Factors associated with recurrent endometriomas after surgical excision

Background Endometriosis affects women in reproductive age and causes a great impact on their lives. When affecting the ovary, excision represents the main management option. However, recurrence represents a challenging situation for patients and physicians. This study aimed to determine factors contributing to endometriomas recur- rence after surgical excision.

This was a quasi-experimental study recruiting 60 patients with ovarian endometrioma. The mean age was 30.33 ± 7.95 years. The mean parity was 1.27 ± 0.69. The recurrence rate after excision was 11/60 (18.3%) after a mean follow-up period of 22.62 ± 4.96 months. None of the patients’ characteristics or endometriosis-related characteristics were significant factors contributing to cyst recurrence (age, parity, history of infertility, preopera- tive endometrioma diameter, preoperative AFC, preoperative AMH, degree of pelvic pain, degree of dysmenorrhea, degree of dyspareunia, pelvic tenderness, and induration) (p value > 0.05).

The patient’s related factors and endometrioma characteristics did not predict its recurrence.

Endometrioma, Recurrence, Prediction

Endometriosis is a gynecological condition which affects women of reproductive age, causing infertility, dysmen - orrhea, and dyspareunia [1]. Surgical excision is the prin - cipal treatment, as medical options are of limited efficacy. Although effective, surgery is associated with multiple complications, with recurrence representing a challeng - ing one reaching 40–45% after 5  years [2] and reopera - tion rates of 27% [3]. Additionally, fertility decline was noted to be more prominent after further interventions rather than after primary surgery [4]. This makes endo - metriosis a dreadful disease, and concerns about avoiding recurrence are paramount [5]. Several studies evaluated the role of adjuvant therapies in preventing recurrence as hormonal treatments [6]. Variable results were reported with a predilection toward the insignificant impact of hormonal treatment in preventing recurrence [7, 8]. Determining possible factors associated with recurrent endometriomas would influence treatment decisions and optimize treatment planes [9]. Accordingly, this study evaluated factors affecting endometrioma recurrence after laparoscopic excision.

This quasi-experimental study was conducted in the Obstetrics and Gynecology Department at Suez Canal University Hospital from November 1, 2020, to July 31, 2022. We recruited eligible patients during the study duration according to prespecified inclusion and exclu - sion criteria. Inclusion criteria: (a) unilateral endome - trioma, (b) unilocular endometrioma 3–8 cm, (c) age 18–45 years, (d) regular cycles, (e) no previous history of ovarian operations, and (f) patients undergoing surgi - cal excision of the endometrioma by laparoscopy. Exclu - sion criteria: (a) suspected or confirmed malignancy, (b) women within 2 years of menarche, (c) women on *Correspondence: Omima T. Taha [email protected] 1 Department of Obstetrics and Gynecology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt Page 2 of 5Atwa et al. Middle East Fertility Society Journal (2023) 28:21 progesterone only or combined hormonal contracep - tion, (d) women refusing to participate in the study, and (f) women preferring medication for the management of endometriomas. Informed consent was obtained from all eligible study participants after adequately explaining the study pro - cedures and aim. Eligible patients were subjected to the following: 1- Complete personal and medical history. Data about pelvic pain, dysmenorrhea, and dyspareunia were obtained and graded as mild, moderate, or severe. 2- The local gynecological examination, performed by the same researcher, focused on evaluating pelvic tenderness and induration and was graded into mild, moderate, or severe. 3- Ultrasound examination to diagnose ovarian endo - metrioma and measure its diameter [10]. The antral follicle count (AFC) of the affected ovary was evalu - ated on days 2–3 of the cycle by determining the number of follicles measuring 2–10 mm [11]. 4- Routine preoperative laboratory investigations such as complete blood count, coagulation profile, liver function test, and anti-mullerian hormone (AMH) were withdrawn. 5- Patients were prepared for laparoscopic cystectomy. Any adhesions were lysed to free the ovary before excision. An incision in the endometrioma was done. Suction of the endometrioma contents was done. Stripping of the cyst wall from the ovarian tissue was done. Handling of the ovary was done using atrau - matic grasping forceps. Bipolar cauterization was used to achieve hemostasis using pinpoint coagula - tions to avoid thermal damage to the ovary. Com - plete removal of the cyst wall was ensured [12]. No hormonal treatment was offered after the operation. 6- Initial follow-up visit was after 3 months. However, longer duration of follow-up was recommended to evaluate recurrences properly. Accordingly, further follow-up was done after at least 1 year of the opera - tion. Recurrence was defined as cyst diameter > 10 mm [5]. Statistical analysis Data were statistically described as mean and stand - ard deviation, frequencies (number of cases), and per - centages when appropriate. P value of less than 0.05 were considered statistically significant. All statistical calculations were done using the computer program SPSS (Statistical Package for the Social Science; SPSS Inc., Chicago, IL, USA), release 23 for Microsoft Win - dows. Comparison between patients with recurrent endometriosis and those without was done by the stu - dent T test. Multivariate and univariate regression analysis was performed to determine possible factors associated with cyst recurrence.

Sixty patients were recruited throughout the study dura - tion. The mean age was 30.33 ± 7.95  years. The study population was either virgins or married/divorced/wid - owed equally. The mean parity of the married/divorced/ widowed patients was 1.27 ± 0.69. The mean follow-up period was 22.62 ± 4.96 months (Table 1). The recurrence rate after excision was 11/60 (18.3%). The mean endometrioma size after recurrence was 3.27 ± 0.17. There was no significant difference in the ovarian reserve either before or after surgery as repre - sented by AMH and AFC levels between patients who had recurrent endometriosis and those who did not (P value > 0.05) (Table  2). There was no significant dif - ference in the extend of dysmenorrhea between both groups (p value 0.575). None of the patients’ characteristics or endometriosis- related characteristics were significant factors contribut - ing to cyst recurrence by multivariate analysis (age, parity, history of infertility, preoperative endometrioma diameter, preoperative AFC, preoperative AMH, degree of pelvic pain, degree of dysmenorrhea, degree of dyspareunia, pel- vic tenderness, and induration) (p value > 0.05) (Table 3).

After surgical excision, recurrence was noted in 18.3% of the participants. The recurrence rate after endome - trioma excision was reported to be high. It ranged from 29 to 56% after 2  years, while after 5  years, it was 43% [13] without postoperative medical treatment. Another study reported a recurrence rate of 6.4%. This study conducted follow-up visits every 3  months of surgery, and the results were reported after a mean follow-up period of 22.62 ± 4.96 months, while they reported their Table 1 Basic demographic data of the studied population (N = 60) Age (years) (mean ± SD) 30.33 ± 7.95 Occupation N (%) Not working 29 (48.33%) Working 31 (51.67%) Residence N (%) Urban 28 (46.67%) Rural 32 (53.33%) Marital status N (%) Virgin 30 (50%) Married/divorced/ widowed 30 (50%) Parity (mean ± SD) 1.27 ± 0.69 Mean follow-up period (months) (mean ± SD) 22.62 ± 4.96 Page 3 of 5 Atwa et al. Middle East Fertility Society Journal (2023) 28:21

after 5  years. A large number of their partici - pants received postoperative hormonal treatment in the form of oral contraceptives, Mirena for at least 1  year, Gonadotropin releasing hormone analogs (GnRHa) for 3–6  months, or GnRHa followed by Mirena. Only 3.4% of their studied population did not receive any hormonal treatment which might impact the recurrence rates after surgery [14]. Hormonal treatment leads to apoptosis of the ectopic endometrial implants either in the pelvis or de novo implants leading to decreased recurrences [15]. The current study provided no medical treatment after surgery. Immune cells and extracellular matrix metallo - proteinase lead to the proliferation and survival of endo - metriotic cells, explaining recurrent endometriosis [16]. Recurrent endometriosis differed in its rate between studies. This was rendered to the variable factors con - tributing to its recurrence as the definition of recurrence depended on subjective pain sensation or clinical and radi- ological evaluation. Also, the type of endometriosis, disease severity, method of excision, surgical skills, and time to recurrence was reported [5]. The evaluation of recurrence depending on symptoms was higher than the sonographic evaluation, with a poor correlation between pain and actual recurrence [17]—the current study evaluated recurrence using ultrasound after 3 months of excision. There was no difference in the endometrioma size before surgery among women with recurrent endome - triosis and those without. Also, there was no difference in age, parity, extend of dysmenorrhea, and the ovarian reserve before and after surgery among both groups. This was evident in an earlier study where there was no differ - ence in patients’ age, parity, and BMI among those with recurrent endometriosis and those without. However, the extent of dysmenorrhea was increased significantly among those with recurrent endometriosis (p value 0.001) [14]. This difference would be related to the pres - ence of concomitant conditions as adenomyosis which was not evaluated in our study population. it has been reported that dysmenorrhea was evident in women with adenomyosis due to associated deeply situated dense endometrial glands in the myometrium [18]. The current study demonstrated no significant risk fac- tor associated with cyst recurrence. Another study done by Koga et al. 2006 demonstrated that previous history of medical treatment and endometrioma size predicted recurrence significantly [19]. An earlier study reported that younger age at surgery was associated with recur - rent endometriosis. This was rendered to the increased estrogen concentration in younger women leading to preoperative hormonal treatment which results in atrophy and reduced size of the endometriotic lesions leading to missed removal in surgery [20]. It has been reported that risk factors contributing to endometrio - sis recurrence were heterogeneous among studies. The stage of endometriosis, adhesions, and size and num - ber of endometrioma did not influence recurrence while previous surgery was significantly associated with recur - rence. This was explained by the progressive and aggres - sive nature of the disease [21]. Another study concluded Table 2 Ovarian reserve and endometrioma size between patients with recurrent endometriomas and those without Recurrent endometrioma 11/60 (18.3%) No recurrence 49/60 (81.7%) P value Age 33.5 ± 6.9 29.6 ± 8.04 0.139 Parity 1.5 ± 0.6 1.2 ± 0.7 0.244 Preoperative endometrioma diameter 5.9 ± 1.6 5.3 ± 1.76 0.354 Postoperative endometrioma diameter 3.27 ± 0.17 0.07 ± 0.53 0.0001 Preoperative AFC 5.9 ± 1.6 5.2 ± 2.2 0.809 Postoperative AFC 3.9 ± 1.4 3.3 ± 1.7 0.469 Preoperative AMH 1.76 ± 0.4 1.8 ± 0.4 0.843 Postoperative AMH 1.5 ± 0.44 1.5 ± 0.43 0.649 Table 3 Multivariate analysis for the factors affecting recurrent endometriomas after laparoscopic excision Beta 95% confidence interval P value Constant − 0.108 − 2.328–2.113 0.920 Age 0.008 − 0.027–0.044 0.626 Parity 0.070 − 0.297–0.436 0.694 Infertility − 0.221 − 0.662–0.221 0.307 Endometrioma diameter 0.003 − 0.137–0.143 0.961 AFC (preoperative) − 0.013 − 0.131–0.106 0.822 AMH (preoperative) 0.086 − 0.462–0.633 0.745 Degree of pain 0.122 − 0.181–0.426 0.408 Degree of dysmenorrhea 0.105 − 0.256–0.466 0.546 Degree of dyspareunia − 0.029 − 0.284–0.227 0.815 Pelvic tenderness − 0.136 − 0.431–0.160 0.347 Induration − 0.054 − 0.351–0.243 0.706 Page 4 of 5Atwa et al. Middle East Fertility Society Journal (2023) 28:21 that dysmenorrhea and ovarian cyst separations were associated with endometrioma recurrence [22]. Dys - menorrhea was rendered to the disease itself as a result of bleeding from focal endometriotic implants, release of inflammatory mediators, and direct irritation of the pel - vic nerves and peritoneum [22]. While Selcuk et al. men - tioned that deeply penetrating endometrial tissue in the ovary was significantly associated with recurrent endo - metrioma [23]. This was explained by decreased apop - tosis and increased proliferation with deeply infiltrated endometriosis [22]. Other mechanical factors explaining recurrent endome- triosis were regrowth of endometriotic lesions from resid- ual loci [24], which was emphasized by the reappearance of endometriotic lesions at the same site after excision [25]. The use of laser ablation results in prevention of recurrence for at least 2  years, which elaborates the role of abnormal uterine contraction in the generation of ectopic endometrial implants [26, 27]. Lymph node involvement has also been reported as a possible cause of recurrence [28]. Immuno - logical factors contribute to endometriotic spots’ de novo or in  situ regeneration. It has been reported that CD-16 expressing natural killer cells are abundant in the peritoneal fluid and blood of women with endometriosis and are not affected by surgical excision or hormonal therapy [29]. Variable results were rendered to multiple factors, includ- ing different surgical procedures adopted, different surgical experiences, different outcome measures, different types and stages of endometriosis between studies, different target populations, and the evaluation duration. Also, a possible bias in selection and recruitment, recall and data reporting, and inaccurate statistical analysis would contribute to the contradictory results. Incomplete removal of endometrio- mas because of extensive pelvic adhesions contributed to endometrioma recurrence. Additionally, different method- ologies and power between studies are paramount [5, 14]. The presence of associated conditions as adenomyosis was associated with increased recurrence rates; however, this was not evaluated in the current study [30]. Strengths of the study The study used the same technique of the surgical excision performed by the same surgical team. The recurrence rate was evaluated depending on recurrence in the same ovary. Recurrence was evaluated depending on ultrasound visu - alization of the cyst rather than depending on symptoms.

of the study The follow-up duration was relatively small from 12 to 30  months. The sample size was small. Pregnancy rates after the intervention was not evaluated. It was performed in a single hospital which limits data generalization. We recruited women with unilocular endometriomas, while the involvement of women with multilocular cysts would be more informative.

The patient’s related factors and endometrioma charac - teristics did not predict its recurrence. Abbreviations ANC Antral follicle count AMH Anti-Mullerian hormone rAFS Revised American Fertility Society Supplementary Information The online version contains supplementary material available at https:// doi. org/ 10. 1186/ s43043- 023- 00146-6. Additional file 1.

Not applicable. The authors are compliant to respond to any post-publication queries regarding this study. Contact would be through the corresponding author. Authors’ contributions KH Atwa: protocol/project development and manuscript writing/editing. OT Taha: data collection and analysis. EM El Bassuony: data collection and management and manuscript writing/editing. ZM Ibrahim: protocol/project development, manuscript writing/editing, data analysis, and manuscript writing/editing. Funding Self-funded. Availability of data and materials Not applicable. Declarations Ethics approval and consent to participate All procedures performed in in the study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was conducted after the approval of our research ethics committee. Informed consent was obtained from all participants before recruitment. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. Received: 4 October 2022 Accepted: 6 August 2023

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