Ovarian Reserve Following Laparoscopic Ovarian Cystectomy vs Cyst Deroofing for Endometriomas

Accepted Manuscript

Ovarian Reserve Following Laparoscopic Ovarian Cystectomy Versus Cyst Deroofing for Endometriomas Mohamed S. Sweed , Ahmed K. Makled , Medhat A. El-Sayed , Mohamed E. Shawky , Hamdy A. Abd-Elhady , Ahmed M. Mansour , Radwa M. Mohamed , Hossam Hemeda , Eman A. Nasr-Eldin , Neveen S. Attia , Ebtihal Eltaieb , Heba Allam , Ahmed Hussein PII: DOI: Reference:

S1553-4650(18)30447-3 https://doi.org/10.1016/j.jmig.2018.06.022 JMIG 3608

To appear in:

The Journal of Minimally Invasive Gynecology

Received date: Revised date: Accepted date:

2 April 2018 19 May 2018 7 June 2018

Please cite this article as: Mohamed S. Sweed , Ahmed K. Makled , Medhat A. El-Sayed , Mohamed E. Shawky , Hamdy A. Abd-Elhady , Ahmed M. Mansour , Radwa M. Mohamed , Hossam Hemeda , Eman A. Nasr-Eldin , Neveen S. Attia , Ebtihal Eltaieb , Heba Allam , Ahmed Hussein , Ovarian Reserve Following Laparoscopic Ovarian Cystectomy Versus Cyst Deroofing for Endometriomas, The Journal of Minimally Invasive Gynecology (2018), doi: https://doi.org/10.1016/j.jmig.2018.06.022

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ACCEPTED MANUSCRIPT 1 Original Article Ovarian Reserve Following Laparoscopic Ovarian Cystectomy Versus Cyst Deroofing for Endometriomas

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Mohamed S. Sweed, MD*, Ahmed K. Makled, MD, Medhat A. El-Sayed, MD, Mohamed E. Shawky, MD, Hamdy A. Abd-Elhady, MD, Ahmed M. Mansour, MD, Radwa M. Mohamed, MD, Hossam Hemeda, MD, Eman A. Nasr-Eldin, MD, Neveen S. Attia, MSc, Ebtihal Eltaieb, MD, Heba Allam, MD, and Ahmed Hussein, MD

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From the Department of Obstetrics and Gynecology, Ain Shams University, Cairo, Egypt (Drs. Sweed, Makled, El-Sayed, Shawky, Abd-Elhady, Mansour, Mohamed, Hemeda, Attia, Eltaieb, Allam, and Husseein); and the Department of Radiodiagnosis, Helwan University, Cairo, Egypt (Dr Nasr-Eldin).

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Corresponding author: Mohamed S. Sweed, MD, Department of Obstetrics and Gynecology, Ain Shams University, Cairo, Egypt 16646. Telephone: +0201001222047. E-mail:

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[email protected] orcid.org/0000-0003-1221-9600

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Disclosure statement: The authors declare that they have no conflicts of interest.

Precis:

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ClinicalTrials.gov Identifier: NCT01808170

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Laparoscopic cyst deroofing is an alternative surgical procedure that when compared with cystectomy reduces the decrease in ovarian reserve in the management of endometriomas.

ACCEPTED MANUSCRIPT 2 ABSTRACT Study Objective: Because laparoscopic ovarian cystectomy of endometriomas is known to adversely impact patient ovarian reserve, the search for other techniques of surgical management is ongoing, and the objective of the current study was to evaluate laparoscopic

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cyst deroofing as a feasible alternative.

Study Design: Prospective, randomized clinical trial (Canadian Task Force classification I). Setting: A university maternity hospital.

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Patients: Women diagnosed with unilateral or bilateral ovarian endometriomas.

Interventions: Patients were managed with either laparoscopic ovarian cystectomy or cyst deroofing.

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Measurements and Main Results: One hundred and twenty-two women with endometriomas were randomized to either laparoscopic cystectomy (group 1) or laparoscopic cyst deroofing

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(group 2). The primary endpoint was the effect on ovarian reserve based on changes of antiMüllerian hormone (AMH). Anti-Müllerian hormone values showed significant decrease (p <

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.001) from preoperative values of 4.25 ± 0.87 ng/mL in the cystectomy group and 4.2 ± 1.69

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ng/mL in the deroofing group compared with 1-month postoperative values of 1.66 ± 1.02 ng/mL in group 1 and 2.15 ± 1.48 ng/mL in group 2, respectively. Also, antral follicle count and ovarian

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volume showed significant decrease (p < .001) in both groups after one month when compared to preoperative values. The decrease in these three parameters was more significant (p < .001) in the cystectomy group than the cyst deroofing group. Conclusion: Laparoscopic cyst deroofing of endometriomas appears to be a promising alternative to laparoscopic cystectomy with less postoperative decrease of ovarian reserve;

ACCEPTED MANUSCRIPT 3 however higher endometrioma recurrence warrants future clinical research to determine the best surgical management for endometriomas. ClinicalTrials.gov Identifier: Laparoscopic Ovarian Cystectomy of Endometrioma vs Deroofing and Ovarian Reserve,

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https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S00043CM&selectaction=Edi t&uid=U0001XEI&ts=1108&cx=-mxb3g8, NCT01808170, registration date 03/06/2013.

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Keywords: Anti-Müllerian hormone; Antral follicle count; Ovarian volume

ACCEPTED MANUSCRIPT 4 Introduction Endometriosis is defined as abnormally situated endometrial glands and stroma outside the uterine cavity and usually presents with pelvic pain, dysmenorrhea, and infertility [1], affecting 7% to 10% of the general female population reaching up to 50% in infertile women [2].

in about 17% to 44% of women with endometriosis [3].

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Ectopic endometrial tissue in the ovary usually forms cysts known as endometriomas, prevalent

The challenge is how to treat ovarian endometriomas for women seeking fertility [4]. Surgical removal of endometriomas is considered standard protocol, although it remains

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controversial [5–7]. One of the foremost concerns is the impact of endometriomas on ovarian reserve and follicle loss [8].

The comparison between different surgical techniques to deal with ovarian

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endometriomas remains a main point of debate [9]. This study was conducted to evaluate the impact of laparoscopic ovarian cystectomy versus laparoscopic cyst de-roofing of

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endometriomas on ovarian reserve measured by serum levels of anti-Müllerian hormone (AMH)

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and antral follicle count (AFC). Material and Methods

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This study was conducted at Ain Shams University Maternity Hospital from June 2013 through March 2017. Approval was obtained from the ethical committee of the hospital’s

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Department of Obstetrics and Gynecology, the trial was registered at ClinicalTrials.gov, and written informed consent was obtained from all participants. One hundred and twenty-two patients were diagnosed with endometrioma and were candidates for laparoscopic surgery. They were selected according to the following inclusion criteria: 18 to 35 years of age and unilateral or bilateral endometrioma diagnosed by

ACCEPTED MANUSCRIPT 5 transvaginal ultrasound with diameter ≥3 cm. Exclusion criteria were any previous ovarian surgery, evidence of polycystic ovary syndrome, evidence of premature ovarian failure (follicle stimulating hormone ≥40 international units/L), endocrinal disorders that might affect ovarian function (e.g., thyroid dysfunction, hyperprolactinemia), previous hormonal medications (e.g.,

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oral contraceptive pills, gonadotropin-releasing hormone analogue) within the last 3 months before surgery, any suspicious findings of ovarian malignant disease diagnosed by transvaginal ultrasound (e.g., irregular solid mass, papillary structures), increased vascularity determined by Doppler ultrasound, presence of ascites, and contraindication to surgery.

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Patients were randomized into 2 groups (61 per group) according to a computer-

generated statistical software (MedCalc Software Version 13.2.2, Ostend, Belgium). One study group underwent laparoscopic ovarian cystectomy; the other underwent laparoscopic cyst deroofing. All patients were evaluated for general anesthesia, AMH was measured, venous

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blood samples were collected and centrifuged, and serum samples were stored at –20°C until assayed using commercially available ELISA kits (Glory Science Co., Ltd, Del Rio, Texas,

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USA). The detection range of AMH was 0.5 to 25 ng/mL. All assays were performed in duplicate and mean values used for data analysis. The intra-assay and interassay coefficients of variation

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(CV) for AMH assay were below 10%. Anti-Müllerian hormone was measured preoperatively,

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and one-month and 1-year postoperatively. Antral follicle count and ovarian volume were assessed on the third day of the last cycle before surgery, the second cycle following the

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surgery, and 1 year after surgery. Antral follicle count was measured as the total number of follicles identified ranging 2 to 9 mm in diameter. The ovarian volume was calculated using the prolate ellipsoid formula: volume (cm3) = 0.5233 X anteroposterior diameter (cm) X transverse diameter (cm) X longitudinal diameter (cm). Ovarian volume was calculated by subtracting the cyst volume from the total ovarian volume [10]. Ultrasound assessment was performed by the same radiologist using SonoACE 6000 (Medison Co., Seoul, South Korea) ultrasound machine

ACCEPTED MANUSCRIPT 6 equipped with a 3.5- to 5-MHz or a 3.5- to 6-MHz convex transducer. Pain was assessed by participants presenting with pain using visual analogue scale (VAS) preoperatively, one month after surgery, and 1-year postoperatively. The VAS ranged from zero to 10: zero defined as no pain and 10 defined as maximum pain.

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Laparoscopic operations were performed under general anesthesia. Visualization of all pelvic organs was done to exclude other possible lesions, confirm ovarian endometrioma, and confirm laterality. In the cystectomy group, a plain of cleavage was identified between the

ovarian tissue and cyst wall; the ovary and cyst wall were pulled gently in opposite directions

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using two non-traumatic grasping forceps. After removing the cyst wall, selective minimal (15 watt) bipolar coagulation of bleeding was performed.

In the cyst deroofing group, only part of the cyst wall was removed, the contents of the cyst removed with the suction-irrigator probe, and the cavity was irrigated. The inner cyst wall

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was coagulated by the touch technique using 30-watt bipolar coagulating forceps only if an

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active bleeding point was identified. Small blood vessels from the ovarian bed and bleeding from the ovarian hilum were controlled with bipolar electrocoagulation (15-watt) if needed.

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Patients of both groups were followed until one year following the surgery; AMH was measured; and transvaginal ultrasound was completed to measure AFC, ovarian volume, and recurrence of

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endometriomas.

Statistical analysis was completed using SPSS Statistics version 22 (IBM© Corp.,

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Armonk, NY, USA). Numerical values are presented as mean ± standard deviation and intergroup differences were compared using the independent-samples Student t test. Paired comparisons were done using the paired t test. Categorical data were presented as ratio or as number (%) and between-group differences were compared using Pearson chi square test or Fisher’s exact test, when appropriate. Multivariable regression was used to determine

ACCEPTED MANUSCRIPT 7 independent predictors of the magnitude of change in the outcome measures. A two-sided p value <.05 was considered statistically significant. Results

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Of 163 women assessed for eligibility, 122 were included in the study and randomized to 2 groups, 61 each (Fig. 1). The demographic data and baseline clinical and sonographic

preoperative characteristics showed no statistical difference between the 2 groups (Table 1). In the cystectomy group, 36 patients (59.1%) presented with pain (12 with dysmenorrhea and 24 with chronic pelvic pain), 23 patients (37.7%) presented with infertility, and 2 (3.2%) with pain

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and infertility. In the cyst deroofing group 38 patients (63.3%) presented with pain (13 with

dysmenorrhea and 25 with chronic pelvic pain), 22 (36.1%) presented with infertility, and 1 (1.6%) presented with pain and infertility.

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Anti-Müllerian hormone, AFC, and ovarian volume all showed significant decrease both 1 month and 1 year postoperative (Table 2), with a more prevalent decrease in the cystectomy

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group when compared with the deroofing group (Table 3). Decrease of AMH was greater in the cystectomy group in both patients with unilateral and bilateral endometriomas (Table 4).

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Patients who originally presented with pain showed marked decrease in symptoms when assessed 1-month postoperatively, but pain intensity increased significantly after 1 year and

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was more prevalent in the deroofing group (Table 5). Multivariable regression analysis showed age, laterality of lesion, and surgical procedure to be significant determinants of change in AMH

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and ovarian volume (Table 6). Laterality of lesions (1.135: 95% CI; 0.185 to 2.084, p = .02) and surgical procedure (4.231: 95% CI; 3.672 to 4.790, p < .001) were found to be significant determinants of change in AFC. Multivariate analysis showed the relationship between the surgical procedure and the decrease in AMH, AFC, and ovarian volume remained statistically significant after adjustment for age, body mass index, laterality, and endometrioma size. One

ACCEPTED MANUSCRIPT 8 hundred and seven patients were followed after 1 year (54 in the cystectomy group and 53 in the deroofing group), recurrence of endometriomas was greater in the deroofing group (22/53, 41.5%) than the cystectomy group (11/54, 20.4%; p = .018). Anti-Müllerian hormone, AFC, and ovarian volume were all significantly higher in the deroofing group (Table 7).

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Discussion

Many still consider surgical excision of ovarian endometriomas as the standard

treatment; however, there are concerns about the negative impact of this technique on ovarian reserve [11]. Previous studies noted that the mere presence of ovarian endometriomas reduces

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the ovarian reserve and is further decreased by interventions like laparoscopic ovarian

cystectomy [12–14]. These studies used both AMH and sonographic markers as determinants of ovarian reserve. Several systematic reviews and meta-analyses have confirmed this noting the decline of both AMH and AFC [6,11]. The ideal surgical approach for managing

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endometriomas with minimal effect on the future fertility and ovarian reserve is still unclear. In

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this study, we compared the effect of both laparoscopic ovarian cystectomy and cyst deroofing on the ovarian reserve assessed by AFC and ovarian volume as sonographic evaluating

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parameters.

Women seek treatment for diagnosed endometriomas for different symptoms including

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chronic pelvic pain, dyspareunia, and severe dysmenorrhea. Infertility remains a major complaint in women with endometriomas; nearly 40% of the current study participants

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complained of delayed fertility. Patient desire for fertility impacts physician treatment of endometriomas and the importance in determining which surgical technique impacts ovarian reserve [4,10,15–17]. Evidence is still inconclusive regarding the surgical method with the least effect on ovarian reserve; moreover, most studies are based on retrospective data with minimal prospective studies [18]. Studies investigating both plasma energy ablation and laser

ACCEPTED MANUSCRIPT 9 vaporization had promising results [4,17,19,20]; yet, there are still major concerns regarding the higher incidence of recurrence compared with cystectomy as well as the higher cost and unavailability in lower income countries. The current study attempted to evaluate a more feasible approach where only the cyst is

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deroofed and evacuated with minimal coagulation, only if needed. This technique did show decreased ovarian reserve (as measured by AMH, AFC, and ovarian volume) both 1 month and 1 year postoperatively, yet, to a significantly less extent when compared with ovarian

cystectomy. Subgroup analysis of laterality of lesions showed less ovarian reserve in the

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cystectomy group in patients with both bilateral endometriomas or unilateral endometriomas when compared separately (Table 4).

Preoperative ovarian reserve should be evaluated before any surgical management of endometriomas, especially the cystectomy technique [18]. The current study suggests that

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laparoscopic cyst deroofing for the management of endometriomas seems to be less damaging

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to ovarian reserve when compared with cystectomy. Still, the higher rate of endometrioma recurrence and associated pain, might favor the use of this technique when fertility is the main

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issue in patients with little pain symptoms. The study was limited by the absence of a control group to measure the possible effect of endometriomas without any surgical intervention and

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ovarian reserve. Also, the heterogeneity of the selected sample made it difficult to address the effect of this technique on later pregnancy rates or in vitro fertilization outcomes, which are

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parameters that many researchers find even more important than ovarian reserve and whether its change actually reflects relevant clinical significance to patients. The current evidence shows no improvement in reproductive outcome of assisted reproduction techniques after removal of endometriomas [18], perhaps the reproductive outcome of these techniques should be studied following deroofing. Still surgical management of endometriomas should be individualized for

ACCEPTED MANUSCRIPT 10 each patient with a significant objective being for maximal ovarian tissue sparing and thus

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maximum ovarian reserve preservation.

ACCEPTED MANUSCRIPT 11 References 1. de Ziegler D, Borghese B, Chapron C. Endometriosis and infertility: pathophysiology and management. Lancet. 2010;376:730–738. 2. Streuli I, de Ziegler D, Gayet V, et al. In women with endometriosis anti-Müllerian

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hormone levels are decreased only in those with previous endometrioma surgery. Hum Reprod. 2012;27:3294–3303.

3. Celik HG, Dogan E, Okyay E, et al. Effect of laparoscopic excision of endometriomas on ovarian reserve: serial changes in the serum antimüllerian hormone levels. Fertil Steril.

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2012;97:1472–1478.

4. Roman H, Auber M, Mokdad C, et al. Ovarian endometrioma ablation using plasma energy versus cystectomy: a step toward better preservation of the ovarian parenchyma in women wishing to conceive. Fertil Steril. 2011;96:1396–1400.

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5. Gelbaya TA, Gordts S, D'Hooghe TM, Gergolet M, Nardo LG. Management of

2010;21:325–330.

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endometrioma prior to IVF: compliance with ESHRE guidelines. Reprod Biomed Online.

6. Raffi F, Metwally M, Amer S. The impact of excision of ovarian endometrioma on ovarian

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reserve: a systematic review and meta-analysis. J Clin Endocrinol Metab.

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2012;97:3146–3154.

7. Raffi F, Shaw RW, Amer SA. National survey of the current management of

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endometriomas in women undergoing assisted reproductive treatment. Hum Reprod. 2012;27:2712–2719.

8. Exacoustos C, Zupi E, Amadio A, et al. Laparoscopic removal of endometriomas: sonographic evaluation of residual functioning ovarian tissue. Am J Obstet Gynecol. 2004;191:68–72.

ACCEPTED MANUSCRIPT 12 9. Somigliana E, Benaglia L, Vigano' P, Candiani M, Vercellini P, Fedele L. Surgical measures for endometriosis-related infertility: a plea for research. Placenta. 2011;32(Suppl 3):S238–S242. 10. Var T, Batioglu S, Tonguc E, Kahyaoglu I. The effect of laparoscopic ovarian cystectomy

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versus coagulation in bilateral endometriomas on ovarian reserve as determined by antral follicle count and ovarian volume: a prospective randomized study. Fertil Steril. 2011;95:2247–2250.

11. Muzii L, Di Tucci C, Di Feliciantonio M, Marchetti C, Perniola G, Panici PB. The effect of

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surgery for endometrioma on ovarian reserve evaluated by antral follicle count: a systematic review and meta-analysis. Hum Reprod. 2014;29:2190–2198.

12. Hwu Y, Wu FS, Li SH, Sun FJ, Lin MH, Lee RK. The impact of endometrioma and laparoscopic cystectomy on serum anti-Müllerian hormone levels. Reprod Biol

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Endocrinol. 2011;9:80–87.

13. Uncu G, Kasapoglu I, Ozerkan K, Seyhan A, Oral Yilmaztepe A, Ata B. Prospective

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assessment of the impact of endometriomas and their removal on ovarian reserve and determinants of the rate of decline in ovarian reserve. Hum Reprod. 2013;28:2140–

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2145.

14. Chen Y, Pei H, Chang Y, et al. The impact of endometrioma and laparoscopic

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cystectomy on ovarian reserve and the exploration of related factors assessed by serum anti-Mullerian hormone: a prospective cohort study. J Ovarian Res. 2014;26:108–115.

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15. Pados G, Tsolakidis D, Assimakopoulos E, Athanatos D, Tarlatzis B. Sonographic changes after laparoscopic cystectomy compared with three-stage management in patients with ovarian endometriomas: a prospective randomized study. Hum Reprod. 2010;25:672–677.

ACCEPTED MANUSCRIPT 13 16. Salem HA, Hegab HM, Elkaffash DM, Azb H, Hosny TA. Assessment of the ovarian reserve before and after laparoscopic surgery using two different techniques for ovarian endometrioma. IOSR J Dent Med Sci (IOSR-JDMS). 2013;6:43–48. 17. Mircea O, Puscasiu L, Resch B, et al. Fertility outcomes after ablation using plasma

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energy versus cystectomy in infertile women with ovarian endometrioma: a multicentric comparative study. J Minim Invasive Gynecol. 2016;23:1138–1145.

18. Cranney R, Condous G, Reid S. An update on the diagnosis, surgical management, and fertility outcomes for women with endometrioma. Acta Obstet Gynecol

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Scand. 2017;96:633–643.

19. Vercellini P, Chapron C, De Giorgi O, Consonni D, Frontino G, Crosignani PG. Coagulation or excision of ovarian endometriomas? Am J Obstet Gynecol. 2003;188:606–610.

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20. Roman H, Auber M, Bourdel N, Martin C, Marpeau L, Puscasiu L. Postoperative recurrence and fertility after endometrioma ablation using plasma energy: retrospective

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assessment of a 3-year experience. J Minim Invasive Gynecol. 2013;20:573–582.

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Figure Legend

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Fig. 1 Flow chart of the study.

p value .135

Mean BMI, kg/m2 ± SD

23.1 ± 2.9

23.1 ± 2.2

.974

Parity, n (NG/MG)

34/27

37/24

.580

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Laterality

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Table 1 Demographic, Clinical, and Sonographic Patient Characteristics Cystectomy Cyst deroofing Variable (n = 61) (n = 61) Mean age, years ± SD 27.1 ± 4.6 25.5 ± 3.6

34 (55.7%)

Bilateral, n (%)

43 (70.5%)

27 (44.3%)

18 (29.5%)

5.2 ± 0.6

5.5 ± 1.01

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Size of lesion, cm3 ± SD

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Unilateral, n (%)

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BMI = body mass index; MG = multigravida; NG = nulligravida; SD = standard deviation.

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.090

.094

ACCEPTED MANUSCRIPT 15 Table 2 Preoperative and Postoperative Within-Group Comparisons

Cyst deroofing (n = 61)

Preoperative AMH level (ng/mL ± SD)

4.25 ± 0.87

4.2 ± 1.69

Postoperative AMH level (ng/mL ± SD)

1.66 ± 1.02

p value*

<.001

AMH level after 1 year, ng/mL ± SD

1.39 ± 0.76

p value†

<.001

Preoperative AFC, number ± SD

8.9 ± 2.6

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Variable

Cystectomy (n = 61)

Postoperative AFC, number ± SD

2.15 ± 1.48 <.001

2.07 ± 1.49 <.001

7.3 ± 2.8

3.2 ± 1.3

5.8 ± 2.7

<.001

<.001

3.17 ± 1.36

5.42 ± 2.68

<.001

<.001

Preoperative ovarian volume, cm3 ± SD

8.3 ± 2.0

7.4 ± 2.6

Postoperative ovarian volume, cm3 ± SD

3.1 ± 1.6

5.7 ± 2.6

p value*

<.001

<.001

Ovarian volume after 1 year, cm3 ± SD

2.89 ± 1.5

5.6 ± 2.56

p value†

<.001

<.001

p value* AFC after 1 year, number ± SD

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p value†

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*Preoperative versus postoperative; †Preoperative versus 1-year postoperative. AFC = antral follicle count; AMH = anti-Müllerian hormone; SD = standard deviation.

ACCEPTED MANUSCRIPT 16 Table 3 Preoperative and Postoperative Between-Group Comparisons

Cystectomy (n = 61)

Cyst deroofing (n = 61)

p value

Preoperative AMH level, ng/mL ± SD

4.25 ± 0.87

4.2 ± 1.69

.916

Postoperative AMH level, ng/mL ± SD

1.66 ± 1.02

2.15 ± 1.48

.035

Change in AMH level, ng/mL ± SD

–2.59 ± 1.05

–2.13 ± 0.95

.012

Preoperative AFC, number ± SD

8.9 ± 2.6

7.3 ± 2.8

.002

Change in AFC, number ± SD Preoperative ovarian volume, cm3 ± SD

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Change in ovarian volume, cm3 ± SD

3.2 ± 1.3

5.8 ± 2.7

<.001

–5.7 ± 1.9

–1.6 ± 0.5

<.001

8.3 ± 2.0

7.4 ± 2.6

.023

3.1 ± 1.6

5.7 ± 2.6

<.001

–5.3 ± 2.6

–1.7 ± 0.4

<.001

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Postoperative ovarian volume, cm3 ± SD

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Postoperative AFC, number ± SD

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Variable

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AFC = antral follicle count; AMH = anti-Müllerian hormone; SD = standard deviation.

ACCEPTED MANUSCRIPT 17 Table 4 Preoperative and Postoperative Between-Group Comparison of AMH in Bilateral and Unilateral Lesions

Cystectomy

Cyst deroofing

p value

Preoperative AMH level, ng/mL ± SD

4.32 ± 0.43

3.94 ± 1.19

.142

Postoperative AMH level, ng/mL ± SD

1.24 ± 1

1.84 ± 0.91

.046

Change in AMH level, ng/mL ± SD

–2.79 ± 2.02

–2.21 ± 0.78

.248

4.52 ± 1.77

.406

2.6 ± 1.5

.035

–1.92 ± 0.71

.012

Variable

Unilateral endometrioma 4.23 ± 0.97

Postoperative AMH level, ng/mL ± SD

1.97 ± 0.93

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Preoperative AMH level, ng/mL ± SD

–2.27 ± 0.4

Change in AMH level, ng/mL ± SD

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AMH = anti-Müllerian hormone; SD = standard deviation.

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Bilateral endometrioma

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Deroofing (n = 39)

Preoperative pain (VAS)

7.55 ± 1.2

7.56 ± 1.2

1-month postoperative pain (VAS)

1.84 ± 1

1.95 ± 1.2

p value*

p < .001 95% CI (5.31– 6.11)

p < .001 95% CI (5.18– 6.05)

1-year postoperative pain (VAS)

3.13 ± 1.1

4.41 ± 1.1

p value†

p < .001 95% CI (3.97– 4.87)

p < .001 95% CI (2.7– 3.61)

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p value‡

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p < .001 95% CI (–1.58 to –0.99)

p value p = .967 95% CI (–0.56 to 0.54) p = .676 95% CI (–0.6 to 0.4)

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Table 5 Within-Group and Intergroup Pain Comparison Cystectomy Variable (n = 38)

p < .001 95% CI (–1.76 to –0.8)

p < .001 95% CI (–2.85 to –2.08)

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*Preoperative versus postoperative, †Preoperative versus 1-year postoperative, ‡1-month postoperative versus 1year postoperative. CI = confidence interval; VAS = Visual Analogue Scale.

ACCEPTED MANUSCRIPT 19 Table 6 Multivariable regression analysis for determinants of change in ovarian volume and AMH Ovarian volume

AMH

Age

–0.109 95% CI (–0.193 to –0.024) p = .013 0.133 95% CI (–1.073 to 1.339) p = .003 3.635 95% CI (2.925 to 4.346) p < .001

–0.063 95% CI (–0.107 to –0.018) p = .006 –0.793 95% CI (–1.428 to –0.159) p = .015 0.478 95% CI (0.104 to 0.852) p = .013

Laterality of lesion

Surgical procedure

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AMH = anti-Müllerian hormone; CI = confidence interval.

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Variable

ACCEPTED MANUSCRIPT 20 Table 7 Between-Group Comparison of AMH, AFC, and Ovarian Volume After 1 Year Cyst deroofing (n = 53) 2.07 ± 1.49

p value

AMH level, ng/mL ± SD

Cystectomy (n = 54) 1.39 ± 0.76

AFC, number ± SD

3.17 ± 1.36

5.42 ± 2.68

<.001

Ovarian volume, cm3 ± SD

2.89 ± 1.5

5.6 ± 2.56

<.001

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AFC = antral follicle count; AMH = anti-Müllerian hormone; SD = standard deviation.

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<.001

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Variable after 1 year