{"paper_id":"1acad768-9afa-402e-9c31-24f946f9de8b","body_text":"M\nechanismsofinfertilityassociatedwithendometriosisarecon -\ntroversial.Itishypothesizedthatendometriosisisassociatedwith \noverproductionofprostaglandins,metalloproteinases,cytokines,\nTurkiyeKlinikleriJGynecolObst2015;25(2) \n71 \nTheEffectofUnilateralEndometriomaExcision \nonOvarianReserve \nAABBSS  TTRRAACCTT   OObbjjeeccttiivvee::To evaluate the effect of laparoscopic cystectomy for endometriomas on \novarian reserve as determined by antral follicle count (AFC) and follicle stimulating hormone (FSH) \nlevel. \nMMaatteerriiaall  aanndd  MMeetthhooddss::In this prospective, observational, operated and non-operated site \ncomparative study, twenty one women between 20-36 ages with previous history of laparoscopic \nsurgery for unilateral ovarian endometriomas greater than 30 mm were called for the evaluation of \novarian reserve at third month. Only first endometrioma removal operations were included. Re -\nmoval of endometrioma was performed by laparoscopic ovarian tissue-sparing stripping technique.\nAFC of both ovaries were evaluated on 2-5 day of postoperative third menstrual cycle by inde -\npendent examiners, blinded to the clinical and surgical history of patients. AFCs of both ovaries \nwere analyzed to compare between operated and non-operated sites. Pre and postoperative FSH \nlevels were recorded also. \nRReessuullttss::  There was statistically significant difference in the mean num -\nber of antral follicles in the operated side ovary (2.61±1.24) when compared to the non-operated side \novary (4.23±0.88) (p<0.001). Although a significant difference was found between pre and postop -\nerative FSH levels (6.7±1.8 vs 6.9±1.6, p=0.011), this did not reach to clinical significance. \nCCoonncclluu--\nssiioonn::  Our study results suggested that excision of endometriomas might have a negative impact on \novarian reserve as evidenced by a significant postoperative fall in ipsilateral AFC level.\nKKeeyy  WW oorrddss::  Endometriosis; laparoscopy; follicle stimulating hormone; follicular fluid \nÖÖZZEETT  AAmmaaçç::  Endometriyoma eksizyonu için yapılan laparoskopik kistektominin over rezervi üze -\nrine etkilerinin antral folikül sayısı (AFS) ve folikül stimülan hormon (FSH) seviyesi açısından de -\nğerlendirilmesi. GGeerreeçç  vvee  YYöönntteemmlleerr::Prospektif, gözlemsel, opere edilen tarafın opere edilmeyen \ntarafla karşılaştırıldığı bu çalışmada tek taraflı, 30 mm üzerinde ovarian endometriyoma nedeniyle \nlaparoskopik operasyon geçirme öyküsü olan 20-36 yaş arası 21 kadın, operasyon sonrası 3. ayda \nçağrıldı. Sadece ilk kez ve laparoskopik stripping yöntemiyle endometriyoma ameliyatı geçirenler çal-\nışmaya dâhil edildi. Her iki overin antral folikülleri, hastanın klinik ve operasyon öyküsüne kör \nbağımsız bir araştırmacı tarafından operasyon sonrası 3. ayda siklusun 2-5. günleri arası değerlendi-\nrildi. Her iki overin AFS’leri opere olan ve olmayan taraf arasında karşılaştırıldı. Pre ve postopera -\ntive FSH düzeyleri kaydedildi. \nBBuullgguullaarr::Opere olan ve olmayan taraf kıyaslandığında ortalama antral\nfolikülleri arasında istatistiksel olarak anlamlı bir fark bulunmaktadır (2,61±1,24 ve 4,23±0,88,\nsırasıyla) (p<0,001). Pre ve postoperatif FSH seviyeleri (6,7±1,8 ve 6,9±1,6, p=0,011) arasında da \nönemli bir fark olmasına rağmen, bu fark klinik olarak anlamlı değildir. \nSSoonnuuçç::  Çalışmamızın so -\nnuçları postoperatif cerrahi tarafindaki AFS seviyelerinde anlamlı bir azalmayı işaret ettiğinden en -\ndometriyoma eksizyonunun over rezervi üzerine negatif bir etki yapabilecegini ortaya koymaktadır.\nAAnnaahh  ttaarr  KKee  llii  mmee  lleerr::Endometriyoz; laparoskopi; folikül stimüle edici hormon; folliküler sıvı\nTTuurrkkiiyyee  KKlliinniikklleerrii  JJ  GGyynneeccooll  OObbsstt  22001155;;2255((22))::7711--55\nSaime SEMİZ, a\nMurat APİ, b\nSemra KAYATAŞ, b\nAyşen BOZA c\naClinic of Family Medicine, \nAdana Numune Training and \nResearch Hospital, \nAdana \nbClinic of Obstetrics and Gynecology, \nZeynep Kamil Women and Children’s \nTraining and Research Hospital, \ncClinic of Obstetrics and Gynecology, \nGöztepe Training and Research Hospital, \nİstanbul\nGe liş Ta ri hi/ Re ce i ved: 06.07.2014 \nKa bul Ta ri hi/ Ac cep ted: 25.02.2015 \nYa zış ma Ad re si/ Cor res pon den ce: \nAyşen BOZA \nGöztepe Training and Research Hospital, \nClinic of Obstetrics and Gynecology, \nİstanbul\nTÜRKİYE/TURKEY \ndoi: 10.5336/gynobstet.2014-41312 \nCop yright © 2015 by Tür ki ye Kli nik le ri \nORİJİNAL ARAŞTIRMA   \n\nand chemokines and that the resulting inflamma -\ntory process impairs ovarian, peritoneal, tubal, and \nendometrial function, leading to defective follicu -\nlogenesis, fertilization, and/or implantation .1,2 \nThese observations may have detrimental effect on \novarian reserve in patients with endometriosis.\nFurthermore, excision of endometrioma may also \naffect the ovarian reserve.\nAlthough laparoscopy was considered as the \nprimary surgical option for the treatment of en -\ndometriomas, there is no definitive laparoscopic \ntechnique preferred.3 The stripping of the pseudo \ncapsule is the most commonly used operative tech -\nnique.4 Fenestration, drainage and coagulation or \nlaser vaporization are the other techniques that \nhave been used.5 At laparoscopy, due to greater pain \nrelief and less recurrence rate, the stripping tech -\nnique has been reported to be preferable to drainage \nand ablative techniques.6 Although the stripping \ntechnique is thought to be a most common opera -\ntive technique which saves future reproductive \nfunction and patient’s fertility, major concern is the \npossible loss of follicles might have a negative im -\npact on ovarian reserve and function.7-9 \nSome literature suggested excisional surgery of \nendometriomas, in particular the stripping tech -\nnique may cause ovarian trauma as loss of follicles \nand also loss of ovarian volume .7,10 In contrast,\nYeung et al. reported advantages of laparoscopic \nexcision of endometrioma by stripping of the cyst \nwall in terms of pain relief, less recurrence rate and \nhigh pregnancy rate.6\nWe designed the present study to assess \nwhether the laparoscopic cystectomy with strip -\nping of ovarian endometrioma was effective on \novarian reserve as determined by ultrasonographic \nmeasurement of antral follicle count (AFC) and \nblood follicle stimulant hormon (FSH) level.\nMATERIAL AND METHODS \nProspective, observational, operated and non-op -\nerated site comparative study has been conducted.\nThe study protocol was elaborated according to the \nrevised Declaration of Helsinki and was approved \nby the local Research and Ethics Committee of our \nhospital. All subjects were provided written in -\nformed consent.\nTwenty one, 20-36 years, regularly menstru -\nating women who underwent laparoscopic cystec -\ntomy for unilateral ovarian endometriomas greater \nthan to 30 mm in diameter which verified by \nhistopathologic  investigation were included. They \nwere called for the evaluation of ovarian reserve at \nthird month. Women who had previously under -\ngone ovarian surgery or received any medication \n(gonadotropin releasing hormone antagonist or oral\ncontraceptive drugs) for endometriosis pre or post -\noperatively, were not included in the study.  Only \nfirst endometrioma removal operations were in -\ncluded.\nAll endometriotic cysts were removed by la -\nparoscopic ovarian tissue-sparing stripping tech -\nnique and entire cyst was enucleated by appliying \ntraction-countertraction technique by the same op -\nerator. Hemostasis was achived by suturing with \npolyglactin 910 suture (2-0 Vicryl) and cyst bed \nwas not coagulated by electrical energy, bleeding \nfrom ovarian hilus was resolved only by suturing.\nThere was no hematoma related to suturing. \nAll patients who had a laparoscopic cystectomy \nwere called for vaginal ultrasound examination on \n2-5 days of follicular phase of the third postopera -\ntive menstrual cycle and also blood FSH level was \nevaluated. The ultrasonography was performed \nwith the use of a 6.5 MHz (5-7.5 MHz) transvaginal\nmicroconvex probe by independent examiner,\nblinded to the clinical and surgical history of the pa -\ntients. The AFCs of both ovaries were recorded as \nthe total number of follicles with a diameter of 2-9 \nmm in each ovary separately postoperatively.\nStatistical analysis was performed by using \nSPSS 1 5 (SPSS Inc. Chicago, IL). Distributions of \nvariables were analyzed by normality tests. Paired- \nSamples T-test was used to evaluate the difference \nbetween the AFC of each ovaries. Preoperative and \npostoperative levels of FSH were evaluated by \nWilcoxon Signed Rank test. Correlation between \ntotal AFC and postoperative FSH level was calcu -\nlated with Spearman’s correlation. A p value of \n<0.05 was accepted as statistically significant. \nSaime SEMİZ et al. THE EFFECT OF UNILATERAL ENDO METR IOMA EXCISION ON OVARIAN RESER VE \nTurkiye Klinikleri J Gynecol Obst 2015;25(2) \n72 \n\nRESULTS  \nThe demographic and clinical characteristics of 21 \nwomen at the time of surgery were shown in Table \n1.All patients were operated due to endometriosis \nrelated pain. The mean diameter of endometrioma \nwas 41.6±18.9 mm. \nThere was statistically significant difference \nin the mean number of antral follicles in the op -\nerated side ovary (2.61±1.24) when compared to \nthe non-operated side ovary (4.23±0.88) (p<0.001) \n(Figure 1). \nThere was also statistically significant differ -\nence between pre and postoperative FSH levels \n(6.7±1.8 vs 6.9±1.6) (p=0.013) (Figure 2). No corre -\nlation was found between total AFC and postoper -\native FSH level (r=-0.24, p=0,28).\nDISCUSSION \nStudies have demonstrated that; treatment of en -\ndometriomas with cyst wall ablation, drainage \nand coagulation or laser vaporization is associated \nwith highe r risk of recurrence than excisional sur -\ngery.11-13 Laparoscopic cyst excision is considered \nto be the best treatment because of the lower re -\ncurrence and a higher pregnancy rate compared \nwith conservative surgery.11 Recent data suggested \nthat excisional surgery of endometriomas, in par -\nticular the stripping technique may cause ovarian \ntrauma.10 Given the possible mechanism of cortical\ninvagination leading to endometrioma formation,\nstripping of the cyst capsule may result in inadver -\ntent removal of primordial, preantral and antral\nfollicles from the healthy cortical tissue. This in \nturn may lead to iatrogenic depletion of ovarian \nfollicles so ovarian reserve .14-16 \nOvarian reserve can be screened by; age, bio -\nchemical tests either static tests as FSH, E2, FSH:LH,\ninhibin-B, anti-Mullerian hormone or dynamic \ntests as clomiphene citrate challenge test and go -\nnadotrophin releasing hormone test or biophysical\ntests  as ovarian volume and antral follicle count .17 \nAFC has been strongly associated with the fol-\nlicle pool and is used as a reliable sonographic in -\ndicator of ovarian reserve .18 The loss of AFC \nassociated with stripping of endometriomas may be \nclinically important in infertile patients, especially \nif they have low ovarian reserve so more careful at -\ntention is advised.10 In the current study, we used \nthe antral follicle count measured transvaginally \nSaime SEMİZ et al. THE EFFECT OF UNILATERAL ENDOMETRIOM A EXCISION ON OVARIAN RESERVE \nTurkiye Klinikleri J Gynecol Obst 2015;25(2) \n73 \nN of patients= 21 \nAge (years, median,25p-75p) 32 (26-35) \nParity (median,25p-75p) 1 (0-2.5) \nBMI (kg/m 2,median,25p-75p) 22 (21-24) \nPrevious complaints related to endometriosis (n,%) \nCPP 19 (90.5) \nDysmenorrhea 16 (76.2) \nDyspareunia 4 (19) \nCPP+dysmenorrhea 16 (76.2) \nCPP+dyspareunia 4 (26.7) \nDysmenorrhea+dyspareunia 3 (20) \nInfertility 0 (0) \nTABLE 1: Demographic and clinical characteristics of \npatients who underwent laparoscopic endometrioma \nremoval. \nBMI: Body mass index; CPP: Chronic pelvic pain. \nFIGURE 1: Antral follicle count in operated and non operated ovaries. \nFIGURE 2: Preoperative and postoperative FSH levels. \nFSH \n\nfor the assessment of ovarian reserve and we \ndemonstrated that after cystectomy by laparoscopic \nstripping technique the mean number of antral fol-\nlicles was significantly lower in operated side when \ncompared with non-operated side ovary. In a re -\ncent randomized study, Var et al. compared the \npost-operative AFC, ovarian volume and response \nto ovulation stimulation in patients with bilateral\nendometriomas treated either by cystectomy or co -\nagulation of cyst capsule with bipolar energy; they \nfound that cystectomy was associated with more \ndamage to the ovaries when assessed for these vari-\nables.10 \nIt is revealed that; stripping of the cyst wall\nmay result in ovarian reserve damage due to the re -\nmoval of healthy ovarian cortex and thermal de -\nstruction of ovarian follicles by use of bipolar \ncoagulation for bleeding, which commonly applied \nafter stripping.19,20 Hemostatic procedure after \nstripping of endometrioma might be one of the \nmost important step in the operation. Ferrero \net al. showed through a randomized controlled trial\nthat laparoscopic stripping of ovarian endometri-\notic cyst significantly decreases ovarian reserve \n[measured by means of serum anti Mullerian hor -\nmon (AMH) and basal FSH levels] independent \nfrom the method used to obtain hemostasis on the \novarian tissue (bipolar coagulation or suturing) .21 \nIn our study, the suturing technique was used to \ncontrol bleeding after cystectomy based on this \ndata but postoperative AFC of operated ovaries was \nshown to be significantly decreased while the post -\noperative FSH levels were found to be increased.\nThis findings could not confirm whether the dam -\nage of residual ovarian tissue caused by suturing or \nnot. The suture might induce ischemic damage to \nthe ovary. Nevertheless, because the increase in \npostoperative FSH levels were not clinically im -\nportant, suturing might contribute to the preserva -\ntion of ovarian reserve.\nOne of the limitations of our study was ; lim -\nited sample of subjects. Sample size could be larger \nto achieve more reliable results. The other limita -\ntions of our study was the measurements of antral\nfollicle count could only be performed after the op -\neration. Endometriosis  per se could have detri-\nmental effect on the affected side. Before and after \nstudy design would be better to accomplish this \nlimitations. Another limitations was the lack of \nAMH measurements before and after the en -\ndometrioma surgery. AMH is a more reliable and \nconsistent ovarian reserve marker. Nevertheless \nour study have the strengths of measuring AFC as \nthe side spesific marker to evaluate the effect of \nunilateral endometrioma surgery.\nIn conclusion, our study results based on a lim -\nited number of subjects suggested that excision of \nendometriomas might have a negative impact on \novarian reserve as demonstrated by a significant \npostoperative fall in ipsilateral AFC in the operated \nsite and increase in blood FSH level. Although this \nis the technique of choice in terms of pain relief \nand less recurrence rate in patients with en -\ndometrioma the possibility of decrease in ovarian \nreserve should be taken into account.\nSaime SEMİZ et al. THE EFFECT OF UNILATERAL ENDO METR IOMA EXCISION ON OVARIAN RESER VE \nTurkiye Klinikleri J Gynecol Obst 2015;25(2) \n74 \n1. Bulun SE. Endometriosis. Engl J Med 2009; \n360(3):268-79. \n2. Gupta S, Goldberg JM, Aziz N, Goldberg E, \nKrajcir N, Agarwal A. Pathogenic mechanisms \nin endometriosis-associated infertility. Fertil\nSteril 2008;90(2):247-57. \n3. Canis M, Mage G, Wattiez A, Chapron C, \nPouly JL, Basil S. Second look laparoscopy \nafter laparoscopic cystectomy of large en -\ndometriomas. Fertil Steril 1992;58(3):617- \n9. \n4. Jones KD, Sutton CJ. Laparoscopic manage -\nment of ovarian endometriomas: a critical re -\nview of current practice. Curr Opin Obstet \nGynecol 2000;12(4):309-15. \n5. Hart R, Hickey M, Maouris P, BuckettW, Gary \nR. Excisional surgery versus ablative surgery \nfor ovarian endometrioma: a Cochrane Re -\nview. Hum Reprod 2005;20(11):3000-7. \n6. Yeung PP Jr, Shwayder J, Pasic RP. La -\nparoscopic management of endometriosis: \ncomprehensive review of best evidence. J \nMinim Invasive Gynecol 2009;16(3):269- \n81. \n7. Ho HY, Lee RK, Hwu YM, Lin MH, Su JT, Tsai\nYC. Poor response of ovaries with endometri-\noma previously treated with cystectomy to \ncontrolled ovarian hyperstimulation. J Assist \nReprod Genet 2002;19(11):507-11. \n8. Brosens IA, Van Ballaer P, Puttemans P, Deprest \nJ. Reconstruction of the ovary containing large \nendometriomas by an extraovarian endosurgical\ntechnique. Fertil Steril 1996;66(4):517- 21. \nREFERENCES \n\n9. Donnez J, Nisolle M, Gillet N, Smets M, Bassil\nS, Casanas-Roux F. Large ovarian endomet- \nriomas. Hum Reprod 1996;11(3):641-6. \n10. Var T, Batioglu S, Tonguc E, Kahyaoglu I. The \neffect of laparoscopic ovarian cystectomy ver -\nsus coagulation in bilateral endometriomas on \novarian reserve as determined by antral folli-\ncle count and ovarian volume: a prospective \nrandomized study. Fertil Steril 2011;95(7): \n2247-50. \n11. Beretta P, Franchi M, Ghezzi F, Busacca M, \nZupi E, Bolis P. Randomized clinical trial of \ntwo laparoscopic treatments of endometri-\nomas: cystectomy versus drainage and coag -\nulation. Fertil Steril 1998;70(6):1176-80. \n12. Vercellini P, Chapron C, DeGiorgi O, Con -\nsonni D, Frontino G, Crosignani PG. Coagu -\nlation or excision of ovarian endometriomas? \nAm J Obstet Gynecol 2003;188(3):606-10. \n13. Busacca M, Marana R, Caruana P, Candiani\nM, Muzii L, Calia C, et al. Recurrence of ovar -\nian endometrioma after laparoscopic excision. \nAm J Obstet Gynecol 1999;180(3 Pt 1):519- \n23. \n14. Busacca M, Vignali M. Endometrioma excision \nand ovarian reserve: a dangerous relation. J \nMinim Invasive Gynecol 2009;16(2):142-8. \n15. van der Weiden RM. Damage to ovarian re -\nserve associated with laparoscopic excision of \nendometriomas: a quantitative rather than \nqualitative injury. Am J Obstet Gynecol 2006; \n195(6):1874. \n16. Ragni G, Somigliana E, Benedetti F, Paffoni\nA, Vegetti W, Restelli L, et al. Damage to ovar -\nian reserve associated with laparoscopic ex -\ncision of endometriomas: a quantitative rather \nthan a qualitative injury. Am J Obstet Gynecol\n2005;193(6):1908-14. \n17. Jirge PR. Ovarian reserve tests. J Hum Re -\nprod Sci 2011;4(3):108-13. \n18. Mattukrishna S, McGarrigle H, Wakim R, \nKhadum I, Ranieri DM, Serhal P. Antral follicle \ncount, antimullerian hormone and inhibin B: \npredictors of ovarian response in assisted re -\nproductive technology? BJOG 2005;112(10): \n1384-90. \n19. Somigliana E, Ragni G, Benedetti F, Borroni\nR, Vegetti W, Crosignani PG. Does laparo -\nscopic excision of endometriotic ovarian cysts \nsignificantly affect ovarian reserve? Insights \nfrom IVF cycles. Hum Reprod 2003;18(11): \n2450-3. \n20. Hachisuga T, Kawarabayashi T. Histopatho -\nlogical analysis of laparoscopically treated \novarian endometriotic cysts with special refer -\nence to loss of follicles. Hum Reprod 2002; \n17(2):432-5. \n21. Ferrero S, Venturini PL, Gillott DJ, Remorgida \nV, Leone Roberti Maggiore U. Hemostasis by \nbipolar coagulation versus suture after surgi-\ncal stripping of bilateral ovarian endometri-\nomas: a randomized controlled trial. J Minim \nInvasive Gynecol 2012;19(6):722-30. \nSaime SEMİZ et al. THE EFFECT OF UNILATERAL ENDOMETRIOM A EXCISION ON OVARIAN RESERVE \nTurkiye Klinikleri J Gynecol Obst 2015;25(2) \n75","source_license":"CC0","license_restricted":false}