- Email: [email protected]
Evaluation of ovarian adhesion formation after laparoscopic ovarian drilling by second-look minilaparoscopy
Evaluation of ovarian adhesion formation after laparoscopic ovarian drilling by second-look minilaparoscopy Francesco Mercorio, M.D.,a Antonio Mercorio, M.D.,b Attilio Di Spiezio Sardo, M.D.,a Gian Vincenzo Barba, M.D.,c Massimiliano Pellicano, M.D.,a and Carmine Nappi, M.D.a a
Department of Gynaecology and Obstetrics, and Pathophysiology of Human Reproduction, University of Naples ‘‘Federico II,’’ Naples; b Department of Obstetrics and Gynaecology, University of Foggia, Foggia; and c Epidemiology of Population Genetics, Institute of Food Science, C.N.R. Avellino, Italy
Objective: To determine the incidence, site, and grade of ovarian adhesion formation after laparoscopic ovarian drilling (LOD) and analyze the association between the number of punctures made and the incidence and grade of adhesions, and evaluate the lateral distribution of the adhesions. Design: Prospective clinical study. Setting: University hospital endocrine and infertility center. Patient(s): Ninety-six anovulatory infertile women with polycystic ovarian syndrome (PCOS) treated with LOD. Intervention(s): Women were randomized into two study groups of 48 women each, one treated with 6 punctures on the left ovary and 12 on the right, and the other treated with 6 punctures on the right ovary and 12 on the left. A short-term second-look minilaparoscopy was performed to evaluate postsurgical adhesion formation. Main Outcome Measure(s): [1] Evaluation of the incidence and grade (thin, dense, cohesive) of ovarian adhesions; [2] comparative analysis of the incidence and grade of ovarian adhesions between ovaries treated with 6 and 12 punctures; and [3] comparative analysis of the incidence and grade of ovarian adhesions between the two sides. Result(s): Adhesion formation was detected in 54 of the 90 women (60%) and in 83 of the 180 ovaries treated (46%). Dense adhesions were more likely to develop on the left ovaries to a statistically significant extent, and independently of the number of ovarian punctures performed (odds ratio [OR] ¼ 4.34, 95% confidence interval [CI] ¼ 1.72–10.94). Logistic regression analysis showed that the incidence of ovarian adhesions was independent of both number of punctures (OR ¼ 1.05, 95% CI ¼ 0.58–1.88) and side (OR ¼ 1.37, 95% CI ¼ 0.76–2.46). Conclusion(s): The incidence of ovarian adhesion formation after LOD was high, and their extent and severity was not influenced by the number of ovarian punctures; however, the left ovary appeared more prone to develop severe adhesions than the contralateral one. (Fertil Steril 2008;89:1229–33. 2008 by American Society for Reproductive Medicine.) Key Words: Laparoscopic ovarian drilling, ovarian adhesions, polycystic ovarian syndrome, punctures, laterality
Laparoscopic ovarian drilling (LOD) is a common surgical approach currently used to treat anovulatory infertility in clomiphene (CC)-resistant women with polycystic ovarian syndrome (PCOS). The mechanism of action is still uncertain but likely lies in the reduction of ovarian androgen production through a decrease in stromal mass, or in the disruption of parenchymal blood flow. The conversion from an adverse androgenic environment to an estrogenic one corrects the defect of the ovarian–pituitary feedback, allowing appropriate gonadotropin stimulation for follicular development and ovulation (1, 2).
Received December 1, 2006; revised and accepted May 2, 2007. Reprint requests: Francesco Mercorio, M.D., Dipartimento di Ginecologia di e Ostetricia e, Fisiopatologia della Riproduzione Umana, Universita Napoli ‘‘Federico II,’’ Via L. Caldieri 140, 80128 Naples, Italy (FAX: 39-081-7463865; E-mail: [email protected]).
0015-0282/08/$34.00 doi:10.1016/j.fertnstert.2007.05.009
Recently, LOD has been evaluated as an alternative approach to the medical treatment of PCO-related anovulatory infertility, because it is not associated with risk of multiple pregnancy or ovarian hyperstimulation, and improves ovarian response to medical treatment (3). Nevertheless, two main drawbacks prevent LOD from being considered a primary approach to the treatment of POS: the risk inherent to any surgical procedure, and the risk of adhesion formation potentially interfering with fertility. Many trials have been designed to evaluate the rate of adhesions after LOD. However, most of them evaluated adhesion formation while performing a cesarean section or during second-look laparoscopies to investigate persisting infertility, whereas other trials involved small series of patients. As a result, currently, the incidence of postoperative adhesion formation ranges from 19% to 43% in some studies (4, 5), and up to 82% in other studies (6), but
Fertility and Sterility Vol. 89, No. 5, May 2008 Copyright ª2008 American Society for Reproductive Medicine, Published by Elsevier Inc.
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such wide variation possibly reflects an inadequate study design. Variations in the surgical techniques can obviously affect the rate of adhesion formation (6–9), and the number of ovarian punctures is one such technical option to account for. Currently, the number of ovarian punctures made during LOD is defined by the gynecologist, case by case, depending on the size of the ovary. In theory, the best way to decrease the risk of adhesion formation is to minimize injury to the ovarian surface. Consequently, the rule should be to perform the lowest possible number of punctures. Unfortunately, the experimental evidence in the literature in support of this theory is scant. In 2002 Amer et al. (10) concluded, on the basis of the reproductive performance, that a thermal energy of 450–900 J produced by 3–6 punctures per ovary (6–12 punctures total) gives a statistically significantly higher ovulation and pregnancy rate. This study, however, did not addressed the problem of the relationship between number of punctures and adhesion development. Furthermore, no study has addressed the importance, if any, of the ovarian side treated in adhesion development. It is worth remembering that endometriotic implants are found more frequently on the left hemipelvis. The greater likelihood that endometriosis develops on the left side has been explained by the presence of the sigmoid colon in that region, which delays the spread of retrograde menstrual blood (11–13). On the basis of these data we have designed this large prospective study to investigate by means of a short-term second-look minilaparoscopy after LOD: [1] the incidence and site of postsurgical ovarian adhesion formation; [2] the correlation between the number of ovarian diathermy punctures and incidence and severity of adhesion; and [3] the side of the ovary treated as risk factor for adhesion formation.
MATERIALS AND METHODS The study population consisted of 96 cases of PCOS-related anovulatory infertility treated with LOD between May 2002 and February 2006. All patients had primary infertility with a mean duration of 1.3 years (range 1–2.3 years). Median age was 28.7 years (range, 20–39 years). The diagnosis of PCOS was based on the following criteria: [1] clinical and biochemical evidence of androgen excess and [2] typical image of PCOS on ultrasound with ovarian stromal hypertrophy and multiple small (6–8 mm) peripheral follicles. The study design was approved by the institutional review board (IRB). Exclusion criteria were any disease potentially responsible of ovarian adhesions (i.e., ovarian cyst, endometriosis, pelvic infections, previous abdominal-pelvic surgery) and tubal diseases. All women gave their written informed consent and agreed to undergo the primary surgical procedure, the short-term 1230
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second-look laparoscopy to evaluate postoperative ovarian adhesions, and a subsequent adhesiolysis to improve fertility. For the purposes of the study, 96 patients were randomized, using a sealed envelope, into two study groups as follows: group 1, 48 women treated with 6 punctures on the left ovary and 12 on the opposite ovary; and group 2, 48 women treated with 6 punctures on the right ovary and 12 on the contralateral ovary. The randomization assignment was done immediately before the surgical procedure. Laparoscopic ovarian electrocautery was performed using a three-puncture technique. A 10-mm laparoscope was inserted by the main subumbilical route and a pair of grasping forceps was introduced through one of the two lower abdominal 5-mm punctures to grasp the utero-ovarian ligament and lift the ovary away from the bowel. The third access was used to introduce the diathermy needle. The LOD was carried out using a specially designed diathermy probe (Rocket of London, Watford, UK) to penetrate the ovarian capsule. The probe consisted of a distal stainless steel needle measuring 8 mm in length and 2 mm in diameter and projecting from an insulated solid cone having a maximum diameter of 6 mm. The electrosurgical unit used was the Force 2 Valleylab electrosurgical generator (Valleylab Inc., Boulder, CO). The entire length of the needle was inserted at a right angle into the ovary with the aid of a short burst of pure cutting diathermy of 40 W followed by a monopolar coagulating current set at 30 W. The ovarian punctures were uniformly distributed on the ovarian surface. The duration of each penetration was 5 seconds. At the end of the procedure each ovary was cooled by irrigation before releasing the ligament, and 1,000 mL of Ringer’s lactate solution was left in the peritoneal cavity. All the primary surgical procedures were performed by the senior author (M.F.). After an average time of 5.3 weeks (range, 4–9 weeks) the women underwent the second-look laparoscopy according to the methods described in our previous study (14). Assessment of the incidence, site, and grade of ovarian adhesions was made with the operator blinded to the previous treatment. Adhesions not involving the ovaries were not the object of this study and were therefore neither scored nor treated. Grading of adhesions was as follows: grade 1, filmy avascular; grade 2, dense or vascular; grade 3, cohesive (15). When different types of lesions coexisted, the grade was assigned to the most severe adhesion. In patients with adhesions, lysis was carried out with monopolar scissors. The incidence and grade of ovarian adhesions after 6 or 12 punctures on the left versus the right ovary were compared by c2 statistics or Fisher’s exact test, as appropriate. Logistic regression analysis was performed to compare the frequency of ovarian adhesions accounting for affected side and number of punctures. The statistical analysis was Vol. 89, No. 5, May 2008
performed separately in the group of women developing monolateral ovarian adhesions. Statistical significance was set at a P value of < .05.
only two cases of cohesive adhesions were found on the left ovary. Logistic regression analysis showed that the greater likelihood of dense adhesion to occur on the left ovary was independent of the number of ovarian punctures (OR ¼ 4.34, 95% CI ¼ 1.72–10.94).
RESULTS Primary laparoscopy confirmed the preoperative diagnosis of PCOS in all patients with no evidence of ovarian adhesions, endometriosis disease, and tubal disease.
In the analysis of the group with monolateral presentation (n ¼ 25), adhesions occurred in 12 cases after 6 punctures and in 13 cases after 12 punctures. These patients showed a significant trend toward a major predisposition of the left ovary to adhesion development (16 vs. 9 cases; P¼.015). In addition, with regard to the grade of adhesions, these patients presented dense adhesions more frequently on the left ovary than on the right one (8 vs. 2 cases; P¼.041) (Fig. 2). Logistic regression analysis in this group showed that the incidence and grade of ovarian adhesions was independent of the number of punctures (data not shown).
Six patients (three for each treatment protocol) decided to withdraw from the study and did not undergo the second-look procedure. Therefore, a total of 90 women were included in the data analysis. Postoperative ovarian adhesion formation was observed in 54 of the 90 women (60%). Bilateral ovarian adhesions were found in 29/54 patients (53.7%), and monolateral adhesions in 25/54 patients (46.3%). Of 180 ovarian sites available to evaluate adhesion development, 83 ovaries (46%) presented adhesion formations (right ovary: n ¼ 38; left ovary: n ¼ 45). Right ovaries developed adhesions in 19 cases after either 6 punctures and 12 punctures; left ovaries developed adhesions in 22 cases after 6 punctures and in 23 cases after 12 punctures. The anatomical sites involved with ovarian adhesions were pelvic wall (n ¼ 68; 81.9%), fallopian tube (n ¼ 7; 8.4%), omentum (n ¼ 6; 7.2%), and large bowel (n ¼ 2; 2.4%). Logistic regression analysis showed that the occurrence of ovarian adhesions was independent of either the number of punctures (odds ratio [OR] ¼ 1.05, 95% confidence interval [CI] ¼ 0.58–1.88) or side (OR ¼ 1.37, 95% CI ¼ 0.76–2.46). Grading of ovarian adhesions is reported in Figure 1. The left ovary developed dense adhesions more frequently than the contralateral side (c2:10.06; P<.01). In addition, the
DISCUSSION To the best of our knowledge, this is the largest prospective series on the relationship between LOD and adhesion formation. In a small sample size, Dabirashrafi et al. (16) reported mild to moderate adhesion formation in 20% of patients after LOD. Gurgan (6) and Grenblatt (17) and their colleagues reported higher postoperative adhesion rate (85%–100%), often of significant extent and severity. In a prospective study involving 62 patients who underwent second-look laparoscopy, Naether et al. (18) found that the rate of adhesions decreased from 19.3% to 16.6% by peritoneal lavage with saline, and all of the lesions observed were minimal. Saravelos and Li (5) found adhesions at second-look laparoscopy in 57% of 21 women and in 38% of the adnexa evaluated
FIGURE 2 FIGURE 1 Incidence and grade of ovarian adhesions at early second-look procedure after laparoscopic ovarian drilling. *P< .01 vs. right ovary.
Incidence and grade of ovarian adhesions at early second-look procedure after laparoscopic ovarian drilling in the group with monolateral ovarian adhesions (n ¼ 25); *P< .05 vs. right ovary.
Mercorio. Ovarian drilling and adhesions. Fertil Steril 2008.
Mercorio. Ovarian drilling and adhesions. Fertil Steril 2008.
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in their series. The adhesions, when they did occur, were often of significant extent and severity. In our study the evaluation of postsurgical ovarian adhesions was made by means of a short-term minilaparoscopy, systematically performed on all patients who underwent the primary procedure, thereby avoiding the selection bias frequently present in the previously mentioned studies. In our experience, ovarian adhesions developed in a large percentage of patients (60%) and of the 180 ovaries treated (46%). Even if adhesions after LOD do not seem to affect reproductive performance (5), the unequivocal high rate of adhesion formation shown in this study suggests the importance of undertaking complete and comprehensive medical therapy before proceeding with surgical treatment. Two important findings in this study are worthy of being underlined. An unexpected result is that the incidence and grade of ovarian adhesions is independent of the number of ovarian punctures. This result is in sharp contrast with the axiom that the greater the amount of damage to the surface of the ovary, the greater the risk of periovarian adhesion formation. The second observation is that the left ovary is more prone to severe adhesion formation compared to the right ovary. This finding is further strengthened by the fact that the only two cohesive adhesions found in our series involved the left ovary. This predisposition for the left side could be explained by a decreased movement of fluids at the left side of the pelvis, caused by the presence of the sigmoid colon (11–13). This decrease impairs the effect of hydroflotation of crystalloid solution and thus favors the cellular mechanism that leads to adhesions (19). Both of these findings have been confirmed in the group of women with monolateral ovarian adhesions. We found worthwhile to perform a separate statistical analysis in this group, hypothesizing that the adhesion phenotype (19) (i.e., the biochemical individual predisposition to adhesion formation), was less developed and active in this group. Thus, the role of other adhesion factors, such as the number of ovarian punctures or the side, could be considered as major determinants; therefore, their role should be more accurately highlighted. In this group we confirmed the greater likelihood for dense adhesions to develop on the left ovary, as already demonstrated in the overall study group. In addition, in this group, we demonstrated a significantly higher incidence of adhesion on the left ovary. Among the 25 women who developed adhesions, 64% involved the left ovary and 36% the right one. In summary, our study provides evidence that: first, LOD was frequently associated with postoperative ovarian adhesion formation; second, adhesion rate was independent of the number of ovarian punctures; and, finally, the left ovary can be considered at greater risk of high grade adhesion formation. 1232
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Based on these three observations and on the report by Balen and Jacobs (20), who showed that unilateral diathermy leads to bilateral ovarian activity through a correction of the abnormal ovarian–pituitary feedback, a strategy based on unilateral right ovarian diathermy limiting the minimal effective number of punctures is plausible. However, before proposing such an approach as a viable surgical option for LOD, further studies are needed to test its feasibility and effectiveness and, in particular, to address the issue of whether unilateral diathermy would provide any clinical benefit in terms of spontaneous ovulation when the contralateral ovary is untreated.
REFERENCES 1. Parsanezhad ME, Bagheri MH, Alborzi S, Pakniat M. Ovarian stromal blood flow changes after laparoscopic ovarian drilling in women with polycystic ovary syndrome. Fertil Steril 2004;82:S137–8. 2. Wu MH, Huang MF, Tsai SJ, Pan HA, Cheng YC, Lin YS. Effects of laparoscopic ovarian drilling on young adult women with polycystic ovarian syndrome. J Am Assoc Gynecol Laparosc 2004;11:184–90. 3. Strowitzki T, Von Wolff M. Laparoscopic ovarian drilling (LOD) in patients with polycystic ovary syndrome (PCOS): an alternative approach to medical treatment. Gynecol Surg 2005;2:71–9. 4. Gurgan T, Urman B. Adhesions after ovarian drilling and intercede. Fertil Steril 1994;62:424–6. 5. Saravelos H, Li TC. Post-operative adhesions after laparoscopic electrosurgical treatment for polycystic ovarian syndrome with the application of Interceed to one ovary—a prospective randomized controlled study. Hum Reprod 1996;11:992–7. 6. Gurgan T, Kisnisci H, Yarali H, Develioglu O, Zeyneloglu H, Aksu T. Evaluation of adhesion formation after laparoscopic treatment of polycystic ovarian disease. Fertil Steril 1991;56:1176–8. 7. Felembam A, Tulandi T. Laparoscopic treatment of polycystic ovarian syndrome-related infertility. Infertil Reprod Med Clin North Am 2000;11:49–60. 8. Felemban A, Tan SL, Tulandi T. Laparoscopic treatment of polycystic ovaries with insulated needle cautery: a reappraisal. Fertil Steril 2000;73:266–9. 9. Gurgan T, Urman B, Aksu T, Yaraly H, Develioglu O, Ksnisci HA. The effect of short-interval laparoscopic lysis of adhesions on pregnancy rate following Nd: YAG laser photocoagulation of polycystic ovaries. Obstet Gynecol 1992;80:45–7. 10. Amer SA, Li TC, Cooke ID. Laparoscopic ovarian diathermy in women with polycystic ovarian syndrome: a retrospective study on the influence of the amount of energy used on the outcome. Hum Reprod 2002;17: 1046–51. 11. Parazzini F, Eur J. Left:right side ratio of endometriotic implants in the pelvis. Obstet Gynecol Reprod Biol 2003;111:65–7. 12. Vercellini P, Aimi G, De Giorni O, Maddalena S, Carinelli S, Crosignani PG. Is cystic ovarian endometriosis an asymmetric disease? BJOG 1998;105:1018–21. 13. Al-Fozan H, Tulandi T. Left lateral predisposition of endometriosis and endometrioma. Obstet Gynecol 2003;101:164–6. 14. Zullo F, Pellicano M, Zupi E, Guida M, Mastrantonio P, Nappi C. Minilaparoscopic ovarian drilling under local anaesthesia in patients with polycystic ovary syndrome. Fertil Steril 2000;74:376–9. 15. Operative Laparoscopy Study Group. Postoperative adhesion development after operative laparoscopy: evaluation at early second-look procedures. Fertil Steril 1991;55:700–4. 16. Dabirashrafi H, Mohamad K, Behjatnia Y, Moghadami-Tabrizi N. Adhesion formation after ovarian electrocauterization on patients with polycystic ovarian syndrome. Fertil Steril 1991;55: 1200–1.
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17. Grenblatt EM, Casper RF. Adhesion formation after laparoscopic ovarian cautery for polycystic ovarian syndrome: lack of correlation with pregnancy rate. Fertil Steril 1993;60:766–70. 18. Naether OGJ, Fisher R, Weise HC, Geiger Kotzler L, Delfs T, Rudolf K. Laparoscopic electrocauterization on patients with polycystic ovarian syndrome. Fertil Steril 1993;60:66–94.
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19. Saed GM, Diamond MP. Molecular characterization of postoperative adhesion: the adhesion phenotype. J Am Assoc Gynecol Laparosc 2004; 11:307–14. 20. Balen A, Jacobs H. A prospective study comparing unilateral and bilateral laparoscopic ovarian in women with the polycystic ovary syndrome (PCOS). Fertil Steril 1994;62:921–5.
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Department of Gynaecology and Obstetrics, and Pathophysiology of Human Reproduction, University of Naples ‘‘Federico II,’’ Naples; b Department of Obstetrics and Gynaecology, University of Foggia, Foggia; and c Epidemiology of Population Genetics, Institute of Food Science, C.N.R. Avellino, Italy
Objective: To determine the incidence, site, and grade of ovarian adhesion formation after laparoscopic ovarian drilling (LOD) and analyze the association between the number of punctures made and the incidence and grade of adhesions, and evaluate the lateral distribution of the adhesions. Design: Prospective clinical study. Setting: University hospital endocrine and infertility center. Patient(s): Ninety-six anovulatory infertile women with polycystic ovarian syndrome (PCOS) treated with LOD. Intervention(s): Women were randomized into two study groups of 48 women each, one treated with 6 punctures on the left ovary and 12 on the right, and the other treated with 6 punctures on the right ovary and 12 on the left. A short-term second-look minilaparoscopy was performed to evaluate postsurgical adhesion formation. Main Outcome Measure(s): [1] Evaluation of the incidence and grade (thin, dense, cohesive) of ovarian adhesions; [2] comparative analysis of the incidence and grade of ovarian adhesions between ovaries treated with 6 and 12 punctures; and [3] comparative analysis of the incidence and grade of ovarian adhesions between the two sides. Result(s): Adhesion formation was detected in 54 of the 90 women (60%) and in 83 of the 180 ovaries treated (46%). Dense adhesions were more likely to develop on the left ovaries to a statistically significant extent, and independently of the number of ovarian punctures performed (odds ratio [OR] ¼ 4.34, 95% confidence interval [CI] ¼ 1.72–10.94). Logistic regression analysis showed that the incidence of ovarian adhesions was independent of both number of punctures (OR ¼ 1.05, 95% CI ¼ 0.58–1.88) and side (OR ¼ 1.37, 95% CI ¼ 0.76–2.46). Conclusion(s): The incidence of ovarian adhesion formation after LOD was high, and their extent and severity was not influenced by the number of ovarian punctures; however, the left ovary appeared more prone to develop severe adhesions than the contralateral one. (Fertil Steril 2008;89:1229–33. 2008 by American Society for Reproductive Medicine.) Key Words: Laparoscopic ovarian drilling, ovarian adhesions, polycystic ovarian syndrome, punctures, laterality
Laparoscopic ovarian drilling (LOD) is a common surgical approach currently used to treat anovulatory infertility in clomiphene (CC)-resistant women with polycystic ovarian syndrome (PCOS). The mechanism of action is still uncertain but likely lies in the reduction of ovarian androgen production through a decrease in stromal mass, or in the disruption of parenchymal blood flow. The conversion from an adverse androgenic environment to an estrogenic one corrects the defect of the ovarian–pituitary feedback, allowing appropriate gonadotropin stimulation for follicular development and ovulation (1, 2).
Received December 1, 2006; revised and accepted May 2, 2007. Reprint requests: Francesco Mercorio, M.D., Dipartimento di Ginecologia di e Ostetricia e, Fisiopatologia della Riproduzione Umana, Universita Napoli ‘‘Federico II,’’ Via L. Caldieri 140, 80128 Naples, Italy (FAX: 39-081-7463865; E-mail: [email protected]).
0015-0282/08/$34.00 doi:10.1016/j.fertnstert.2007.05.009
Recently, LOD has been evaluated as an alternative approach to the medical treatment of PCO-related anovulatory infertility, because it is not associated with risk of multiple pregnancy or ovarian hyperstimulation, and improves ovarian response to medical treatment (3). Nevertheless, two main drawbacks prevent LOD from being considered a primary approach to the treatment of POS: the risk inherent to any surgical procedure, and the risk of adhesion formation potentially interfering with fertility. Many trials have been designed to evaluate the rate of adhesions after LOD. However, most of them evaluated adhesion formation while performing a cesarean section or during second-look laparoscopies to investigate persisting infertility, whereas other trials involved small series of patients. As a result, currently, the incidence of postoperative adhesion formation ranges from 19% to 43% in some studies (4, 5), and up to 82% in other studies (6), but
Fertility and Sterility Vol. 89, No. 5, May 2008 Copyright ª2008 American Society for Reproductive Medicine, Published by Elsevier Inc.
1229
such wide variation possibly reflects an inadequate study design. Variations in the surgical techniques can obviously affect the rate of adhesion formation (6–9), and the number of ovarian punctures is one such technical option to account for. Currently, the number of ovarian punctures made during LOD is defined by the gynecologist, case by case, depending on the size of the ovary. In theory, the best way to decrease the risk of adhesion formation is to minimize injury to the ovarian surface. Consequently, the rule should be to perform the lowest possible number of punctures. Unfortunately, the experimental evidence in the literature in support of this theory is scant. In 2002 Amer et al. (10) concluded, on the basis of the reproductive performance, that a thermal energy of 450–900 J produced by 3–6 punctures per ovary (6–12 punctures total) gives a statistically significantly higher ovulation and pregnancy rate. This study, however, did not addressed the problem of the relationship between number of punctures and adhesion development. Furthermore, no study has addressed the importance, if any, of the ovarian side treated in adhesion development. It is worth remembering that endometriotic implants are found more frequently on the left hemipelvis. The greater likelihood that endometriosis develops on the left side has been explained by the presence of the sigmoid colon in that region, which delays the spread of retrograde menstrual blood (11–13). On the basis of these data we have designed this large prospective study to investigate by means of a short-term second-look minilaparoscopy after LOD: [1] the incidence and site of postsurgical ovarian adhesion formation; [2] the correlation between the number of ovarian diathermy punctures and incidence and severity of adhesion; and [3] the side of the ovary treated as risk factor for adhesion formation.
MATERIALS AND METHODS The study population consisted of 96 cases of PCOS-related anovulatory infertility treated with LOD between May 2002 and February 2006. All patients had primary infertility with a mean duration of 1.3 years (range 1–2.3 years). Median age was 28.7 years (range, 20–39 years). The diagnosis of PCOS was based on the following criteria: [1] clinical and biochemical evidence of androgen excess and [2] typical image of PCOS on ultrasound with ovarian stromal hypertrophy and multiple small (6–8 mm) peripheral follicles. The study design was approved by the institutional review board (IRB). Exclusion criteria were any disease potentially responsible of ovarian adhesions (i.e., ovarian cyst, endometriosis, pelvic infections, previous abdominal-pelvic surgery) and tubal diseases. All women gave their written informed consent and agreed to undergo the primary surgical procedure, the short-term 1230
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second-look laparoscopy to evaluate postoperative ovarian adhesions, and a subsequent adhesiolysis to improve fertility. For the purposes of the study, 96 patients were randomized, using a sealed envelope, into two study groups as follows: group 1, 48 women treated with 6 punctures on the left ovary and 12 on the opposite ovary; and group 2, 48 women treated with 6 punctures on the right ovary and 12 on the contralateral ovary. The randomization assignment was done immediately before the surgical procedure. Laparoscopic ovarian electrocautery was performed using a three-puncture technique. A 10-mm laparoscope was inserted by the main subumbilical route and a pair of grasping forceps was introduced through one of the two lower abdominal 5-mm punctures to grasp the utero-ovarian ligament and lift the ovary away from the bowel. The third access was used to introduce the diathermy needle. The LOD was carried out using a specially designed diathermy probe (Rocket of London, Watford, UK) to penetrate the ovarian capsule. The probe consisted of a distal stainless steel needle measuring 8 mm in length and 2 mm in diameter and projecting from an insulated solid cone having a maximum diameter of 6 mm. The electrosurgical unit used was the Force 2 Valleylab electrosurgical generator (Valleylab Inc., Boulder, CO). The entire length of the needle was inserted at a right angle into the ovary with the aid of a short burst of pure cutting diathermy of 40 W followed by a monopolar coagulating current set at 30 W. The ovarian punctures were uniformly distributed on the ovarian surface. The duration of each penetration was 5 seconds. At the end of the procedure each ovary was cooled by irrigation before releasing the ligament, and 1,000 mL of Ringer’s lactate solution was left in the peritoneal cavity. All the primary surgical procedures were performed by the senior author (M.F.). After an average time of 5.3 weeks (range, 4–9 weeks) the women underwent the second-look laparoscopy according to the methods described in our previous study (14). Assessment of the incidence, site, and grade of ovarian adhesions was made with the operator blinded to the previous treatment. Adhesions not involving the ovaries were not the object of this study and were therefore neither scored nor treated. Grading of adhesions was as follows: grade 1, filmy avascular; grade 2, dense or vascular; grade 3, cohesive (15). When different types of lesions coexisted, the grade was assigned to the most severe adhesion. In patients with adhesions, lysis was carried out with monopolar scissors. The incidence and grade of ovarian adhesions after 6 or 12 punctures on the left versus the right ovary were compared by c2 statistics or Fisher’s exact test, as appropriate. Logistic regression analysis was performed to compare the frequency of ovarian adhesions accounting for affected side and number of punctures. The statistical analysis was Vol. 89, No. 5, May 2008
performed separately in the group of women developing monolateral ovarian adhesions. Statistical significance was set at a P value of < .05.
only two cases of cohesive adhesions were found on the left ovary. Logistic regression analysis showed that the greater likelihood of dense adhesion to occur on the left ovary was independent of the number of ovarian punctures (OR ¼ 4.34, 95% CI ¼ 1.72–10.94).
RESULTS Primary laparoscopy confirmed the preoperative diagnosis of PCOS in all patients with no evidence of ovarian adhesions, endometriosis disease, and tubal disease.
In the analysis of the group with monolateral presentation (n ¼ 25), adhesions occurred in 12 cases after 6 punctures and in 13 cases after 12 punctures. These patients showed a significant trend toward a major predisposition of the left ovary to adhesion development (16 vs. 9 cases; P¼.015). In addition, with regard to the grade of adhesions, these patients presented dense adhesions more frequently on the left ovary than on the right one (8 vs. 2 cases; P¼.041) (Fig. 2). Logistic regression analysis in this group showed that the incidence and grade of ovarian adhesions was independent of the number of punctures (data not shown).
Six patients (three for each treatment protocol) decided to withdraw from the study and did not undergo the second-look procedure. Therefore, a total of 90 women were included in the data analysis. Postoperative ovarian adhesion formation was observed in 54 of the 90 women (60%). Bilateral ovarian adhesions were found in 29/54 patients (53.7%), and monolateral adhesions in 25/54 patients (46.3%). Of 180 ovarian sites available to evaluate adhesion development, 83 ovaries (46%) presented adhesion formations (right ovary: n ¼ 38; left ovary: n ¼ 45). Right ovaries developed adhesions in 19 cases after either 6 punctures and 12 punctures; left ovaries developed adhesions in 22 cases after 6 punctures and in 23 cases after 12 punctures. The anatomical sites involved with ovarian adhesions were pelvic wall (n ¼ 68; 81.9%), fallopian tube (n ¼ 7; 8.4%), omentum (n ¼ 6; 7.2%), and large bowel (n ¼ 2; 2.4%). Logistic regression analysis showed that the occurrence of ovarian adhesions was independent of either the number of punctures (odds ratio [OR] ¼ 1.05, 95% confidence interval [CI] ¼ 0.58–1.88) or side (OR ¼ 1.37, 95% CI ¼ 0.76–2.46). Grading of ovarian adhesions is reported in Figure 1. The left ovary developed dense adhesions more frequently than the contralateral side (c2:10.06; P<.01). In addition, the
DISCUSSION To the best of our knowledge, this is the largest prospective series on the relationship between LOD and adhesion formation. In a small sample size, Dabirashrafi et al. (16) reported mild to moderate adhesion formation in 20% of patients after LOD. Gurgan (6) and Grenblatt (17) and their colleagues reported higher postoperative adhesion rate (85%–100%), often of significant extent and severity. In a prospective study involving 62 patients who underwent second-look laparoscopy, Naether et al. (18) found that the rate of adhesions decreased from 19.3% to 16.6% by peritoneal lavage with saline, and all of the lesions observed were minimal. Saravelos and Li (5) found adhesions at second-look laparoscopy in 57% of 21 women and in 38% of the adnexa evaluated
FIGURE 2 FIGURE 1 Incidence and grade of ovarian adhesions at early second-look procedure after laparoscopic ovarian drilling. *P< .01 vs. right ovary.
Incidence and grade of ovarian adhesions at early second-look procedure after laparoscopic ovarian drilling in the group with monolateral ovarian adhesions (n ¼ 25); *P< .05 vs. right ovary.
Mercorio. Ovarian drilling and adhesions. Fertil Steril 2008.
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in their series. The adhesions, when they did occur, were often of significant extent and severity. In our study the evaluation of postsurgical ovarian adhesions was made by means of a short-term minilaparoscopy, systematically performed on all patients who underwent the primary procedure, thereby avoiding the selection bias frequently present in the previously mentioned studies. In our experience, ovarian adhesions developed in a large percentage of patients (60%) and of the 180 ovaries treated (46%). Even if adhesions after LOD do not seem to affect reproductive performance (5), the unequivocal high rate of adhesion formation shown in this study suggests the importance of undertaking complete and comprehensive medical therapy before proceeding with surgical treatment. Two important findings in this study are worthy of being underlined. An unexpected result is that the incidence and grade of ovarian adhesions is independent of the number of ovarian punctures. This result is in sharp contrast with the axiom that the greater the amount of damage to the surface of the ovary, the greater the risk of periovarian adhesion formation. The second observation is that the left ovary is more prone to severe adhesion formation compared to the right ovary. This finding is further strengthened by the fact that the only two cohesive adhesions found in our series involved the left ovary. This predisposition for the left side could be explained by a decreased movement of fluids at the left side of the pelvis, caused by the presence of the sigmoid colon (11–13). This decrease impairs the effect of hydroflotation of crystalloid solution and thus favors the cellular mechanism that leads to adhesions (19). Both of these findings have been confirmed in the group of women with monolateral ovarian adhesions. We found worthwhile to perform a separate statistical analysis in this group, hypothesizing that the adhesion phenotype (19) (i.e., the biochemical individual predisposition to adhesion formation), was less developed and active in this group. Thus, the role of other adhesion factors, such as the number of ovarian punctures or the side, could be considered as major determinants; therefore, their role should be more accurately highlighted. In this group we confirmed the greater likelihood for dense adhesions to develop on the left ovary, as already demonstrated in the overall study group. In addition, in this group, we demonstrated a significantly higher incidence of adhesion on the left ovary. Among the 25 women who developed adhesions, 64% involved the left ovary and 36% the right one. In summary, our study provides evidence that: first, LOD was frequently associated with postoperative ovarian adhesion formation; second, adhesion rate was independent of the number of ovarian punctures; and, finally, the left ovary can be considered at greater risk of high grade adhesion formation. 1232
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Based on these three observations and on the report by Balen and Jacobs (20), who showed that unilateral diathermy leads to bilateral ovarian activity through a correction of the abnormal ovarian–pituitary feedback, a strategy based on unilateral right ovarian diathermy limiting the minimal effective number of punctures is plausible. However, before proposing such an approach as a viable surgical option for LOD, further studies are needed to test its feasibility and effectiveness and, in particular, to address the issue of whether unilateral diathermy would provide any clinical benefit in terms of spontaneous ovulation when the contralateral ovary is untreated.
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