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Effects of excision of ovarian endometrioma on the antral follicle count and collected oocytes for in vitro fertilization

2010; Elsevier BV; Volume: 94; Issue: 6 Linguagem: Inglês

10.1016/j.fertnstert.2010.01.055

1556-5653

Benny Almog, Boaz Sheizaf, Einat Shalom‐Paz, Fady Shehata, Ayman Al‐Talib, Togas Tulandi,

Uterine Myomas and Treatments

We compared the response of operated and nonoperated ovaries to gonadotropin stimulation in 38 women who had had excision of ovarian endometrioma. The antral follicle count, numbers of dominant follicles, and number of oocytes collected in the operated ovaries were significantly lower than in the nonoperated ovaries suggesting reduced ovarian reserve after excision of ovarian endometrioma. We compared the response of operated and nonoperated ovaries to gonadotropin stimulation in 38 women who had had excision of ovarian endometrioma. The antral follicle count, numbers of dominant follicles, and number of oocytes collected in the operated ovaries were significantly lower than in the nonoperated ovaries suggesting reduced ovarian reserve after excision of ovarian endometrioma. Endometriosis is found in 10–22% of fertile women and in 20–35% of the infertile population (1Ajossa S. Mais V. Guerriero S. Paoletti A.M. Caffiero A. Murgia C. et al.The prevalence of endometriosis in premenopausal women undergoing gynecological surgery.Clin Exp Obstet Gynecol. 1994; 21: 195-197PubMed Google Scholar, 2Farquhar C.M. Extracts from the "clinical evidence".Endometriosis. BMJ. 2000; 320: 1449-1452Crossref PubMed Scopus (155) Google Scholar). Approximately 30–40% of women with endometriosis also harbor ovarian endometrioma (3Vercellini P. Chapron C. De Giorgi O. Consonni D. Frontino G. Crosignani P.G. Coagulation or excision of ovarian endometriomas?.Am J Obstet Gynecol. 2003; 188: 606-610Abstract Full Text Full Text PDF PubMed Scopus (153) Google Scholar, 4Jenkins S. Olive D.L. Haney A.F. Endometriosis: pathogenetic implications of the anatomic distribution.Obstet Gynecol. 1986; 67: 335-338PubMed Google Scholar). One of the treatments of ovarian endometrioma is ovarian cystectomy. The beneficial effects of cystectomy for endometrioma on dyspareunia and dysmenorrhea have been well established (5Hart R. Hickey M. Maouris P. Buckett W. Garry R. Excisional surgery versus ablative surgery for ovarian endometriomata: a Cochrane Review.Hum Reprod. 2005; 20: 3000-3007Crossref PubMed Scopus (83) Google Scholar). However, the optimal management of endometriomas in women with infertility remains unclear. It appears that surgical removal of the endometrioma may affect fertility negatively. Indeed, reduced ovarian reserve after cystectomy for endometriomas has been demonstrated in both natural and stimulated cycles (6Horikawa T. Nakagawa K. Ohgi S. Kojima R. Nakashima A. Ito M. et al.The frequency of ovulation from the affected ovary decreases following laparoscopic cystectomy in infertile women with unilateral endometrioma during a natural cycle.J Assist Reprod Genet. 2008; 25: 239-244Crossref PubMed Scopus (59) Google Scholar, 7Somigliana E. Arnoldi M. Benaglia L. Iemmello R. Nicolosi A. Ragni G. IVF-ICSI outcome in women operated on for bilateral endometriomas.Hum Reprod. 2008; 23: 1526-1530Crossref PubMed Scopus (131) Google Scholar, 8Benaglia L. Somigliana E. Vercellini P. Abbiati A. Ragni G. Fedele L. Endometriotic ovarian cysts negatively affect the rate of spontaneous ovulation.Hum Reprod. 2009; 24: 2183-2186Crossref PubMed Scopus (113) Google Scholar); however, a few authors contradicted these findings (9Alborzi S. Ravanbakhsh R. Parsanezhad M.E. Alborzi M. Alborzi S. Dehbashi S. A comparison of follicular response of ovaries to ovulation induction after laparoscopic ovarian cystectomy or fenestration and coagulation versus normal ovaries in patients with endometrioma.Fertil Steril. 2007; 88: 507-509Abstract Full Text Full Text PDF PubMed Scopus (68) Google Scholar, 10Tsoumpou I. Kyrgiou M. Gelbaya T.A. Nardo L.G. The effect of surgical treatment for endometrioma on in vitro fertilization outcomes: a systematic review and meta-analysis.Fertil Steril. 2009; 92: 75-87Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar). The precise effect of endometriosis itself and the effects of different types of surgery for endometrioma on the ovarian reserve are yet to be defined. Various indicators have been used in both natural and stimulated cycles including, anti-müllerian hormone levels, cycle day 3 FSH, antral follicle count, dynamic tests, and different indexes of IVF outcome (10Tsoumpou I. Kyrgiou M. Gelbaya T.A. Nardo L.G. The effect of surgical treatment for endometrioma on in vitro fertilization outcomes: a systematic review and meta-analysis.Fertil Steril. 2009; 92: 75-87Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar, 11Tsolakidis D. Pados G. Vavilis D. Athanatos D. Tsalikis T. Giannakou A. et al.The impact on ovarian reserve after laparoscopic ovarian cystectomy versus three-stage management in patients with endometriomas: a prospective randomized study.Fertil Steril. 2009; ([Epub ahead of print])PubMed Google Scholar, 12Maheshwari A. Gibreel A. Bhattacharya S. Johnson N.P. Dynamic tests of ovarian reserve: a systematic review of diagnostic accuracy.Reprod Biomed Online. 2009; 18: 717-734Abstract Full Text PDF PubMed Scopus (39) Google Scholar). One of the direct indicators is ovarian response to a high dose of gonadotropin stimulation (13Broekmans F.J. Kwee J. Hendriks D.J. Mol B.W. Lambalk C.B. A systematic review of tests predicting ovarian reserve and IVF outcome.Hum Reprod Update. 2006; 12: 685-718Crossref PubMed Scopus (921) Google Scholar). The purpose of our study was to evaluate and compare the response of operated and nonoperated ovaries to gonadotropin stimulation in women whose endometrioma had been excised. We evaluated the number of antral follicle count, number of dominant follicle, and the number of collected oocyte. We examined the medical records of 38 women who had laparoscopic excision of ovarian endometrioma followed by IVF treatment at McGill University Health Center (Montreal, Quebec, Canada) between January 1998 and December 2008. The laparoscopy was performed by one surgeon (T.T.), and histopathologic examination confirmed the diagnosis of endometrioma in all patients. IVF treatment was performed as previously described (14Buckett W. Chian R. Dean N. Sylvestre C. Holzer H. Tan S. Pregnancy loss in pregnancies conceived after in vitro oocyte maturation, conventional in vitro fertilization, and intracytoplasmic sperm injection.Fertil Steril. 2008; 90: 546-550Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar). An injection of hCG was administered when three follicles were >18 mm. Transvaginal ultrasound–guided oocyte retrieval was performed 36 hours after hCG administration. Excision of ovarian endometrioma was performed by stripping the cyst wall from the surrounding ovarian tissue as described previously (15Saleh A. Tulandi T. Reoperation after laparoscopic treatment of ovarian endometriomas by excision and by fenestration.Fertil Steril. 1999; 72: 322-324Abstract Full Text Full Text PDF PubMed Scopus (141) Google Scholar). The ovarian edges were inverted by light application of bipolar coagulation to the inner side of the ovarian surface approximately 1 cm from the margin. Institutional review board approval was not required because of the retrospective nature of our study. Data recorded included demography, operative and pathology reports, location of the endometrioma (right or left), day 3 basal hormone levels, treatment cycle parameters, antral follicle count, and number of oocytes. We compared the number of oocytes collected from the operated and nonoperated ovaries. Patients with bilateral endometriomas (n = 9) were excluded. The statistical analysis was performed using the SPSS software package (SPSS Inc., Chicago, IL). Data were analyzed using chi-square test and Student's t test or Mann-Whitney test when appropriate. P < 0.05 was required to reject the null hypothesis. Of 38 women, 28 had left ovarian cystectomy, and 10 had right ovarian cystectomy with 80 IVF cycles in total. The values here are represented as mean ± SD. The patient's age was 34.8 ± 4.2 years, body mass index was 23.5 ± 6.8, and the diameter of the endometrioma was 3.9 ± 1.9. Baseline FSH levels (on day 3 of cycle) were 7.6 ± 3.3 IU/L, LH 3.8 ±1.7 IU/L, and E2 158.7 ± 101.3 pmol/L. The antral follicle count, the number of dominant follicles, and the number of collected oocytes in the operated ovary were significantly lower than in the nonoperated ovaries (4.5 ± 3.8 vs.7.4 ± 5.2, P=0.003; 4.7 ± 3.9 vs. 7.6 ± 4.7, P < 0.0001; 4.3 ± 3.9 vs. 7.4 ± 4.8, P < 0.0001, respectively; Table 1).Table 1Number of antral follicle count, dominant follicle, and collected oocytes in the operated ovaries and in the nonoperated ovaries among women with previous ovarian endometrioma.Operated side (n = 80)Nonoperated side (n = 80)P value95% CIAntral follicle count4.5 ± 3.87.4 ± 5.20.0031.0–5.0No. of dominant follicles4.7 ± 3.97.5 ± 4.7<0.00011.5–4.2No. of dominant follicles ≤ 2 (%)24 (30%)10 (12.5%)0.025.1–29.8No. of collected oocytes4.3 ± 3.97.4 ± 4.8<0.00011.7–4.4No. of collected oocytes ≤ 2 (%)32 (40%)13 (16.2%)0.00810.3–37.2No. of zero oocytes collected (percent)15 (18.7%)1 (1.2%)0.00028.6–26.4 Open table in a new tab The proportion of ovaries with at most two dominant follicles was significantly higher in the operated side compared to the nonoperated side. Similarly, the proportion of ovaries with at most two collected oocytes was significantly higher in the operated ovaries than in the nonoperated ovaries (Table 1). The odds ratio for having more than two dominant follicles in the nonoperated ovaries compared to the operated side was 3.0 (95% confidence interval [CI], 1.3–6.7), and the odds ratio for collecting more than two oocytes in the nonoperated side compared to the operated side was 3.4 (95% CI, 1.6–7.2). We could not retrieve any oocyte from 15 operated ovaries (18.75%) and from one nonoperated ovary (1.2%; P=0.0002). The average time from operation to IVF-ET cycle was 2.3 ± 1.7 years. There was no correlation (r = 0.06) between the time passed and the difference in the number of antral follicles and oocytes collected (operated vs. nonoperated). The results of our study show reduced ovarian response in ovaries treated for endometriomas compared with the nonoperated ovaries. This reduction was demonstrated by decreased number of dominant follicles and oocytes collected for IVF treatment. The reduction in mean dominant follicle number was 38% (4.7 vs. 7.6 follicles per ovary) with even more significant reduction of 41% (4.3 vs. 7.4 oocytes per ovary) in the number of oocytes. In addition, we could not retrieve any oocytes from the operated ovaries in 15 women (18.75%). To the best of our knowledge, there have been only two studies demonstrating differential oocyte numbers between operated and nonoperated ovaries in women with ovarian endometrioma (16Ragni G. Somigliana E. Benedetti F. Paffoni A. Vegetti W. Restelli L. et al.Damage to ovarian reserve associated with laparoscopic excision of endometriomas: a quantitative rather than a qualitative injury.Am J Obstet Gynecol. 2005; 193: 1908-1914Abstract Full Text Full Text PDF PubMed Scopus (122) Google Scholar, 17Ho H. Lee R. Hwu Y. Lin M. Su J. Tsai Y. Poor response of ovaries with endometrioma previously treated with cystectomy to controlled ovarian hyperstimulation.J assist reprod genet. 2002; 19: 507-511Crossref PubMed Scopus (156) Google Scholar). Overall, our results are in agreement with those of the previous studies. However, our study group (80 cycles analyzed) is larger than the previous two studies (38 cycles in both). The proportions of decrease in the number of dominant follicles (38% vs. 60%) and oocytes (41% vs. 53%) in the operated ovaries were less than in those previously reported. In addition, the previous studies did not address the AFC. We demonstrated that decreased antral follicle count (AFC) corresponded with reduced number of dominant follicles and the number of collected oocytes. In this study, we evaluated removal of ovarian endometrioma by the "stripping" technique (excision). Compared with fenestration and drainage of the content of endometrioma followed by ablation of the endometrioma bed, the recurrence rate of excision is lower (15Saleh A. Tulandi T. Reoperation after laparoscopic treatment of ovarian endometriomas by excision and by fenestration.Fertil Steril. 1999; 72: 322-324Abstract Full Text Full Text PDF PubMed Scopus (141) Google Scholar). Donnez et al. (18Donnez J. Wyns C. Nisolle M. Does ovarian surgery for endometriomas impair the ovarian response to gonadotropin?.Fertil Steril. 2001; 76: 662-665Abstract Full Text Full Text PDF PubMed Scopus (154) Google Scholar) reported that fenestration and ablation for unilateral endometrioma did not impair postsurgical ovarian response to gonadotropins. However, in a randomized study, Beretta et al. (19Beretta P. Franchi M. Ghezzi F. Busacca M. Zupi E. Bolis P. Randomized clinical trial of two laparoscopic treatments of endometriomas: cystectomy versus drainage and coagulation.Fertil Steril. 1998; 70: 1176-1180Abstract Full Text Full Text PDF PubMed Scopus (353) Google Scholar) found that the recurrence rate after fenestration and ablation was higher, and the pregnancy rate was lower than after excision. Accordingly, excision of ovarian endometrioma is still the recommended treatment of choice (5Hart R. Hickey M. Maouris P. Buckett W. Garry R. Excisional surgery versus ablative surgery for ovarian endometriomata: a Cochrane Review.Hum Reprod. 2005; 20: 3000-3007Crossref PubMed Scopus (83) Google Scholar). Ovarian function could be affected by the mere presence of endometriosis, endometrioma, or ovarian surgery (20Lemos N.A. Arbo E. Scalco R. Weiler E. Rosa V. Cunha-Filho J.S. Decreased anti-Mullerian hormone and altered ovarian follicular cohort in infertile patients with mild/minimal endometriosis.Fertil Steril. 2008; 89: 1064-1068Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar, 21Somigliana E. Infantino M. Benedetti F. Arnoldi M. Calanna G. Ragni G. The presence of ovarian endometriomas is associated with a reduced responsiveness to gonadotropins.Fertil Steril. 2006; 86: 192-196Abstract Full Text Full Text PDF PubMed Scopus (131) Google Scholar). In one histopathologic study, follicular number in ovaries with endometriomas was less than in those with dermoid cysts or benign cystadenomas (22Maneschi F. Marasa L. Incandela S. Mazzarese M. Zupi E. Ovarian cortex surrounding benign neoplasms: a histologic study.Am J Obstet Gynecol. 1993; 169: 388-393Abstract Full Text PDF PubMed Scopus (183) Google Scholar). In another study, the ovulation rate was reduced in the ovary that contained endometrioma (8Benaglia L. Somigliana E. Vercellini P. Abbiati A. Ragni G. Fedele L. Endometriotic ovarian cysts negatively affect the rate of spontaneous ovulation.Hum Reprod. 2009; 24: 2183-2186Crossref PubMed Scopus (113) Google Scholar). The authors concluded that the physiologic mechanisms leading to ovulation were impaired in ovaries with endometriomas. Others have also suggested that the presence of endometrioma impairs oocyte quality, as demonstrated by reduced rates of fertilization and implantation after controlled ovarian hyperstimulation and IVF treatments (23Gupta S. Agarwal A. Agarwal R. Loret de Mola J.R. Impact of ovarian endometrioma on assisted reproduction outcomes.Reprod Biomed Online. 2006; 13: 349-360Abstract Full Text PDF PubMed Scopus (112) Google Scholar). It appears that ovarian cystectomy for ovarian cyst other than endometrioma might reduce ovarian reserve as well (24Nargund G. Cheng W. Parsons J. The impact of ovarian cystectomy on ovarian response to stimulation during in-vitro fertilization cycles.Hum Reprod. 1996; 11: 81-83Crossref PubMed Scopus (111) Google Scholar). This may result from an inadvertent excision of healthy ovarian tissue or vascular injury and ischemia secondary to electrocoagulation. Reactive local inflammation and formation of scar tissue are other possible mechanisms. Scarring may result in diminished volume of healthy ovarian tissue and technical difficulty of oocyte collection (7Somigliana E. Arnoldi M. Benaglia L. Iemmello R. Nicolosi A. Ragni G. IVF-ICSI outcome in women operated on for bilateral endometriomas.Hum Reprod. 2008; 23: 1526-1530Crossref PubMed Scopus (131) Google Scholar, 25Busacca M. Vignali M. Endometrioma excision and ovarian reserve: a dangerous relation.J Minim Invasive Gynecol. 2009; 16: 142-148Abstract Full Text Full Text PDF PubMed Scopus (82) Google Scholar). The clinical significance of reduced ovarian reserve and responsiveness to gonadotropin stimulation after excision of endometriomas remains unclear (26Somigliana E. Vercellini P. Vigano P. Ragni G. Crosignani P.G. Should endometriomas be treated before IVF-ICSI cycles?.Hum Reprod Update. 2006; 12: 57-64Crossref PubMed Scopus (122) Google Scholar). A recent metaanalysis shows that surgical management of endometriomas, although damaging the ovarian response, has no significant effect on the pregnancy rate (10Tsoumpou I. Kyrgiou M. Gelbaya T.A. Nardo L.G. The effect of surgical treatment for endometrioma on in vitro fertilization outcomes: a systematic review and meta-analysis.Fertil Steril. 2009; 92: 75-87Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar). In agreement with Garcia-Velasco and Somigliana (27Garcia-Velasco J.A. Somigliana E. Management of endometriomas in women requiring IVF: to touch or not to touch.Hum Reprod. 2009; 24: 496-501Crossref PubMed Scopus (203) Google Scholar), we question the necessity of removal of ovarian endometrioma before IVF. Surgery should be performed only in the presences of a large endometrioma that interferes with oocyte collection and severe symptoms or when there is a suspicion of malignancy. Our study has some limitations. It is a retrospective study and most patients never tried IVF before surgery, which does not allow us to compare preoperative and postoperative data. Moreover, spontaneous conception after surgery is not included in the study. Our findings and those of others (16Ragni G. Somigliana E. Benedetti F. Paffoni A. Vegetti W. Restelli L. et al.Damage to ovarian reserve associated with laparoscopic excision of endometriomas: a quantitative rather than a qualitative injury.Am J Obstet Gynecol. 2005; 193: 1908-1914Abstract Full Text Full Text PDF PubMed Scopus (122) Google Scholar, 17Ho H. Lee R. Hwu Y. Lin M. Su J. Tsai Y. Poor response of ovaries with endometrioma previously treated with cystectomy to controlled ovarian hyperstimulation.J assist reprod genet. 2002; 19: 507-511Crossref PubMed Scopus (156) Google Scholar) could not distinguish the extent of ovarian damage inflicted by the presence of endometriomas from that caused by surgery. In addition, we could not compare fertilization rates and embryo quality between the operated and nonoperated ovaries, because oocytes collected were treated together. The results of our study suggest that excision of ovarian endometrioma is followed by a reduced number of oocytes and a high percentage of ovaries that are not responsive to gonadotropin stimulation.