Gynecological Endocrinology
ISSN: 0951-3590 (Print) 1473-0766 (Online) Journal homepage: http://www.tandfonline.com/loi/igye20
Impact of laparoscopic cystectomy of endometriotic and non-endometriotic cysts on ovarian volume, antral follicle count (AFC) and ovarian doppler velocimetry Angelo Cagnacci, Manuela Bellafronte, Anjeza Xholli, Federica Palma, Maria Maddalena Carbone, Costantino Di Carlo & Giovanni Grandi To cite this article: Angelo Cagnacci, Manuela Bellafronte, Anjeza Xholli, Federica Palma, Maria Maddalena Carbone, Costantino Di Carlo & Giovanni Grandi (2016): Impact of laparoscopic cystectomy of endometriotic and non-endometriotic cysts on ovarian volume, antral follicle count (AFC) and ovarian doppler velocimetry, Gynecological Endocrinology, DOI: 10.3109/09513590.2016.1142523 To link to this article: http://dx.doi.org/10.3109/09513590.2016.1142523
Published online: 05 Feb 2016.
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Date: 08 February 2016, At: 11:18
http://informahealthcare.com/gye ISSN: 0951-3590 (print), 1473-0766 (electronic) Gynecol Endocrinol, Early Online: 1–4 ! 2016 Taylor & Francis. DOI: 10.3109/09513590.2016.1142523
ORIGINAL ARTICLE
Impact of laparoscopic cystectomy of endometriotic and non-endometriotic cysts on ovarian volume, antral follicle count (AFC) and ovarian doppler velocimetry Angelo Cagnacci1, Manuela Bellafronte1, Anjeza Xholli1, Federica Palma1, Maria Maddalena Carbone1, Costantino Di Carlo2, and Giovanni Grandi1 Downloaded by [Orta Dogu Teknik Universitesi] at 11:18 08 February 2016
1
Department of Obstetrics, Gynecology and Pediatrics, Obstetrics and Gynecology Unit, Azienda Ospedaliero Universitaria Policlinico of Modena, Modena, Italy and 2Department of Obstetrics and Gynecology, University Federico II, Naples, Italy Abstract
Keywords
Objective: To evaluate the effect on ovarian reserve and blood flow of unilateral laparoscopic stripping of endometriotic versus non-endometriotic cysts. Design: Prospective observational study. Setting: Tertiary university gynecology unit. Patients: During the study period, 71 subjects underwent the first laparoscopic surgery for removal of a monolateral benign ovarian cyst. Interventions: Trans-vaginal ultrasound scans of the pelvis about six months after surgery. Main outcome measures: Ovarian volume, Antral Follicle Count (AFC) and Resistance Index (RI) of ovarian artery of the operated and the contralateral ovary. Results: Among 71 cysts, 39.4% were endometriotic and 60.6% non-endometriotic benign cysts. All the procedures were performed by the same experienced surgeons with a standardized technique. No major complications were reported during surgery. The mean (±SD) age and BMI of women were 31.0 ± 6.8 years and 24.2 ± 3.3 kg/m2, respectively. Mean diameter of the removed cysts was smaller for endometriotic than non-endometriotic cysts (4.35 ± 1.77 cm versus 6.33 ± 3.71 cm, p ¼ 0.046). In comparison to non-operated, volume of the operated ovary was significantly lower and with a reduced AFC, with no difference between endometriotic and non-endometriotic cysts (2.41 ± 2.35 versus 2.00 ± 2.23 cm3, p ¼ 0.496) (3.45 ± 3.07 versus 2.43 ± 1.95, p ¼ 0.11). Ovarian artery RI was higher in the operated ovary with no difference between endometriotic and non-endometriotic cysts (0.19 ± 0.14 versus 0.14 ± 0.10, p ¼ 0.455). The difference in ovarian volume (r ¼ 0.178), AFC (r ¼ 0.094) and RI (r ¼ 0.079) between operated and non-operated ovary was not dependent on the diameter of the removed cyst. Conclusion: Ovarian surgery is associated with a decline of ovarian reserve, independently on the histological type and the diameter of the removed cyst.
Antral follicle count, benign ovarian cyst, endometrioma, endometriosis, ovarian reserve, ovarian volume, stripping, teratoma
Introduction The ovarian follicular heritage undergoes a slow but inexorable decline during the reproductive life [1]. There is a slew of more or less validated markers of ovarian reserve, that in general can be separated in serum (follicle stimulating hormone (FSH), estradiol (E2), inhibin B and anti-Mu¨llerian hormone (AMH)) and ultrasound-determined (ovarian volume, antral follicle count (AFC)). Some exogenous insults, like gonadal surgery, can speed up the process of ovarian follicle loss and lead to early menopause. Surgery for endometriomas has been extensively associated with a risk of reduced ovarian reserve [2,3], documented with a decrease of several ovarian markers like AFC [2], AMH [4] and volume [5]. Furthermore, it was demonstrated that ovarian color Doppler velocimetry changed after endometriomas Address for correspondence: Angelo Cagnacci, Ginecologia e Ostetricia, Dipartimento Integrato Materno Infantile, Azienda Ospedaliero Universitaria Policlinico di Modena, via del Pozzo 71, 41121 Modena, Italia. Tel: +39 059 4224511. Fax: +39 059 4224394; E-mail [email protected]
History Received 30 November 2015 Revised 6 December 2015 Accepted 12 January 2016 Published online 2 February 2016
removal, with an increase of the resistance index (RI) [6]. Less scientific interest has been devoted to the understanding of how surgical cystectomy for other benign ovarian cyst types is going to impact ovarian reserve and blood flow. In the present study, we evaluated the effect of unilateral laparoscopic stripping of any type of ovarian cyst on ovarian reserve and blood flow.
Methods This monocenter prospective observational study was performed at the University Hospital of Modena (Italy) between January 2012 and April 2014. The internal review board approved it (December 2007 196/3) and an informed consent was obtained from each woman. Consecutive patients who have been subjected to a laparoscopic stripping of a single benign monolateral ovarian cyst were prospectively asked to participate. The presence of a single unilateral cyst was diagnosed at the preoperative transvaginal ultrasound (TVUS) scan and confirmed at laparoscopy. Diameter of the cyst was recorded at time of the preoperative TVUS. The same surgeons performed all the procedures with a standardized
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technique. The ovary was incised by using non-electrified scissors in its anti-mesial part. The content of the cyst was aspirated and then the capsule was removed by stripping. During stripping, small bleedings were selectively coagulated. At the end of the procedure, the inner part of the ovary was rinsed with cold saline and residual small bleedings selectively coagulated. Women were enrolled if they were less than 40 years old and with regular menstrual cycles. Women with more than one cyst either unilateral or bilateral, or with recurrent ovarian surgery were excluded. Eligible women were enrolled at the time of surgery and were asked to repeat a TVUS of the pelvis six months after surgery. All the TVUS were performed by the same operator (MB) using a 25 Gold MylabÕ (Esaote SpAÕ , Genoa, Italy) with an endo-vaginal probe model equipped for color Doppler imaging and power Doppler angiography (Model EC 1123). Post-operative TVUS were performed in the follicular phase (day 3–6) of the menstrual cycles. For women under hormonal contraceptives, the TVUS was performed at any time of the blister. The operator was blind regarding the side of the operated ovary and the histological type of the removed cyst. The following parameters were evaluated: Volume of both operated and contralateral ovary by the prolate ellipsoid (PE) method (LD APD TD 0.5233) described by Gohari [7]. AFC of operated and contralateral ovary. For AFC all echofree structures in the ovaries with a mean diameter of 2–10 mm were counted as AF. RI of ovarian artery of operated and contralateral ovary. Ovarian arteries were displayed in the ligamentum infundibulo-pelvicum at the infero-lateral side of the ovaries [8]. After the determination of waveforms, RI were measured for each side three times and the mean was used. RI was defined as the difference between the peak systolic and end-diastolic mean blood flow velocity divided by peak systolic blood flow. Histological type of the removed cyst was retrieved by the histological examination. Comparisons among groups were performed by Students’ t test. When necessary, prevalence was compared by contingency tables and the chi-squared test. Regression analysis was used to relate cyst volume and indexes of ovarian reserve to blood flow resistance. Multiple regression analysis was used to identify independent determinants of ovarian damage (Volume, AFC, RI). For each ovarian index determinants entered into multiple regression analysis were cyst diameter, age and BMI and dichotomous variables such as cyst type, use of hormonal contraceptives and side of the cysts. Statistical analysis was performed using StatView (version 5.01.98, SAS Institute Inc, Cary, NC). For all analyses a statistical significance was considered at a two-tails p values of 0.05. All the results are expressed as the mean ± standard deviation (SD).
Results During the study period, 82 subjects underwent surgery for the removal of a unilateral benign ovarian cyst. Four of these women were excluded for cyst recurrence, and seven for multiple ovarian cysts. The final study group consists of 71 women. The performed surgical technique was always cyst wall stripping with minimal bipolar coagulation on the residual ovary. No major complications were reported during and/or post the operations and an extensive coagulation for controlling heavy bleeding from the ovary was not necessary in any case. In 43/71 (60.6%), a non-endometriotic cyst was removed (16 teratomas, 12 simple cysts, 10 serous cystoadenomas, 5 mucinous cystoadenomas). The rest of the cases were endometriomas (28/71, 39.4%). Women with endometriomas were significantly older (34.8 versus 29.4 years, p ¼ 0.003) and with the same BMI (23.8 versus 24.4 kg/m2, p ¼ 0.501) than women with nonendometriotic cyst. Mean diameter of the removed cysts was 5.2 ± 2.9 cm, significantly smaller for endometriotic than nonendometriotic cysts (4.35 ± 1.77 versus 6.33 ± 3.71 cm, p ¼ 0.046). Endometriomas were more frequently on the left side (left 20/28, right 8/20; p ¼ 0.0008), while the other benign ovarian cysts were equally divided (left 23/43, right 20/43; p ¼ 0.666). Both in endometriotic and non-endometriotic cysts the mean volume and AFC of the operated ovary was significantly lower (p50.0001) than that of the contralateral non-operated ovary (Table 1), while RI was significantly higher (p50.0001). The difference in volume versus non-operated ovary was similar for operated ovaries containing endometriotic and non-endometriotic cysts (2.41 ± 2.35 versus 2.00 ± 2.23 cm3; p ¼ 0.496). The same was true for AFC (3.45 ± 3.07 versus 2.43 ± 1.95; p ¼ 0.11) (Table 1, Figure 1). Similarly, the increased RI of the operated versus non-operated ovary did not differ between endometriotic and non-endometriotic cysts (0.19 ± 0.14 versus 0.14 ± 0.10, p ¼ 0.455) (Table 1, Figure 1). A direct relation was found between the mean ovarian volume difference between operated and non-operated ovary and the difference of ovarian artery RI (R ¼ 0.40, p ¼ 0.007) (Figure 2). The difference in ovarian volume (r ¼ 0.178; p ¼ 0.216), AFC (r ¼ 0.094; p ¼ 0.518) and RI (r ¼ 0.079; p ¼ 0.550) between operated and non-operated ovary was not dependent on the diameter of the removed cyst. When called for the ultrasound examination, 21 of the 71 women (29.6%) of which 9 with endometriotic (32.1%) and 12 with non-endometriotic (27.9%) cysts were on hormonal contraceptive use. In all cases, the use of hormonal contraceptives exceeded a three-month period. In comparison to untreated, those using hormonal contraceptives had a reduced volume of the non-operated ovary (2.86 ± 1.21 cm3, p50.0001), a reduced AFC of both operated (3.83 ± 0.79, p50.0001) and non-operated (7.51 ± 1.10, p50.0001) ovary and an increased RI (+0.07 ± 0.04, p ¼ 0.001) of the non–operated ovary. These effects were not dependent on
Table 1. Mean features (±SD) of women with non endometriotic (n ¼ 43) and endometriotic (n ¼ 28) ovarian cysts. Operated Non-endometriotic cysts group (n ¼ 43) Ovarian volume (cm3) 4.48 ± 1.75 AFC (n) 3.19 ± 2.48 RI 0.98 ± 0.09 Endometriotic cysts group (n ¼ 28) Ovarian volume (cm3) 4.37 ± 2.60 AFC (n) 3.41 ± 2.13 RI 1.01 ± 0.97
Contralateral
Net
p
p inter-groups
6.48 ± 2.40 5.62 ± 3.87 0.84 ± 0.05
2.00 ± 2.23 2.43 ± 1.95 0.14 ± 0.10
50.0001 50.0001 50.0001
0.496 0.110 0.455
6.78 ± 3.19 6.86 ± 4.37 0.82 ± 0.05
2.41 ± 2.35 3.45 ± 3.07 0.19 ± 0.14
50.0001 50.0001 50.0001
Surgery and ovarian reserve
DOI: 10.3109/09513590.2016.1142523
Figure 1. Difference (mean ± SD) of ovarian volume (cm3), antral follicular count (AFC; n) and Resistance Index (RI) between operated and non-operated ovary in women with single endometriotic (hatched columns) or non-endometriotic (black columns) ovarian cyst.
cm3 0 −0,5 −1 −1,5 −2 −2,5 −3 −3,5 −4
Difference in Volume
,3 Difference in RI
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,4
,2 r=0.40 P=0.007
,1 0
−,1 −,2 −1
0
1
2
3
4
5
6
7
8
9
Difference in volume (cm3)
Figure 2. Simple regression between the difference between nonoperated and operated ovary of ovarian volume and ovarian artery resistance index (RI).
length of contraceptive use and did not significantly affect the results of the study. Indeed in multiple regression analysis the difference of ovarian volume (R2 ¼ 0.233) and AFC (R2 ¼ 0.493) between operated and non-operated ovary was inversely related to contraceptive use (p50.0001) but not to the histological type of the cyst (endometriotic versus non-endometriotic cyst; p ¼ 0.915 for ovarian volume and p ¼ 0.277 for AFC).
Discussion In this study, we have studied the impact on ovarian reserve of the removal of an endometriotic and non-endometriotic cyst, using ultrasound-determined markers like ovarian volume [5,9,10] and AFC [11]. Both methods have been previously used and are directly related to ovarian reserve [2,5]. The investigation was performed six months following surgery, a period sufficient to document the reduction of ovarian volume, which is almost accomplished three months after surgery [10]. As previously performed by others [2], the effect of surgery was evaluated by comparing parameters of the operated ovary versus those of the non-operated ovary. All the surgeries were performed by the same experienced surgeons with a standardized technique. The results showed that the removal of any ovarian cyst reduces follicular ovarian reserve in a similar way. Although in the case of endometriomas ovarian reserve may be affected by the presence of the disease itself [12–14], studies evaluating ovarian reserve by AFC [2], volume [5] or even AMH [4] reported, almost consistently, that ovarian reserve is reduced by the surgical removal of an endometriotic cyst [12]. It was proposed that endometriotic cyst wall is formed by the
n 0 −0,5 −1 −1,5 −2 −2,5 −3 −3,5 −4 −4,5 −5
3
RI 0,3 0,25 0,2 0,15 0,1 0,05 0
Difference in AFC
Difference in RI
invagination of ovarian cortex, and that it’s stripping removes a consistent part of ovarian follicles [15–19]. Cyst diameter [20], surgeon experience [15] and type of surgery [21], are all factors determining the extent of ovarian damage induced by surgery. In our series the decrease of ovarian reserve was independent on the diameter of the removed cyst. The effect of removal of other types of cysts has drawn less attention. In our series more than half of ovarian cysts were of non-endometriotic origin, and their removal had the same effect on ovarian volume or AFC than removal of an endometrioma. In the limited experiences published in the literature, a reduction of ovarian volume during the removal of a dermoid cyst was reported in a selected population of infertile women [22], but it was not documented by others [7,23]. Data on non-endometriotic ovarian cysts obtained with AFC reported either a reduction [22] or no effect of cyst removal, in spite of a reduced ovarian volume [10]. Biochemical indexes of ovarian reserve such as AMH declined following the removal of non-endometriotic ovarian cysts [24]. Our data confirm previous data obtained with AFC [22] and AMH measurement [24]. We did not evaluate the prevalence of ovarian cortex removed with endometriotic and non-endometriotic cysts. In some studies prevalence was found much higher with endometriotic than non-endometriotic cysts [17,18], in others this prevalence was the same [16,19]. Removed tissue was of not normal ovarian morphology in endometriotic cysts and of normal morphology in non-endometriotic cysts [25]. In no case histological studies could quantify the amount of ovarian damage induced by specimen removal, this evaluation pertaining only to the post-surgical evaluation of ovarian reserve. In comparison to non-treated, women receiving combined hormonal contraceptive showed a reduced ovarian volume and AFC of the non-operated ovary. In this group, the difference between operated and non-operated ovary was less evident but still present. Accordingly, including this type of women blunted the difference between operated and non-operated ovary but did not change the conclusions of our study. Ovarian velocimetry has not been extensively used to evaluate post-surgical ovarian damage. RI represents downstream vascular resistance to blood flow, being related to microvascular bed: this parameter was higher in the operated than in the non-operated ovary independently on the histological type of the removed cysts. In two previous studies, an increase of RI was observed following the removal of an endometrioma [6] but not of a mixed group of benign ovarian cysts [10]. Our results are consistent with the similar reduction of ovarian volume observed following removal of any type of benign ovarian cyst. Indeed the difference of RI between non-operated and operated ovary was directly related to the difference in volume between the two. Ovarian stripping is considered an appropriate technique for the removal of endometrioma but also for non-endometriotic cysts [12]. Alternative methods such as ablation and coagulation,
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aspiration and sclerotherapy, and laser vaporization of cyst wall have been proposed for endometriomas but cannot be used with other types of benign cysts [12]. Present data suggest that, by using the same surgical technique, all indexes of ovarian reserve decline independent on the histological type of the removed cysts. When confined to a single ovary this damage may not have relevant effects on fertility [26] as expected by the evidence that fertility is conserved also following unilateral ovariectomy [27,28]. Nevertheless, when surgery is performed on both ovaries either concomitantly or subsequently this negative effect may become clearly manifest. For this reason, in the presence of an endometrioma but also of a non-endometriotic cyst, the indication to surgical remove must be carefully evaluated [12].
Gynecol Endocrinol, Early Online: 1–4
12. 13. 14. 15. 16.
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Declaration of interest All authors state explicitly that potential conflicts of interest don’t exist. All authors deny any financial relationship with biotechnology manufacturers, pharmaceutical companies and other commercial entities in relation to this original research study.
References 1. te Velde ER, Dorland M, Broekmans FJ. Age at menopause as a marker of reproductive ageing. Maturitas 1998;30:119–25. 2. Muzii L, Di Tucci C, Di Feliciantonio M, et al. The effect of surgery for endometrioma on ovarian reserve evaluated by antral follicle count: a systematic review and meta-analysis. Hum Reprod 2014;29: 2190–8. 3. Vercellini P, Chapron C, De Giorgi O, et al. Coagulation or excision of ovarian endometriomas? Am J Obstet Gynecol 2003;188:606–10. 4. Somigliana E, Berlanda N, Benaglia L, et al. Surgical excision of endometriomas and ovarian reserve: a systematic review on serum antimu¨llerian hormone level modifications. Fertil Steril 2012;98: 1531–8. 5. 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. 6. La Torre R, Montanino-Oliva M, Marchiani E, et al. Ovarian blood flow before and after conservative laparoscopic treatment for endometrioma. Clin Exp Obstet Gynecol 1998;25:12–14. 7. Gohari P, Berkowitz RL, Hobbins JC. Prediction of intrauterine growth retardation by determination of total intrauterine volume. Am J Obstet Gynecol 1977;127:255–60. 8. Kutlar I, Ozkur A, Balat O, et al. Effects of three different sterilization methods on utero-ovarian Doppler blood flow and serum levels of ovarian hormones. Eur J Obstet Gynecol Reprod Biol 2005;122:112–17. 9. Lass A, Brinsden P. The role of ovarian volume in reproductive medicine. Hum Reprod Update 1999;5:256–66. 10. Candiani M, Barbieri M, Bottani B, et al. Ovarian recovery after laparoscopic enucleation of ovarian cysts: Insights from echographic short-term postsurgical follow-up. J Minim Invasive Gynecol 2005; 12:409–14. 11. Bancsi LF, Broekmans FJ, Eijkemans MJ, et al. Predictors of poor ovarian response in in vitro fertilization: a prospective study
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comparing basal markers of ovarian reserve. Fertil Steril 2002;77: 328–36. Legendre G, Catala L, Morinie`re C, et al. Relationship between ovarian cysts and infertility: what surgery and when? Fertil Steril 2014;101:608–14. Matsuzaki S, Schubert B. Oxidative stress status in normal ovarian cortex surrounding ovarian endometriosis. Fertil Steril 2010;93: 2431–2. Schubert B, Canis M, Darcha C, et al. Human ovarian tissue from cortex surrounding benign cysts: a model to study ovarian tissue cryopreservation. Hum Reprod 2005;20:1786–92. Muzii L, Bianchi A, Bellati F, et al. Histologic analysis of endometriomas: what the surgeon needs to know. Fertil Steril 2007;87:362–6. Dogan E, Ulukus EC, Okyay E, et al. Retrospective analysis of follicle loss after laparoscopic excision of endometrioma compared with benign nonendometriotic ovarian cysts. Int J Gynaecol Obstet 2011;114:124–7. Muzii L, Bianchi A, Croce` C, et al. Laparoscopic excision of ovarian cysts: is the stripping technique a tissue-sparing procedure? Fertil Steril 2002;77:609–14. Matsuzaki S, Houlle C, Darcha C, et al. Analysis of risk factors for the removal of normal ovarian tissue during laparoscopic cystectomy for ovarian endometriosis. Hum Reprod 2009;24:1402–6. Dilek U, Pata O, Tataroglu C, et al. Excision of endometriotic cyst wall may cause loss of functional ovarian tissue. Fertil Steril 2006; 85:758–60. Muzii L, Marana R, Angioli R, et al. Histologic analysis of specimens from laparoscopic endometrioma excision performed by different surgeons: does the surgeon matter? Fertil Steril 2011;95: 2116–19. Alborzi S, Foroughinia L, Kumar PV, et al. A comparison of histopathologic findings of ovarian tissue inadvertently excised with endometrioma and other kinds of benign ovarian cyst in patients undergoing laparoscopy versus laparotomy. Fertil Steril 2009;92: 2004–7. Somigliana E, Ragni G, Infantino M, et al. Does laparoscopic removal of nonendometriotic benign ovarian cysts affect ovarian reserve? Acta Obstet Gynecol Scand 2006;85:74–7. Zupi E, Exacoustos C, Szabolcs B, et al. Laparoscopic approach to dermoid cysts: combined surgical technique and ultrasonographic evaluation of residual functioning ovarian tissue. J Am Assoc Gynecol Laparosc 2003;10:154–8. Kwon SK, Kim SH, Yun SC, et al. Decline of serum antimu¨llerian hormone levels after laparoscopic ovarian cystectomy in endometrioma and other benign cysts: a prospective cohort study. Fertil Steril 2014;101:435–41. Maneschi F, Marasa` L, Incandela S, et al. Ovarian cortex surrounding benign neoplasms: a histologic study. Am J Obstet Gynecol 1993;169:388–93. Canis M, Bassil S, Wattiez A, et al. Fertility following laparoscopic management of benign adnexal cysts. Hum Reprod 1992;7:529–31. Bellati F, Ruscito I, Gasparri ML, et al. Effects of unilateral ovariectomy on female fertility outcome. Arch Gynecol Obstet 2014; 290:349–53. Khan Z, Gada RP, Tabbaa ZM, et al. Unilateral oophorectomy results in compensatory follicular recruitment in the remaining ovary at time of ovarian stimulation for in vitro fertilization. Fertil Steril 2014;101:722–7.
ISSN: 0951-3590 (Print) 1473-0766 (Online) Journal homepage: http://www.tandfonline.com/loi/igye20
Impact of laparoscopic cystectomy of endometriotic and non-endometriotic cysts on ovarian volume, antral follicle count (AFC) and ovarian doppler velocimetry Angelo Cagnacci, Manuela Bellafronte, Anjeza Xholli, Federica Palma, Maria Maddalena Carbone, Costantino Di Carlo & Giovanni Grandi To cite this article: Angelo Cagnacci, Manuela Bellafronte, Anjeza Xholli, Federica Palma, Maria Maddalena Carbone, Costantino Di Carlo & Giovanni Grandi (2016): Impact of laparoscopic cystectomy of endometriotic and non-endometriotic cysts on ovarian volume, antral follicle count (AFC) and ovarian doppler velocimetry, Gynecological Endocrinology, DOI: 10.3109/09513590.2016.1142523 To link to this article: http://dx.doi.org/10.3109/09513590.2016.1142523
Published online: 05 Feb 2016.
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Article views: 1
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Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=igye20 Download by: [Orta Dogu Teknik Universitesi]
Date: 08 February 2016, At: 11:18
http://informahealthcare.com/gye ISSN: 0951-3590 (print), 1473-0766 (electronic) Gynecol Endocrinol, Early Online: 1–4 ! 2016 Taylor & Francis. DOI: 10.3109/09513590.2016.1142523
ORIGINAL ARTICLE
Impact of laparoscopic cystectomy of endometriotic and non-endometriotic cysts on ovarian volume, antral follicle count (AFC) and ovarian doppler velocimetry Angelo Cagnacci1, Manuela Bellafronte1, Anjeza Xholli1, Federica Palma1, Maria Maddalena Carbone1, Costantino Di Carlo2, and Giovanni Grandi1 Downloaded by [Orta Dogu Teknik Universitesi] at 11:18 08 February 2016
1
Department of Obstetrics, Gynecology and Pediatrics, Obstetrics and Gynecology Unit, Azienda Ospedaliero Universitaria Policlinico of Modena, Modena, Italy and 2Department of Obstetrics and Gynecology, University Federico II, Naples, Italy Abstract
Keywords
Objective: To evaluate the effect on ovarian reserve and blood flow of unilateral laparoscopic stripping of endometriotic versus non-endometriotic cysts. Design: Prospective observational study. Setting: Tertiary university gynecology unit. Patients: During the study period, 71 subjects underwent the first laparoscopic surgery for removal of a monolateral benign ovarian cyst. Interventions: Trans-vaginal ultrasound scans of the pelvis about six months after surgery. Main outcome measures: Ovarian volume, Antral Follicle Count (AFC) and Resistance Index (RI) of ovarian artery of the operated and the contralateral ovary. Results: Among 71 cysts, 39.4% were endometriotic and 60.6% non-endometriotic benign cysts. All the procedures were performed by the same experienced surgeons with a standardized technique. No major complications were reported during surgery. The mean (±SD) age and BMI of women were 31.0 ± 6.8 years and 24.2 ± 3.3 kg/m2, respectively. Mean diameter of the removed cysts was smaller for endometriotic than non-endometriotic cysts (4.35 ± 1.77 cm versus 6.33 ± 3.71 cm, p ¼ 0.046). In comparison to non-operated, volume of the operated ovary was significantly lower and with a reduced AFC, with no difference between endometriotic and non-endometriotic cysts (2.41 ± 2.35 versus 2.00 ± 2.23 cm3, p ¼ 0.496) (3.45 ± 3.07 versus 2.43 ± 1.95, p ¼ 0.11). Ovarian artery RI was higher in the operated ovary with no difference between endometriotic and non-endometriotic cysts (0.19 ± 0.14 versus 0.14 ± 0.10, p ¼ 0.455). The difference in ovarian volume (r ¼ 0.178), AFC (r ¼ 0.094) and RI (r ¼ 0.079) between operated and non-operated ovary was not dependent on the diameter of the removed cyst. Conclusion: Ovarian surgery is associated with a decline of ovarian reserve, independently on the histological type and the diameter of the removed cyst.
Antral follicle count, benign ovarian cyst, endometrioma, endometriosis, ovarian reserve, ovarian volume, stripping, teratoma
Introduction The ovarian follicular heritage undergoes a slow but inexorable decline during the reproductive life [1]. There is a slew of more or less validated markers of ovarian reserve, that in general can be separated in serum (follicle stimulating hormone (FSH), estradiol (E2), inhibin B and anti-Mu¨llerian hormone (AMH)) and ultrasound-determined (ovarian volume, antral follicle count (AFC)). Some exogenous insults, like gonadal surgery, can speed up the process of ovarian follicle loss and lead to early menopause. Surgery for endometriomas has been extensively associated with a risk of reduced ovarian reserve [2,3], documented with a decrease of several ovarian markers like AFC [2], AMH [4] and volume [5]. Furthermore, it was demonstrated that ovarian color Doppler velocimetry changed after endometriomas Address for correspondence: Angelo Cagnacci, Ginecologia e Ostetricia, Dipartimento Integrato Materno Infantile, Azienda Ospedaliero Universitaria Policlinico di Modena, via del Pozzo 71, 41121 Modena, Italia. Tel: +39 059 4224511. Fax: +39 059 4224394; E-mail [email protected]
History Received 30 November 2015 Revised 6 December 2015 Accepted 12 January 2016 Published online 2 February 2016
removal, with an increase of the resistance index (RI) [6]. Less scientific interest has been devoted to the understanding of how surgical cystectomy for other benign ovarian cyst types is going to impact ovarian reserve and blood flow. In the present study, we evaluated the effect of unilateral laparoscopic stripping of any type of ovarian cyst on ovarian reserve and blood flow.
Methods This monocenter prospective observational study was performed at the University Hospital of Modena (Italy) between January 2012 and April 2014. The internal review board approved it (December 2007 196/3) and an informed consent was obtained from each woman. Consecutive patients who have been subjected to a laparoscopic stripping of a single benign monolateral ovarian cyst were prospectively asked to participate. The presence of a single unilateral cyst was diagnosed at the preoperative transvaginal ultrasound (TVUS) scan and confirmed at laparoscopy. Diameter of the cyst was recorded at time of the preoperative TVUS. The same surgeons performed all the procedures with a standardized
Downloaded by [Orta Dogu Teknik Universitesi] at 11:18 08 February 2016
2
A. Cagnacci et al.
Gynecol Endocrinol, Early Online: 1–4
technique. The ovary was incised by using non-electrified scissors in its anti-mesial part. The content of the cyst was aspirated and then the capsule was removed by stripping. During stripping, small bleedings were selectively coagulated. At the end of the procedure, the inner part of the ovary was rinsed with cold saline and residual small bleedings selectively coagulated. Women were enrolled if they were less than 40 years old and with regular menstrual cycles. Women with more than one cyst either unilateral or bilateral, or with recurrent ovarian surgery were excluded. Eligible women were enrolled at the time of surgery and were asked to repeat a TVUS of the pelvis six months after surgery. All the TVUS were performed by the same operator (MB) using a 25 Gold MylabÕ (Esaote SpAÕ , Genoa, Italy) with an endo-vaginal probe model equipped for color Doppler imaging and power Doppler angiography (Model EC 1123). Post-operative TVUS were performed in the follicular phase (day 3–6) of the menstrual cycles. For women under hormonal contraceptives, the TVUS was performed at any time of the blister. The operator was blind regarding the side of the operated ovary and the histological type of the removed cyst. The following parameters were evaluated: Volume of both operated and contralateral ovary by the prolate ellipsoid (PE) method (LD APD TD 0.5233) described by Gohari [7]. AFC of operated and contralateral ovary. For AFC all echofree structures in the ovaries with a mean diameter of 2–10 mm were counted as AF. RI of ovarian artery of operated and contralateral ovary. Ovarian arteries were displayed in the ligamentum infundibulo-pelvicum at the infero-lateral side of the ovaries [8]. After the determination of waveforms, RI were measured for each side three times and the mean was used. RI was defined as the difference between the peak systolic and end-diastolic mean blood flow velocity divided by peak systolic blood flow. Histological type of the removed cyst was retrieved by the histological examination. Comparisons among groups were performed by Students’ t test. When necessary, prevalence was compared by contingency tables and the chi-squared test. Regression analysis was used to relate cyst volume and indexes of ovarian reserve to blood flow resistance. Multiple regression analysis was used to identify independent determinants of ovarian damage (Volume, AFC, RI). For each ovarian index determinants entered into multiple regression analysis were cyst diameter, age and BMI and dichotomous variables such as cyst type, use of hormonal contraceptives and side of the cysts. Statistical analysis was performed using StatView (version 5.01.98, SAS Institute Inc, Cary, NC). For all analyses a statistical significance was considered at a two-tails p values of 0.05. All the results are expressed as the mean ± standard deviation (SD).
Results During the study period, 82 subjects underwent surgery for the removal of a unilateral benign ovarian cyst. Four of these women were excluded for cyst recurrence, and seven for multiple ovarian cysts. The final study group consists of 71 women. The performed surgical technique was always cyst wall stripping with minimal bipolar coagulation on the residual ovary. No major complications were reported during and/or post the operations and an extensive coagulation for controlling heavy bleeding from the ovary was not necessary in any case. In 43/71 (60.6%), a non-endometriotic cyst was removed (16 teratomas, 12 simple cysts, 10 serous cystoadenomas, 5 mucinous cystoadenomas). The rest of the cases were endometriomas (28/71, 39.4%). Women with endometriomas were significantly older (34.8 versus 29.4 years, p ¼ 0.003) and with the same BMI (23.8 versus 24.4 kg/m2, p ¼ 0.501) than women with nonendometriotic cyst. Mean diameter of the removed cysts was 5.2 ± 2.9 cm, significantly smaller for endometriotic than nonendometriotic cysts (4.35 ± 1.77 versus 6.33 ± 3.71 cm, p ¼ 0.046). Endometriomas were more frequently on the left side (left 20/28, right 8/20; p ¼ 0.0008), while the other benign ovarian cysts were equally divided (left 23/43, right 20/43; p ¼ 0.666). Both in endometriotic and non-endometriotic cysts the mean volume and AFC of the operated ovary was significantly lower (p50.0001) than that of the contralateral non-operated ovary (Table 1), while RI was significantly higher (p50.0001). The difference in volume versus non-operated ovary was similar for operated ovaries containing endometriotic and non-endometriotic cysts (2.41 ± 2.35 versus 2.00 ± 2.23 cm3; p ¼ 0.496). The same was true for AFC (3.45 ± 3.07 versus 2.43 ± 1.95; p ¼ 0.11) (Table 1, Figure 1). Similarly, the increased RI of the operated versus non-operated ovary did not differ between endometriotic and non-endometriotic cysts (0.19 ± 0.14 versus 0.14 ± 0.10, p ¼ 0.455) (Table 1, Figure 1). A direct relation was found between the mean ovarian volume difference between operated and non-operated ovary and the difference of ovarian artery RI (R ¼ 0.40, p ¼ 0.007) (Figure 2). The difference in ovarian volume (r ¼ 0.178; p ¼ 0.216), AFC (r ¼ 0.094; p ¼ 0.518) and RI (r ¼ 0.079; p ¼ 0.550) between operated and non-operated ovary was not dependent on the diameter of the removed cyst. When called for the ultrasound examination, 21 of the 71 women (29.6%) of which 9 with endometriotic (32.1%) and 12 with non-endometriotic (27.9%) cysts were on hormonal contraceptive use. In all cases, the use of hormonal contraceptives exceeded a three-month period. In comparison to untreated, those using hormonal contraceptives had a reduced volume of the non-operated ovary (2.86 ± 1.21 cm3, p50.0001), a reduced AFC of both operated (3.83 ± 0.79, p50.0001) and non-operated (7.51 ± 1.10, p50.0001) ovary and an increased RI (+0.07 ± 0.04, p ¼ 0.001) of the non–operated ovary. These effects were not dependent on
Table 1. Mean features (±SD) of women with non endometriotic (n ¼ 43) and endometriotic (n ¼ 28) ovarian cysts. Operated Non-endometriotic cysts group (n ¼ 43) Ovarian volume (cm3) 4.48 ± 1.75 AFC (n) 3.19 ± 2.48 RI 0.98 ± 0.09 Endometriotic cysts group (n ¼ 28) Ovarian volume (cm3) 4.37 ± 2.60 AFC (n) 3.41 ± 2.13 RI 1.01 ± 0.97
Contralateral
Net
p
p inter-groups
6.48 ± 2.40 5.62 ± 3.87 0.84 ± 0.05
2.00 ± 2.23 2.43 ± 1.95 0.14 ± 0.10
50.0001 50.0001 50.0001
0.496 0.110 0.455
6.78 ± 3.19 6.86 ± 4.37 0.82 ± 0.05
2.41 ± 2.35 3.45 ± 3.07 0.19 ± 0.14
50.0001 50.0001 50.0001
Surgery and ovarian reserve
DOI: 10.3109/09513590.2016.1142523
Figure 1. Difference (mean ± SD) of ovarian volume (cm3), antral follicular count (AFC; n) and Resistance Index (RI) between operated and non-operated ovary in women with single endometriotic (hatched columns) or non-endometriotic (black columns) ovarian cyst.
cm3 0 −0,5 −1 −1,5 −2 −2,5 −3 −3,5 −4
Difference in Volume
,3 Difference in RI
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,4
,2 r=0.40 P=0.007
,1 0
−,1 −,2 −1
0
1
2
3
4
5
6
7
8
9
Difference in volume (cm3)
Figure 2. Simple regression between the difference between nonoperated and operated ovary of ovarian volume and ovarian artery resistance index (RI).
length of contraceptive use and did not significantly affect the results of the study. Indeed in multiple regression analysis the difference of ovarian volume (R2 ¼ 0.233) and AFC (R2 ¼ 0.493) between operated and non-operated ovary was inversely related to contraceptive use (p50.0001) but not to the histological type of the cyst (endometriotic versus non-endometriotic cyst; p ¼ 0.915 for ovarian volume and p ¼ 0.277 for AFC).
Discussion In this study, we have studied the impact on ovarian reserve of the removal of an endometriotic and non-endometriotic cyst, using ultrasound-determined markers like ovarian volume [5,9,10] and AFC [11]. Both methods have been previously used and are directly related to ovarian reserve [2,5]. The investigation was performed six months following surgery, a period sufficient to document the reduction of ovarian volume, which is almost accomplished three months after surgery [10]. As previously performed by others [2], the effect of surgery was evaluated by comparing parameters of the operated ovary versus those of the non-operated ovary. All the surgeries were performed by the same experienced surgeons with a standardized technique. The results showed that the removal of any ovarian cyst reduces follicular ovarian reserve in a similar way. Although in the case of endometriomas ovarian reserve may be affected by the presence of the disease itself [12–14], studies evaluating ovarian reserve by AFC [2], volume [5] or even AMH [4] reported, almost consistently, that ovarian reserve is reduced by the surgical removal of an endometriotic cyst [12]. It was proposed that endometriotic cyst wall is formed by the
n 0 −0,5 −1 −1,5 −2 −2,5 −3 −3,5 −4 −4,5 −5
3
RI 0,3 0,25 0,2 0,15 0,1 0,05 0
Difference in AFC
Difference in RI
invagination of ovarian cortex, and that it’s stripping removes a consistent part of ovarian follicles [15–19]. Cyst diameter [20], surgeon experience [15] and type of surgery [21], are all factors determining the extent of ovarian damage induced by surgery. In our series the decrease of ovarian reserve was independent on the diameter of the removed cyst. The effect of removal of other types of cysts has drawn less attention. In our series more than half of ovarian cysts were of non-endometriotic origin, and their removal had the same effect on ovarian volume or AFC than removal of an endometrioma. In the limited experiences published in the literature, a reduction of ovarian volume during the removal of a dermoid cyst was reported in a selected population of infertile women [22], but it was not documented by others [7,23]. Data on non-endometriotic ovarian cysts obtained with AFC reported either a reduction [22] or no effect of cyst removal, in spite of a reduced ovarian volume [10]. Biochemical indexes of ovarian reserve such as AMH declined following the removal of non-endometriotic ovarian cysts [24]. Our data confirm previous data obtained with AFC [22] and AMH measurement [24]. We did not evaluate the prevalence of ovarian cortex removed with endometriotic and non-endometriotic cysts. In some studies prevalence was found much higher with endometriotic than non-endometriotic cysts [17,18], in others this prevalence was the same [16,19]. Removed tissue was of not normal ovarian morphology in endometriotic cysts and of normal morphology in non-endometriotic cysts [25]. In no case histological studies could quantify the amount of ovarian damage induced by specimen removal, this evaluation pertaining only to the post-surgical evaluation of ovarian reserve. In comparison to non-treated, women receiving combined hormonal contraceptive showed a reduced ovarian volume and AFC of the non-operated ovary. In this group, the difference between operated and non-operated ovary was less evident but still present. Accordingly, including this type of women blunted the difference between operated and non-operated ovary but did not change the conclusions of our study. Ovarian velocimetry has not been extensively used to evaluate post-surgical ovarian damage. RI represents downstream vascular resistance to blood flow, being related to microvascular bed: this parameter was higher in the operated than in the non-operated ovary independently on the histological type of the removed cysts. In two previous studies, an increase of RI was observed following the removal of an endometrioma [6] but not of a mixed group of benign ovarian cysts [10]. Our results are consistent with the similar reduction of ovarian volume observed following removal of any type of benign ovarian cyst. Indeed the difference of RI between non-operated and operated ovary was directly related to the difference in volume between the two. Ovarian stripping is considered an appropriate technique for the removal of endometrioma but also for non-endometriotic cysts [12]. Alternative methods such as ablation and coagulation,
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aspiration and sclerotherapy, and laser vaporization of cyst wall have been proposed for endometriomas but cannot be used with other types of benign cysts [12]. Present data suggest that, by using the same surgical technique, all indexes of ovarian reserve decline independent on the histological type of the removed cysts. When confined to a single ovary this damage may not have relevant effects on fertility [26] as expected by the evidence that fertility is conserved also following unilateral ovariectomy [27,28]. Nevertheless, when surgery is performed on both ovaries either concomitantly or subsequently this negative effect may become clearly manifest. For this reason, in the presence of an endometrioma but also of a non-endometriotic cyst, the indication to surgical remove must be carefully evaluated [12].
Gynecol Endocrinol, Early Online: 1–4
12. 13. 14. 15. 16.
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Declaration of interest All authors state explicitly that potential conflicts of interest don’t exist. All authors deny any financial relationship with biotechnology manufacturers, pharmaceutical companies and other commercial entities in relation to this original research study.
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