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Surgical Management of Polycystic Ovarian Syndrome: Laparoscopic Ovarian Drilling
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GYNAECOLOGY
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SURGICAL MANAGEMENT OF POLYCYSTIC OVARIAN SYNDROME: LAPAROSCOPIC OVARIAN DRILLING Sundus Al~Took, MD,1 Togas Tulandi, MD, FRCSC,2 1Fellow of Reproductive Endocrinology and Infertility, 2 Professor of Obstetrics and Gynaecology, Director, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, 1,2Reproductive Centre, McGill University
ABSTRACT Objective: to review the role of surgical management of polycystic ovarian syndrome (PCOS) in infertile women with special attention to /aparoscopic ovarian drilling. Design: pertinent studies and their references were identified through computer medline search. Results: to date there is no standardization of the technique of /aparoscopic ovarian drilling. However, it appears that the results are promising with a high ovulation rate ranging between 70 to 90 percent, and a pregnancy rate of 70 percent. Conclusion: clomiphene citrate remains the first line of treatment to induce ovulation in infertile women with PCOS. Laparoscopic ovarian driUing can be offered to clomiphene resistant women especiaUy to those who have also failed to respond to gonadotrophin treatment. It appears that the pregnancy rate after ovarian drilling is comparable to that of gonadotrophin therapy. However, until more complete and long term data are available, caution must be exercised when offering this type of treatment. The possible risks of the procedure are adhesion formation and premature ovarian failure. Standardization of the technique is stiU needed.
RESUME Objectif: Examiner le role du traitement chirurgical du syndrome de Stein-Leventhal (SSL, syndrome des ovaires polykystiques) chez les femmes infertiles, en insistant sur le forage laparoscopique des ovaires. Plan : On a identifie les etudes pertinentes et leurs references gri'lce aune recherche informatisee sur Medline. Resultats : A ce jour, Ia technique de forage /aparoscopique des ovaires n' a fait l' objet d' aucune normalisation. Les resultats semblent toutefois prometteurs etant donne un taux d' ovulation eleve, de 70 a90 pour cent, et un taux de grossesse de 70 pour cent. Conclusion : Le citrate de clomifene demeure le traitement privilegie pour stimuler l' ovulation chez les femmes infertiles atteintes du SSL. On peut offrir le forage /aparoscopique des ovaires aux femmes qui presentent une resistance au clomifene, en particulier ceUes qui
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' ' ' ne reagissent pas au traitement a Ia gonadotrophine. Cependant, Ia prudence est de mise au moment d' offrir ce type de traitement jusqu' a ce que nous disposions de donnees plus completes eta long terme. La formation d' adherences et Ia carence ovarienne precoce constituent les risques potentiels de cette intervention. La normalisation de Ia technique s'impose toujours.
J SOC OBSTET GYNAECOL CAN 1997;19:721-29 KEY WORDS
Polycystic ovaries, laparoscopy, ovarian drilling, ovulation induction. Received on December 17th, 1996. Revised and accepted on February 4th, 1997.
that the thick ovarian surface prevented follicles from reaching the surface and that OWR provided a mechanical passage for the follicles to ovulate. Subsequent studies showed that OWR was associated with a decrease in serum androgen levels along with changes in gonadotrophin secretion and estrogen levels.9·1l The reduction of serum androgen levels after destruction of the androgen producing stroma of the ovaries may decrease the amount of substrate available for peripheral aromatization to estrogen. This restores the feed back mechanism to the hypothalamus and the pituitary gland allowing appropriate gonadotrophin stimulation of follicular development and ovulation. At the ovarian level, the elevated intrafollicular androgen levels may inhibit granulosa cell function and follicular growth. Reduction in intra-ovarian androgen levels by OWR allows follicular development and ovulation to occur. A third mechanism that may explain the beneficial effects of OWR is the reduction that occurs in the circulating levels of inhibin following ovarian wedge resection. A secondary rise in the FSH level in combination with the reduction of local androgen levels may facilitate follicular growth and ovulation. 12 Wedge resection may also provoke an increased blood flow to the ovary allowing for the increased delivery of gonadotrophin and leading to stimulation of follicular development and escape from the tonic endocrine environment. The overall ovulation rate afrer OWR is 80 percent, but the pregnancy rate is lower, ranging from 25 13 to 86 percent. 14 This is due to the high incidence of periadnexal adhesion formation after this procedure (30-100%)Y· 17 Peri-adnexal adhesions decrease fertility and are a further cause of infertility in addition to the primary anovulatory problem. In an effort to reduce postoperative adhesion formation, a micro-surgical technique was developed. 18 In a primate model, the micro-surgical technique was associated with less adhesion formation (10% compared to 50% with macro-surgical technique).
INTRODUCTION
A symptom complex associated with anovulation, oligomenorrhoea, hirsutism, and obesity was first described by Stein and Leventhal in 1935. 1 This syndrome is currently called polycystic ovarian syndrome (PCOS), and is known to be variable in its clinical and biochemical presentations. However, chronic anovulation and hyperandrogenaemia remain the hall marks of this syndrome. Among infertile women with anovulation, approximately 75 percent will have PCOS, 2·3 and the first line of treatment is clomiphene citrate. The ovulation rate with this drug is 80 to 85 percent. 2·4•5 However, 15 to 20 percent of women remain anovulatory despite receiving incremental doses of clomiphene citrate. Furthermore, there is a discrepancy between the ovulation rate and the conception rate (40-50 percent)/·7 and the abortion rate is high (30-40 percent). This has been attributed to high serum levels of luteinizing hormone (LH) that may produce an adverse environment for the oocyte.8 Women who are clomiphene resistant can be treated with gonadotrophin or luteinizing hormone releasing hormone (LHRH), but neither treatment is universally successful. An alternative treatment is surgery. In this review, we will evaluate the surgical treatment of polycystic ovarian syndrome with special emphasis on the laparoscopic approach. OVARIAN WEDGE RESECTION
At the Michael Reese Hospital in Chicago, Irving Stein and Michael Leventhal first described a surgical treatment for PCOS or Stein Leventhal syndrome. 1 They performed a wedge resection of the ovaries of seven women, and approximately 50 to 75 percent of ovarian tissue from each ovary was removed. This ovarian wedge resection (OWR) restored menstruation in all patients and led to pregnancy in two women. They postulated
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Ethical Considerations of the New Reproductive Technologies A Report of the Combined Ethics Committee of the Canadian Fertility and Andrology Society and the Society of Obstetricians and Gynaecologists of Canada
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' ' ' Laparoscopic OWR has also been done. McLaughin performed micro-laser ovarian wedge resection by laparoscopy in 25 consecutive patients. 19 The pregnancy rate after this procedure was 60 percent. However, 36 percent of the ovaries treated were involved with adhesions. Of these, 83 percent were mild adhesions. Kojima et al. reported laparoscopic ovarian wedge resection using an Nd:YAG laser with sapphire tips. 20
FIGU RE I
LAPAROSCOPIC OVARIAN DRILLING
The interest in laparoscopic treatment ofPCOS was renewed after Gjonnaess reported an ovulation rate of 90 percent and a pregnancy rate of 80 percent among 35 patients who underwent a new laparoscopic treatment of PCOS. 21 Using a unipolar electrode at 300 to 400 watts for two to four seconds, he created eight to 15 craters two to four mm deep on the capsule of each ovary. This technique is less invasive than ovarian wedge resection by laparotomy. Following this report, other laparoscopic techniques were described. Most involved the formation of multiple holes on the surface of the ovary either with laser or with electrocautery, procedures known as ovarian drilling. 12'21 ' 28 Other procedures including multiple ovarian punch biopsy29 are less popular. We prefer to use an insulated needle unipolar electrode (Figure 1).30 The ovary is immobilized with laparoscopic forceps and the treatment is performed using the needle electrode on both ovaries. The needle is inserted as perpendicularly as possible to the ovarian surface. A short duration of cutting current of 100 watts is used to aid the entry of the needle. The whole length of the needle (8 mm) is inserted into the ovary, and it is activated with 40 watts of coagulating current for two seconds at each point. Depending upon the size of the ovary, we created 10 to 15 punctures per ovary. Release of fluid from the underlying "follicles" is usually seen with each puncture. During the procedure, it is important to hold the ovary away from the bowel and other vital structures to avoid potential sparking and arcing from electrical current. Care must be taken to avoid the hilum of the ovary and the ovarian blood supply. At the completion of the procedure, the ovarian surface is lavaged, and 500 to 1,000 mL of Ringer's lactate solution is left in the peritoneal cavity. Several lasers including carbon dioxide (COz), Argon, KTP, and Nd:YAG laser have also been used for laparoscopic treatment of PCOS. The technique is similar to
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Laparoscopic ovarian drilling using an insulated needle electrode. Thermal injury to the ovarian surface is limited by inserting the whole length of the needle (8 mm} into the ovary. The insulated part of the needle should be inside the ovarian stroma. From Tulandi T, Operative Laparoscopy, In Te Linde's Update in Operative Gynecology, 1997. Reproduced with permission.
that of electrocautery. The use of the COzlaser is associated with smoke production that might obscure the view and require to be evacuated intermittently. Argon and KTP lasers are associated with less smoke production and allow for deeper penetration. Contrary to other lasers, the Nd:YAG laser can be delivered using a flexible fibre delivery system equipped with sapphire tips. The procedure is done with a similar contact technique to electrocautery.31 The advantage of this technique is that laser vaporization of the ovarian surface is limited. As will be discussed later, the results of laser surgery for PCOS are inferior to those of electrocautery. ENDOCRINE CHANGES AFTER LAPAROSCOPIC OVARIAN DRILLING
Hormonal changes after laparoscopic ovarian drilling are similar to those following OWR. A transient increase in the first 24 to 48 hours after surgery followed by a decrease in serum LH concentrations have been reported. 29 •32 The decrease is mainly in the LH pulse amplitude rather than the pulse frequency. Similar to that following OWR, serum androgen concentrations decrease after ovarian drilling. 23 This is due to destruction of the androgen producing ovarian stroma and drainage of the follicles which have high androgen levels.
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' ' ' Gurgan et al. compared the effectiveness ofNd:YAG laser photocoagulation with electrocauterization in 17 women with clomiphene-resistant PCOS. 35 The pregnancy rate within six months afrer surgery with electrocautery was 57 percent and after laser surgery was 40 percent. Naether et al. reported a mean pregnancy rate of 65.4 percent following cauterization versus 47.4 percent following laser vaporization. 33 Abdel Gadir et al. reported that ovarian electrocautery is as effective as gonadotrophin administration for induction of ovulation in women with PCOS resistant to clomiphene citrate. 24 In a prospective randomized trial in 88 clomiphene-resistant women with PCOS, they compared the efficacy of ovarian electrocautery, RESULTS OF LAPAROSCOPIC OVARIAN human menopausal gonadotrophin (hMG), and pure DRILLING FSH, and reported ovulation rates of 71, 71, and 6 7 percent, respectively. The cumulative pregnancy rates in six In the first report of laparoscopic ovarian drilling, the cycles were 52, 55 , and 38 percent, respectively. The spontaneous ovulation rate among 62 women was 92 21 same group of investigators subsequently compared the percent. Of 35 women desiring pregnancy, 69 percent response of 33 women with PCOS treated with hMG conceived spontaneously after surgery, while a further 11 after ovarian electrocautery or after LHRH analogue percent conceived after additional treatment with 80 of rate pregnancy treatment.37 Sixteen patients were treated with ovarian total a giving clomiphene citrate, cautery followed by hMG, and 17 were treated with percent. Subsequent studies confirmed a similar ovulaintranasal LHRH analogue and hMG. Although no diftion rate between 70 percent to 92 percent, and a pregnancy rate o£70 percent (Table l),U·1 5-17.26-2s,3o,35,36 ference was found between the two groups in regard to ovulation or pregnancy rate, this could be due to a type II error. number of cycles with mulThe TABLE 1 dominant follicles, luteal tiple OVULATION AND PREGNANCY RATES AFTER DIFFERENT SURGICAL TREATMENTS FOR SYNDROME OVARIAN POLYCYSTIC phase serum testosterone values, and the miscarriage rate were all Ovulation Technique Pregnancy Year Authors lower in the group pretreated Rate Rate % % ovarian drilling. with 2/16 12 6 9/1 1969 Kistner 56 OWR et al. reported a reducFarhi 64/150 43 NA NA 1975 OWR Buttram et a/. 38/57 67 NA NA 1975 Weinstein eta/. OWR tion in the number of ampules, 43/90 82/90 48 1981 Adashi eta/. 91 OWR daily effective dose, and duration 48/85 84/85 56 99 1989 Daniell eta/. C02+KTP* of hMG treatment in women 7/19 15/19 1990 laser* 44 79 C0 2 Keckstein eta/. who were pretreated with ovarian 0/8 5/8 0 62 1989 Huber eta/. Nd:YAG laser* electrocautery. 38 Fukaya et al. 4/10 7/10 40 1991 70 Nd:YAG laser* Gurgan eta/ reported a reduction in the inci24/35 1984 57/62 80 92 Gjonnaess Electrocoagulation* of ovarian hyperstimuladence 4/6 5/6 1987 Greenblatt eta/. 66 83 Electrocoagulation* tion syndrome (OHSS) after 11/21 17/21 52 81 Electrocoagulation* 1990 Armar eta/. drilling in 26 patients ovarian 4/7 5/7 57 71 1991 Electrocoagulation* Gurgan eta/. who had previously PCOS with 04 73/1 90/104 70 1993 Neather eta/. 86 Electrocoagulation* 30/34 70 88.2 1996 Tulandi eta/. Electrocoagulation* ** experienced OHSS.39 Because there is no standardLaparoscopy. ** Cumulative probability of conception at 12 months ization in the surgical technique
The decrease in the peripheral androgen levels leads to a decrease in their peripheral aromatization to estrogens. The endocrinological changes following ovarian electrocautery are only temporary, but are sufficient to allow ovulation and pregnancy to occur. Gjonnaess et al. reported a return to a state of chronic anovulation within two years in six of the 12 women. 26 Naether et al. found that the endocrine changes induced by laparoscopic ovarian drilling persisted for up to 72 months after surgeryY Of interest, unilateral ovarian drilling produces ovulation from both ovaries, suggesting that the effect is a systemic restoration of hypothalamic pituitary ovarian function.34
.
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' ' ' among different centres (the number of ovarian punctures, the duration of the drilling, and the power output), it is difficult to compare the results of those studies. However, it appears that the ovulation and the pregnancy rates after ovarian drilling, especially with electrocautery, are consistently high.
The most important clinical study demonstrating the benefits of laparoscopy in reduction of adhesion formation was published by Lundorff et al. 41 They conducted a randomized study comparing surgical treatment for ectopic pregnancy by laparoscopy and by laparotomy, and found that the incidence of peri-adnexal adhesions was significantly lower after laparoscopic surgery. The POTENTIAL RISKS AND Operative Laparoscopy Group reported that de novo COMPLICATIONS OF LAPAROSCOPIC adhesion formation after operative laparoscopy occurred OVARIAN DRILLING in only 12 percent of cases versus >50 percent after Apart from the general complications which can laparotomy. 41 occur during any laparoscopic surgery, there are two Adhesions are almost always formed after ovarian main potential complications associated with laparowedge resection (Table 2) .11 •15-17·43 •44 Laparoscopic ovarian scopic ovarian drilling . These are peri-adnexal adhesion drilling produces fewer adhesions than conventional ovarformation and premature ovarian failure . ian wedge resection. 17•35 JMS-4? It appears that laser produces Compared to laparotomy, laparoscopic surgery offers more adhesions than electrocautery. Rittenhouse et al. 48 special advantages for the prevention of adhesion forcompared adhesion formation following ovarian drilling mation. Operating in a closed environment prevents tiswith C02 laser versus electrocautery in a rabbit model, sue drying, a condition that may predispose to adhesion and found a significantly higher mean adhesion score in formation. Contamination with glove powder or lint is the group treated with C02 laser than in the electroless likely to occur. Because of the tamponade effect of cautery group. Using the Nd:YAG laser for ovarian the pneumoperitoneum gas, bleeding during laparoscopy drilling, Gurgan et al. found that 68 percent of the is limited and, thus, can be controlled more easily. In a patients had adhesions at the time of second-look rabbit study, adhesion formation after a standardized laser laparoscopy. 49 injury by laparoscopy was significantly less than by In an attempt to minimize postoperative adhesions, laparotomy. 40 Lysis of adhesions by laparoscopy was also oxidized regenerated cellulose (lnterceed, Johnson & associated with a marked reduction in the adhesion Johnson Medical Inc., New Brunswick, NJ) has been scores in the laparoscopy group, but not in the laparotomy used to cover the ovary after the procedure. The results, group. however, are disappointing. 50•51 Another adhesion barrier is expanded polytetrafluoroethylene (Preclude, Gore-Tex TABLE 2 surgical membrane, WL Gore & THE RATE OF ADNEXAL ADHESION AT SECOND-LOOK LAPAROSCOPY Ass. Inc., Flagstaff, AZ). HowNo. of patients Rate of Adnexal Adhesion Year Technique Authors ever, this fabric is not absorbable % and will cover the ovary perma16/16 100 Kistner 16 1969 OWR nently. Its use after ovarian 100 59/59 Buttram et ai. 173 1975 OWR drilling is not recommended. 8/19 OWR 42 Weinstein et ai. 72 1975 We feel that the best way to 7/7 100 Toaff et ai. 1976 OWR 7 decrease adhesion formation is 100 717 Adashi et ai. 90 1981 OWR to minimize any injury to the 11/12 91 Protuondo et ai. 12 1984 OWR ovarian surface. The use of an 0/8 0 Daniell et ai. 1989 C0 2 +KTP* 85 8/10 Nd:YAG laser* Gurgan et ai. 1991 10 80 insulated needle electrode serves Electrocoagulation 7/10 Weise etai. 70 39 1991 this purpose. As the insulated Electrocoagulation Gurgan et al. 1991 7 85 6n part of the needle is inside the 2/12 Electrocoagulation 16 Dabirashrafi et al. 1991 31 ovarian stroma, thermal injury to 7/26 Naether et al. 133 26 1993 Electrocoagulation the surface of the ovary is limited. 12/62 19 Neather & Fischer 199 1993 Electrocoagulation At the end of the procedure, the
I
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' ' ' peritoneal cavity is liberally irrigated to remove any debris, and Ringer's lactate solution is instilled. In a rat model, we and others52 •53 found that Ringer's lactate instillation decreased adhesion formation. Perhaps Ringer's lactate removes the newly formed fibrin exudate from the raw peritoneal surfaces. Fibrin exudate serves as a matrix for fibroblast and capillary formation. If not quickly removed by absorption or fibrinolysis, the initial fibrin deposition produces an inflammatory response, fibroblast proliferation, and adhesion formation. Naether found that instillation of normal saline solution (300 to 500 ml) afrer laparoscopic ovarian drilling for polycystic ovaries reduced adhesion formation. 54 Laparoscopic ovarian drilling is associated with a high pregnancy rate, and lysis of adhesions does not seem to improve the pregnancy rate. Another potential complication of laparoscopic ovarian drilling is ovarian failure. Accordingly, excessive ovarian drilling and electrocoagulation of the ovarian hilum and the ovarian blood supply should be avoided. 55 Currently, there is no standardization of the procedure. However, we feel that more than 20 punctures per ovary is excessive. Destruction of the ovarian androgenproducing stroma is associated with the destruction of nearby follicular units, but there has been no long term study undertaken to evaluate the effect of ovarian drilling or ovarian wedge resection on the age of menopause. McComb et al. reported significantly decreased concentration of ovarian follicles in a rabbit model subjected to laser wedge resection when compared with ovaries treated by electrosurgical wedge resection. 56
largest study published, the incidence of adnexal adhesions was 19 percent. It seems that the use oflaser is associated with more adhesion formation and lower pregnancy rates compared to electrocautery; perhaps the laser produces more surface injury than the insulated needle electrode. To date, there is no standardization of the technique. In our clinical experience, 10 to 15 ovarian punctures per ovary (8 mm depth) at 40 wat?> for two seconds produces promising pregnancy rates. We recommend the use of an insulated needle cautery, making less than 20 punctures, liberal irrigation of the peritoneal cavity, and the instillation of large amounts of crystalloid solution at the conclusion of the procedure. Until more complete and long term data are available, caution must be exercised when offering this type of treatment, and complete information about the possible adverse effects should be provided to the patient.
CONCLUSIONS
6.
REFERENCES 1, 2.
3.
4.
5.
Obstet Gynecol1982;60:497. Chong AP, Lee JL, Forte CC. Identification and management of clomiphene citrate responses. Fertil Steril 1987;48:941-7. 7. Garcia J, Jones GS, Wentz AC. The use of clomiphene citrate. Fertil Steril1977;28:707-17. 8. Sagle M, Bishop K, Ridley N, Alexander FM, Michel M, Bonney RC, Beard RW, Franks S. Recurrent early miscarriage and ovaries. Br Med J 1988;297:9027-8. 9. Judd HL, Rigg LA, Anderson DC. The effect of ovarian wedge resection on circulating gonadotropin and ovarian steroid levels in patients with polycystic ovaries. J Clin Endocrinol Metab 1976;43:347-55. 10. Katz M, Carr PJ, Cohen BM, Millar RP. Hormonal effects of wedge resection of polycystic ovaries. Obstet Gynecol 1978;54:437-44. 11. Adashi EY, Rock JA, Guzick D, Wentz AC, Jones GS, Jones HW. Fertility following bilateral ovarian wedge resection: a critical analysis of 90 consecutive cases of polycystic ovarian syndrome. Fertil Steril1981 ;36:320-5.
Clomiphene citrate remains the first line of treatment to induce ovulation in infertile women with PCOS. Those who do not respond to up to 200 mg of clomiphene citrate daily can be treated with gonadotrophin. Laparoscopic ovarian drilling can be offered to clomiphene-resistant women, especially to those who have also failed to respond to gonadotrophin treatment. The pregnancy rate after ovarian drilling is comparable to that of gonadotrophin therapy. The mechanism of action is not known exactly but it appears to be mediated by the decrease in intraovarian androgen levels. Using a variety of techniques with different electrical wattages, duration of thermal injury, and number of ovarian punctures, the incidence of peri-ovarian adhesions has been reported to be between 10.8 and 100 percent . In the
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Stein IF, Leventhal ML. Amenorrhea associated with bilateral polycystic ovaries. Am J Obstet Gynecol1935;29:181-91, FrankS, Adams J, Mason H. Ovulatory disorders in women with polycystic ovarian syndrome. Clin Obstet Gynecol 1985; 12:605-32. Hull MG. Infertility and ovarian disease. Endocrinological and demographic studies. Gynecol Endocrinol 1987; 1:235-45. Hammond MG. Monitoring technique for improved pregnancy rate during clomiphene ovulation induction. Fertil Steril1984;42:499-509. Lobo RA, Paul L, Granger L. Clomiphene and dexamethasone in women unresponsive to clomiphene alone.
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New mlmitrex® Nasal Spray* starts to work in half the time of our own mlmitrex® tablets I** •15 minute onset of action vs. 30 minutes with Imitrex® tablets1 • Efficacy similiar to Imitrex® tablets 1t • Generally well toleratedHtt • Easy to use, convenient single dose devicettt
' ' ' 12. Kovacs G, Buckler H, Gangah M, Burger H, Healy D, Baker G, Phillips S. Treatment of anovulation due to polycystic ovarian syndrome by laparoscopic ovarian cautery. Br J Obstet Gynaecol1991 ;98:30-5. 13. Vejlsted H, Albrechtsen R. Biochemical and clinical effects of ovarian wedge resection in polycystic ovarian syndrome. Obstet Gynecol1976;47:575-80. 14. Stein I. Duration of fertility following ovarian wedge resection. Stein-Leventhal syndrome. West J Surg Obstet Gynecol1964;78:124-7. 15. Kistner RW. Peritubal and periovarian adhesions subsequent to wedge resection of the ovaries. Fertil Steril 1969;20:35-42. 16. Buttram V, Vaquero C. Post ovarian wedge resection and adhesive disease. Fertil Steril1975;26:874-6. 17. Weinstein D, PolishukWZ. The role of wedge resection of the ovary as a cause for mechanical sterility. Surg Gynecol Obstet 1975;141:417-8. 18. Eddy CA, Asch RH, Balmaceda JP. Pelvic adhesion following microsurgical and macrosurgical wedge resection ofthe ovary. Fertil Steril1980;33:557-61. 19. McLaughlin DS. Evaluation of adhesion reformation by early second look laparoscopy following microlaser ovarian resection. Fertil Steril1984;42:531-7. 20. Kojima E, Yanagibori A, Otaka K. Ovarian wedge resection with contact Nd:YAG laser irradiation used laparoscopically. J Reprod Med 1989;34:444-6. 21. Gjonnaess H. Polycystic ovarian syndrome treated by ovarian electrocautery through the laparoscope. Fertil Steril1984;4:20-5. 22. Aakvaag A, Gjonnaess H. Hormonal response to electrocautery of the ovary in patients with polycystic ovarian disease. Obstet Gynecol1985;92:1258-64. 23. Greenblatt EM, Casper RF. Endocrine changes after laparoscopic ovarian cautery in polycystic ovarian syndrome. Am J Obstet Gynecol1987;156:279-85. 24. Abdel Gadir A, Mowafi RS, AI Naser H, AI Rashid AH, AI Onazi OM, Shaw RW. Ovarian electrocautery versus human menopausal gonadotropins and pure follicle stimulating hormone therapy in the treatment of patients with polycystic ovarian disease. Clin Endocrinol 1990;33:585-92. 25. Armar NA, McGarrigle HG, Holownia P, Jacobs HS, Lacheline GCL. Laparoscopic ovarian diathermy in the management of anovulatory infertility in women with polycystic ovaries: endocrine changes and clinical outcome. Fertil Steril1990;53:45-9. 26. Huber J, Hosmann J, Spona J. Polycystic ovarian syndrome treated by laser through the laparoscope. Lancet 1988;ii:215 (letter). 27. Daniell JF, Miller W. Polycystic ovaries treated by laparoscopic laser vaporization. Fertil Steril 1989;51 :232-6. 28. Keckstein J. Laparoscopic treatment of polycystic ovarian syndrome. In: Sutton CJG (Ed). Laparoscopic Surgery. Baillieres Clin Obstet Gynaecol1989;3:563-81.
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29. Sumioki H, Utsumomyiya K, Korenaga M, Kadota T. The effect of laparoscopic multiple punch resection of the ovary on the hypothalamic-pituitary axis in polycystic ovarian syndrome. Fertil Steril 1988;50: 567-72. 30. Tulandi T, Watkin K, Tan SL. Reproductive performance and three dimensional ultrasound volume determination of polycystic ovaries following laparoscopic ovarian drilling. lnt J Fertil (in press). 31. Frishman GN, Kratka SA, Maier DB, Luciano AA. Comparative analysis of adhesion reduction, tissue effects and incising characteristics of electrosurgery, C02 laser, Nd:YAG laser at operative laparoscopy. 47th Annual Meeting of the American Fertility Society, October 21-24, New Orleans, abst 0-014. 32. Sakata M, Tasaka K, Kurachi H, Terakawa N, Miyake A, Tanizawa 0. Changes of bioactive luteinizing hormone after laparoscopic ovarian cautery in patients with polycystic ovarian syndrome. Fertil Steril1990;53: 610-3. 33. Naether OGJ, Baukloh V, Fischer R, Kowalczyk T. Long term follow up in 206 infertility patients with polycystic ovarian syndrome after laparoscopic electrocautery of the ovarian surface. Hum Reprod 1994;9:2342-9. 34. Balen A, Jacob E. A prospective study comparing unilateral and bilaterallaparoscopic ovarian diathermy in women with polycystic ovarian syndrome. Fertil Steril 1994;62:921-5. 35. Gurgan T, Kisnisci H, Yarali H, Develioglu 0, Zeyneloglu H, Aksu T. Evaluation of adhesion formation after laparoscopic treatment of polycystic ovarian disease. Fertil Steril 1991;56:1176-8. 36. Neather OGJ, Fischer R, Weise HC, Geiger-Kotzler L, Delfs T, Rudolf K. Laparoscopic electrocoagulation of the ovarian surface in infertile patients with polycystic ovarian disease. Fertil Steril1993;60:88-94. 37. Abdel Gadir A, AI Naser H, Mowafi R, Shaw R. The response of patients with polycystic ovarian disease to human menopausal gonadotropin therapy after ovarian electrocautery or luteinizing hormone releasing hormone agonist. Fertil Steril1992;57:309-13. 38. Farhi J, Soules S, Jacobs HS. Effect of laparoscopic ovarian electrocautery on ovarian response and outcome of treatment with gonadotropins in clomiphene citrate-resistant patients with polycystic ovarian syndrome. Fertil Steril1995;64:930-5. 39. Fukaya T, Murakami T, Tamura M, Watanabe T, Terada Y, Yajima A. Laser vaporization of the ovarian surface in polycystic ovarian disease results in reduced ovarian hyperstimulation and improved pregnancy rate. Am J Obstet Gynecol1995;173:119-25. 40. Luciano AA, Maier DB, Koch El, Nulsen JC, Whitman GF. A comparative study of postoperative adhesions following laser surgery by laparoscopy versus laparotomy in the rabbit model. Obstet Gynecol 1989;74:220-4.
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' ' ' 55. Dabirashrafi H. Complication of laparoscopic ovarian cauterization. Fertil Steril1989;52:878-9. 56. McComb OP. Infertility surgery: operative endoscopy, new instruments and techniques. Clin Obstet Gynecol 1989;32:564-75.
41. Lundorff P, Hahlin M, Kallfelt B, Thorburn J, Lindblom B. Adhesion formation after laparoscopic surgery in tubal pregnancy: a randomized trial versus laparotomy. Fertil Steril1991 ;55:911-5. 42. Operative Laparoscopy Study Group. Postoperative adhesion development after operative laparoscopy: evaluation at early second-look laparoscopy. Fertil Steril 1991 ;55:700-4. 43. Toaff R, Toaff ME, Peyser MR. Infertility following wedge resection of the ovaries. Am J Obstet Gynecol 1976;124:92-6. 44. Portuondo J, Melchor J, NeyroJ, Alegre A. Periovarian adhesions following ovarian wedge resection or laparoscopic biopsy. Endoscopy 1984;16:143-5. 45. Weise HC, Naether 0, Fischer R, Berger-Bispink S, Defls T. Behandlungsergebnisse mit der oberflachenkuater-isierung polyzystischer ovarien bei Sterilitatspatientinnen.Geburtshilfe Frauenheilkd 1991 ;51 :920-4. 46. Dabirshrafi H, Mohamad K, Behjatnia Y, MoghadamiTabrizi N. Adhesion formation after ovarian electrocauterization on patients with polycystic ovarian syndrome. Fertil Steril1991;55:1200-1. 47. Neather OGJ, Fischer R. Adhesion formation after laparoscopic electrocoagulation of the ovarian surface in polycystic ovary patients. Fertil Steril1993;60:95-8. 48. Rittenhouse D, Reyes J, Beingesser K, Vasquez C, Bezmalinovic Z, Sueldo C. Adhesion formation following multiple ovarian drilling with laser and electrocautery. The 48th Annual Meeting of the American Fertility Society November 2-5,1992, New Orleans, Louisiana. In the program supplement, published by the American Fertility Society, Birmingham, AL, 1992:534. 49. Gurgan T, Urman B, Aksu T, Yarali H, Develioglu 0, Kisnisci H. The effect of short intervallaparoscopic lysis of adhesions on pregnancy rate following Nd:YAG laser photocoagulation of polycystic ovaries. Obstet Gynecol 1992;80:45-7. 50. Greenblatt EM, Casper RF. Adhesion formation after laparoscopic ovarian cautery for polycystic ovarian syndrome: lack of correlation with pregnancy rate. Fertil Steril1993;60:766-70. 51. Saravelos H, Li TC. Postoperative adhesions after laparoscopic electrosurgical treatment for polycystic ovarian syndrome with the application of lnterceed to one ovary: a prospective randomized controlled study. Hum Reprod 1996;11 :992-7. 52. Pagidas K, Tulandi T. Effects of Ringer's lactate, INTERCEED(TC7) and Gore-Tex surgical membrane on postsurgical adhesion formation. Fertil Steril1992;57:199-201. 53. Sahakian V, Rodgers R, Halme J, eta/. Effects of carbon dioxide saturated normal saline and Ringer's lactate on postsurgical adhesion formation in the rabbit. Obstet Gynecol1993;82:851-3. 54. Naether OGJ. Significant reduction of adnexal adhesions following ovarian electrocautery by lavage and artificial ascites. Gynecol Endoscopy 1994;3:344.
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GYNAECOLOGY
' ' ' ' ' '
SURGICAL MANAGEMENT OF POLYCYSTIC OVARIAN SYNDROME: LAPAROSCOPIC OVARIAN DRILLING Sundus Al~Took, MD,1 Togas Tulandi, MD, FRCSC,2 1Fellow of Reproductive Endocrinology and Infertility, 2 Professor of Obstetrics and Gynaecology, Director, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, 1,2Reproductive Centre, McGill University
ABSTRACT Objective: to review the role of surgical management of polycystic ovarian syndrome (PCOS) in infertile women with special attention to /aparoscopic ovarian drilling. Design: pertinent studies and their references were identified through computer medline search. Results: to date there is no standardization of the technique of /aparoscopic ovarian drilling. However, it appears that the results are promising with a high ovulation rate ranging between 70 to 90 percent, and a pregnancy rate of 70 percent. Conclusion: clomiphene citrate remains the first line of treatment to induce ovulation in infertile women with PCOS. Laparoscopic ovarian driUing can be offered to clomiphene resistant women especiaUy to those who have also failed to respond to gonadotrophin treatment. It appears that the pregnancy rate after ovarian drilling is comparable to that of gonadotrophin therapy. However, until more complete and long term data are available, caution must be exercised when offering this type of treatment. The possible risks of the procedure are adhesion formation and premature ovarian failure. Standardization of the technique is stiU needed.
RESUME Objectif: Examiner le role du traitement chirurgical du syndrome de Stein-Leventhal (SSL, syndrome des ovaires polykystiques) chez les femmes infertiles, en insistant sur le forage laparoscopique des ovaires. Plan : On a identifie les etudes pertinentes et leurs references gri'lce aune recherche informatisee sur Medline. Resultats : A ce jour, Ia technique de forage /aparoscopique des ovaires n' a fait l' objet d' aucune normalisation. Les resultats semblent toutefois prometteurs etant donne un taux d' ovulation eleve, de 70 a90 pour cent, et un taux de grossesse de 70 pour cent. Conclusion : Le citrate de clomifene demeure le traitement privilegie pour stimuler l' ovulation chez les femmes infertiles atteintes du SSL. On peut offrir le forage /aparoscopique des ovaires aux femmes qui presentent une resistance au clomifene, en particulier ceUes qui
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' ' ' ne reagissent pas au traitement a Ia gonadotrophine. Cependant, Ia prudence est de mise au moment d' offrir ce type de traitement jusqu' a ce que nous disposions de donnees plus completes eta long terme. La formation d' adherences et Ia carence ovarienne precoce constituent les risques potentiels de cette intervention. La normalisation de Ia technique s'impose toujours.
J SOC OBSTET GYNAECOL CAN 1997;19:721-29 KEY WORDS
Polycystic ovaries, laparoscopy, ovarian drilling, ovulation induction. Received on December 17th, 1996. Revised and accepted on February 4th, 1997.
that the thick ovarian surface prevented follicles from reaching the surface and that OWR provided a mechanical passage for the follicles to ovulate. Subsequent studies showed that OWR was associated with a decrease in serum androgen levels along with changes in gonadotrophin secretion and estrogen levels.9·1l The reduction of serum androgen levels after destruction of the androgen producing stroma of the ovaries may decrease the amount of substrate available for peripheral aromatization to estrogen. This restores the feed back mechanism to the hypothalamus and the pituitary gland allowing appropriate gonadotrophin stimulation of follicular development and ovulation. At the ovarian level, the elevated intrafollicular androgen levels may inhibit granulosa cell function and follicular growth. Reduction in intra-ovarian androgen levels by OWR allows follicular development and ovulation to occur. A third mechanism that may explain the beneficial effects of OWR is the reduction that occurs in the circulating levels of inhibin following ovarian wedge resection. A secondary rise in the FSH level in combination with the reduction of local androgen levels may facilitate follicular growth and ovulation. 12 Wedge resection may also provoke an increased blood flow to the ovary allowing for the increased delivery of gonadotrophin and leading to stimulation of follicular development and escape from the tonic endocrine environment. The overall ovulation rate afrer OWR is 80 percent, but the pregnancy rate is lower, ranging from 25 13 to 86 percent. 14 This is due to the high incidence of periadnexal adhesion formation after this procedure (30-100%)Y· 17 Peri-adnexal adhesions decrease fertility and are a further cause of infertility in addition to the primary anovulatory problem. In an effort to reduce postoperative adhesion formation, a micro-surgical technique was developed. 18 In a primate model, the micro-surgical technique was associated with less adhesion formation (10% compared to 50% with macro-surgical technique).
INTRODUCTION
A symptom complex associated with anovulation, oligomenorrhoea, hirsutism, and obesity was first described by Stein and Leventhal in 1935. 1 This syndrome is currently called polycystic ovarian syndrome (PCOS), and is known to be variable in its clinical and biochemical presentations. However, chronic anovulation and hyperandrogenaemia remain the hall marks of this syndrome. Among infertile women with anovulation, approximately 75 percent will have PCOS, 2·3 and the first line of treatment is clomiphene citrate. The ovulation rate with this drug is 80 to 85 percent. 2·4•5 However, 15 to 20 percent of women remain anovulatory despite receiving incremental doses of clomiphene citrate. Furthermore, there is a discrepancy between the ovulation rate and the conception rate (40-50 percent)/·7 and the abortion rate is high (30-40 percent). This has been attributed to high serum levels of luteinizing hormone (LH) that may produce an adverse environment for the oocyte.8 Women who are clomiphene resistant can be treated with gonadotrophin or luteinizing hormone releasing hormone (LHRH), but neither treatment is universally successful. An alternative treatment is surgery. In this review, we will evaluate the surgical treatment of polycystic ovarian syndrome with special emphasis on the laparoscopic approach. OVARIAN WEDGE RESECTION
At the Michael Reese Hospital in Chicago, Irving Stein and Michael Leventhal first described a surgical treatment for PCOS or Stein Leventhal syndrome. 1 They performed a wedge resection of the ovaries of seven women, and approximately 50 to 75 percent of ovarian tissue from each ovary was removed. This ovarian wedge resection (OWR) restored menstruation in all patients and led to pregnancy in two women. They postulated
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Ethical Considerations of the New Reproductive Technologies A Report of the Combined Ethics Committee of the Canadian Fertility and Andrology Society and the Society of Obstetricians and Gynaecologists of Canada
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Ethical Considerations of the New
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' ' ' Laparoscopic OWR has also been done. McLaughin performed micro-laser ovarian wedge resection by laparoscopy in 25 consecutive patients. 19 The pregnancy rate after this procedure was 60 percent. However, 36 percent of the ovaries treated were involved with adhesions. Of these, 83 percent were mild adhesions. Kojima et al. reported laparoscopic ovarian wedge resection using an Nd:YAG laser with sapphire tips. 20
FIGU RE I
LAPAROSCOPIC OVARIAN DRILLING
The interest in laparoscopic treatment ofPCOS was renewed after Gjonnaess reported an ovulation rate of 90 percent and a pregnancy rate of 80 percent among 35 patients who underwent a new laparoscopic treatment of PCOS. 21 Using a unipolar electrode at 300 to 400 watts for two to four seconds, he created eight to 15 craters two to four mm deep on the capsule of each ovary. This technique is less invasive than ovarian wedge resection by laparotomy. Following this report, other laparoscopic techniques were described. Most involved the formation of multiple holes on the surface of the ovary either with laser or with electrocautery, procedures known as ovarian drilling. 12'21 ' 28 Other procedures including multiple ovarian punch biopsy29 are less popular. We prefer to use an insulated needle unipolar electrode (Figure 1).30 The ovary is immobilized with laparoscopic forceps and the treatment is performed using the needle electrode on both ovaries. The needle is inserted as perpendicularly as possible to the ovarian surface. A short duration of cutting current of 100 watts is used to aid the entry of the needle. The whole length of the needle (8 mm) is inserted into the ovary, and it is activated with 40 watts of coagulating current for two seconds at each point. Depending upon the size of the ovary, we created 10 to 15 punctures per ovary. Release of fluid from the underlying "follicles" is usually seen with each puncture. During the procedure, it is important to hold the ovary away from the bowel and other vital structures to avoid potential sparking and arcing from electrical current. Care must be taken to avoid the hilum of the ovary and the ovarian blood supply. At the completion of the procedure, the ovarian surface is lavaged, and 500 to 1,000 mL of Ringer's lactate solution is left in the peritoneal cavity. Several lasers including carbon dioxide (COz), Argon, KTP, and Nd:YAG laser have also been used for laparoscopic treatment of PCOS. The technique is similar to
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Laparoscopic ovarian drilling using an insulated needle electrode. Thermal injury to the ovarian surface is limited by inserting the whole length of the needle (8 mm} into the ovary. The insulated part of the needle should be inside the ovarian stroma. From Tulandi T, Operative Laparoscopy, In Te Linde's Update in Operative Gynecology, 1997. Reproduced with permission.
that of electrocautery. The use of the COzlaser is associated with smoke production that might obscure the view and require to be evacuated intermittently. Argon and KTP lasers are associated with less smoke production and allow for deeper penetration. Contrary to other lasers, the Nd:YAG laser can be delivered using a flexible fibre delivery system equipped with sapphire tips. The procedure is done with a similar contact technique to electrocautery.31 The advantage of this technique is that laser vaporization of the ovarian surface is limited. As will be discussed later, the results of laser surgery for PCOS are inferior to those of electrocautery. ENDOCRINE CHANGES AFTER LAPAROSCOPIC OVARIAN DRILLING
Hormonal changes after laparoscopic ovarian drilling are similar to those following OWR. A transient increase in the first 24 to 48 hours after surgery followed by a decrease in serum LH concentrations have been reported. 29 •32 The decrease is mainly in the LH pulse amplitude rather than the pulse frequency. Similar to that following OWR, serum androgen concentrations decrease after ovarian drilling. 23 This is due to destruction of the androgen producing ovarian stroma and drainage of the follicles which have high androgen levels.
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' ' ' Gurgan et al. compared the effectiveness ofNd:YAG laser photocoagulation with electrocauterization in 17 women with clomiphene-resistant PCOS. 35 The pregnancy rate within six months afrer surgery with electrocautery was 57 percent and after laser surgery was 40 percent. Naether et al. reported a mean pregnancy rate of 65.4 percent following cauterization versus 47.4 percent following laser vaporization. 33 Abdel Gadir et al. reported that ovarian electrocautery is as effective as gonadotrophin administration for induction of ovulation in women with PCOS resistant to clomiphene citrate. 24 In a prospective randomized trial in 88 clomiphene-resistant women with PCOS, they compared the efficacy of ovarian electrocautery, RESULTS OF LAPAROSCOPIC OVARIAN human menopausal gonadotrophin (hMG), and pure DRILLING FSH, and reported ovulation rates of 71, 71, and 6 7 percent, respectively. The cumulative pregnancy rates in six In the first report of laparoscopic ovarian drilling, the cycles were 52, 55 , and 38 percent, respectively. The spontaneous ovulation rate among 62 women was 92 21 same group of investigators subsequently compared the percent. Of 35 women desiring pregnancy, 69 percent response of 33 women with PCOS treated with hMG conceived spontaneously after surgery, while a further 11 after ovarian electrocautery or after LHRH analogue percent conceived after additional treatment with 80 of rate pregnancy treatment.37 Sixteen patients were treated with ovarian total a giving clomiphene citrate, cautery followed by hMG, and 17 were treated with percent. Subsequent studies confirmed a similar ovulaintranasal LHRH analogue and hMG. Although no diftion rate between 70 percent to 92 percent, and a pregnancy rate o£70 percent (Table l),U·1 5-17.26-2s,3o,35,36 ference was found between the two groups in regard to ovulation or pregnancy rate, this could be due to a type II error. number of cycles with mulThe TABLE 1 dominant follicles, luteal tiple OVULATION AND PREGNANCY RATES AFTER DIFFERENT SURGICAL TREATMENTS FOR SYNDROME OVARIAN POLYCYSTIC phase serum testosterone values, and the miscarriage rate were all Ovulation Technique Pregnancy Year Authors lower in the group pretreated Rate Rate % % ovarian drilling. with 2/16 12 6 9/1 1969 Kistner 56 OWR et al. reported a reducFarhi 64/150 43 NA NA 1975 OWR Buttram et a/. 38/57 67 NA NA 1975 Weinstein eta/. OWR tion in the number of ampules, 43/90 82/90 48 1981 Adashi eta/. 91 OWR daily effective dose, and duration 48/85 84/85 56 99 1989 Daniell eta/. C02+KTP* of hMG treatment in women 7/19 15/19 1990 laser* 44 79 C0 2 Keckstein eta/. who were pretreated with ovarian 0/8 5/8 0 62 1989 Huber eta/. Nd:YAG laser* electrocautery. 38 Fukaya et al. 4/10 7/10 40 1991 70 Nd:YAG laser* Gurgan eta/ reported a reduction in the inci24/35 1984 57/62 80 92 Gjonnaess Electrocoagulation* of ovarian hyperstimuladence 4/6 5/6 1987 Greenblatt eta/. 66 83 Electrocoagulation* tion syndrome (OHSS) after 11/21 17/21 52 81 Electrocoagulation* 1990 Armar eta/. drilling in 26 patients ovarian 4/7 5/7 57 71 1991 Electrocoagulation* Gurgan eta/. who had previously PCOS with 04 73/1 90/104 70 1993 Neather eta/. 86 Electrocoagulation* 30/34 70 88.2 1996 Tulandi eta/. Electrocoagulation* ** experienced OHSS.39 Because there is no standardLaparoscopy. ** Cumulative probability of conception at 12 months ization in the surgical technique
The decrease in the peripheral androgen levels leads to a decrease in their peripheral aromatization to estrogens. The endocrinological changes following ovarian electrocautery are only temporary, but are sufficient to allow ovulation and pregnancy to occur. Gjonnaess et al. reported a return to a state of chronic anovulation within two years in six of the 12 women. 26 Naether et al. found that the endocrine changes induced by laparoscopic ovarian drilling persisted for up to 72 months after surgeryY Of interest, unilateral ovarian drilling produces ovulation from both ovaries, suggesting that the effect is a systemic restoration of hypothalamic pituitary ovarian function.34
.
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' ' ' among different centres (the number of ovarian punctures, the duration of the drilling, and the power output), it is difficult to compare the results of those studies. However, it appears that the ovulation and the pregnancy rates after ovarian drilling, especially with electrocautery, are consistently high.
The most important clinical study demonstrating the benefits of laparoscopy in reduction of adhesion formation was published by Lundorff et al. 41 They conducted a randomized study comparing surgical treatment for ectopic pregnancy by laparoscopy and by laparotomy, and found that the incidence of peri-adnexal adhesions was significantly lower after laparoscopic surgery. The POTENTIAL RISKS AND Operative Laparoscopy Group reported that de novo COMPLICATIONS OF LAPAROSCOPIC adhesion formation after operative laparoscopy occurred OVARIAN DRILLING in only 12 percent of cases versus >50 percent after Apart from the general complications which can laparotomy. 41 occur during any laparoscopic surgery, there are two Adhesions are almost always formed after ovarian main potential complications associated with laparowedge resection (Table 2) .11 •15-17·43 •44 Laparoscopic ovarian scopic ovarian drilling . These are peri-adnexal adhesion drilling produces fewer adhesions than conventional ovarformation and premature ovarian failure . ian wedge resection. 17•35 JMS-4? It appears that laser produces Compared to laparotomy, laparoscopic surgery offers more adhesions than electrocautery. Rittenhouse et al. 48 special advantages for the prevention of adhesion forcompared adhesion formation following ovarian drilling mation. Operating in a closed environment prevents tiswith C02 laser versus electrocautery in a rabbit model, sue drying, a condition that may predispose to adhesion and found a significantly higher mean adhesion score in formation. Contamination with glove powder or lint is the group treated with C02 laser than in the electroless likely to occur. Because of the tamponade effect of cautery group. Using the Nd:YAG laser for ovarian the pneumoperitoneum gas, bleeding during laparoscopy drilling, Gurgan et al. found that 68 percent of the is limited and, thus, can be controlled more easily. In a patients had adhesions at the time of second-look rabbit study, adhesion formation after a standardized laser laparoscopy. 49 injury by laparoscopy was significantly less than by In an attempt to minimize postoperative adhesions, laparotomy. 40 Lysis of adhesions by laparoscopy was also oxidized regenerated cellulose (lnterceed, Johnson & associated with a marked reduction in the adhesion Johnson Medical Inc., New Brunswick, NJ) has been scores in the laparoscopy group, but not in the laparotomy used to cover the ovary after the procedure. The results, group. however, are disappointing. 50•51 Another adhesion barrier is expanded polytetrafluoroethylene (Preclude, Gore-Tex TABLE 2 surgical membrane, WL Gore & THE RATE OF ADNEXAL ADHESION AT SECOND-LOOK LAPAROSCOPY Ass. Inc., Flagstaff, AZ). HowNo. of patients Rate of Adnexal Adhesion Year Technique Authors ever, this fabric is not absorbable % and will cover the ovary perma16/16 100 Kistner 16 1969 OWR nently. Its use after ovarian 100 59/59 Buttram et ai. 173 1975 OWR drilling is not recommended. 8/19 OWR 42 Weinstein et ai. 72 1975 We feel that the best way to 7/7 100 Toaff et ai. 1976 OWR 7 decrease adhesion formation is 100 717 Adashi et ai. 90 1981 OWR to minimize any injury to the 11/12 91 Protuondo et ai. 12 1984 OWR ovarian surface. The use of an 0/8 0 Daniell et ai. 1989 C0 2 +KTP* 85 8/10 Nd:YAG laser* Gurgan et ai. 1991 10 80 insulated needle electrode serves Electrocoagulation 7/10 Weise etai. 70 39 1991 this purpose. As the insulated Electrocoagulation Gurgan et al. 1991 7 85 6n part of the needle is inside the 2/12 Electrocoagulation 16 Dabirashrafi et al. 1991 31 ovarian stroma, thermal injury to 7/26 Naether et al. 133 26 1993 Electrocoagulation the surface of the ovary is limited. 12/62 19 Neather & Fischer 199 1993 Electrocoagulation At the end of the procedure, the
I
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' ' ' peritoneal cavity is liberally irrigated to remove any debris, and Ringer's lactate solution is instilled. In a rat model, we and others52 •53 found that Ringer's lactate instillation decreased adhesion formation. Perhaps Ringer's lactate removes the newly formed fibrin exudate from the raw peritoneal surfaces. Fibrin exudate serves as a matrix for fibroblast and capillary formation. If not quickly removed by absorption or fibrinolysis, the initial fibrin deposition produces an inflammatory response, fibroblast proliferation, and adhesion formation. Naether found that instillation of normal saline solution (300 to 500 ml) afrer laparoscopic ovarian drilling for polycystic ovaries reduced adhesion formation. 54 Laparoscopic ovarian drilling is associated with a high pregnancy rate, and lysis of adhesions does not seem to improve the pregnancy rate. Another potential complication of laparoscopic ovarian drilling is ovarian failure. Accordingly, excessive ovarian drilling and electrocoagulation of the ovarian hilum and the ovarian blood supply should be avoided. 55 Currently, there is no standardization of the procedure. However, we feel that more than 20 punctures per ovary is excessive. Destruction of the ovarian androgenproducing stroma is associated with the destruction of nearby follicular units, but there has been no long term study undertaken to evaluate the effect of ovarian drilling or ovarian wedge resection on the age of menopause. McComb et al. reported significantly decreased concentration of ovarian follicles in a rabbit model subjected to laser wedge resection when compared with ovaries treated by electrosurgical wedge resection. 56
largest study published, the incidence of adnexal adhesions was 19 percent. It seems that the use oflaser is associated with more adhesion formation and lower pregnancy rates compared to electrocautery; perhaps the laser produces more surface injury than the insulated needle electrode. To date, there is no standardization of the technique. In our clinical experience, 10 to 15 ovarian punctures per ovary (8 mm depth) at 40 wat?> for two seconds produces promising pregnancy rates. We recommend the use of an insulated needle cautery, making less than 20 punctures, liberal irrigation of the peritoneal cavity, and the instillation of large amounts of crystalloid solution at the conclusion of the procedure. Until more complete and long term data are available, caution must be exercised when offering this type of treatment, and complete information about the possible adverse effects should be provided to the patient.
CONCLUSIONS
6.
REFERENCES 1, 2.
3.
4.
5.
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Clomiphene citrate remains the first line of treatment to induce ovulation in infertile women with PCOS. Those who do not respond to up to 200 mg of clomiphene citrate daily can be treated with gonadotrophin. Laparoscopic ovarian drilling can be offered to clomiphene-resistant women, especially to those who have also failed to respond to gonadotrophin treatment. The pregnancy rate after ovarian drilling is comparable to that of gonadotrophin therapy. The mechanism of action is not known exactly but it appears to be mediated by the decrease in intraovarian androgen levels. Using a variety of techniques with different electrical wattages, duration of thermal injury, and number of ovarian punctures, the incidence of peri-ovarian adhesions has been reported to be between 10.8 and 100 percent . In the
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New mlmitrex® Nasal Spray* starts to work in half the time of our own mlmitrex® tablets I** •15 minute onset of action vs. 30 minutes with Imitrex® tablets1 • Efficacy similiar to Imitrex® tablets 1t • Generally well toleratedHtt • Easy to use, convenient single dose devicettt
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29. Sumioki H, Utsumomyiya K, Korenaga M, Kadota T. The effect of laparoscopic multiple punch resection of the ovary on the hypothalamic-pituitary axis in polycystic ovarian syndrome. Fertil Steril 1988;50: 567-72. 30. Tulandi T, Watkin K, Tan SL. Reproductive performance and three dimensional ultrasound volume determination of polycystic ovaries following laparoscopic ovarian drilling. lnt J Fertil (in press). 31. Frishman GN, Kratka SA, Maier DB, Luciano AA. Comparative analysis of adhesion reduction, tissue effects and incising characteristics of electrosurgery, C02 laser, Nd:YAG laser at operative laparoscopy. 47th Annual Meeting of the American Fertility Society, October 21-24, New Orleans, abst 0-014. 32. Sakata M, Tasaka K, Kurachi H, Terakawa N, Miyake A, Tanizawa 0. Changes of bioactive luteinizing hormone after laparoscopic ovarian cautery in patients with polycystic ovarian syndrome. Fertil Steril1990;53: 610-3. 33. Naether OGJ, Baukloh V, Fischer R, Kowalczyk T. Long term follow up in 206 infertility patients with polycystic ovarian syndrome after laparoscopic electrocautery of the ovarian surface. Hum Reprod 1994;9:2342-9. 34. Balen A, Jacob E. A prospective study comparing unilateral and bilaterallaparoscopic ovarian diathermy in women with polycystic ovarian syndrome. Fertil Steril 1994;62:921-5. 35. Gurgan T, Kisnisci H, Yarali H, Develioglu 0, Zeyneloglu H, Aksu T. Evaluation of adhesion formation after laparoscopic treatment of polycystic ovarian disease. Fertil Steril 1991;56:1176-8. 36. Neather OGJ, Fischer R, Weise HC, Geiger-Kotzler L, Delfs T, Rudolf K. Laparoscopic electrocoagulation of the ovarian surface in infertile patients with polycystic ovarian disease. Fertil Steril1993;60:88-94. 37. Abdel Gadir A, AI Naser H, Mowafi R, Shaw R. The response of patients with polycystic ovarian disease to human menopausal gonadotropin therapy after ovarian electrocautery or luteinizing hormone releasing hormone agonist. Fertil Steril1992;57:309-13. 38. Farhi J, Soules S, Jacobs HS. Effect of laparoscopic ovarian electrocautery on ovarian response and outcome of treatment with gonadotropins in clomiphene citrate-resistant patients with polycystic ovarian syndrome. Fertil Steril1995;64:930-5. 39. Fukaya T, Murakami T, Tamura M, Watanabe T, Terada Y, Yajima A. Laser vaporization of the ovarian surface in polycystic ovarian disease results in reduced ovarian hyperstimulation and improved pregnancy rate. Am J Obstet Gynecol1995;173:119-25. 40. Luciano AA, Maier DB, Koch El, Nulsen JC, Whitman GF. A comparative study of postoperative adhesions following laser surgery by laparoscopy versus laparotomy in the rabbit model. Obstet Gynecol 1989;74:220-4.
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