARTICLE: FERTILITY PRESERVATION 78. 79. 80. 16 Giana M, Montella F, Surico D, Vigone A, Bozzola C, Ruspa G. Large intramyometrial cystic adenomyosis: a hysteroscopic approach with bipolar resectoscope: case report. Eur J Gynaecol Oncol 2005;26:462–3. Somigliana E, Vercellini P, Daguati R, Pasin R, De Giorgi O, Crosignani PG. Fibroids and female reproduction: a critical analysis of the evidence. Hum Reprod Update 2007;13:465–76. Maheshwari A, Gurunath S, Fatima F, Bhattacharya S. Adenomyosis and subfertility: a systematic review of prevalence, diagnosis, treatment and fertility outcomes. Hum Reprod Update 2012;18:374–92. 81. 82. 83. Guise JM, McDonagh MS, Osterweil P, Nygren P, Chan BK, Helfand M. Systematic review of the incidence and consequences of uterine rupture in women with previous caesarean section. BMJ 2004;329:19–25. Levgur M. Therapeutic options for adenomyosis: a review. Arch Gynecol Obstet 2007;276:1–15. Wang PH, Yang TS, Lee WL, Chao HT, Chang SP, Yuan CC. Treatment of infertile women with adenomyosis with a conservative microsurgical technique and a gonadotropin-releasing hormone agonist. Fertil Steril 2000; 73:1061–2. VOL. - NO. - / - 2013 Fertility and Sterility® SUPPLEMENTAL FIGURE 1 Flow diagram of search strategy. Grimbizis. Uterus sparing surgery for adenomyosis. Fertil Steril 2013. VOL. - NO. - / - 2013 16.e1 ORIGINAL ARTICLE: FERTILITY PRESERVATION SUPPLEMENTAL TABLE 1 Criteria for evaluation of the studies included in the review. Selection 1. Type of study design 2. No. of patients 3. Is the definition of the extent of the adenomyosis adequate? Is the definition of the type of adenomyosis adequate? 4. Representativeness of the cases Exposure 5. Ascertainment of surgical technique Is there a detailed description of the surgical technique? Outcome 6. Outcome evaluation 7. Was follow-up long enough for outcomes to occur? 8. Adequacy of follow-up of cohorts 9. Statistical analysis Maximum grading Criteria for study evaluation Grading Prospective Retrospective >25 <25 Clinical/not reported MRI or U/S and clinical Yes No Consecutive or obviously representative series of cases Potential for selection biases or not stated 1 0 1 0 1 0 1 0 1 0 Secure record (e.g., surgical records) Written self report of medical record only No description Yes No 1 0 0 1 0 Structured questionnaire 1 Self report/No description >24 months <24 months Complete follow-up/all subjects accounted for Subjects lost to follow-up unlikely to introduce bias, small number lost Inadequate follow-up rate No statement Existence of statistical analysis Absence of statistical analysis 0 1 0 1 1 0 0 1 0 9/9 Note: Studies accumulating a score R5 were considered as trials with powerful evidence of their results, but those with a score <5 were considered as poor. MRI ¼ magnetic resonance imaging; U/S ¼ ultrasound. Grimbizis. Uterus sparing surgery for adenomyosis. Fertil Steril 2013. 16.e2 VOL. - NO. - / - 2013 VOL. - NO. - / - 2013 SUPPLEMENTAL TABLE 2 Complete adenomyomectomy: quality assessment of the relevant studies. Author, year Study No. of design patients Prospective studies Dai Pro 2012/EJOGRB 1 Focal 1 Consecutive adenomyosis (adenomyoma) 1 104 1 U/S, MRI Diffuse/focal 1 Consecutive adenomyosis Pro Wang PH 2009/FS Pro 1 165 1 U/S Takeuchi 2006/JMIG Pro 1 Retrospective studies Al Jama Retro 0 2011/Oman Koo Retro 0 2011/Pak JMS Sun Retro 0 2011/Chin MJ Grimbizis 2008/FS Retro 0 Fedele 1993/HR Retro 0 14 0 MRI Focal 1 Consecutive adenomyosis (adenomyoma) Focal 1 Consecutive adenomyosis (adenomyoma) 18 0 U/S, MRI Focal 1 Consecutive adenomyosis (adenomyoma) 18 0 U/S Focal 1 Consecutive adenomyosis (adenomyoma) 40 0 NA Focal 0 Consecutive adenomyosis (adenomyoma) 6 0 U/S Focal 1 Consecutive adenomyosis (adenomyoma) 18 1 Histology Focal 0 Consecutive adenomyosis (adenomyoma) Retro 0 2 0 U/S Retro 0 1 0 U/S Focal 1 NA adenomyosis (adenomyoma) Focal 1 NA adenomyosis (adenomyoma) Grimbizis. Uterus sparing surgery for adenomyosis. Fertil Steril 2013. Outcome evaluation Follow Adequacy of up/adequate follow-up Statistical Total length of cohorts analysis grade 1 Surgical Open records excision/classic technique 1 Surgical Open records excision/triple flap technique 1 Surgical Open or lap records excision/classic technique 1 Surgical Lap excision/ records uterine wall reconstruction with overlapping flaps 1 Structured 1 24/12 questionnaire 1 Yes 1 Yes 1 9 1 Structured 1 24/12 questionnaire 1 Yes 1 Yes 1 9 1 Structured 1 24/12 questionnaire 1 Yes 1 Yes 1 9 1 Structured 1 NA questionnaire 0 No 0 Yes 1 6 1 Surgical Open or Lap records excision/classic technique 1 Surgical Open or Lap records excision/classic technique 1 Surgical Open or Lap records complete excision/classic technique with additional Ushape suturing 1 Surgical Lap records excision/classic technique 1 Surgical Open records excision/classic technique 1 Self-report 1 Yes 1 Yes 1 6 1 9/12 1 Structured questionnaire 0 Yes 1 Yes 1 6 1 Self-report 0 27/12 1 Yes 1 Yes 1 5 1 Structured 1 13/12 questionnaire 0 Yes 1 No 0 5 1 Self-report 0 53/12 1 Yes 1 No 0 5 1 Self-report 0 25/12 1 NA 0 No 0 3 1 Self-report 0 NA 0 NA 0 No 0 2 0 Surgical Lap records excision/classic technique 0 Surgical Open records excisiona/classic technique 0 36/12 16.e3 Fertility and Sterility® Ferrero 2005, AOG Representativeness Ascertainment of of the cases exposure/detailed surgical technique 38 1 U/S Osada 2011/RBM Case reports Wang CJ 2006/FS Modality of initial diagnosis/definition of extent of the disease Continued. Author, year Study No. of design patients Modality of initial diagnosis/definition of extent of the disease La Fianza 2004/JCU Retro 0 1 0 U/S Morita 2004/JAAGL Retro 0 3 0 MRI Wei 2004, Gyn Oncol Retro 0 1 0 Clinical Ozaki 1999/IJFWM Retro 0 1 0 MRI Kataoka 1998, JCAT Retro 0 3 0 MRI Hoffman 1989/O&G Retro 0 1 0 HSG Honore 1988/JRM Retro 0 3 0 U/S Hyams 1952 Retro 0 2 0 Clinical Coghlin 1947/CMJ Retro 0 1 0 Clinical Focal adenomyosis (adenomyoma) Focal adenomyosis (adenomyoma) Focal adenomyosis (adenomyoma) Focal adenomyosis (adenomyoma) Focal adenomyosis (adenomyoma) Focal adenomyosis (adenomyoma) Focal adenomyosis (adenomyoma) Diffuse adenomyosis Representativeness Ascertainment of of the cases exposure/detailed surgical technique 1 NA 0 Medical record 1 NA 0 Surgical records 0 NA 0 Surgical records 1 NA 0 Surgical records 1 NA 0 Surgical records 0 NA 0 Surgical records 1 NA 0 Surgical records 0 NA 0 Surgical records Focal 0 NA adenomyosis (adenomyoma) 0 Surgical records Open excisiona/classic technique Lap excision/classic technique Open excisiona/classic technique Open excisiona/classic technique Open excision/classic technique Open excision/classic technique Open excision/classic technique Open excision/classic technique (hysteroplasty) Open excision/classic technique Follow Adequacy of up/adequate follow-up Statistical Total length of cohorts analysis grade 0 Self-report 0 NA 0 NA 0 No 0 1 1 Self-report 0 36/12 1 NA 0 No 0 3 1 Self-report 0 6/12 0 NA 0 No 0 1 1 Self-report 0 5/12 0 NA 0 No 0 2 1 Self-report 0 NA 0 NA 0 No 0 2 1 Self-report 0 NA 0 NA 0 No 0 1 1 Self-report 0 36/12 1 NA 0 No 0 3 1 Self-report 0 36/12 1 NA 0 No 0 2 1 Self-report 0 NA 0 NA 0 No 0 1 Note: HSG ¼ hysterosalpingogram; Lap ¼ laparoscopic; MRI ¼ magnetic resonance imaging; NA ¼ not applicable; Pro ¼ prospective; Retro ¼ retrospective; U/S ¼ ultrasound. a Unclear description of the radicality of adenomyotic tissue excision. Grimbizis. Uterus sparing surgery for adenomyosis. Fertil Steril 2013. Outcome evaluation ORIGINAL ARTICLE: FERTILITY PRESERVATION 16.e4 SUPPLEMENTAL TABLE 2 VOL. - NO. - / - 2013 VOL. - NO. - / - 2013 SUPPLEMENTAL TABLE 3 Partial excision of adenomyosis/partial adenomyomectomy: quality assessment of the relevant studies. Author, year Study No. of design patients Retrospective studies Sun Retro 0 13 2011/Chin MJ Modality of initial diagnosis/definition of extent of the disease Representativeness of the cases 0 NA Focal 0 Consecutive adenomyosis (adenomyoma) Ascertainment of exposure/detailed surgical technique 1 Surgical Lap records partial excision/classic reconstruction 1 Surgical Open records excisiona/Asymmetric dissection of uterus 1 Surgical Open records excisiona/classic technique 1 Surgical Open records partial excision/modified H incision 0 Surgical Lap records excisiona/classic technique Outcome evaluation 0 Yes 1 Yes 1 4 1 Structured 1 12/12 questionnaire 0 Yes 1 No 0 6 1 Structured 1 36/12 questionnaire 1 Yes 1 Yes 1 8 1 Self-report 0 36/12 1 Yes 1 Yes 1 6 1 Self-report 0 24/12 1 Yes 1 No 0 4 0 Surgical Lap assisted vaginal records excisiona/classic technique 0 Surgical Lap excision/classic records technique 1 Self-report 0 12/12 0 NA 0 No 0 1 1 Self-report 0 3/12 0 NA 0 No 0 1 0 NA 0 Surgical Open excisiona/classic technique records 1 Self-report 0 12/12 0 NA 0 No 0 1 0 NA 0 Surgical Open excisiona/classic technique records 1 Self-report 0 1/12 0 NA 0 No 0 1 0 NA 0 Surgical Open excision/classic records technique 0 Surgical Open records excision/wedge resection 1 Self-report 0 12/12 0 NA 0 No 0 1 1 Self-report 0 <24/12 0 NA 0 No 0 1 Retro 0 44 1 MRI Diffuse adenomyosis 1 Consecutive Wang PH 2009/JOGR Retro 0 28 1 U/S Diffuse adenomyosis 1 Consecutive Fujishita 2004/GOI Retro 0 11 0 U/S, MRI Diffuse adenomyosis 1 Consecutive Wood 1998/HRU Retro 0 25 1 NA Diffuse/focal adenomyosis 0 NA Case reports Wada 2006/JMIG Retro 0 1 0 MRI 0 NA Lin 2000/CMJa Retro 0 2 Huang 1998, CMJ Retro 0 1 Kammerer-Doak 1996/JRM Retro 0 1 Van Praagh CJMA, 1965 Naidu 1958 Retro 0 1 Retro 0 1 Unclear description of lesion 0 U/S Unclear description of lesion 0 NA Unclear description of lesion 0 CT Unclear description of lesion 0 Clinical Diffuse adenomyosis 0 Clinical Diffuse adenomyosis 0 NA 0 NA Note: HSG ¼ hysterosalpingogram; Lap ¼ laparoscopic; MRI ¼ magnetic resonance imaging; NA ¼ not applicable; Pro ¼ prospective; Retro ¼ retrospective; U/S ¼ ultrasound. a Unclear description of the radicality of adenomyotic tissue excision. Grimbizis. Uterus sparing surgery for adenomyosis. Fertil Steril 2013. 16.e5 Fertility and Sterility® 0 20/12 Nishida 2010/FS 1 Self-report Follow Adequacy of up/adequate follow-up Statistical Total length of cohorts analysis grade Cystic adenomyomas and juvenile cystic adenomyomas: quality assessment of the relevant studies. Author, year Retrospective studies Takeuchi 2010/FS Kriplani 2011/JMIG Cases: Juvenile Acien 2012/HR Study design No. of patients Retro 1 9 Retro 0 4 Retro 0 3 Chun 2011/JLAST Retro 0 <5 Acien 2010/O&G Akar 2010/F&S Retro 0 <25 Modality of initial diagnosis/definition of extent of the disease 0 U/S, MRI JCA 0 U/S, MRI JCA 0 U/S, MRI JCA (reported as ACUM) 1 MRI JCA Representativeness of the cases 1 Consecutive 1 Consecutive 1 1 1 NA 0 1 NA 0 1 NA 0 Retro 0 <25 2 U/S, MRI JCA (reported as ACUM) 1 U/S JCA 1 NA 0 Liang 2010/F&S Ball 2009/ GynSurg Ho 2009/JPAG Dogan 2008/AOG Retro 0 <25 1 U/S 1 NA 0 Retro 0 <25 1 U/S 1 NA 0 JCA (reported as ACUM) JCA Ascertainment of exposure/detailed surgical technique VOL. - NO. - / - 2013 0 Retro 0 1 0 MRI JCA 1 NA 0 Nabeshima 2008/JMIG Retro 0 1 0 MRI JCA 1 NA 0 Surgical records Kamio 2007/JOGR Takeda 2007/JMIG Retro 0 1 0 MRI JCA 1 NA 0 Retro 0 1 0 MRI JCA 1 NA 0 Surgical records Surgical records Nabeshima Retro 0 2003/JAAGL 1 0 MRI JCA 1 NA 0 Surgical records Potter 1998/F&S Retro 0 1 0 U/S 1 NA 0 Surgical records Surgical records Tamura 1996/TJEM Cases: adults Retro 0 1 Grimbizis. Uterus sparing surgery for adenomyosis. Fertil Steril 2013. 1 NA 0 Yes 1 8 1 Structured 1 18/12 questionnaire 0 Yes 1 No 0 5 Open excisiona 1 Self-report 0 2/12 0 NA 0 No 0 2 Lap 1 Self-report 0 12/12 0 NA 0 No 0 2 excision/classic technique Open excisiona 1 Self-report 0 18/12 0 NA 0 No 0 2 Robotic excision/classic technique Open excisiona 1 Self-report 0 NA 0 NA 0 No 0 2 1 Self-report 0 18/12 0 NA 0 No 0 2 Lap 1 Self-report 0 18/12 0 NA 0 No 0 2 excision/classic technique Open excisiona 1 Self-report 0 NA 0 NA 0 No 0 2 1 Self-report 0 NA 0 NA 0 No 0 2 1 Self-report 0 12/12 0 NA 0 No 0 2 1 Self-report 0 NA 0 NA 0 No 0 2 1 Self-report 0 3/12 0 NA 0 No 0 2 1 Self-report 0 3/12 0 NA 0 No 0 2 1 Self-report 0 12/12 0 NA 0 No 0 2 1 Self-report 0 NA 0 NA 0 No 0 2 Surgical records Surgical records 1 NA JCA (reported as ACUM) 0 U/S, MRI JCA 1 Lap 1 U/S, MRI JCA Surgical records Surgical records Statistical Total analysis grade Yes Surgical records Retro 0 <25 Adequacy of follow-up of cohorts 1 Lap Surgical records Surgical records Follow up/adequate length 1 Structured 1 35/12 questionnaire Surgical records Surgical records Surgical records Outcome evaluation excision/classic technique excision/classic technique Open excision/classic technique Lap excision/classic technique Open excisiona Lap excision/classic technique Lap excision/classic technique Open excisiona Open excision a ORIGINAL ARTICLE: FERTILITY PRESERVATION 16.e6 SUPPLEMENTAL TABLE 4 VOL. - NO. - / - 2013 SUPPLEMENTAL TABLE 4 Continued. Study design No. of patients Retro 0 1 Ors 2009/Anatol Retro 0 1 Protopapas 2008 Retro 0 3 Wang JH 2007/FS Retro 0 1 Iribarne 1994, JCUS Retro 0 1 Parulekar 1990/JPGM Retro 0 1 Author, year Acien 2010/O&G Modality of initial diagnosis/definition of extent of the disease 0 U/S, MRI Cystic adenomyoma (reported as ACUM) 0 U/S, MRI Cystic adenomyoma (Focal adenomyosis) 0 U/S Cystic adenomyoma (Focal adenomyosis) 0 U/S Cystic adenomyoma (Focal adenomyosis) 0 U/S Cystic adenomyoma (Focal adenomyosis) 0 U/S Cystic adenomyoma (Focal adenomyosis) Representativeness of the cases Ascertainment of exposure/detailed surgical technique Outcome evaluation Follow up/adequate length Adequacy of follow-up of cohorts Statistical Total analysis grade 1 NA 0 Surgical records Open excisiona 1 Self-report 0 NA 0 NA 0 No 0 2 1 NA 0 Surgical records Open excision/classic technique 1 Self-report 0 NA 0 NA 0 No 0 2 1 NA 0 Surgical records Open excisiona 1 Self-report 0 NA 0 NA 0 No 0 2 1 NA 0 Surgical records Open excision/classic technique 1 Self-report 0 10/12 0 NA 0 No 0 2 1 NA 0 Surgical records Open excision/classic technique 1 Self-report 0 NA 0 NA 0 No 0 2 1 NA 0 Surgical records Open excision/classic technique 1 Self-report 0 NA 0 NA 0 No 0 2 Note: HSG ¼ hysterosalpingogram; JCA ¼ juvenile cystic adenomyoma; Lap ¼ laparoscopic; MRI ¼ magnetic resonance imaging; NA ¼ not applicable; Pro ¼ prospective; Retro ¼ retrospective; U/S ¼ ultrasound. a Unclear description of the radicality of adenomyotic tissue excision. Grimbizis. Uterus sparing surgery for adenomyosis. Fertil Steril 2013. Fertility and Sterility® 16.e7 Nonexcisional techniques of surgical treatment of adenomyosis: quality assessment of the relevant studies. Author, year Kang 2009/JMIG Study design Retro 0 No. of Patients Modality of initial diagnosis/definition of extent of the disease 37 1 U/S 1 Consecutive 1 1 20 0 U/S, MRI Unclear 0 Consecutive description of lesion 1 Retro 0 11 0 NA Pro 10 0 MRI Retro 0 190 1 U/S Retro 0 1 0 U/S Retro 0 1 0 Clinical Retro 0 1 0 U/S Maia Retro 0 2003/JAAGL Wood Retro 0 1998/HRU Yang 2009/FS Pro 1 95 1 U/S 18 0 NA 7 0 U/S Retro 0 1 0 U/S Retro 0 1 0 U/S Kanaoka Retro 0 2004/Osaka Retro 0 Chan 2001/Med J Malaysia 1 1 Wang Pro 2002/JAAGL Wood 1998/HRU Philips 1996/JAAGL Preutthupan, 2010/JOGR Fernadez 2007/JMIG Kumar 2007/JMIG Giana 2005/EJGO Furman 2007/UOG Ryo 2006/JRM 1 Diffuse/focal adenomyosis Representativeness of the cases Diffuse/focal adenomyosis Unclear description of lesion Diffuse/focal adenomyosis Diffuse adenomyosis 0 NA 0 0 NA 0 1 Consecutive 1 1 NA 0 Unclear description of lesion Focal adenomyosis (cystic adenomyoma) Unclear description of lesion Diffuse/focal adenomyosis Focal adenomyosis 0 NA 0 1 NA 0 0 Consecutive 1 0 NA 0 1 Consecutive 1 0 0 MRI Focal Adenomyosis 1 NA (cystic adenomyoma) Focal Adenomyosis 1 NA (cystic adenomyoma) Diffuse adenomyosis 1 NA 0 U/S Diffuse adenomyosis 0 1 NA 0 0 Ascertainment of exposure/detailed surgical technique Follow up/adequate length Adequacy of follow-up of cohorts Statistical Total analysis grade 1 Structured 1 12/12 questionnaire 0 Yes 1 Yes 1 7 1 Structured 1 8/12 questionnaire 0 Yes 1 Yes 1 6 1 Self-report 0 24/12 1 Yes 1 No 0 3 1 Self-report 0 25/12 1 Yes 1 No 0 4 1 Self-report 0 60/12 1 Yes 1 Yes 1 7 1 Self-report 0 NA 0 NA 0 No 0 2 1 Self-report 0 18/12 0 NA 0 No 0 1 1 Self-report 0 6/12 0 NA 0 No 0 2 TCRE Mirena 1 Self-report 0 12/12 0 Yes 1 Yes 1 5 Endomyometrial resection Open HIFU 1 Self-report 0 24/12 1 Yes 1 No 0 3 1 NA 0 NA 0 NA 0 Yes 1 4 0 36/12 1 NA 0 No 0 3 0 NA 0 NA 0 No 0 2 0 12/12 0 NA 0 No 0 2 1 Structured 1 36/12 questionnaire 1 NA 0 No 0 4 Surgical Laparoscopic records partial resection of adenomyosis þ UAO Surgical Laparoscopic records uterine artery ligation Surgical Myometrial records electrocoagulation Surgical Laparoscopic bipolar records coagulation Surgical Rollerball endometrial records ablation Surgical Operative records hysteroscopy Surgical TCRE records Surgical Resectoscope records Surgical records Surgical records Surgical records Surgical records Surgical records Surgical records Surgical records Outcome evaluation U/S aspiration, 1 Self-report alcohol instillation Radiofrequency 1 Self-report ablation MEA 1 Self-report Balloon thermoablation VOL. - NO. - / - 2013 Note: HIFU ¼ high-intensity focal ultrasound; HSG ¼ hysterosalpingogram; JCA ¼ juvenile cystic adenomyoma; Lap ¼ laparoscopic; MEA ¼ microwave endometrial ablation; MRI ¼ magnetic resonance imaging; NA ¼ not applicable; Pro ¼ prospective; Retro ¼ retrospective; TCRE ¼ transcervical endometrial resection; UAO ¼ uterine artery occlusion; U/S ¼ ultrasound. Grimbizis. Uterus sparing surgery for adenomyosis. Fertil Steril 2013. ORIGINAL ARTICLE: FERTILITY PRESERVATION 16.e8 SUPPLEMENTAL TABLE 5
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