The Effect of Unilateral Endometrioma Excision on Ovarian Reserve

In: Turkiye Klinikleri Journal of Gynecology and Obstetrics · 2015 · vol. 25(2) , pp. 71–75 · doi:10.5336/gynobstet.2014-41312 · W2058428481
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Laparoscopic endometrioma excision significantly reduced antral follicle count in the operated ovary compared to the contralateral ovary, indicating a potential negative impact on ovarian reserve.

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This prospective, observational, operated versus non-operated site comparative study evaluated 21 women aged 20–36 with unilateral ovarian endometriomas (>30 mm) who underwent laparoscopic ovarian tissue-sparing stripping cystectomy, with ovarian reserve assessed at the third postoperative month using antral follicle counts (AFC) and blood FSH. AFCs on days 2–5 of the third postoperative follicular phase were measured by independent blinded examiners and compared between operated and non-operated ovaries; pre- and postoperative FSH were also compared. The operated side had significantly fewer AFCs than the non-operated side (2.61±1.24 vs 4.23±0.88), while FSH showed a statistically significant but reportedly clinically non-significant difference (6.7±1.8 vs 6.9±1.6), and no correlation was found between AFC and postoperative FSH. The study is limited by its small sample size and short follow-up focusing on AFC/FSH rather than longer-term fertility outcomes. This paper is centrally about endometriosis—specifically how unilateral laparoscopic endometrioma excision via stripping affects ovarian reserve markers.

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Abstract

Amaç: Endometriyoma eksizyonu için yapılan laparoskopik kistektominin over rezervi üzerine etkilerinin antral folikül sayısı (AFS) ve folikül stimülan hormon (FSH) seviyesi açısından değerlendirilmesi. Gereç ve Yöntemler: Prospektif, gözlemsel, opere edilen tarafın opere edilmeyen tarafla karşılaştırıldığı bu çalışmada tek taraflı, 30 mm üzerinde ovarian endometriyoma nedeniyle laparoskopik operasyon geçirme öyküsü olan 20-36 yaş arası 21 kadın, operasyon sonrası 3. ayda çağrıldı. Sadece ilk kez ve laparoskopik stripping yöntemiyle endometriyoma ameliyatı geçirenler çalışmaya dâhil edildi. Her iki overin antral folikülleri, hastanın klinik ve operasyon öyküsüne kör bağımsız bir araştırmacı tarafından operasyon sonrası 3. ayda siklusun 2-5. günleri arası değerlendirildi. Her iki overin AFS'leri opere olan ve olmayan taraf arasında karşılaştırıldı. Pre ve postoperative FSH düzeyleri kaydedildi. Bulgular: Opere olan ve olmayan taraf kıyaslandığında ortalama antral folikülleri arasında istatistiksel olarak anlamlı bir fark bulunmaktadır (2,61±1,24 ve 4,23±0,88, sırasıyla) (p<0,001). Pre ve postoperatif FSH seviyeleri (6,7±1,8 ve 6,9±1,6, p=0,011) arasında da önemli bir fark olmasına rağmen, bu fark klinik olarak anlamlı değildir. Sonuç: Çalışmamızın sonuçları postoperatif cerrahi tarafindaki AFS seviyelerinde anlamlı bir azalmayı işaret ettiğinden endometriyoma eksizyonunun over rezervi üzerine negatif bir etki yapabilecegini ortaya koymaktadır. Objective: To evaluate the effect of laparoscopic cystectomy for endometriomas on ovarian reserve as determined by antral follicle count (AFC) and follicle stimulating hormone (FSH) level. Material and Methods: In this prospective, observational, operated and non-operated site comparative study, twenty one women between 20-36 ages with previous history of laparoscopic surgery for unilateral ovarian endometriomas greater than 30 mm were called for the evaluation of ovarian reserve at third month. Only first endometrioma removal operations were included. Removal of endometrioma was performed by laparoscopic ovarian tissue-sparing stripping technique. AFC of both ovaries were evaluated on 2-5 day of postoperative third menstrual cycle by independent examiners, blinded to the clinical and surgical history of patients. AFCs of both ovaries were analyzed to compare between operated and non-operated sites. Pre and postoperative FSH levels were recorded also. Results: There was statistically significant difference in the mean number of antral follicles in the operated side ovary (2.61±1.24) when compared to the non-operated side ovary (4.23±0.88) (p<0.001). Although a significant difference was found between pre and postoperative FSH levels (6.7±1.8 vs 6.9±1.6, p=0.011), this did not reach to clinical significance. Conclusion: Our study results suggested that excision of endometriomas might have a negative impact on ovarian reserve as evidenced by a significant postoperative fall in ipsilateral AFC level.
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Material and methods

Prospective, observational, operated and non-op - erated site comparative study has been conducted. The study protocol was elaborated according to the revised Declaration of Helsinki and was approved by the local Research and Ethics Committee of our hospital. All subjects were provided written in - formed consent. Twenty one, 20-36 years, regularly menstru - ating women who underwent laparoscopic cystec - tomy for unilateral ovarian endometriomas greater than to 30 mm in diameter which verified by histopathologic investigation were included. They were called for the evaluation of ovarian reserve at third month. Women who had previously under - gone ovarian surgery or received any medication (gonadotropin releasing hormone antagonist or oral contraceptive drugs) for endometriosis pre or post - operatively, were not included in the study. Only first endometrioma removal operations were in - cluded. All endometriotic cysts were removed by la - paroscopic ovarian tissue-sparing stripping tech - nique and entire cyst was enucleated by appliying traction-countertraction technique by the same op - erator. Hemostasis was achived by suturing with polyglactin 910 suture (2-0 Vicryl) and cyst bed was not coagulated by electrical energy, bleeding from ovarian hilus was resolved only by suturing. There was no hematoma related to suturing. All patients who had a laparoscopic cystectomy were called for vaginal ultrasound examination on 2-5 days of follicular phase of the third postopera - tive menstrual cycle and also blood FSH level was evaluated. The ultrasonography was performed with the use of a 6.5 MHz (5-7.5 MHz) transvaginal microconvex probe by independent examiner, blinded to the clinical and surgical history of the pa - tients. The AFCs of both ovaries were recorded as the total number of follicles with a diameter of 2-9 mm in each ovary separately postoperatively. Statistical analysis was performed by using SPSS 1 5 (SPSS Inc. Chicago, IL). Distributions of variables were analyzed by normality tests. Paired- Samples T-test was used to evaluate the difference between the AFC of each ovaries. Preoperative and postoperative levels of FSH were evaluated by Wilcoxon Signed Rank test. Correlation between total AFC and postoperative FSH level was calcu - lated with Spearman’s correlation. A p value of <0.05 was accepted as statistically significant. Saime SEMİZ et al. THE EFFECT OF UNILATERAL ENDO METR IOMA EXCISION ON OVARIAN RESER VE Turkiye Klinikleri J Gynecol Obst 2015;25(2) 72

Results

The demographic and clinical characteristics of 21 women at the time of surgery were shown in Table 1.All patients were operated due to endometriosis related pain. The mean diameter of endometrioma was 41.6±18.9 mm. There was statistically significant difference in the mean number of antral follicles in the op - erated side ovary (2.61±1.24) when compared to the non-operated side ovary (4.23±0.88) (p<0.001) (Figure 1). There was also statistically significant differ - ence between pre and postoperative FSH levels (6.7±1.8 vs 6.9±1.6) (p=0.013) (Figure 2). No corre - lation was found between total AFC and postoper - ative FSH level (r=-0.24, p=0,28).

Discussion

Studies have demonstrated that; treatment of en - dometriomas with cyst wall ablation, drainage and coagulation or laser vaporization is associated with highe r risk of recurrence than excisional sur - gery.11-13 Laparoscopic cyst excision is considered to be the best treatment because of the lower re - currence and a higher pregnancy rate compared with conservative surgery.11 Recent data suggested that excisional surgery of endometriomas, in par - ticular the stripping technique may cause ovarian trauma.10 Given the possible mechanism of cortical invagination leading to endometrioma formation, stripping of the cyst capsule may result in inadver - tent removal of primordial, preantral and antral follicles from the healthy cortical tissue. This in turn may lead to iatrogenic depletion of ovarian follicles so ovarian reserve .14-16 Ovarian reserve can be screened by; age, bio - chemical tests either static tests as FSH, E2, FSH:LH, inhibin-B, anti-Mullerian hormone or dynamic tests as clomiphene citrate challenge test and go - nadotrophin releasing hormone test or biophysical tests as ovarian volume and antral follicle count .17 AFC has been strongly associated with the fol- licle pool and is used as a reliable sonographic in - dicator of ovarian reserve .18 The loss of AFC associated with stripping of endometriomas may be clinically important in infertile patients, especially if they have low ovarian reserve so more careful at - tention is advised.10 In the current study, we used the antral follicle count measured transvaginally Saime SEMİZ et al. THE EFFECT OF UNILATERAL ENDOMETRIOM A EXCISION ON OVARIAN RESERVE Turkiye Klinikleri J Gynecol Obst 2015;25(2) 73 N of patients= 21 Age (years, median,25p-75p) 32 (26-35) Parity (median,25p-75p) 1 (0-2.5) BMI (kg/m 2,median,25p-75p) 22 (21-24) Previous complaints related to endometriosis (n,%) CPP 19 (90.5) Dysmenorrhea 16 (76.2) Dyspareunia 4 (19) CPP+dysmenorrhea 16 (76.2) CPP+dyspareunia 4 (26.7) Dysmenorrhea+dyspareunia 3 (20) Infertility 0 (0) TABLE 1: Demographic and clinical characteristics of patients who underwent laparoscopic endometrioma removal. BMI: Body mass index; CPP: Chronic pelvic pain. FIGURE 1: Antral follicle count in operated and non operated ovaries. FIGURE 2: Preoperative and postoperative FSH levels. FSH for the assessment of ovarian reserve and we demonstrated that after cystectomy by laparoscopic stripping technique the mean number of antral fol- licles was significantly lower in operated side when compared with non-operated side ovary. In a re - cent randomized study, Var et al. compared the post-operative AFC, ovarian volume and response to ovulation stimulation in patients with bilateral endometriomas treated either by cystectomy or co - agulation of cyst capsule with bipolar energy; they found that cystectomy was associated with more damage to the ovaries when assessed for these vari- ables.10 It is revealed that; stripping of the cyst wall may result in ovarian reserve damage due to the re - moval of healthy ovarian cortex and thermal de - struction of ovarian follicles by use of bipolar coagulation for bleeding, which commonly applied after stripping.19,20 Hemostatic procedure after stripping of endometrioma might be one of the most important step in the operation. Ferrero et al. showed through a randomized controlled trial that laparoscopic stripping of ovarian endometri- otic cyst significantly decreases ovarian reserve [measured by means of serum anti Mullerian hor - mon (AMH) and basal FSH levels] independent from the method used to obtain hemostasis on the ovarian tissue (bipolar coagulation or suturing) .21 In our study, the suturing technique was used to control bleeding after cystectomy based on this data but postoperative AFC of operated ovaries was shown to be significantly decreased while the post - operative FSH levels were found to be increased. This findings could not confirm whether the dam - age of residual ovarian tissue caused by suturing or not. The suture might induce ischemic damage to the ovary. Nevertheless, because the increase in postoperative FSH levels were not clinically im - portant, suturing might contribute to the preserva - tion of ovarian reserve. One of the limitations of our study was ; lim - ited sample of subjects. Sample size could be larger to achieve more reliable results. The other limita - tions of our study was the measurements of antral follicle count could only be performed after the op - eration. Endometriosis per se could have detri- mental effect on the affected side. Before and after study design would be better to accomplish this limitations. Another limitations was the lack of AMH measurements before and after the en - dometrioma surgery. AMH is a more reliable and consistent ovarian reserve marker. Nevertheless our study have the strengths of measuring AFC as the side spesific marker to evaluate the effect of unilateral endometrioma surgery. In conclusion, our study results based on a lim - ited number of subjects suggested that excision of endometriomas might have a negative impact on ovarian reserve as demonstrated by a significant postoperative fall in ipsilateral AFC in the operated site and increase in blood FSH level. Although this is the technique of choice in terms of pain relief and less recurrence rate in patients with en - dometrioma the possibility of decrease in ovarian reserve should be taken into account. Saime SEMİZ et al. THE EFFECT OF UNILATERAL ENDO METR IOMA EXCISION ON OVARIAN RESER VE Turkiye Klinikleri J Gynecol Obst 2015;25(2) 74 1. Bulun SE. Endometriosis. Engl J Med 2009; 360(3):268-79. 2. Gupta S, Goldberg JM, Aziz N, Goldberg E, Krajcir N, Agarwal A. Pathogenic mechanisms in endometriosis-associated infertility. Fertil Steril 2008;90(2):247-57. 3. Canis M, Mage G, Wattiez A, Chapron C, Pouly JL, Basil S. Second look laparoscopy after laparoscopic cystectomy of large en - dometriomas. Fertil Steril 1992;58(3):617- 9. 4. Jones KD, Sutton CJ. Laparoscopic manage - ment of ovarian endometriomas: a critical re - view of current practice. Curr Opin Obstet Gynecol 2000;12(4):309-15. 5. Hart R, Hickey M, Maouris P, BuckettW, Gary R. Excisional surgery versus ablative surgery for ovarian endometrioma: a Cochrane Re - view. Hum Reprod 2005;20(11):3000-7. 6. Yeung PP Jr, Shwayder J, Pasic RP. La - paroscopic management of endometriosis: comprehensive review of best evidence. J Minim Invasive Gynecol 2009;16(3):269- 81. 7. Ho HY, Lee RK, Hwu YM, Lin MH, Su JT, Tsai YC. Poor response of ovaries with endometri- oma previously treated with cystectomy to controlled ovarian hyperstimulation. J Assist Reprod Genet 2002;19(11):507-11. 8. Brosens IA, Van Ballaer P, Puttemans P, Deprest J. Reconstruction of the ovary containing large endometriomas by an extraovarian endosurgical technique. Fertil Steril 1996;66(4):517- 21.

References

9. Donnez J, Nisolle M, Gillet N, Smets M, Bassil S, Casanas-Roux F. Large ovarian endomet- riomas. Hum Reprod 1996;11(3):641-6. 10. Var T, Batioglu S, Tonguc E, Kahyaoglu I. The effect of laparoscopic ovarian cystectomy ver - sus coagulation in bilateral endometriomas on ovarian reserve as determined by antral folli- cle count and ovarian volume: a prospective randomized study. Fertil Steril 2011;95(7): 2247-50. 11. Beretta P, Franchi M, Ghezzi F, Busacca M, Zupi E, Bolis P. Randomized clinical trial of two laparoscopic treatments of endometri- omas: cystectomy versus drainage and coag - ulation. Fertil Steril 1998;70(6):1176-80. 12. Vercellini P, Chapron C, DeGiorgi O, Con - sonni D, Frontino G, Crosignani PG. Coagu - lation or excision of ovarian endometriomas? Am J Obstet Gynecol 2003;188(3):606-10. 13. Busacca M, Marana R, Caruana P, Candiani M, Muzii L, Calia C, et al. Recurrence of ovar - ian endometrioma after laparoscopic excision. Am J Obstet Gynecol 1999;180(3 Pt 1):519- 23. 14. Busacca M, Vignali M. Endometrioma excision and ovarian reserve: a dangerous relation. J Minim Invasive Gynecol 2009;16(2):142-8. 15. van der Weiden RM. Damage to ovarian re - serve associated with laparoscopic excision of endometriomas: a quantitative rather than qualitative injury. Am J Obstet Gynecol 2006; 195(6):1874. 16. Ragni G, Somigliana E, Benedetti F, Paffoni A, Vegetti W, Restelli L, et al. Damage to ovar - ian reserve associated with laparoscopic ex - cision of endometriomas: a quantitative rather than a qualitative injury. Am J Obstet Gynecol 2005;193(6):1908-14. 17. Jirge PR. Ovarian reserve tests. J Hum Re - prod Sci 2011;4(3):108-13. 18. Mattukrishna S, McGarrigle H, Wakim R, Khadum I, Ranieri DM, Serhal P. Antral follicle count, antimullerian hormone and inhibin B: predictors of ovarian response in assisted re - productive technology? BJOG 2005;112(10): 1384-90. 19. Somigliana E, Ragni G, Benedetti F, Borroni R, Vegetti W, Crosignani PG. Does laparo - scopic excision of endometriotic ovarian cysts significantly affect ovarian reserve? Insights from IVF cycles. Hum Reprod 2003;18(11): 2450-3. 20. Hachisuga T, Kawarabayashi T. Histopatho - logical analysis of laparoscopically treated ovarian endometriotic cysts with special refer - ence to loss of follicles. Hum Reprod 2002; 17(2):432-5. 21. Ferrero S, Venturini PL, Gillott DJ, Remorgida V, Leone Roberti Maggiore U. Hemostasis by bipolar coagulation versus suture after surgi- cal stripping of bilateral ovarian endometri- omas: a randomized controlled trial. J Minim Invasive Gynecol 2012;19(6):722-30. Saime SEMİZ et al. THE EFFECT OF UNILATERAL ENDOMETRIOM A EXCISION ON OVARIAN RESERVE Turkiye Klinikleri J Gynecol Obst 2015;25(2) 75

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