Maryam hashemi,MD,OB & GYN Fellowship of MIS 1397 IN THE NAME OF GOD Maryam hashemi,MD,OB & GYN Fellowship of MIS 1397

In adolescence, there is a significant delay in diagnosis, often because of physician non responsiveness SUMMARY: Early diagnosis of adolescent endometriosis is critical. An understanding of the complex pro inflammatory pathways underlying its progression and tailored medical-surgical treatment offers the greatest potential to decrease disease symptomatology.

It has to be remembered that dysmenorrhoea is a Sarıdog˘an / European Journal of Obstetrics & Gynecology and Reproductive Biology (2017) They calculated that the overall prevalence of visually confirmed endometriosis was 62% (range 25–100%) in all adolescent girls undergoing laparoscopic investigation for pain. It has to be remembered that dysmenorrhoea is a common symptom in teenagers and that it affects up to 40–50% of young women, with severe forms in 15% Reported risk factors for adolescent endometriosis include early menarche, positive family history and obstructive type Mullerian anomalies.

Sarıdog˘an / European Journal of Obstetrics & Gynecology and Reproductive Biology (2017) The most common type of pain in adolescents with endometriosis is classical dysmeorrhea and pelvic pain . Adolescents may be more likely to present with non-cyclical pain,unlike adult women with endometriosis, who are more likely to complain of cyclical pain, i.e. dysmenorrhoea [5]. Other symptoms include dyschezia, constipation, intestinal cramps, exercise pain and bladder pain. Sexually active teenagers may report dyspareunia

Sarıdog˘an / European Journal of Obstetrics & Gynecology and Reproductive Biology (2017) Transvaginal or transrectal ultrasound examinations, when possible, may be helpful in identifying deep nodules or adherent ovaries in experienced hands A normal ultrasound examination in the absence of endometriomas or obvious deep nodules does not rule out endometriosis. Laparoscopy still remains the gold standard in diagnosing or ruling out pelvic endometriosis

Sarıdog˘an / European Journal of Obstetrics & Gynecology and Reproductive Biology (2017) Dysmenorrhoea in adolescence is common and treating young girls with dysmenorrhoea with NSAIDs and/or COC pill is a common practice. Both primary dysmenorrhoea and secondary dysmenorrhoea due to endometriosis can respond to these therapies and symptomatic improvement does not rule out endometriosis. This approach may improve the symptoms and avoid a significant number of further unnecessary investigations including laparoscopy. However, it is also possible that endometriosis may progress whilst the symptoms are masked. Hence,there is an urgent need to start prospective research to establish long term benefits and potential disadvantages of empirical treatment with the COC or NSAIDs.

If the pain symptom persists despite the COC and/or NSAIDs, probability of endometriosis needs to be remembered.

Data from the published reports with follow up confirm that recurrence of pain and/or disease is a significant problem and it appears to occur regardless of postoperative adjuvant treatment. This picture is probably not dissimilar to the situation in adult women and highlights the long term nature of endometriosis. There is currently no consensus as to whether surgery should be avoided as much as possible, or surgical treatment should be considered at an early stage and should aim to eliminate endometriosis completely, including DE. Whilst some recommend a conservative approach due to high recurrence rates, the others suggest early intervention before more severe lesions develop. Further research is required to determine which approach would offer a better long term outcome.

R E P R O D U C T I V E B I O M E D I C I N E ( 2 0 1 8 )

R E P R O D U C T I V E B I O M E D I C I N E ( 2 0 1 8 ) The median number of physicians who evaluated the adolescents was three Clearly, physicians are reluctant to submit an adolescent to traditional laparoscopy. For this reason, we believe that a new, stepwise, minimally invasive approach to EOE is now fully justified.

R E P R O D U C T I V E B I O M E D I C I N E ( 2 0 1 8 ) These observations prompted us to develop a new theory on the origin of EOE based on the hypothesis that naive endometrial progenitor cells can be seeded into the pelvic cavity in concomitance with NUB. These cells, once settled in the pelvic cavity, would stay dormant for years and in the presence of factors known to lead to the development of endometriosis, can be activated at the time of thelarche, resulting in the development of a specific phenotype characterized by more florid and progressive disease because of the presence of highly angiogenic implants, recurrent ectopic bleeding and endometrioma formation (Brosens et al., 2016).

R E P R O D U C T I V E B I O M E D I C I N E ( 2 0 1 8 ) correlation between stage of endometriosis and age was found to be small

Recurrence In reviewing published data up to 2009, Guo (2009a) reported a high overall recurrence rate for adult disease, estimated as 21.5% at 2 and40–50% at 5 years. In an investigation specifically aimed at adolescents, Tandoi et al (2011) followed 57 women aged 21 years or younger over a 5-year period and in 32 (56%) observed a recurrence of the disease after surgery.

R E P R O D U C T I V E B I O M E D I C I N E ( 2 0 1 8 ) Young age seems to be a major risk factor for recurrence of ovarian endometriomas after cystectomy, risk being inversely related to the age at surgery. They assessed potential risk factors for recurrence in patients receiving no medication and, again found that age at surgery was the only significant risk factor for recurrence. When evaluating these results a word of caution is mandatory, as patients with appropriate follow-up usually represent a selected group and may well not be representative of the general population.

R E P R O D U C T I V E B I O M E D I C I N E ( 2 0 1 8 ) The search for signs and symptoms five practical ways to diagnose endometriosis as early as possible and detect patients at risk of developing the disease in the future: 1) never underestimate the pain; 2)always consider endometriosis as a possible cause of severe cyclic pain; obtain a detailed and accurate history before performing clinical evaluation and pelvic sonography; 3) treat the pain with hormonal therapies and analgesics; plan frequent follow-up visits to reevaluate the patient. Although these recommendations have value, more is required to speed up diagnosis, including indirectly detecting an increased risk of NUB. Low birth weight preeclampsia Post-maturity

Progress in management Imaging techniques

R E P R O D U C T I V E B I O M E D I C I N E ( 2 0 1 8 ) TVS and MRI. Both can identify and characterize severe endometriotic lesions, but unfortunately, virtually no information is available on their application in adolescents. To determine progression of disease through interstitial fibrosis and microvascular injuries associated with ovarian endometriotic cysts,Qiu et al. (2012) used transvaginal colour Doppler sonography and evaluated ovarian interstitial blood flow, finding that changes in resistance indices in ovaries with endometriosis were related to interstitial fibrosis and devascularization.

Medical treatment

R E P R O D U C T I V E B I O M E D I C I N E ( 2 0 1 8 ) the consensus was that, in dealing with EOE, both medical and surgical modalities have the potential of improving quality of life, alleviating symptoms, preventing the development of more severe disease later in life and minimizing the likelihood that future fertility may become compromised Although surgery is effective in treating endometriosis in adults, it may well be a double-edged sword in adolescents. This is why medical treatments assume a special importance in treating adolescents.

R E P R O D U C T I V E B I O M E D I C I N E ( 2 0 1 8) In principle, the same drugs can be used in adolescent and adult patients. In a mini review of dysmenorrhoea in adolescence, Harel (2006)states: ‘If dysmenorrhea does not improve within 6 months of treatment with non-steroidal anti-inflammatory drugs (NSAID) and oral contraceptive pill, a laparoscopy is indicated to look for endometriosis’. Once diagnosis is posed, Unger and Laufer (2011) have proposed a combined medical–surgical approach as the best method to slow its progression. This, together with no delay in treatment, seem key to the disease’s successful containment. At any rate, an attempt with a medical regimen should represent the first choice.

Stepwise minimally invasive approach

R E P R O D U C T I V E B I O M E D I C I N E ( 2 0 1 8) Laparoscopy should be considered if adolescents with chronic pelvic pain who do not respond to medical treatment (NSAID and oral contraceptive pills) since endometriosis is very common under these circumstances(ESHRE 2016) Nearly 60% of the patients had a treatable pelvic disease, leading to the conclusion that diagnostic laparoscopy is an invaluable tool in the diagnosis of chronic pelvic pain in adolescents and should be carried out before prescribing long term medical treatment or starting a psychiatric evaluation(Vercellini et al). (1989)

Journal of Minimally Invasive Gynecology, Vol 25, No 5, July/August 2018 Of the 255 patients included in this study, 186 (73%) showed pelvic adhesions and 134 (53%) had myometrial adenomyosis. Only 57 patients (22%) showed a single ovarian lesion with a mobile ovary and without any other ultrasound signs of pelvic endometriosis or adhesions, and in 19 of them adenomyosis was found at TVS, resulting in a completely isolated endometrioma seen in only 38 women (15%). Of the 255 women, 55 patients (21.5%) showed posterior rectal DIE and 93 patients (36.4%) exhibited a thickening of at least 1 USL at TVS. The presence of DIE (anterior and posterior) was detected in 113 patients (44.3%) with endometriomas.

Journal of Minimally Invasive Gynecology, Vol 25, No 5, July/August 2018 Comparing laparoscopic and histologic findings with TVS mapping, despite the low number of patients who underwent surgery, the accuracy in diagnosing endometriosis in different pelvic locations ranged from 88% to 100%.

Journal of Minimally Invasive Gynecology, Vol 25, No 5, July/August 2018 No correlation was found between the size of the endometrioma or an endometrioma with a maximum diameter ≥ 4 cm and the presence of DIE. Ovarian endometriomas are present in approximately one third of patients with endometriosis

Because treatment options differ, the sonographer must search for all endometriotic lesions to map all disease within the pelvis and postulate an accurate plan for the patient, whether it be surgical, medical, or fertility-focused.

Journal of Minimally Invasive Gynecology, Vol 25, No 5, July/August 2018 The current study results clearly underline the importance of an accurate TVS pelvic evaluation and precise mapping of the pelvic sites, not only soft markers. Furthermore, a thorough TVS investigation must be completed in all women with endometriomas, not just those planning to undergo surgical treatment but also patients planning medical or assisted reproductive technology management.

More than half of the women in the current study with small endometriomas had adhesions and adenomyosis that could decrease fertility. Indeed, in the 44% of current patients with endometriomas and associated DIE, TVS detected the exact locations of concomitant adhesions. Also in the current study, adenomyosis and adhesions were found in 52% and 72%, respectively, of women with endometriomas, implying that TVS could be useful in asymptomatic women with endometriomas who do not desire pregnancy.

In conclusion, ovarian endometriomas are indicators for pelvic endometriosis and are rarely isolated. Ovarian endometriomas are easy to recognize, even small ones; adhesions and DIE require a skilled imaging professional both for TVS and magnetic resonance imaging.

Determining appropriate management, whether clinical or surgical, is critical for ovarian endometriomas and concomitant adhesions, endometriosis, and adenomyosis in patients desiring future fertility. To overcome the challenges in TVS diagnosis of concomitant lesions of ovarian endometriomas, it is our hope that dedicated training for sonographers can take place to alert professionals regarding detailed lesion mapping in this patient population.

Semin Reprod Med 2017 Review Article Management of Endometriomas Nonsurgical Management In case of ovarian endometriomas, the more conservative approach is obviously expectant management. This approach may be followed when there are no associated symptoms, and when sonographic features are reassuring in terms of the possibility of an unexpected ovarian malignancy.[5] [6] When choosing expectant management, follow-up should include serial ultrasound scans, preferably after 3 to 6 months if the cyst is diagnosed for the first time, and then yearly if there is no fast growth or change in sonographic features in the short-term period.

Semin Reprod Med 2017 Review Article Management of Endometriomas No current guideline indicates a threshold cyst size below which surgery may be safely withheld, in the absence of associated symptoms or suspicious ultrasound features. The 2005 guidelines of the European Society of Human Reproduction and Embryology (ESHRE) indicated 3 cm as the threshold above which histology, through surgical excision, “should be obtained to identify endometriosis and exclude rare instances of malignancy.”[7] In the updated ESHRE guidelines,[8] published in 2014, it is recommended that “clinicians should obtain tissue for histology in women undergoing surgery for ovarian endometrioma to exclude rare instances of malignancy,” without any mention on a cut-off level to mandate surgery. It is possible that the 3-cm threshold in the 2005 guidelines has been deleted in the updated 2014 version due to the recent concerns regarding “the risks of reduced ovarian function after surgery and the possible loss of the ovary.”[8]

Therefore, today it may seem reasonable, in a balance between the surgical risk of damaging the ovarian reserve and the advantages of surgery in terms of obtaining tissue specimen for ruling out an unexpected ovarian malignancy, to withhold surgery in selected cases also when the endometrioma is larger than 3 cm in maximal cyst diameter with typical ultrasound features. A two-dimensional parameter that may be reasonably taken into account in the selection of patients for surgery is the endometrioma growth rate, although no study has ever correlated the cyst growth rate to the incidence of ovarian malignancy.

In two studies by Alcázar et al,[9] [10] in no case of endometrioma without growth over time was ovarian malignancy detected. Therefore, absent or slow cyst growth during follow-up may be reassuring from an oncological point of view. If no other additional concerns, such as personal history of breast or ovarian cancer, or suspicious ultrasound features, are present, surgery may be withheld for asymptomatic endometriomas smaller than 5 cm. In the 5- to 10-cm range in largest cyst diameter, only selected cases may be managed expectantly, and the decision to withhold surgery should be discussed with the patient

An upper limit above which surgery should be mandatory, even in the absence of pain or infertility, and in the presence of reassuring ultrasound features and patient characteristics, may be set at 10 cm. Early ovarian cancers, in fact, may sometimes be misdiagnosed as benign cyst, due to the limits of ultrasonography in detecting suspect ultrasound features (septa, papillary projections, solid parts, and vascularization) in cysts larger than 10 cm

In case of infertility-associated endometrioma, abstention from surgery may seem a reasonable option, particularly for small cysts in the absence of pain symptoms. However, there is a lack of randomized clinical trials (RCTs) comparing expectant management to surgery in case of ovarian endometriomas in infertile patients. Case series of stage III–IV endometriosis patients managed expectantly report spontaneous pregnancy rates of 0 to 25%.[4] [12] On the other hand, Guzick et al reported 36-month cumulative pregnancy rates of 54 and 47% after surgery, respectively, for stage III and stage IV patients.[13] Vercellini et al, in a meta-analysis of uncontrolled studies of surgery for stage III–IV endometriosis, reported an overall pregnancy rate after surgery of 50%.[14]

Therefore, even in the absence of RCTs, expectant management seems unjustified, given the very low spontaneous pregnancy rate in advanced endometriosis patients left untreated, compared with pregnancy rates that can be obtained after surgery. The common association with pelvic pain, and the possibility of an unexpected ovarian malignancy, switches the balance further toward surgery as opposed to expectant management. The option of expectant management should therefore be thoroughly discussed with the infertile patient, considering additional factors such as patient age, duration of infertility, and ovarian reserve, and may be reserved for small cysts in young patients with preserved ovarian reserve. IVF-ET, as opposed to expectant management or surgery, should also be discussed with the patient

A nonsurgical treatment option that has been suggested by few authors is ultrasound-guided aspiration.[17] [18] Although less invasive than laparoscopy, ultrasound-guided aspiration is burdened by high rates of recurrences,[1] [18] [19] [20] infectious complications,[19] [21] and adhesion formation postprocedure.[22] Also, cyst fluid cytology is highly inaccurate to detect possible malignancy.[1] [23] The addition of a sclerosing agent within the cyst wall after aspiration does not seem to lower the recurrence rates.[20] Therefore, in view of the unsatisfactory recurrence rates and the associated risks, ultrasound-guided aspiration should not be considered a treatment option in case of ovarian endometriomas

ovarian cancer in endometrioma

Management of Ovarian Endometriomas and Pregnancy?

BILATERAL DECIDUALIZED ENDOMETRIOMAS DURING PREGNANCY G. NAKAI et al In the management of adnexal masses in pregnancy, surgical intervention is an additional option besides expectant management even for benign adnexal masses, especially when they are large in size (>8 –10 cm). This is because even benign adnexal masses can cause symptoms or obstetric complications such as torsion, rupture, and labor dystocia that may necessitate emergency surgery in the third trimester, thus adding an increased risk of complications(26). When malignancy is suspected, surgical treatment cannot be avoided to confirm the presence of malignancy pathologically (27). In conclusion, MRI can assist in the prospective diagnosis of decidualized ovarian endometrioma. However, considering that it is not yet possible to clearly differentiate decidualized endometriomas from ovarian cancer, surgery or watchful observation may still be needed to exclude the possibility of malignancy.

All patients were re-contacted by phone at the end of 2014. M. Bailleux et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 209 (2017) 100–104 This was a retrospective observational study in patients presenting with an endometriotic ovarian cyst diagnosed during ultrasound examination in the first trimester of pregnancy. Inclusion criteria were as follows: we included all (n = 46) pregnant women for whom the diagnosis of endometrioma was made in our institution, during the ultrasound examination in the first trimester of pregnancy between 2004 and 2013. Some women (7 patients) had endometriotic bilateral cysts, so our study concerned 53 cysts suspected to be endometriomas. All patients were re-contacted by phone at the end of 2014.

Surgery was used in 10 (19%) cysts In 8 of the 10 cases scheduled surgery was laparoscopy and in the other 2 cases emergency surgery was performed during cesarean section. Surgery was performed between 14 and 17 WG in 2 patients:

Histopathological examination confirmed an endometrioma for only 4 cysts (40%), including one that was decidualized. The other cysts were not endometriomas, but benign cysts: 4 mucinous cystadenomas, 1 serous cystadenoma and 1 dermoid cyst. the discrepancy between the suspicion of endometrioma on ultrasound and the histopathological results in pregnancy

5 women underwent surgery in the postpartum period. Interestingly, for ovarian cysts operated on postpartum, there was a better correlation between imaging and histopathology, suggesting that endometriomas resume a more typical appearance after pregnancy.

Decidualized endometrioma can mimic ovarian malignancy during pregnancy, since hyperechogenic papillary excrescences are vascularized on color Doppler, suggesting a malignant transformation. However, rounded papillary projections are supposed to be a typical ultrasound feature of decidualized endometriomas during pregnancy, while papillary projections usually have an irregular surface in borderline or malignant tumors.

Furthermore, papillary excrescences show a marked similarity in signal intensity and texture to decidualized endometrium in the uterus on MRI.

Conclusion In our study, fewer than half of cysts suspected to be endometriomas actually turned out to be endometriomas on histopathological examination. This emphasizes the difficulty of diagnosing endometriomas during pregnancy and the absolute necessity for surgical removal when ultrasonographic findings are doubtful. Decidualized endometrioma can mimic an ovarian malignancy during pregnancy, but this is a rare phenomenon.

Is there endometriosis after menopause?

We probably should think twice when proposing a non surgical approach to patients diagnosed with ovarian endometriomas

THANKS FOR YOUR ATTENTION