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Treatment of polycystic ovary disease with laparoscopic low-watt bipolar electrocoagulation of the ovaries
August 1996, Vol. 3, No. 4
The Journal of the American Association of Gynecologic Laparoscopists
Treatment of Polycystic Ovary Disease with Laparoscopic Low-Watt Bipolar Electrocoagulation of the Ovaries Rohinee N. Merchant, M.D., D.G.O.
Abstract Study Objective. To assess the efficacy of laparoscopic low-watt bipolar electrocoagulation of the ovaries in women with polycystic ovary disease (PCOD). Design. Prospective case series. Setting. Hospital-based infertility clinic. Patients. Seventy-four consecutive infertile women with PCOD resistant to conventional ovulation-induction regimens. Interventions. Laparoscopic bipolar low-watt electrocoagulation of the ovarian surface (25 W for 5-12 sec/cyst). Measurements and Main Results. Postoperative follow-up ranged from 18 months to 7 years. Menstrual rhythm returned to normal in all 74 women. All 40 women in whom infertility was solely due to anovulation eventually conceived. Overall, 62 (84%) of the 74 women conceived, 42 spontaneously after surgery and 20 after supplementation with clomiphene. These 62 women had a total of 93 pregnancies: 79 singleton live births, 4 sets of twins, and 10 miscarriages. Twenty-five women conceived twice and three conceived three times. At second-look laparoscopy or cesarean section in 20 women, fine stringlike adhesions on the ovaries were found in 2. Conclusion. Laparoscopic low-watt bipolar electrocoagulation of the ovaries is an effective treatment for women with PCOD who fail medical therapy.
Treatment of polycystic ovary disease (PCOD) is often difficult. A variety of medical therapies have been attempted, but with limited success. Treatment with clomiphene citrate (CC) is reported to result in an ovulation rate of about 60% and a pregnancy rate of about 30%. 1Gonadotropin and gonadotropin-releasing hormone (GnRH) have similar reported success rates, but have
drawbacks such as high cost, need for close monitoring, and the possibility of hyperstimulation syndrome?' 3 Surgical treatment of PCOD initially consisted of wedge resection of the ovaries.4 It did result in ovulation and pregnancy, but has been abandoned since it requires a major procedure (laparotomy), the benefits are short lived, and it carries the risk of postoperative adhesions.5
From the Department of Obstetrics and Gynecology, Dr. Merchant's Hospital; and Prof. Emeritus, Department of Obstetrics and Gynecology, B.Y.L. Nair Hospital and T.N. Medical College, University of Bombay, Bombay, India. Address reprint requests to Rohinee N. Merchant, M.D., 20 Milldam Road, Acton, MA 01720.
503
Low-Watt Bipolar Electrocoagulation of the Ovaries Merchant
With the advent of less invasive laparoscopic surgery, endoscopic electrocoagulation of the ovarian cysts was first described in 1984. 6 Since then, several reports of laparoscopic treatment have appeared, including unipolar electrosurgery]-9 multiple ovarian biopsies,10,11 mad laser vaporization. 1~14These techniques are effective, but sometimes have limitations, such as the risk of bleeding and postoperative adhesions with multiple ovarian biopsies, relatively high cost and nonavailability in developing countries for laser vaporization, and the risk of overtreatment and consequent ovarian atrophy with unipolar coagulation. A new technique of laparoscopic electrocoagulation of the ovaries uses low-watt bipolar current, and has been performed successfully for a number of years. To the best of my knowledge, the literature contains no reports on the use of low-watt bipolar electrosurgery in the treatment of PCOD. Materials and Methods Patients Subjects in this prospective study were 74 consecutive women who were treated between January 1988 and December 1992 for infertility due to PCOD
(Table 1). In each patient, the diagnosis of PCOD was made by the presence of all of four criteria. 1. Chronic anovulation associated with oligomenorrhea or amenorrhea, with or without hirsutism. Anovulation was established on the basis of endometrial biopsy (which was performed on every patient), ultrasonography, basal body temperature records, and evaluation of cervical mucus. 2. Typical appearance of ovaries on ultrasonography; that is, many tiny cysts studded all along the periphery. 3. Elevated basal levels of serum luteinizing hormone (LH) with normal or decreased levels of follicle-stimulating hormone (FSH), and normal or high serum testosterone levels. 4. Typical appearance at laparoscopy of enlarged ovaries with thick, white capsules. Before enrolling in the study, all 74 women had been unsuccessfully treated with incremental doses of CC alone 50 to 150 mg/day for 5 days for 6 to 18 months. In addition, some of the women failed other ovulation-induction regimens. Twenty failed to conceive with CC plus human chorionic gonadotropin (hCG) for an additional 3 to 8 cycles; eight failed CC plus betamethasone for an additional 3 cycles; six
TABLE 1. Patient Characteristics and Preoperative Clinical Profiles
Variable Age at time of surgery (yrs) Evidence of anovulation Interval of menstrual cycle (days) 25-45 46-120 >120 (secondary amenorrhea) Hirsutism Mild to moderate Severe (with clitoromegaly) Duration of unsuccessful treatment (mo) 8-18 >18 Duration of infertility (yrs) Primary infertility Secondary infertility Preoperative hormone levels Basal LH (mlU/ml) LH:FSH ratio Prolactin (ng/ml) Testosterone (ng/m])
No. of Women
Mean (+ SD)
Range
74 74
26.4 (+ 3.9)
18-34
52 15 7
35.5 (_+ 4.0) 60.6 (_+ 20.1 )
25-45 47-105
21 53
12.2 (_+ 3.4) 41.3 (_+ 18.5)
8-18 24-96
68 6
5.0 (-+ 3.4) 4.2 (___1.8)
1.5-16.0 2.6-6.0
67 67 67 64
16.8 (+_ 8.6) 3.4 (_+ 2.3) 14.2 (_+ 9.8) 0.99 (_+ 0.4)
1.9-42.0 1.14-16.8 3.2-62 0.6-2.9
40 4
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failed CC plus hCG plus human menopausal gonadotropin for an additional 4 cycles; and four failed in vitro fertilization. To facilitate analysis of results, the women were classified into four groups based on reasons for infertility. In group 1 (40 women) the sole reason for infertility was anovulation due to PCOD. The 12 women in group 2 suffered from pelvic inflammatory disease (PID) in addition to anovulation due to PCOD. In group 3 six women had mild to moderate endometriosis over and above anovulation due to PCOD. Group 4 consisted of 16 patients with anovulation due to PCOD, and their partners had subfertility factors.
Operative Technique With the patient under general anesthesia, a threepuncture technique was employed. A 10-ram operative laparoscope was passed through a subumbilical incision. The pelvis was evaluated with a probe introduced through a 5-mm cannula passed through a second puncture. The diagnosis of PCOD was confirmed, and tubal patency was tested. Finally, a bipolar spot coagulation probe (Elmed Inc., Addision, IL) or a bipolar suction-coagulator was passed through a third puncture for treating the ovaries. Each ovary was stabilized by grasping the utero-ovarian ligament with an atraumatic forceps. The bipolar spot coagulator was pressed at right angles to the surface of a cyst and a current of 25 W (50 Hz with a setting at 40) was passed for 5 to 12 seconds until the capsule was penetrated and cyst fluid welled out. As many cysts as were visible and accessible, but lying away from the hilum of the ovary, were coagulated. A distance of 7 to 15 mm was left uncoagulated between two adjacent treatment points. The number of cysts treated in this manner in each ovary averaged from 6 to 12, depending on the size of the ovary. When the ovarian capsule was very thick and could not be penetrated, it was punctured with a needle before electrocoagulation. The procedure was completed by a saline wash followed by instillation of 300 to 500 ml heparinized saline. At the end of the procedure, each ovary was left studded with several 4- to 5-ram irregular slits representing cysts that had been treated (Figure 1). The six patients who had endometriosis in addition to PCOD also underwent conservative treatment at the same time with adhesiolysis, coagulation of superficial endometriotic lesions with bipolar current, or both. In four women who had secondary amenorrhea, an
FIGURE 1. Appearance of the ovary at laparoscopy after low-watt bipolar electrocoagulation. A bipolar suctioncoagulator is seen at the left edge. The ovarian capsule is thick and white, and has several irregularly shaped slits representing cysts that have been treated.
ovarian biopsy was performed to rule out other causes of amenorrhea besides PCOD, such as functioning tumors of the ovary. Mild oozing occurred at the biopsy site and was controlled with bipolar coagulation. All four biopsy specimens were negative. There were no intraoperative complications. All women were discharged on the same day as surgery.
Postoperative Management The preoperative evaluation for ovulation in each subject consisted of endometrial biopsy, basal body temperature records, ultrasonography, and testing of cervical mucus. Postoperatively, the same procedures were performed, monitoring ovarian follicles by ultrasound; an endometrial biopsy was deliberately avoided for fear of disturbing a possible pregnancy. Serum midluteal progesterone assays were performed if the basal body temperature raised the possibility of luteal phase deficiency, if there was no evidence of follicular rupture on ultrasound, or if the first pregnancy ended in a first-trimester miscarriage. After laparoscopic treatment, patients were advised to have coitus around the time of ovulation. Three women received intrauterine insemination of a washed sample of their husband's semen and another one received artificial insemination of donor semen during the cycle after surgery. Women who did not ovulate
505
Low-Watt Bipolar ElectrocoaguJation of the Ovaries Merchant
ond or third cycle. Thus, spontaneous ovulation occurred in 65 (88%) of 74 women within 3 months of surgery. The temperature records of the remaining nine women (12%) were biphasic, but the luteal phase was defective as evidenced by low serum progesterone levels (<10 ng/ml); however, these women now responded to CC 50 mg/day for 5 days, although they were resistant earlier. Thus, ovulatory cycles were established in all 74 women (100%) by the sixth postoperative month (Table 2).
spontaneously within 3 months of surgery or conceive within three cycles, or whose first pregnancy terminated in a first-trimester miscarriage were given CC 50 mg/day for 5 days. In the first six procedures, only four to six cysts in each ovary were electrocoagulated. These women had biphasic temperature records, but in four, the midluteal progesterone levels were less than 10 ng/ml. They responded to CC and conceived thereafter. At this point in the study, I concluded that spontaneous ovulation and conception might be improved by increasing the number of cysts that were treated. Consequently, for the remainder of the study, 6 to 12 cysts were treated in each ovary.
Pregnancy Sixty-two women (84%) conceived 42 (57%) spontaneously within three cycles and 20 (27%) after supplementation with CC. All of these patients had not responded to CC before surgery. All 40 women with anovulation as the only factor responsible for infertilit3, (group 1) conceived within six cycles after ovarian electrocoagulation, with 32 conceiving spontaneously within 3 months, and 8 between the fourth and sixth cycles after CC supplementation. In group 2 (anovulation and pelvic inflammatory disease), six women conceived within 3 months, two between 4 and 6 months, and two 14 months after surgery. Two women in this group were lost to follow-up after 8 months, although they were ovulating until the time of last visit. All six women in group 3 (anovulation and endometriosis) conceived between 8 and 14 months after surgery, which was concomitant with improvement of their pelvic pathology. They all received CC before becoming pregnant. In group 4 (anovulation and male infertility factors), four women conceived within three cycles, one with artificial insemination using donor
Results
Return of Menstrual Regularity Establishment of a regular monthly flow (interval 27-30 days) occurred postoperatively in all 74 women. In seven women who had secondary amenorrhea, menstrual flow occurred within 48 to 72 hours of ovarian electrocoagulation. In the remaining 67 women who had oligomenorrhea, it occurred within 6 to 20 days. The basal body temperatures in all women in whom it remained above 97 ~ F preoperatively now dipped to lower ranges during the follicular phase, and a biphasic pattern was established. Return of Ovulation Fifty-three women (72%) ovulated between 6 and 27 days (mean + SD 13 + 4.2 days) after electrocoagulation. Another 12 (16%) ovulated during the sec-
TABLE 2. Onset of Ovulation and Pregnancy
Group 1, 2, 3, 4,
A only A + PID A + endometriosis A + subfertile partner Total no. (%)
No. of Women
Onset of Ovulation <3 Mo. 4 - 6 Mo. a
Onset of First Pregnancy <3 Mo. 4 - 6 Mo. a >6 Mo. a
No. Lost to Follow-up or Did Not Conceive
40 12 6 16 74 (100)
37 10 3 15 65 (88)
32 6 -4 42 (57)
-2 -10 12 (16)
3 2 3 1 9 (12)
apatients received clomiphene citrate 50 mg/day for 5 days. A = anovulation due to PCOD; PID = pelvic inflammatory disease. Ovulation rates: spontaneous 88%; total 100%. Pregnancy rates: spontaneous 57%; total 84%.
506
8 2 -2 12 (16)
-2 6 -8 (11 )
August 1996, Vd. 3, No. 4
The Journal of the American Association of Gynecologic Laparoscopists
semen and three with intrauterine insemination of washed semen from the husbands. Two other women in this group responded to CC and conceived between 3 and 6 months postoperatively. The remaining 10 women in group 4 continued to ovulate until the date of last follow-up but could not become pregnant because of their partner's subfertility. The outcomes of the first pregnancies among 62 women were as follows. Of 42 women who conceived within 3 months, 38 delivered full-term singleton live births and 4 had a first-trimester miscarriage. Of 12 women who conceived between the fourth and sixth cycles and who also received CC, 2 had a second-trimester miscarriage and 8 delivered live singleton births; there were two sets of twins. All eight women who conceived between 8 and 14 months (6 with endometriosis, 2 with PID) had fullterm live births. Altogether, these 62 women had 93 pregnancies: 34 conceived once, 25 twice, and 3 three times. All women who delivered at term had normal lactation and resumption of normal menstrual rhythm. Currently, most women in this series use some form of contraception. Hirsutism present before surgery did not disappear. However, a majority of these women did experience improvement of their skin and abnormal hair distribution, particularly after pregnancy and childbirth.
Discussion A breakthrough in our understanding of the complex condition of PCOD occurred when ovarian wedge resection was introduced. This procedure brought about a marked improvement in ovulation and pregnancy rates,4.15 a dramatic reduction of serum androgen and estradiol levels, 16' 17 and a return to normal of the LH:FSH ratio. 17Similar clinical and endocrine improvements of PCOD also were reported after laparoscopic coagulation of ovaries with unipolar c u r r e n t 7-9' 18 or laser vaporization, 12' 13,19 or on taking several biopsy specimens from the ovarian surface.l~ 11It was suggested that in PCOD any impairment of the ovarian surface acts on the hypothalamus to reduce pituitary hypersensitivity, and that the key factor behind the resultant hormonal changes lies in the superficial ovarian capsule and not deep inside the ovarian stroma. 10The data from this study appear to support that hypothesis. The results of this study suggest that bipolar electrocoagulation of the ovaries is effective in the treatment of PCOD. Its merits include favorable success rates, long-term efficacy, and safety. In developing countries, its availability and relatively low cost compared with laser vaporization are additional benefits. However, this new technique should be subjected to the test of time, and more studies, including controlled clinical trials comparing this method with other more established therapies, have to be conducted.
Findings at Second-look Surgery It was possible to assess the ovaries in 20 women during cesarean section or at second-look laparoscopy. The external appearance of the ovaries was normal in these women except for two to three fine, stringlike adhesions in two. In both patients the adhesions were limited to one ovary.
Success Rates of Induction of Ovulation and Pregnancy Low-watt bipolar electrocoagulation resulted in a spontaneous ovulation rate of 87% and a spontaneous pregnancy rate of 57%, which increased to 100% and 84%, respectively, on supplementation with CC (these women did not respond to CC before surgery). These results compare favorably with the reported ovulation and pregnancy rates for other surgical modalities used to treat PCOD. The reported ovulation rates are 83% to 92% for unipolar coagulation, 6' 7,9,18,20 45% to 86% for multiple ovarian biopsies, 1~ 11and 62% to 73% for laser vaporization.12-14' 19The respective pregnancy rates for the three procedures are 33 % to 80%, 6'7,9,18,e0 42% to 57%, 1~11and zero to 5 6 % . T M 19
Long-term Follow-up The minimum follow-up was 8 months. There were three groups of patients based on duration of follow-up. Twelve women (16%) were followed for 8 to 18 months and were ovulating at their last office visit. For the 33 (45%) who were followed for 18 months to 3 years, each patient had one live birth and continued to have regular menstrual cycles. In the third group, 29 women were followed for longer than 3 years. Of these, 25 conceived twice, 3 three times, and 1 once. All 29 continued to have regular menstrual cycles. Ten of the 29 patients have been followed for at least 4 years, 5 for at least 5 years, and 2 for over 6 years.
Safety and Complications Bipolar coagulation is devoid of electrical hazards and does not cause excessive tissue trauma. This is
507
Low-Watt Bipolar Electrocoagulationof the Ovaries Merchant
because spread of current is limited to tissue between the two coagulation poles, and because a low intensity of current (25 W for 5-12 sec) is employed. Furthermore, treatment points on the ovarian surface are deliberately separated by 7 to 15 mm, thus preventing widespread loss of tissue. ! attribute the low 10% rate of postoperative adhesions to lack of bleeding from the ovarian surface at time of coagulation and creation of artificial ascites at the end of the procedure.
8. Arlnar NA, Mcgarrigle HHG, Honour J, et al: Lapaxoscopic ovarian diathermy in the management of anovulatory infertilityin women with polycystic ovaries: Endocrine changes and clinical outcome. Fertil Steril 53:45-49, 1990
The safety of the bipolar technique is at least comparable with that of the more established conventional therapies. Laser vaporization is safe and devoid of significant complications. 1~14.19Multiple ovarian biopsies can result in bleeding and postoperative adhesions, l~With unipolar coagulation one has to be careful to avoid both undertreatment, 2~ which may require recoagulation, as well as overtreatment, which can occasionally lead to ovarian atrophy. 21 This study showed that the beneficial effects of bipolar coagulation in returning ovarian function to normal appear to be long lasting.
10. Sumioki H, UtsunomyiyaT, Matsuoka K, et ah The effect of laparoscopic multiple punch resection of the ovary on hypothalamo-pituitary axis in polycystic ovary syndrome. Fertil Steril 50:567-572, 1988
9. Naether OGJ, Fisher R, Weise H, et al: Laparoscopic electrocoagulation of the ovarian surface in infertile patients with polycystic ovarian disease. Fertil Steril 60:88-94, 1993
11. Campo S, Garcea N, CarusoA, et al: Effects of cefioscopic ovarian resection in patients with polycystic ovaries. Gynecol Obstet Invest 15:213-222, 1983 12. Daniell J, Miller W: Polycystic ovaries treated by laparoscopic laser vaporization. Fertil Steril 51:232-236, 1989 13. Huber J, Hosmann J, Spona J: Polycystic ovarian syndrome treated by laser through the laparoscope. Lancet 2:215, 1988 14. Gurgan T, Kisnisci H, Yarali H, et al: Evaluation of adhesion formation after laparoscopic treatment of polycystic ovarian disease. Fertil Steri156:1176-1178, 1991
References
1. Franks S, Adams J, Mason H, et al: Ovulatory disorders in women with polycystic ovary syndrome. Clin Obstet Gynecol 12:605~527, 1985
15. Rhodes P: The effects of wedge resection of ovaries in 63 cases of Stein-keventhal syndrome. J Obstet Gynaecol Br Commonw 75:1108-1112, 1968
2. Wang CF, Gamzell CR: The use of human gonadotrophin for induction of ovulation in women with PCOD. Fertil Steri133:479-486, 1980
16. Judd HL, Rigg LA, Anderson DC, et al: The effects of ovarian wedge resection on circulating gonadotrophins and ovarian steroid levels in patients with PCO syndrome. J Clin Endoclinol Metab 43:347, 1976
3. lnsler V, Potashnik G, Lunenfeld E, et al: Ovulation induction with HMG following down regulation of the pituitaryovarian axis by LHRH analogs. Gynecol Endocrinol 2 (suppl 1):67, 1988
17. Katz M, Carr PJ, Cohen BM, et al: Hormonal effects of wedge resection of polycystic ovaries. Obstet Gynecol 51:437 4A4, 1978 18. Sakata M, Tasaka K, Kurachi H, et ah Changes of bioacrive luteinizing hormone after laparoscopic ovarian cautery in patients with polycystic ovarian syndrome. Fertil Steril 53:610q513, 1990
4. Adashi EY, Rock JA, Guzick D, et al: Fertility following bilateral wedge resection: A critical analysis of 90 consecutive cases of the polycystic ovary syndrome. Fertil Steri136:320-325, 1981
19. Rossmanith WG, Keckstein J, Spatzier K, et al: The impact of ovarian laser surgery on the gonadotrophin secretion in women with polycystic ovarian disease. Clin Endocrinol 34:223-230, 1991
5. Buttram V, Vaquero C: Post-ovarian wedge resection adhesive disease. Fertil Stefil 6:874-876, 1975 6. Gjonnaess H: Polycystic ovarian syndrome treated by ovarian electrocautery through the laparoscope. Fertil Steril 141:20-25, 1984
20. Armar NA, Lachelin GC: Laparoscopic ovarian diathermy: An effective treatment for anti-oestrogen resistant anovulatory infertility in women with polycystic ovary syndrome. Br1 J Obstet Gynaecol 100:161-164, 1993
7. Greenblatt E, Casper R: Endocrine changes after laparoscopic ovarian cautery in polycystic ovarian syndrome. Am J Obstet Gynecol 156:279-285, 1987
21. Dabirashrafi H: Complications of laparoscopic ovarian catheterization [letter]. Fertil Steri152:878, 1989
508
The Journal of the American Association of Gynecologic Laparoscopists
Treatment of Polycystic Ovary Disease with Laparoscopic Low-Watt Bipolar Electrocoagulation of the Ovaries Rohinee N. Merchant, M.D., D.G.O.
Abstract Study Objective. To assess the efficacy of laparoscopic low-watt bipolar electrocoagulation of the ovaries in women with polycystic ovary disease (PCOD). Design. Prospective case series. Setting. Hospital-based infertility clinic. Patients. Seventy-four consecutive infertile women with PCOD resistant to conventional ovulation-induction regimens. Interventions. Laparoscopic bipolar low-watt electrocoagulation of the ovarian surface (25 W for 5-12 sec/cyst). Measurements and Main Results. Postoperative follow-up ranged from 18 months to 7 years. Menstrual rhythm returned to normal in all 74 women. All 40 women in whom infertility was solely due to anovulation eventually conceived. Overall, 62 (84%) of the 74 women conceived, 42 spontaneously after surgery and 20 after supplementation with clomiphene. These 62 women had a total of 93 pregnancies: 79 singleton live births, 4 sets of twins, and 10 miscarriages. Twenty-five women conceived twice and three conceived three times. At second-look laparoscopy or cesarean section in 20 women, fine stringlike adhesions on the ovaries were found in 2. Conclusion. Laparoscopic low-watt bipolar electrocoagulation of the ovaries is an effective treatment for women with PCOD who fail medical therapy.
Treatment of polycystic ovary disease (PCOD) is often difficult. A variety of medical therapies have been attempted, but with limited success. Treatment with clomiphene citrate (CC) is reported to result in an ovulation rate of about 60% and a pregnancy rate of about 30%. 1Gonadotropin and gonadotropin-releasing hormone (GnRH) have similar reported success rates, but have
drawbacks such as high cost, need for close monitoring, and the possibility of hyperstimulation syndrome?' 3 Surgical treatment of PCOD initially consisted of wedge resection of the ovaries.4 It did result in ovulation and pregnancy, but has been abandoned since it requires a major procedure (laparotomy), the benefits are short lived, and it carries the risk of postoperative adhesions.5
From the Department of Obstetrics and Gynecology, Dr. Merchant's Hospital; and Prof. Emeritus, Department of Obstetrics and Gynecology, B.Y.L. Nair Hospital and T.N. Medical College, University of Bombay, Bombay, India. Address reprint requests to Rohinee N. Merchant, M.D., 20 Milldam Road, Acton, MA 01720.
503
Low-Watt Bipolar Electrocoagulation of the Ovaries Merchant
With the advent of less invasive laparoscopic surgery, endoscopic electrocoagulation of the ovarian cysts was first described in 1984. 6 Since then, several reports of laparoscopic treatment have appeared, including unipolar electrosurgery]-9 multiple ovarian biopsies,10,11 mad laser vaporization. 1~14These techniques are effective, but sometimes have limitations, such as the risk of bleeding and postoperative adhesions with multiple ovarian biopsies, relatively high cost and nonavailability in developing countries for laser vaporization, and the risk of overtreatment and consequent ovarian atrophy with unipolar coagulation. A new technique of laparoscopic electrocoagulation of the ovaries uses low-watt bipolar current, and has been performed successfully for a number of years. To the best of my knowledge, the literature contains no reports on the use of low-watt bipolar electrosurgery in the treatment of PCOD. Materials and Methods Patients Subjects in this prospective study were 74 consecutive women who were treated between January 1988 and December 1992 for infertility due to PCOD
(Table 1). In each patient, the diagnosis of PCOD was made by the presence of all of four criteria. 1. Chronic anovulation associated with oligomenorrhea or amenorrhea, with or without hirsutism. Anovulation was established on the basis of endometrial biopsy (which was performed on every patient), ultrasonography, basal body temperature records, and evaluation of cervical mucus. 2. Typical appearance of ovaries on ultrasonography; that is, many tiny cysts studded all along the periphery. 3. Elevated basal levels of serum luteinizing hormone (LH) with normal or decreased levels of follicle-stimulating hormone (FSH), and normal or high serum testosterone levels. 4. Typical appearance at laparoscopy of enlarged ovaries with thick, white capsules. Before enrolling in the study, all 74 women had been unsuccessfully treated with incremental doses of CC alone 50 to 150 mg/day for 5 days for 6 to 18 months. In addition, some of the women failed other ovulation-induction regimens. Twenty failed to conceive with CC plus human chorionic gonadotropin (hCG) for an additional 3 to 8 cycles; eight failed CC plus betamethasone for an additional 3 cycles; six
TABLE 1. Patient Characteristics and Preoperative Clinical Profiles
Variable Age at time of surgery (yrs) Evidence of anovulation Interval of menstrual cycle (days) 25-45 46-120 >120 (secondary amenorrhea) Hirsutism Mild to moderate Severe (with clitoromegaly) Duration of unsuccessful treatment (mo) 8-18 >18 Duration of infertility (yrs) Primary infertility Secondary infertility Preoperative hormone levels Basal LH (mlU/ml) LH:FSH ratio Prolactin (ng/ml) Testosterone (ng/m])
No. of Women
Mean (+ SD)
Range
74 74
26.4 (+ 3.9)
18-34
52 15 7
35.5 (_+ 4.0) 60.6 (_+ 20.1 )
25-45 47-105
21 53
12.2 (_+ 3.4) 41.3 (_+ 18.5)
8-18 24-96
68 6
5.0 (-+ 3.4) 4.2 (___1.8)
1.5-16.0 2.6-6.0
67 67 67 64
16.8 (+_ 8.6) 3.4 (_+ 2.3) 14.2 (_+ 9.8) 0.99 (_+ 0.4)
1.9-42.0 1.14-16.8 3.2-62 0.6-2.9
40 4
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failed CC plus hCG plus human menopausal gonadotropin for an additional 4 cycles; and four failed in vitro fertilization. To facilitate analysis of results, the women were classified into four groups based on reasons for infertility. In group 1 (40 women) the sole reason for infertility was anovulation due to PCOD. The 12 women in group 2 suffered from pelvic inflammatory disease (PID) in addition to anovulation due to PCOD. In group 3 six women had mild to moderate endometriosis over and above anovulation due to PCOD. Group 4 consisted of 16 patients with anovulation due to PCOD, and their partners had subfertility factors.
Operative Technique With the patient under general anesthesia, a threepuncture technique was employed. A 10-ram operative laparoscope was passed through a subumbilical incision. The pelvis was evaluated with a probe introduced through a 5-mm cannula passed through a second puncture. The diagnosis of PCOD was confirmed, and tubal patency was tested. Finally, a bipolar spot coagulation probe (Elmed Inc., Addision, IL) or a bipolar suction-coagulator was passed through a third puncture for treating the ovaries. Each ovary was stabilized by grasping the utero-ovarian ligament with an atraumatic forceps. The bipolar spot coagulator was pressed at right angles to the surface of a cyst and a current of 25 W (50 Hz with a setting at 40) was passed for 5 to 12 seconds until the capsule was penetrated and cyst fluid welled out. As many cysts as were visible and accessible, but lying away from the hilum of the ovary, were coagulated. A distance of 7 to 15 mm was left uncoagulated between two adjacent treatment points. The number of cysts treated in this manner in each ovary averaged from 6 to 12, depending on the size of the ovary. When the ovarian capsule was very thick and could not be penetrated, it was punctured with a needle before electrocoagulation. The procedure was completed by a saline wash followed by instillation of 300 to 500 ml heparinized saline. At the end of the procedure, each ovary was left studded with several 4- to 5-ram irregular slits representing cysts that had been treated (Figure 1). The six patients who had endometriosis in addition to PCOD also underwent conservative treatment at the same time with adhesiolysis, coagulation of superficial endometriotic lesions with bipolar current, or both. In four women who had secondary amenorrhea, an
FIGURE 1. Appearance of the ovary at laparoscopy after low-watt bipolar electrocoagulation. A bipolar suctioncoagulator is seen at the left edge. The ovarian capsule is thick and white, and has several irregularly shaped slits representing cysts that have been treated.
ovarian biopsy was performed to rule out other causes of amenorrhea besides PCOD, such as functioning tumors of the ovary. Mild oozing occurred at the biopsy site and was controlled with bipolar coagulation. All four biopsy specimens were negative. There were no intraoperative complications. All women were discharged on the same day as surgery.
Postoperative Management The preoperative evaluation for ovulation in each subject consisted of endometrial biopsy, basal body temperature records, ultrasonography, and testing of cervical mucus. Postoperatively, the same procedures were performed, monitoring ovarian follicles by ultrasound; an endometrial biopsy was deliberately avoided for fear of disturbing a possible pregnancy. Serum midluteal progesterone assays were performed if the basal body temperature raised the possibility of luteal phase deficiency, if there was no evidence of follicular rupture on ultrasound, or if the first pregnancy ended in a first-trimester miscarriage. After laparoscopic treatment, patients were advised to have coitus around the time of ovulation. Three women received intrauterine insemination of a washed sample of their husband's semen and another one received artificial insemination of donor semen during the cycle after surgery. Women who did not ovulate
505
Low-Watt Bipolar ElectrocoaguJation of the Ovaries Merchant
ond or third cycle. Thus, spontaneous ovulation occurred in 65 (88%) of 74 women within 3 months of surgery. The temperature records of the remaining nine women (12%) were biphasic, but the luteal phase was defective as evidenced by low serum progesterone levels (<10 ng/ml); however, these women now responded to CC 50 mg/day for 5 days, although they were resistant earlier. Thus, ovulatory cycles were established in all 74 women (100%) by the sixth postoperative month (Table 2).
spontaneously within 3 months of surgery or conceive within three cycles, or whose first pregnancy terminated in a first-trimester miscarriage were given CC 50 mg/day for 5 days. In the first six procedures, only four to six cysts in each ovary were electrocoagulated. These women had biphasic temperature records, but in four, the midluteal progesterone levels were less than 10 ng/ml. They responded to CC and conceived thereafter. At this point in the study, I concluded that spontaneous ovulation and conception might be improved by increasing the number of cysts that were treated. Consequently, for the remainder of the study, 6 to 12 cysts were treated in each ovary.
Pregnancy Sixty-two women (84%) conceived 42 (57%) spontaneously within three cycles and 20 (27%) after supplementation with CC. All of these patients had not responded to CC before surgery. All 40 women with anovulation as the only factor responsible for infertilit3, (group 1) conceived within six cycles after ovarian electrocoagulation, with 32 conceiving spontaneously within 3 months, and 8 between the fourth and sixth cycles after CC supplementation. In group 2 (anovulation and pelvic inflammatory disease), six women conceived within 3 months, two between 4 and 6 months, and two 14 months after surgery. Two women in this group were lost to follow-up after 8 months, although they were ovulating until the time of last visit. All six women in group 3 (anovulation and endometriosis) conceived between 8 and 14 months after surgery, which was concomitant with improvement of their pelvic pathology. They all received CC before becoming pregnant. In group 4 (anovulation and male infertility factors), four women conceived within three cycles, one with artificial insemination using donor
Results
Return of Menstrual Regularity Establishment of a regular monthly flow (interval 27-30 days) occurred postoperatively in all 74 women. In seven women who had secondary amenorrhea, menstrual flow occurred within 48 to 72 hours of ovarian electrocoagulation. In the remaining 67 women who had oligomenorrhea, it occurred within 6 to 20 days. The basal body temperatures in all women in whom it remained above 97 ~ F preoperatively now dipped to lower ranges during the follicular phase, and a biphasic pattern was established. Return of Ovulation Fifty-three women (72%) ovulated between 6 and 27 days (mean + SD 13 + 4.2 days) after electrocoagulation. Another 12 (16%) ovulated during the sec-
TABLE 2. Onset of Ovulation and Pregnancy
Group 1, 2, 3, 4,
A only A + PID A + endometriosis A + subfertile partner Total no. (%)
No. of Women
Onset of Ovulation <3 Mo. 4 - 6 Mo. a
Onset of First Pregnancy <3 Mo. 4 - 6 Mo. a >6 Mo. a
No. Lost to Follow-up or Did Not Conceive
40 12 6 16 74 (100)
37 10 3 15 65 (88)
32 6 -4 42 (57)
-2 -10 12 (16)
3 2 3 1 9 (12)
apatients received clomiphene citrate 50 mg/day for 5 days. A = anovulation due to PCOD; PID = pelvic inflammatory disease. Ovulation rates: spontaneous 88%; total 100%. Pregnancy rates: spontaneous 57%; total 84%.
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8 2 -2 12 (16)
-2 6 -8 (11 )
August 1996, Vd. 3, No. 4
The Journal of the American Association of Gynecologic Laparoscopists
semen and three with intrauterine insemination of washed semen from the husbands. Two other women in this group responded to CC and conceived between 3 and 6 months postoperatively. The remaining 10 women in group 4 continued to ovulate until the date of last follow-up but could not become pregnant because of their partner's subfertility. The outcomes of the first pregnancies among 62 women were as follows. Of 42 women who conceived within 3 months, 38 delivered full-term singleton live births and 4 had a first-trimester miscarriage. Of 12 women who conceived between the fourth and sixth cycles and who also received CC, 2 had a second-trimester miscarriage and 8 delivered live singleton births; there were two sets of twins. All eight women who conceived between 8 and 14 months (6 with endometriosis, 2 with PID) had fullterm live births. Altogether, these 62 women had 93 pregnancies: 34 conceived once, 25 twice, and 3 three times. All women who delivered at term had normal lactation and resumption of normal menstrual rhythm. Currently, most women in this series use some form of contraception. Hirsutism present before surgery did not disappear. However, a majority of these women did experience improvement of their skin and abnormal hair distribution, particularly after pregnancy and childbirth.
Discussion A breakthrough in our understanding of the complex condition of PCOD occurred when ovarian wedge resection was introduced. This procedure brought about a marked improvement in ovulation and pregnancy rates,4.15 a dramatic reduction of serum androgen and estradiol levels, 16' 17 and a return to normal of the LH:FSH ratio. 17Similar clinical and endocrine improvements of PCOD also were reported after laparoscopic coagulation of ovaries with unipolar c u r r e n t 7-9' 18 or laser vaporization, 12' 13,19 or on taking several biopsy specimens from the ovarian surface.l~ 11It was suggested that in PCOD any impairment of the ovarian surface acts on the hypothalamus to reduce pituitary hypersensitivity, and that the key factor behind the resultant hormonal changes lies in the superficial ovarian capsule and not deep inside the ovarian stroma. 10The data from this study appear to support that hypothesis. The results of this study suggest that bipolar electrocoagulation of the ovaries is effective in the treatment of PCOD. Its merits include favorable success rates, long-term efficacy, and safety. In developing countries, its availability and relatively low cost compared with laser vaporization are additional benefits. However, this new technique should be subjected to the test of time, and more studies, including controlled clinical trials comparing this method with other more established therapies, have to be conducted.
Findings at Second-look Surgery It was possible to assess the ovaries in 20 women during cesarean section or at second-look laparoscopy. The external appearance of the ovaries was normal in these women except for two to three fine, stringlike adhesions in two. In both patients the adhesions were limited to one ovary.
Success Rates of Induction of Ovulation and Pregnancy Low-watt bipolar electrocoagulation resulted in a spontaneous ovulation rate of 87% and a spontaneous pregnancy rate of 57%, which increased to 100% and 84%, respectively, on supplementation with CC (these women did not respond to CC before surgery). These results compare favorably with the reported ovulation and pregnancy rates for other surgical modalities used to treat PCOD. The reported ovulation rates are 83% to 92% for unipolar coagulation, 6' 7,9,18,20 45% to 86% for multiple ovarian biopsies, 1~ 11and 62% to 73% for laser vaporization.12-14' 19The respective pregnancy rates for the three procedures are 33 % to 80%, 6'7,9,18,e0 42% to 57%, 1~11and zero to 5 6 % . T M 19
Long-term Follow-up The minimum follow-up was 8 months. There were three groups of patients based on duration of follow-up. Twelve women (16%) were followed for 8 to 18 months and were ovulating at their last office visit. For the 33 (45%) who were followed for 18 months to 3 years, each patient had one live birth and continued to have regular menstrual cycles. In the third group, 29 women were followed for longer than 3 years. Of these, 25 conceived twice, 3 three times, and 1 once. All 29 continued to have regular menstrual cycles. Ten of the 29 patients have been followed for at least 4 years, 5 for at least 5 years, and 2 for over 6 years.
Safety and Complications Bipolar coagulation is devoid of electrical hazards and does not cause excessive tissue trauma. This is
507
Low-Watt Bipolar Electrocoagulationof the Ovaries Merchant
because spread of current is limited to tissue between the two coagulation poles, and because a low intensity of current (25 W for 5-12 sec) is employed. Furthermore, treatment points on the ovarian surface are deliberately separated by 7 to 15 mm, thus preventing widespread loss of tissue. ! attribute the low 10% rate of postoperative adhesions to lack of bleeding from the ovarian surface at time of coagulation and creation of artificial ascites at the end of the procedure.
8. Arlnar NA, Mcgarrigle HHG, Honour J, et al: Lapaxoscopic ovarian diathermy in the management of anovulatory infertilityin women with polycystic ovaries: Endocrine changes and clinical outcome. Fertil Steril 53:45-49, 1990
The safety of the bipolar technique is at least comparable with that of the more established conventional therapies. Laser vaporization is safe and devoid of significant complications. 1~14.19Multiple ovarian biopsies can result in bleeding and postoperative adhesions, l~With unipolar coagulation one has to be careful to avoid both undertreatment, 2~ which may require recoagulation, as well as overtreatment, which can occasionally lead to ovarian atrophy. 21 This study showed that the beneficial effects of bipolar coagulation in returning ovarian function to normal appear to be long lasting.
10. Sumioki H, UtsunomyiyaT, Matsuoka K, et ah The effect of laparoscopic multiple punch resection of the ovary on hypothalamo-pituitary axis in polycystic ovary syndrome. Fertil Steril 50:567-572, 1988
9. Naether OGJ, Fisher R, Weise H, et al: Laparoscopic electrocoagulation of the ovarian surface in infertile patients with polycystic ovarian disease. Fertil Steril 60:88-94, 1993
11. Campo S, Garcea N, CarusoA, et al: Effects of cefioscopic ovarian resection in patients with polycystic ovaries. Gynecol Obstet Invest 15:213-222, 1983 12. Daniell J, Miller W: Polycystic ovaries treated by laparoscopic laser vaporization. Fertil Steril 51:232-236, 1989 13. Huber J, Hosmann J, Spona J: Polycystic ovarian syndrome treated by laser through the laparoscope. Lancet 2:215, 1988 14. Gurgan T, Kisnisci H, Yarali H, et al: Evaluation of adhesion formation after laparoscopic treatment of polycystic ovarian disease. Fertil Steri156:1176-1178, 1991
References
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17. Katz M, Carr PJ, Cohen BM, et al: Hormonal effects of wedge resection of polycystic ovaries. Obstet Gynecol 51:437 4A4, 1978 18. Sakata M, Tasaka K, Kurachi H, et ah Changes of bioacrive luteinizing hormone after laparoscopic ovarian cautery in patients with polycystic ovarian syndrome. Fertil Steril 53:610q513, 1990
4. Adashi EY, Rock JA, Guzick D, et al: Fertility following bilateral wedge resection: A critical analysis of 90 consecutive cases of the polycystic ovary syndrome. Fertil Steri136:320-325, 1981
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5. Buttram V, Vaquero C: Post-ovarian wedge resection adhesive disease. Fertil Stefil 6:874-876, 1975 6. Gjonnaess H: Polycystic ovarian syndrome treated by ovarian electrocautery through the laparoscope. Fertil Steril 141:20-25, 1984
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