Critiques of selected articles November 2020

🚩Clinical Characteristics and Postoperative Symptoms of 85 Adolescents with Endometriosis.

Song XC, Yu X, Luo M, Yu Q, Zhu L. J Pediatr Adolesc Gynecol. 2020 Jun 30:S1083- 3188(20)30258-8

📢 Critique by Ertan SARIDOGAN MD, PhD

This article by Song et al is a retrospective analysis of 85 girls aged 19 years or younger who were treated surgically for endometriosis at Peking Union Medical College Hospital between     2008     and     2018.     The manuscript describes the clinical characteristics of the patients and gives some outcome data. The most striking feature is that more than half (44/85) adolescents were found to have a genital tract malformation and that most (97.7%) were obstructive malformations. In addition, 67% of the patients had an adnexal mass. These features indicate that these are a highly selected group of patients and do not reflect the features of adolescents with endometriosis in general. The authors except that their hospital is a referral centre for genital malformation and that surgery is usually performed when there is a pelvic mass. It is unclear how the genital malformations were treated. Previously published articles suggested that 7.3-24% of adolescents with endometriosis have a genital malformation. Even these numbers may be an overestimate, hence >50% genital malformation risk in an adolescent with endometriosis is unlikely. The follow-up information is also somewhat limited, but the patients had been followed for up to 140 months and the majority of patients had improvement of pain, particularly those with moderate to severe disease. Small number of patients with mild endometriosis were more likely to have persistent pain. Recurrence was described as detection of endometrioma of 2 cm or larger and 27% of the patients were found to have a ‘recurrence’. In conclusion, this retrospective analysis gives clinical characteristics of 85 adolescents with endometriosis and emphasizes the presence of genital malformations in this age group.

🚩Oocyte vitrification for fertility preservation in women with endometriosis: an observational study

Cobo A, Giles J, Paolelli S, Pellicer A, Remohí J, García-Velasco JA. Fertil Steril. 2020 Apr;113(4):836-844.

📢 Critique by Omar SHEBL, MD

In this retrospective multicenter study, the authors analyzed data from their fertility preservation program, freezing of unfertilized oocytes, regarding women with endometriosis. The time span from 2007 to 2018 is quite long and within this time 1044 women with endometriosis underwent the fertility preservation program. Of these 1044 women 485 women with endometriosis (46.5%), aged 35.7 ± 3.7 years at the time of vitrification and 37.3 ± 2.1 years at the time of warming, returned to use the vitrified oocytes, which is a high number. Main Outcome measures were oocyte survival rate and cumulative live-birth rate (CLBR). Inclusion criteria were age up to 42 years, endometrioma larger than 1 cm, and a serum AMH value of more than 0.5 ng/ml. 97.7% of the 485 women have been diagnosed with an endometriosis stage III-IV. 47.8% of the women attended the program after endometriosis surgery. A lower number of oocytes were obtained when surgery was performed before fertility preservation. 22% of embryo transfers were canceled for different reasons. However, the CLBR per patient was described with 46.4%, in women under 35 years 61.9% and over 35 years 28.4%. The authors stated that the most relevant finding of their study was that if women with endometriosis under 35 years wish to preserve fertility the oocyte retrieval should be performed before surgery. These patients have the best chances to get pregnant through such a fertility preservation program. The full article is worth reading and clinicians should use the given information in counseling their patients.  

🚩Outcome after surgery for deep endometriosis infiltrating the rectum

Bafort C, van Elst B, Neutens S, Meuleman C, Laenen A, d'Hoore A, Wolthuis A, Tomassetti C. Fertil Steril. 2020 Jun;113(6):1319-1327.e3.

📢 Critique by Gernot HUDELIST, MD

The work by Bafort et al. investigates differences in complication rates in women undergoing either conservative surgery or full-thickness segmental resection for intestinal deep endometriosis (DE). The design is retrospective, a single center experience and includes a total of 232 patients. A subgroup analysis is performed in women with and without previous surgery for endometriosis. Clavien-Dindo type 3 complications were more frequent in the segmental resection       group       (1/61       [1.6%] conservative      vs.      18/171      [10.5%] segmental), but after propensity analysis only a trend is observed. In the subgroup analysis, no difference or trend     was     found     (1/27     [3.7%] conservative       vs.       5/81       [6.2%] segmental). The authors therefore conclude that repeated surgery may potentially increase morbidity based on the observation that the modest difference in complication rates does not show up in the subgroup analysis. In my opinion, the results do not allow a clear conclusion. First and foremost, the paper is retrospective. Secondly, the comparison of the 2 surgical techniques does not take into account factors that are known to influence major complication rates. These include height of the anastomosis, concomitant vaginal opening and number of stapling magazines used etc.. This does significantly influence outcomes but no data are provided on these issues. Finally, the decision to do either one technique or the other appears to be purely individual and is not randomized. We know that as a consequence, surgeons using both techniques might be tempted to do segmental resection in more complicated cases with large rectal lesions which often involve the vagina and result in low anastomosis. One exception is the use of the  Rouen technique using transanal stapling which is not described to have been used in this study. The very modest increase in Clavien Dindo 3 complication rates does also not prove statistically significant after propensity analysis and is quite low and acceptable with a leakage rate of 2.9% in the segmental resection group. The subgroup analysis included women with previous surgeries but no data are provided on the type and extent of the previous procedures. This might blur the results of the subgroup analysis. Finally, the use of the rASRM score for DE is not the recommended tool since the score does not adequately describe DE such as the ENZIAN classification which is also recommended in the CORDES statement. I see this study as a retrospective evaluation of outcomes following surgery for DE but the conclusions made by the authors are, in my opinion, not clearly supported by the data they present.  

🚩Clinical Characteristics and Postoperative Symptoms of 85 Adolescents with Endometriosis

Xiao-Chen Song, Xin Yu, Min Luo, Qi Yu, Lan Zhu J Pediatr Adolesc Gynecol. 2020 Oct;33(5):519-523

📢 Critique by Caterina EXACOUSTOS, MD

The diagnosis of endometriosis in young adolescent girls is particularly challenging despite growing recognition that endometriosis often begins in adolescence. Dysmenorrhea is a frequent symptom in adolescent and can be associated with endometriosis. According to a review by Chapron et al.(2011), the main signs of endometriosis in young girls are the following: prolonged use of nonsteroidal anti-inflammatory drugs (NSAIDs), familiarity for endometriosis, frequent absenteeism from school or work during menstruation. In 10% of cases dysmenorrhea is related to Müllerian congenital anomalies, pelvic inflammatory disease, functional ovarian cysts or adhesions (4).  In the article of Zannoni et al (2014) were enrolled 250 teenagers who came to the family doctor for different indications and 12% showed suggestive symptoms of endometriosis Until now the only recognized diagnosis for endometriosis, called gold standard, was laparoscopy. Janssen (2013), in a meta-analysis reported a prevalence of endometriosis of 63% in adolescents with chronic pelvic pain and / or dysmenorrhea undergoing laparoscopic surgery. This percentage is certainly burdened by a bias in the selection of the population, which includes all adolescent patients undergoing surgery, and probably affected by important symptoms, often resistant to medical therapy. Also a very recently study of Song (2020) evaluate by laparoscopy the presence of endometriosis in 85 adolescents, 85% of them affected by severe dysmenorrhea.  Only 9% of adolescence present endometriosis in stage 1-2 and more than a half (51%) had a genital tract malformation. The conclusion of this paper, that surgery improves painful symptoms, is quite obvious, however any other type of medical treatment for endometriosis as alternative to surgery was not evaluated. The results of another very recently paper (Hirsch 2020), reported a metanalysis on endometriosis in adolescents again with laparoscopic diagnosis considered as gold standard and imaging (MRI or ultrasound) only as a less accurate option. The prevalence of only visually confirmed endometriosis in adolescents varied widely from 25 to 1005, with a mean prevalence of 64.5%, 70% of adolescents showed stage1-2 endometriosis. Diagnostic accuracy of ultrasound or MRI in diagnosing endometriosis has been described repetitively surprising it is accurate in adult but not used in adolescents, thus because transvaginal ultrasound is often contraindicated, but transrectal ultrasound and MRI could be alternative tools. However, it remains unclear whether preoperative imaging can diagnose small endometriosis lesions typical in adolescents. More specifically it is unclear whether an imaging is able to perform non-invasive diagnosis of all the endometriosis types (ovarian, superficial deep, adhesions) Therefore laparoscopic diagnosis is often considered the golden standard, because it is supposed to diagnose the presence or absence of endometriosis with 100% accuracy. However laparoscopy cannot always differentiate between deeper typical lesions and often DIE is missed when located under a normal peritoneal surface or in the upper abdomen or in the sigmoid.  We are now recognizing that for endometriosis but in particular for DIE there is an absence of a golden standard test to evaluate the accuracy of imaging but also of symptoms. We also realized that the classification of ASRM is often not adequate because it completely miss DIE. Thus actually we should accept that diagnosis of endometriosis are limited in adolescents undergoing a laparoscopy only for some type and site of the disease. Only location of endometriosis seen by normal laparoscopic approach are general reported what about endometriosis in deeper sites (for example ischiatic nerve) or in organs (uterus, sigma...). I believe that a new era should start where a combination of clinical and non-invasive imaging should be diagnostic for endometriosis without a surgical confirmation. The concept of offering surgery to adolescents due to chronic pelvic pain in order to have a visual /histological diagnosis of the disease is nowadays inappropriate. An accurate clinical and imaging evaluation could be much more effective and non invasive for the patient, allowing an early diagnosis and adequate clinical management that justifies surgery only in indispensable cases. A recent study of my group on ultrasound diagnosis of endometriosis in adolescents (Martire et al Fertil Steril in press) clearly showed that a dedicated ultrasound examination in expert hands is able to detect in adolescence the disease also for small DIE foci. However, we must admit that ultrasound cannot diagnose superficial endometriosis of the peritoneum, a form found in many laparoscopies in adolescents where surgical treatment is quite controversial. At the same time, we now know that retroperitoneal endometriosis can be better visualized with ultrasound examination than with a simple diagnostic laparoscopy that certainly does not investigate the retroperitoneum. Especially in a teenager without suspected DIE at imaging, laparoscopy should avoid unnecessary large retroperitoneal tissue resection in order to prevent lesion of functional organs and related complications. Furthermore, the discussion remains open as to whether it is appropriate and beneficial to treat the forms of minimal endometriosis early with a laparoscopy or whether it might be better to use only hormonal medical therapy to inactivate the foci of disease and reduce pain. Supporting surgery is the fact that DIE is often found in patients already taking estro-progestin therapy from adolescence and that perhaps an early-stage surgical treatment might have eradicated the initial disease. On the other hand, surgical treatment of endometriomas in adolescence is often the cause of reduced ovarian reserve and adhesion syndrome (Pirtea 2020). I feel that we need now in adolescents a non-surgical mode of diagnosing endometriosis and laparoscopy should be no more a diagnostic tool for endometriosi especially in adolescents Adolescents diagnosed with endometriosis at ultrasound (Martire 2020, Pirtea 2020) or with symptoms very suspicious for endometriosis, in particular severe dysmenorrhea, should be put on medical therapy (oral contraceptive or progestin-only pill) (Martire 2020, Pirtea 2020) and only those refractory to medical treatment should be explored and treated surgically, considering always particularly if ovarian or deep lesions are present, the possibility of fertility preservation. References
  1. Chapron C, Lafay-Pillet MC, Monceau E, Borghese B, Ngô C, Souza C. Questioning patients about their adolescent history can identify markers associated with deep infiltrating endometriosis. Fertil Steril. 2011; 95:877-88
  2. Dun EC, Kho KA, Morozov VV, Kearney S, Zurawin JL, Nezhat CH. Endometriosis in adolescents. JSLS 2015; 19(2):e2015
  3. Hirsch M, Dhillon-Smith R, Cutner A, Yap M, M Creighton S. The prevalence of endometriosis in adolescents with pelvic pain: a systematic review [published online ahead of print, 2020 Jul 28]. J Pediatr Adolesc Gynecol. 2020;S1083-3188(20)30287-4.
  4. Janssen EB, Rijkers AC, Hoppenbrouwers K, Meuleman C, D’Hooghe TM. Prevalence of endometriosis diagnosed by laparoscopy in adolescents with dysmenorrhea or chronic pelvic pain: a systematic review. Hum Reprod Update. 2013; 19:570–582.
  5. Martire FG, Lazzeri L, Conway F, Siciliano T, Pietropolli A, Piccione E, Zupi E, Exacoustos C. Adolescence and endometriosis: symptoms, ultrasound signs and early diagnosis. [published online ahead of print, 2020 Aug 8]. Fertil Steril. 2020;S0015-0282(20)30693-2
  6. Pirtea P, de Ziegler D, Ayoubi JM. Diagnosing endometriosis in adolescents: ultrasound is a game changer [published online ahead of print, 2020 Aug 8]. Fertil Steril. 2020;S0015-0282(20)30693-2.
  7. Song XC, Yu X, Luo M, Yu Q, Zhu L. Clinical Characteristics and Postoperative Symptoms of 85 Adolescents with Endometriosis [published online ahead of print, 2020 Jun 30]. J Pediatr Adolesc Gynecol. 2020;S1083-3188(20)30258-8.
  8. Zannoni L, Giorgi M, Spagnolo E, Montanari G, Villa G, Seracchioli R. Dysmenorrhea, absenteeism from school, and symptoms suspicious for endometriosis in adolescents. J Pediatr Adolesc Gynecol. 2014; 27:258-265

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