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OVARIAN DRILLING: A MISSED OPPORTUNITY FOR INFERTILE PCO PATIENTS?

Bruce I. Rose PhD, MD

Key Words: polycystic ovarian disease, laparoscopic surgery, ovarian drilling

Introduction

Bilateral ovarian wedge resection, a surgical treatment of polycystic ovarian syndrome, has appropriately decreased in popularity over the last decades. This decline is due to the availability of effective medical therapies and the potential for severe adhesion formation even when microsurgical techniques are used. However, with the wide availability of laparoscopy and surgeons with advanced laparoscopic skills, laparoscopic techniques (ovarian drilling) for treating polycystic ovarian syndrome have been developed.

Because of the recent publication of two series of greater than 200 patients each, we can now begin to better understand both the effectiveness and the adverse consequences of this surgery.1,2 Although we can lament the lack of large scale controlled studies on ovarian drilling and our inability to understand why this surgery works as well as it does,3 I believe that it is now inappropriate to deny this surgery as a treatment option to patients.

We will endeavor to review the history of ovarian drilling, review the consequences of ovarian drilling, describe ovarian drilling in detail focusing on avoiding adhesion formation, and finally move to suggestions for appropriate patient selection.

Background

Polycystic ovarian disease remains a controversial entity with overlapping clinical, endocrine and morphological definitions as well as fragmentary and conflicting underlying endocrine mechanisms.4 Medical treatment is occasionally directed at correcting a well defined endocrinopathy, but generally it is targeted at preventing complications of long term unopposed estrogen exposure, cosmetically improving hirsutism, or achieving pregnancy without impacting on the underlying disease entity. The primary challenge of medical therapy lies in helping patients attain pregnancy because patients exhibit varied responses to the pharmacological tools available. Bilateral wedge resection of the ovaries was done as early as 1935 by Stein and Leventhal. The procedure was slow to enter mainstream gynecology. It was never evaluated in a controlled study, but increased in popularity as surgeons developed more experience with it. No explanation of its effectiveness was ever advanced which was able to survive scientific scrutiny over time. Most patients ovulated, many achieved pregnancy, and in some the effect of the procedure was long lasting. The procedure was largely abandoned with the realization that the development of severe adhesion formation was a common complication and as more gynecologists developed facility with inducing ovulation and achieving pregnancy by medical means. The risk benefit comparison between major abdominal surgery with a high incidence of adhesion formation and either clomiphene citrate or a more complicated gonadotropin ovulation induction was easy to make.

Many different techniques for laparoscopic treatment of polycystic ovarian disease have been described. All are attempts to adapt bilateral wedge resection to a laparoscopic setting. They include bivalving the ovary on its longitudinal axis,5 taking multiple biopsies along the longitudinal axis of the ovaries laparoscopically,6 and dissecting out multiple subcapsular cysts.7 However, the predominant technique in the literature involves making multiple holes in the surface of both ovaries using either a laser or electrocautery. GjËnnaess was one of the first to describe this procedure using electrocautery in the literature.1 His technique and derivatives of it constitute the bulk of the cases in the published literature and therefore the consequences of this particular technique are best understood. I will refer to it as ovarian drilling, although it has also been referred to as ovarian diathermy, ovarian cautery, ovarian electrocautery, ovarian laser vaporization, selective follicular reduction, laser photocoagulation, laparoscopic argon laser capsule drilling, multiple punch resection, LEOS (laparoscopic electrocauterization of the ovarian surface), and likely other names. I prefer the electrosurgical approach over the use of any laser. Although it is likely that laser techniques work as well as electrosurgical, the equipment is more complicated and the variations of the GjËnnaess-derived techniques described are more time consuming than with the electrosurgical approach.

Results of ovarian drilling

Although many small series demonstrate high ovulation and pregnancy rates, I am aware of only 2 different series containing more than 100 patients (Table 1).1,2 Although patient selection in these two series was quite different, presumptive spontaneous ovulation rates and pregnancy rates were quite similar (ovulation rates of 82 and 92%; pregnancy rates of 69 and 70%). In the Naether, et al series,2 patients were selected on the basis of poor or no response to ovulation inducing drugs. Most first pregnancies were conceived utilizing ovulation inducing drugs (80/145). In GjËnnaess's series of patients,1 ovarian drilling was used as a primary therapy for polycystic ovarian syndrome. In patients without non-ovulatory infertility factors, the spontaneous pregnancy rate was 84%. If other problems were present, the pregnancy rate was 36%. Both series reported significant numbers of spontaneous second pregnancies. Pregnancies and ovulation after ovarian drilling were more likely to occur in non clomiphene resistant patients than in clomiphine resistant patients. However, new responsiveness to clomiphene or improved response to gonadotropins after ovarian drilling was common.

From an endocrinological basis, most investigators have found that ovarian drilling results in decreased LH levels, decreased androgen levels, and increased FSH levels when postoperative levels are compared to preoperative levels in the same patient.8,9,10,11 Clinical androgenic effects of polycystic ovarian syndrome improve after ovarian drilling.2 Serum insulin levels and levels of insulin growth factor binding protein-1 do not change after surgery.12 The impact of ovarian drilling appears to be long lasting for many patients. In GjËnnaess's large cohort of women, of the patients who ovulated in response to ovarian drilling and were not lost to follow-up, only 3 to 4% stopped ovulating in each subsequent year.1 For example, of 51 responders followed for 5 years, only 2 stopped ovulating in the fifth year. Naether, et al., followed 206 patients for up to 72 months and reported that many patients had persistent normalization of cycle length; 70% of cycles evaluated after 72 months were ovulatory.2

Surgical procedure

The surgeon should be skilled in operative laparoscopy. The Society of Reproductive Surgeons has appropriately classified this as a level 2 laparoscopic procedure.13 Inadequate surgical skills have the potential of leading to severe morbidity. The key is your ability to control the operative field. Slippage of instruments could lead to devastating bowel or large vessel injury. Surgical technique is also related to the likelihood of severe adhesion formation. Laparoscopy is performed in appropriately selected patients. Two 5 mm ancillary ports are placed lateral to the rectus muscles approximately 3 cm above the symphysis pubis. The bowel is mobilized from the operative field. Trying to operate around bowel that is partially stuck to the pelvic side-wall or is unable to be completely moved out of the pelvis increases the likelihood of bowel injury. Pregnancy prognosis after this procedure is impaired in patients who have non-ovulatory in addition to ovulatory causes for their infertility. If additional operative procedures are performed for infertility, then an early second look operative laparoscopy may be desirable to enhance prognosis. Approximately 6 to 12 holes or defects are made in each ovary depending on ovarian size. As few as 4 holes in one of the two ovaries can result in ovulatory cycles,14 but currently most investigators treat each ovary with at least 8 holes and with a larger number of holes directed to the more severe cases. Holes should be uniformly distributed over the surface of the ovary. However, avoid the hilum to avoid bleeding problems as well as potentially damaging the viability of the ovary. Also avoid placing any holes on the part of the ovary that sits in the ovarian fossa. Placement of defects here can result adhesions of the ovary to the pelvic side wall.

I use unipolar current with a 5 mm cone tip probe that comes to a point. I use a Valleylab Force 2 electrosurgical unit (Valleylab, Inc., Boulder, CO) at a setting of 120 W, cutting blend 1. Ideally one wishes to have a very high power density at the tip of your instrument so that it will rapidly enter into the ovary. This increases the safety of the procedure by preventing the instrument from slipping after the current has been applied. Slipping will result in cauterization of more of the surface area of the ovary than is required and increases the risk of adhesion formation. Slippage off the ovary could also potentially damage the tube, the bowel, or large blood vessels. Greenblatt and Casper use the tip of a unipolar scissors and this may be the most suitable readily available instrument to most surgeons.9 Armar, et al uses an instrument optimally designed for this procedure.10 It has a needle tip on the end of a blunt probe. The tip enhamces entry into the ovary and the probe coagulates stroma.

Prior to placement of these holes, the ovary must be stabilized. The electrocautery instrument and the ovarian surface need to positioned perpendicular to one another. I prefer to stabilize the ovary as much as possible without grasping it, because grasping the adenexa increases the potential for damage to the ovary and subsequent adhesion formation to the site of damage. The ovary is stabilized by using a probe and irrigator to optimally position the ovary. The probe on the side of the ovary to fixes the ovary against the pelvic side wall. Many investigators position the ovary by grasping the utero-ovarian ligament with a non-traumatic grasper. Naether, et al.22 directly grasps the ovary by placing tips of the grasper in two adjacent holes in the ovarian surface. When care is taken to avoid tearing the ovary, this technique can provide a high level of control. After the ovarian cortex is pierced, current is applied for 2 to 4 seconds. Excessive heat damage to the cortex may increase the likelihood of adhesion formation. The ovarian surface should be intermittently cooled with irrigation solution. Damage to the stroma appears to be as effective as damage to the cortex in causing ovulation.15 Therefore it is preferable to trade off coagulation inside the ovary for that on the surface.

Irrigation should also be used to decrease carbon particle adherence to the ovary which potentially are a nidus for adhesion formation. We irrigate with warmed Lactated Ringer's solution. A effort is made to remove all free floating carbon particles and tissue debris with multiple liter irrigation and aspiration. Adhesion formation between damaged surfaces and other surfaces requires that these surfaces remain in contact with one another. For this reason, in manner of Harry Reich,16 we leave behind at least one liter of fluid in the abdomen and post-operatively encourage normal ambulation. Naether showed that leaving 300-500 ml of Lactated Ringers decreased adhesion formation by 50% (from 22% to 11% based on unselected second look laparoscopies done 2 to 14 days after the original procedure) and the resulting adhesions were very mild in character.17 This technique of leaving large volumes of fluid in the abdomen after surgery probably impacts on adhesion formation for the first day or two after surgery.18 Most adhesion formation initially occurs hours after surgery. Late adhesion formation is only likely to occur to those areas of more extensive injury and thus on a theoretical basis, should not occur with this procedure. The use of Interceed (Ethicon, Inc., Summerville, NJ) has been shown to be ineffective in preventing adhesions in this setting.19 Some patients leak fluid from their incisions for a day after surgery. With appropriate expectations, this presents little problem to either the patient or the recovery room. Post-operatively, patients need to be observed to confirm adequate urinary function since delayed function (within 12 hours) occasionally appears when this volume of fluid is left behind. I also close the fascia of my umbilical incision to prevent herniation of the bowel through the incision. Since the bowel floats close to the umbilical wound, it is more likely to herniate in response to an increase in abdominal pressure than when no fluid is left in the abdomen.

Patient Selection

Table 2 contains suggestions on which patients should be offered this procedure. It is based on the published literature and my clinical experience. For example, I recommend ovarian drilling to those patients who fail to ovulate on adequate doses of clomiphine citrate and who require a laparoscopy as part of their ongoing infertility evaluation. If they have already had a laparoscopy, I feel that they are entitled to know that this procedure may work as well for them as gonadotropin therapy. This class of patients satisfies the entry criteria of many of the papers in the literature. Gidar, et al's randomized study suggests that ovarian drilling may be as efficacious as gonadotropin therapy in achieving pregnancy in this class of patients.20 It may also decrease that patient's potential for miscarriage, multiple gestation, and the ovarian hyperstimulation syndrome.20,21,22 It will likely decrease the cost of her infertility therapy. On the down-side, it may not work at all and it may cause pelvic adhesions. Those adhesions can be minimized with appropriate surgical technique and gonadotropins can be used if the surgery fails (and can compensate for low grade adhesions). An important area of current inquiry is to try to characterize that subset of patients which does not respond to ovarian drilling. Normal or near normal weight women respond better than obese women.1 Patients with an elevated preoperative LH level respond better than those with a normal level. Non-smokers respond much better than smokers.8,22 Pregnancy rates after ovarian drilling drop significantly after age 35.2 Pregnancy rates are much lower in patients with identifiable subfertility factors in addition to ovulatory dysfunction.1

Given the limitations of the literature, it is desirable for surgeons to track those patients in whom they perform this procedure over time. There are many opportunities for research that can contribute to our understanding of ovarian drilling. For example, does the polycystic ovarian syndrome variant, HAIR-AN syndrome respond to ovarian drilling? Given the provocative results of Naether, et al,2 is there a subset of hirsute patients who can best be treated with ovarian drilling?

Surgeon Selection

Not every gynecologist should be doing this procedure. Sufficient operative laparoscopic experience is one prerequisite. Another is to be able to diagnose and treat the occasional endocrinopathy that presents as polycystic ovarian disease. Finally, it is easier to appropriately counsel patients about the risks and benefits of surgical therapy compared to gonadotropin therapy if your practice offers both therapies. Although gonadotropins are hard to use in PCO patients, it is a very effective therapy. Our patients deserve an opportunity to truly make a choice.

Summary

Ovarian drilling is a surgical treatment for polycystic ovarian disease. We don't understand why it works as well as it does. However, at least 600 patients treated with this modality have been described in the literature. The data is sufficiently strong that we should be offering it to certain groups of patients as an optional method for their treatment of their infertility and polycystic ovarian syndrome.

References

1. Gjonnaess H: Ovarian Electrocautery in the Treatment of Women with Polycystic Ovary Syndrome (PCOS). Acta Obstet Gynecol Scand 1994: 73;407-412

2. Naether O, Baukloh V, Fisher R, et al.: Long-Term Follow-Up in 206 Infertility Patients with Polycystic Ovarian Syndrome After Laparoscopic Electrocautery of the Ovarian Surface. Human Reproduction 1994: 9;2341-2349

3.Donesky BW, Adashi EY: Surgically induced ovulation in the polycystic ovary syndrome: wedge resection revisited in the age of laparoscopy. Fertil Steril 1995: 63;439-463

4. Vaclav I, Bruno L: Pathophysiology of Polycystic Ovarian Disease: New Insights. Human Reproduction 1991: 6;1025-1029

5. Ostrzenski A: Endoscopic Carbon Dioxide Laser Ovarian Wedge Resection in Resistant Polycystic Ovarian Disease. Int J Fertil 1992: 37;295-299

6. Campo S, Felli A, Lamanna MA, et al.: Endocrine Changes and Clinical Outcome After Laparoscopic Ovarian Resection in Women with Polycystic Ovaries. Human Reproduction 1993: 8;359-363

7. Utsunomiya T, Sumioki H, Taniguchi I: Hormonal and Clinical Effects of Multifollicular Puncture and Resection on the Ovaries of Polycystic Ovary Syndrome. Horm Res 1990: 33;35-39

8. Gadir AA, Khatim MS, Alnaser HMI, et al.: Ovarian Electrocautery: Responders versus Nonresponders. Gynecol Endocrinol 1993: 7;43-48

9. Greenblatt E, Casper R: Endocrine Changes After Laparoscopic Ovarian Cautery in Polycystic Ovarian Syndrome. Am J Obstet Gynecol 1987: 156;279-285

10. Armar N, McGarrigle H, Honour J, et al.: Laparoscopic Ovarian Diathermy in the Management of Anovulatory Infertility in Women with Polycystic Ovaries: Endocrine Changes and Clinical Outcome. Fertil Steril 1990: 53;45-49

11. Rossmanith W, Keckstein J, Spatzier K, et al.: The Impact of Ovarian Laser Surgery on the Gonadotrophin Secretion in Women with Polycystic Ovarian Disease. Clinical Endocrinology 1991: 34;223-230

12. Tiitinen A, Tenhunen A, Seppala M: Ovarian Electrocauterization Causes LH-Regulated but not Insulin-Regulated Endocrine Changes. Clinical Endocrinology 1993: 39;181-184

13. Society of Reproductive Surgeons, American Fertility Society: Guidelines for attaining privileges in gynecologic operative endoscopy. Fertil Steril 1994: 62;1118-1119

14. Balen A, Jacobs H: A Prospective Study Comparing Unilateral and Bilateral Laparoscopic Ovarian Diathermy in Women with the Polycystic Ovary Syndrome. Fertil Steril 1994: 62;921-924

15. Heylen S, Puttemans P, Brosens I: Polycystic Ovarian Disease Treated by Laparoscopic Argon Laser Capsule Drilling: Comparison of Vaporization Versus Perforation Technique. Human Reproduction 1994: 9;1038-1042

16. Reich H: New Techniques in Advanced Laparoscopic Surgery. In Balliere's Clinical Obstetrics and Gynecology. Sutton C, editor. Philadelphia, PA, WB Saunders, 1989, 655-681

17. Naether O, Fischer R: Adhesion Formation After Laparoscopic Electrocoagulation of the Ovarian Surface in Polycystic Ovary Patients. Fertil Steril 1993: 60;95-98

18. Rose BI, MacNeill C, Larrain R, et al., Abdominal Instillation of High-Mollectular-Weight Dextran or Lactated Ringer's Solution After Laparoscopic Surgery: A Randomized Comparison of the Effect on Weight Change. J Reproductive Medicine. 1991: 36;339-342

19. Greenblatt E, Casper R: Adhesion Formation After Laparoscopic Ovarian Cautery for Polycystic Ovarian Syndrome: Lack of Correlation with Pregnancy Rate. Fertil Steril 1993: 60;766-770

20. Gadir A, Mowafi R, Alnaser H, et al.: Ovarian Electrocautery Versus Human Menopausal Gonadotrophins and Pure Follicle Stimulating Hormone Therapy in the Treatment of Patients with Polycystic Ovarian Disease. Clinical Endocrinology 1990: 33;585-592

21. Gadir A, Alnaser H, Mowafi R, et al.: The Response of Patients with Polycystic Ovarian Disease to Human Menopausal Gonadotropin Therapy After Ovarian Electrocautery or a Luteinizing Hormone-Releasing Hormone Agonist. Fertil Steril 1992: 57;309-313

22. Naether O, Fischer R, Weise H, et al.:Laparoscopic Electrocoagulation of the Ovarian Surface in Infertile Patients with Polycystic Ovarian Disease. Fertil Steril 1993: 60;88-94

23. Balen A, Tan S, MacDougall J, et al.: Miscarriage Rates Following In-Vitro Fertilization are Increased in Women with Polycystic Ovaries and Reduced by Pituitary Desensitization with Buserelin. Human Reproduction 1993: 8;959-964

 

 

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