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Laparoscopic ovarian electrocautery in the treatment of clomiphene-resistant polycystic ovary syndrome
HO T O FF TH E PO D I UM
Laparoscopic ovarian electrocautery in the treatment of clomiphene-resistant polycystic ovary syndrome Report from the 17th Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE), Lausanne, Switzerland, July 1d4, 2001
INTRODUCTION Polycystic ovary syndrome (PCOS) is a relatively common condition in women with infertility. The anovulation associated with this disorder is first managed with clomiphene citrate, which is usually effective in inducing ovulation. However, a sizeable proportion of women remain anovulatory, even with increasing doses of clomiphene citrate. These women are then offered gonadotropin therapy, with good results as far as inducing ovulation and attaining pregnancy are concerned. Unfortunately, this approach is more expensive and requires intensive and careful monitoring of the cycle, using hormonal measurements and ultrasonographic examinations. In addition, the risks of ovarian hyperstimulation syndrome (OHSS) and multiple pregnancy are significant. Surgical treatment of PCOS was first introduced almost one century ago when ovarian wedge resection by laparotomy was performed with good results. This procedure resulted in spontaneous ovulation and become popular in the 1950s and 1960s. A significant reduction in androgen levels was observed, resulting in normal folliculogenesis. Unfortunately, the effect was short-lived and was associated with an increased likelihood of periadnexal adhesions. Among women who failed to conceive, a diagnostic laparoscopy demonstrated pelvic adhesions in 15–100%.1,2 As a result, ovarian wedge resection fell into disrepute and was largely abandoned. Recently, interest in surgical treatment of PCOS has been renewed with the increased availability and use of operative laparoscopy. Several techniques have been introduced to restore ovulation in women with clomiphene citrate-resistant PCOS. These techniques include ovarian biopsy, multiple ovarian punch biopsy, ovarian capsule resection, ovarian electrocautery, and laser vaporization.3 The rationale for the surgical approach is unchanged, i.e. reduction of ovarian androgen levels so that follicular development can take place by avoiding the atresia that results from excess androgens. The evidence to date indicates that laparoscopic ovarian electrocautery is a promising intervention to 164
Evidence-based Obstetrics and Gynecology (2001) 3, 164d165 doi:10.1054/ebog.2001.0276, available online at http://www.idealibrary.com on
restore ovulation. However, it is important to compare this intervention with the standard therapy of using gonadotropins. The following studies addressed this issue. Randomized clinical trial of laparoscopic electrocoagulation of the ovaries versus recombinant FSH for ovulation induction in subfertility associated with polycystic ovary syndrome. NV Bayram, M Van Wely, PMM Bossuyt, F Van der Veen, Amsterdam, The Netherlands. This was a multicentre, randomized clinical trial in women with polycystic ovaries, chronic anovulation, and resistance to clomiphene citrate. The randomization was performed at the time of diagnostic laparoscopy; subjects underwent either ovarian electrocautery using bipolar electrodes to make 5–10 punctures per ovary or ovulation induction with recombinant follicle stimulating hormone (rFSH) in the chronic low dose step-up regimen. Women who remained anovulatory in the surgical treatment arm then received clomiphene citrate to induce ovulation and, if still anovulatory, underwent treatment with rFSH. The primary outcome of interest was the ongoing pregnancy rate. Among the 168 women randomized, there were 83 women in the ovarian cautery group and 85 women in the rFSH group; in each group 74 women completed the study. Although the overall pregnancy rates were similar in the two groups (68% become pregnant after 6 cycles with rFSH and 74% became pregnant after 12 cycles in the experimental group), the experimental group was deliberately contaminated by ovulation induction with clomiphene citrate in some women and rFSH in the rest who did not conceive. When comparing the control group with the experimental group without contamination, it was clear that the pregnancy rate was much higher on a per cycle basis with rFSH; after three cycles, the cumulative pregnancy rate was almost twice as high with rFSH and continued to rise, whereas it levelled off in the surgical treatment arm. At 6 months, the cumulative ongoing pregnancy rate was 37% in the ^ 2001 Harcourt Publishers Ltd
ovarian cautery group and 68% with rFSH (relative risk 0.54, 95% CI 0.39–0.76). Laparoscopic electrocoagulation versus treatment with gonadotrophin. Impact on patients’ health-related quality of life. M Van Wely, N V Bayram, PMM Bossuyt, F Van der Veen, Amsterdam, The Netherlands. It is generally assumed that ovulation induction with gonadotropins is burdensome for the patient, because of the intensive monitoring that is required and the risk of complications. In contrast, laparoscopic ovarian cautery may be less troublesome, because of the short duration of treatment. The randomized trial described above also evaluated the effect of rFSH and ovarian cautery on the health-related quality of life (HRQOL) for the women who participated in the study. Three self-administered questionnaires were utilized to assess HRQOL: the Short Form 36, the Rotterdam Symptom Checklist, and the Centre for Epidemiological Studies Depression Scale. Assessments were performed before randomization and at 2, 12, and 24 weeks after randomization. Overall, the HRQOL was not affected in the experimental and control groups. In women still under treatment, rFSH appeared to be more burdensome than ovarian cautery for HRQOL, but this effect disappeared when the women became pregnant. The results of these studies indicate that ovarian electrocautery is not as efficacious as ovulation induction with rFSH, unless the two interventions are used sequentially. Also, neither treatment has a significant effect on the health-related quality of life of the women. Hormonal profiles after ovarian electrocautery demonstrate a reduction in the levels of luteinizing hormone (LH), testosterone, DHEAS, and
^ 2001 Harcourt Publishers Ltd doi:10.1054/ebog.2001.0276, available online at http://www.idealibrary.com on
androstenedione,4,5 but glucose ultilization during an euglycemic-hyperinsulinemic clamp did not change, indicating that insulin sensitivity is not improved.5 Insulin resistance is believed to be a major factor in the persistence of anovulation in women with PCOS treated with clomiphene citrate or gonadotropins. The inability of ovarian cautery to affect insulin sensitivity may, in part, explain the lower efficacy of this approach to treating clomiphene citrate-resistant PCOS, compared to rFSH. In addition, it is increasingly being reported that ovarian electrocautery is associated with pelvic adhesions, which may further compromise fertility in these women and, in the long term, affect their quality of life. SUMMARY The data from this study demonstrate that even though electrocautery may confer benefit (in terms of achieving pregnancy) to some women with clomiphene citrate-resistant PCOS, it is not as efficacious an option as ovulation induction with rFSH. Salim Daya, MB, MSc McMaster University, Hamilton ON, Canada Literature cited 1. Buttram V, Vaguero C. Post-ovarian wedge resection adhesive disease. Fertil Steril 1975; 26: 874d876. 2. Toaff R, Toaff ME, Peyser MR. Infertility following wedge resection of the ovaries. Am J Obstet Gynecol 1976; 124: 92d96. 3. Gurgan T, Yarali H, Urman B. Laparoscopic treatment of polycystic ovarian disease. Hum Reprod 1994; 9: 573d577. 4. Felemban A, Tan SL, Tulandi T. Laparoscopic treatment of polycystic ovaries with insulated needle cautery: a reappraisal. Fertil Steril 2000; 73: 266d269. 5. Lemieux S, Lewis GF, Ben-Chetrit A et al. Correction of hyperandrogenemia by laparoscopic ovarian cautery in women with polycystic ovarian syndrome is not accompanied by improved insulin sensitivity or lipid-lipoprotein levels. J Clin Endocrinol Metab 1999; 84: 4278d4282.
Evidence-based Obstetrics and Gynecology (2001) 3, 164d165
165
Laparoscopic ovarian electrocautery in the treatment of clomiphene-resistant polycystic ovary syndrome Report from the 17th Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE), Lausanne, Switzerland, July 1d4, 2001
INTRODUCTION Polycystic ovary syndrome (PCOS) is a relatively common condition in women with infertility. The anovulation associated with this disorder is first managed with clomiphene citrate, which is usually effective in inducing ovulation. However, a sizeable proportion of women remain anovulatory, even with increasing doses of clomiphene citrate. These women are then offered gonadotropin therapy, with good results as far as inducing ovulation and attaining pregnancy are concerned. Unfortunately, this approach is more expensive and requires intensive and careful monitoring of the cycle, using hormonal measurements and ultrasonographic examinations. In addition, the risks of ovarian hyperstimulation syndrome (OHSS) and multiple pregnancy are significant. Surgical treatment of PCOS was first introduced almost one century ago when ovarian wedge resection by laparotomy was performed with good results. This procedure resulted in spontaneous ovulation and become popular in the 1950s and 1960s. A significant reduction in androgen levels was observed, resulting in normal folliculogenesis. Unfortunately, the effect was short-lived and was associated with an increased likelihood of periadnexal adhesions. Among women who failed to conceive, a diagnostic laparoscopy demonstrated pelvic adhesions in 15–100%.1,2 As a result, ovarian wedge resection fell into disrepute and was largely abandoned. Recently, interest in surgical treatment of PCOS has been renewed with the increased availability and use of operative laparoscopy. Several techniques have been introduced to restore ovulation in women with clomiphene citrate-resistant PCOS. These techniques include ovarian biopsy, multiple ovarian punch biopsy, ovarian capsule resection, ovarian electrocautery, and laser vaporization.3 The rationale for the surgical approach is unchanged, i.e. reduction of ovarian androgen levels so that follicular development can take place by avoiding the atresia that results from excess androgens. The evidence to date indicates that laparoscopic ovarian electrocautery is a promising intervention to 164
Evidence-based Obstetrics and Gynecology (2001) 3, 164d165 doi:10.1054/ebog.2001.0276, available online at http://www.idealibrary.com on
restore ovulation. However, it is important to compare this intervention with the standard therapy of using gonadotropins. The following studies addressed this issue. Randomized clinical trial of laparoscopic electrocoagulation of the ovaries versus recombinant FSH for ovulation induction in subfertility associated with polycystic ovary syndrome. NV Bayram, M Van Wely, PMM Bossuyt, F Van der Veen, Amsterdam, The Netherlands. This was a multicentre, randomized clinical trial in women with polycystic ovaries, chronic anovulation, and resistance to clomiphene citrate. The randomization was performed at the time of diagnostic laparoscopy; subjects underwent either ovarian electrocautery using bipolar electrodes to make 5–10 punctures per ovary or ovulation induction with recombinant follicle stimulating hormone (rFSH) in the chronic low dose step-up regimen. Women who remained anovulatory in the surgical treatment arm then received clomiphene citrate to induce ovulation and, if still anovulatory, underwent treatment with rFSH. The primary outcome of interest was the ongoing pregnancy rate. Among the 168 women randomized, there were 83 women in the ovarian cautery group and 85 women in the rFSH group; in each group 74 women completed the study. Although the overall pregnancy rates were similar in the two groups (68% become pregnant after 6 cycles with rFSH and 74% became pregnant after 12 cycles in the experimental group), the experimental group was deliberately contaminated by ovulation induction with clomiphene citrate in some women and rFSH in the rest who did not conceive. When comparing the control group with the experimental group without contamination, it was clear that the pregnancy rate was much higher on a per cycle basis with rFSH; after three cycles, the cumulative pregnancy rate was almost twice as high with rFSH and continued to rise, whereas it levelled off in the surgical treatment arm. At 6 months, the cumulative ongoing pregnancy rate was 37% in the ^ 2001 Harcourt Publishers Ltd
ovarian cautery group and 68% with rFSH (relative risk 0.54, 95% CI 0.39–0.76). Laparoscopic electrocoagulation versus treatment with gonadotrophin. Impact on patients’ health-related quality of life. M Van Wely, N V Bayram, PMM Bossuyt, F Van der Veen, Amsterdam, The Netherlands. It is generally assumed that ovulation induction with gonadotropins is burdensome for the patient, because of the intensive monitoring that is required and the risk of complications. In contrast, laparoscopic ovarian cautery may be less troublesome, because of the short duration of treatment. The randomized trial described above also evaluated the effect of rFSH and ovarian cautery on the health-related quality of life (HRQOL) for the women who participated in the study. Three self-administered questionnaires were utilized to assess HRQOL: the Short Form 36, the Rotterdam Symptom Checklist, and the Centre for Epidemiological Studies Depression Scale. Assessments were performed before randomization and at 2, 12, and 24 weeks after randomization. Overall, the HRQOL was not affected in the experimental and control groups. In women still under treatment, rFSH appeared to be more burdensome than ovarian cautery for HRQOL, but this effect disappeared when the women became pregnant. The results of these studies indicate that ovarian electrocautery is not as efficacious as ovulation induction with rFSH, unless the two interventions are used sequentially. Also, neither treatment has a significant effect on the health-related quality of life of the women. Hormonal profiles after ovarian electrocautery demonstrate a reduction in the levels of luteinizing hormone (LH), testosterone, DHEAS, and
^ 2001 Harcourt Publishers Ltd doi:10.1054/ebog.2001.0276, available online at http://www.idealibrary.com on
androstenedione,4,5 but glucose ultilization during an euglycemic-hyperinsulinemic clamp did not change, indicating that insulin sensitivity is not improved.5 Insulin resistance is believed to be a major factor in the persistence of anovulation in women with PCOS treated with clomiphene citrate or gonadotropins. The inability of ovarian cautery to affect insulin sensitivity may, in part, explain the lower efficacy of this approach to treating clomiphene citrate-resistant PCOS, compared to rFSH. In addition, it is increasingly being reported that ovarian electrocautery is associated with pelvic adhesions, which may further compromise fertility in these women and, in the long term, affect their quality of life. SUMMARY The data from this study demonstrate that even though electrocautery may confer benefit (in terms of achieving pregnancy) to some women with clomiphene citrate-resistant PCOS, it is not as efficacious an option as ovulation induction with rFSH. Salim Daya, MB, MSc McMaster University, Hamilton ON, Canada Literature cited 1. Buttram V, Vaguero C. Post-ovarian wedge resection adhesive disease. Fertil Steril 1975; 26: 874d876. 2. Toaff R, Toaff ME, Peyser MR. Infertility following wedge resection of the ovaries. Am J Obstet Gynecol 1976; 124: 92d96. 3. Gurgan T, Yarali H, Urman B. Laparoscopic treatment of polycystic ovarian disease. Hum Reprod 1994; 9: 573d577. 4. Felemban A, Tan SL, Tulandi T. Laparoscopic treatment of polycystic ovaries with insulated needle cautery: a reappraisal. Fertil Steril 2000; 73: 266d269. 5. Lemieux S, Lewis GF, Ben-Chetrit A et al. Correction of hyperandrogenemia by laparoscopic ovarian cautery in women with polycystic ovarian syndrome is not accompanied by improved insulin sensitivity or lipid-lipoprotein levels. J Clin Endocrinol Metab 1999; 84: 4278d4282.
Evidence-based Obstetrics and Gynecology (2001) 3, 164d165
165