The University of Sheffield, Jessop Wing, Sheffield Teaching Hospitals, Tree Root Walk, Sheffield S10 2SF, UK
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Key words: laparoscopic ovarian diathermy/polycystic ovarian syndrome/polycystic ovaries
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
In this retrospective study we wish to investigate the doseresponse relationship of LOD by analysing the influence of the amount of thermal energy delivered to each ovary on the clinical outcome.
![]() |
Materials and methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
A diagnosis of PCOS was based on the following criteria: (i) early follicular phase (defined as days 25 of the menstrual cycle) serum LH:FSH ratio was >2 and/or raised serum androgen levels [testosterone 2.5 nmol/l, androstenedione
10 nmol/l or free androgen index (FAI) >4]. FAI has been found to be a useful test for detecting patients with PCOS (Eden et al., 1989
). It is calculated using the formula: testosteronex100/sex hormone-binding globulin (SHBG) (Carter et al., 1983
). In women who were oligo-/amenorrhoeic, a random blood sample was acceptable; or (ii) there was ultrasonographic evidence of ovarian stromal hypertrophy and multiple (
10), small (68 mm) follicles arranged in the periphery of the ovary (Adams et al., 1985
).
Laparoscopic ovarian diathermy
The techniques of laparoscopic ovarian drilling used in our centre have been previously published (Li et al., 1998). Over 10 gynaecologists of varying degrees of experience (senior house officers under supervision, registrars and consultants) carried out the treatment over the10 year period. In most cases a three-puncture laparoscopy was performed. A 10 mm laparoscope was inserted via the main subumbilical entry and a pair of grasping forceps was introduced through one of the two lower abdominal 5 mm punctures to grasp the uteroovarian ligament and to lift the ovary away from the bowel. The third entry was used to introduce the diathermy needle. A specially designed probe (Rockett of London, Watford, UK) was used to penetrate the ovarian capsule to a standard depth (8 mm) at a number of points with the aid of a short burst of diathermy. The probe has a distal stainless steel needle measuring 8 mm in length and 2 mm in diameter and projecting from an insulated solid cone of 6 mm maximum diameter. The electrosurgical unit used was the Force 2 Valleylab® electrosurgical generator (Valleylab Inc., Boulder, CO, USA). A monopolar coagulating current at 30 watt power setting was used and the duration of each penetration was about 5 s. A total of two to 10 punctures were made in each ovary depending on its size. Each ovary was cooled by irrigation using Hartmann's solution before releasing the ligament. At the end of the procedure, ~200 ml of Hartmann's solution were left in the pelvis.
Post-operative monitoring
Following ovarian diathermy, women were asked to keep a record of their menstrual cycle. If the patient started a menstrual period within 6 weeks of the surgery, a blood sample was taken on day 2 of that cycle for measurement of serum concentrations of LH, FSH, testosterone, androstenedione and SHBG. Another blood sample was taken on day 21 of the same cycle for measurement of serum concentration of progesterone. Ovulation was diagnosed when the progesterone level was 30 nmol/l. Two more mid-luteal phase blood samples were taken in the subsequent cycles to measure serum progesterone levels. If spontaneous menstruation did not occur during the 6 weeks following surgery, a random blood sample was taken to measure all the above hormones.
Analysis of the data
The clinical and biochemical data before and after LOD were documented from the hospital records. The age of the patients and other demographic details including body mass index (BMI), primary or secondary infertility, and the duration of infertility were also documented.
Patients were divided into six groups according to the number of punctures made in their ovaries during LOD as follows: group 1 (n = 12) treated with two punctures per ovary, group 2 (n = 15) three punctures, group 3 (n = 27) four punctures, group 4 (n = 43) five punctures, group 5 (n = 25) six punctures and group 6 (n = 39) seven to 10 punctures.
The clinical data were entered into the Statistical Package for Social Science for PC version 10.0.5. Appropriate statistical tests including contingency table analysis and analysis of variance were used.
![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
|
|
Menstrual pattern
Figure 1c shows the proportion of women with regular menstrual cycles after ovarian diathermy. Contingency table analysis showed that the proportion of women with regular menstrual cycles after LOD in group 1 (27%) was significantly lower (P < 0.05) than the other groups (6178%).
Endocrine changes
The magnitude of changes in the gonadotrophin levels after ovarian diathermy, using different amounts of thermal energy, is shown in Figure 2. Analysis of variance showed no difference between groups 15 in the percentage change of LH levels. LH/FSH ratio showed a 10% increase in group 1 compared with a reduction of 2243% in the rest of the groups. The reduction in LH levels and LH/FSH ratio after LOD was highest (40 and 43% respectively) in group 6 (
7 punctures per ovary). The changes of the serum levels of FSH after LOD were variable and insignificant in groups 15 (10 to +9%), but there was a significant increase of 29% in group 6.
|
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Seven percent of women in this study had apparently regular menstrual cycles prior to LOD. Although chronic anovulation in women with PCOS is usually associated with menstrual irregularities (Franks, 1995), several authors have reported that a proportion of these women do have apparently `regular' menstrual cycles. It was reported that 21% of anovulatory PCOS women have regular menstrual cycles (Carmina and Lobo, 1999
). Similarly, a 24% incidence of regular menstrual cycles among anovulatory PCOS patients undergoing ovarian diathermy was reported (Naether et al., 1994
). In a classic review of 187 reports describing 1079 cases of PCOS, a 16% incidence of regular menses was reported (Goldzieher and Axelrod, 1963
). This observation was confirmed in a recent study of 1741 women with PCOS in which 30% of patients had regular menses (Balen et al., 1995
). Furthermore, many anovulatory PCOS patients ovulate occasionally and some may resume regular menstrual cycles for variable periods of time. This explains why some anovulatory PCOS patients conceive spontaneously while being investigated for infertility or waiting for treatment.
Calculation of thermal energy
Gjonnaess correlated the ovulation rates after LOD to different numbers of points cauterized (Gjonnaess, 1984). He reported that the best results [ovulation rate = 96.7% (n = 30)] were obtained when the number of points was more than five per ovary (>10 points per patient). However, this referred to the use of biopsy or sterilization forceps applied against the ovarian surface and activating the electricity at 200300 watts for 3 ± 1 s. Hence the amount of thermal energy delivered to each ovary, on average, was 250 wattsx3 sx>5 = >3750 joules. Armar et al. found that four diathermy holes per ovary were sufficient to achieve good results and that no improvement was achieved when applying more holes (Armar et al., 1990
). This referred to the use of a specially designed needle to penetrate the ovary with activation of the electricity (40 watts) for 4 s at each point. The amount of thermal energy delivered to each ovary was 40 wattsx4 sx4 = 640 joules, which is significantly lower than that used by Gjonnaess (Gjonnaess, 1984
). In our study, the amounts of thermal energy used in each group are as follows. Group 1: 30x5x2 = 300 joules; group 2: 30x5x3 = 450 joules; group 3: 30x5x4 = 600 joules; group 4: 30x5x5 = 750 joules; group 5: 30x5x6 = 900 joules; and group 6: 30x5x
7 =
1050 joules.
It is important that the comparison between different studies should take into consideration the total amount of thermal energy delivered to each ovary, not just the number of holes made in the ovary.
Threshold dose
In our study, the application of two holes per ovary, equivalent to the delivery of 300 joules, was found to produce significantly poorer results than the other groups, measured in terms of restoration of menstrual regularity, ovulation rate and conception rate. While it is possible that two punctures (300 joules) per ovary represent the threshold dose (i.e. the lowest dose at which a response could be seen), it is of interest to note that the LH/FSH ratio did not decrease in group 1 (treated with two punctures per ovary), suggesting that the responders in this group could represent treatment-independent events. The threshold dose may therefore be higher than two punctures per ovary.
Plateau dose
The plateau dose refers to the lowest dose at which all subjects who will respond are observed to respond. In our study, there did not appear to be significant differences in the outcomes (menstrual pattern, ovulation and conception) of groups 26. It seems that three punctures (450 joules) per ovary produce results as good as higher numbers of punctures. However, this is a retrospective study, and caution should be exercised in the interpretation of results. Firstly, it is possible that there was selection bias by the surgeons in the choice of the number of punctures. One example is that surgeons might have applied more punctures to larger ovaries. Secondly, our own analysis suggested that LH and FSH levels were lower in group 3 (four punctures per ovary). There is no obvious explanation for such a finding, apart from some form of selection bias or purely a chance occurrence. The lower LH levels may also indicate that women in this group had a milder form of the syndrome and this might have an impact on their response to the treatment. Thirdly, in a retrospective study such as this one, while the number of punctures made and the power setting could be accurately quantified, the duration of application of thermal energy (5 s) is only approximate. Consequently, our study only provides a rough guide to the dose of thermal energy used. A prospective dose-finding study is required to estimate more accurately the optimal amount of energy required for LOD.
Excessive thermal energy
Ovarian atrophy and failure is a rare complication of LOD. Dabirashrafi reported a case of severe ovarian atrophy following LOD in which eight punctures were created at 400 watts for 5 s per each puncture, equivalent to 16000 joules (Dabirashrafi, 1989). It is therefore possible that application of excessive amounts of thermal energy to the ovary during LOD will produce irreversible damage to the ovary, leading to ovarian failure.
FSH is considered to be a reasonable marker of ovarian reserve and function. In our study, it is of interest that the application of seven or more punctures (1050 joules) per ovary resulted in a 29% increase in the FSH levels after LOD, compared with 10 to 9% change in the other groups. It seems possible that the application of seven or more punctures per ovary represents an excessive amount of thermal energy used for LOD and should therefore be discouraged.
Depth of penetration of energy
Gjonnaess used a significantly greater amount of thermal energy (>3750 joules per ovary) than that used in our study (Gjonnaess, 1984). However, Gjonnaess, using a pair of biopsy or sterilization forceps, applied the thermal energy to the ovarian surface and the depth of penetration was therefore between 24 mm, i.e. superficial. In contrast, the depth of penetration in our study using the specially designed ovarian diathermy needle (Rocket of London) was up to 8 mm. A similar instrument was used by others, who found that the amount of thermal energy used to produce a good result was ~640 joules per ovary, which is similar to that found in our study (Armar et al., 1990
). Similarly, Felemban et al. delivered the energy to a depth of 8 mm and achieved good success rates (73% ovulation and 54% conception rates) with amounts of thermal energy (40 wattsx2 sx1015 = 8001200 joules) significantly lower than those applied by Gjonnaess (Gjonnaess, 1984
; Felemban et al., 2000
). It is therefore possible to conclude that with deeper penetration during LOD, the amount of thermal energy can be reduced without compromising the outcome. Furthermore, achieving good results with deep penetration using low energy supports the hypothesis that LOD works by destroying androgen-producing ovarian stroma.
Endocrine outcome
It is of interest to note that the magnitude of decrease in LH levels and LH/FSH ratio after LOD seems to be dose-dependent, with the highest reduction being achieved in group 6 (seven or more punctures per ovary). This greater reduction of LH levels could be explained by the greater reduction of serum androgen concentrations as a result of greater destruction of the androgen-producing ovarian stroma with higher doses of thermal energy. This in turn results in reduction of the peripheral aromatization of androgens to estrone. The resulting fall in estrone may be responsible for decreased positive feedback on LH and decreased negative feedback on FSH at the level of the pituitary. However, the greater reduction of the serum LH levels achieved with higher doses of thermal energy was not associated with an increase of the ovulation and pregnancy rates. This indicates that mechanisms of actions other than that described above may be responsible for the effects of LOD. For instance, it has recently been suggested that the ovary produces a number of growth factors, such as insulin-like growth factor-I in response to tissue injury, which sensitize the ovary to circulating FSH resulting in stimulation of follicular growth. It has also been hypothesized that minimal ovarian injury leads to the production of non-steroidal factors which affect the ovarianpituitary feedback resulting in an attenuated response of LH secretion to stimulation with GnRH, which leads to a decrease in serum LH concentrations (Rossmanith et al., 1991).
Although groups 2, 3, 4 and 6 showed post-operative increase of the mean serum levels of FSH, group 5 unexpectedly showed a reduction of FSH levels. This resulted in a lower than expected magnitude of post-operative reduction of LH/FSH ratio in this group. As mentioned above, the choice of the number of punctures to be made during ovarian diathermy was based on the ovarian size. Therefore, it is possible that women in groups 5 and 6 had larger ovaries, which may indicate a severer form of the syndrome. It is possible that the amount of thermal energy used in group 5 (900 joules per ovary) was not enough to produce an increase of FSH levels due to the relatively larger size of the ovaries in this group. In group 6, the amount of energy used (10501500 joules) was significantly greater than that of group 5 and therefore the endocrine changes were greater.
The serum androgen levels and ovarian volumes were not routinely measured after LOD and therefore the available data were limited and insufficient for analysis.
In conclusion, in this retrospective study we analysed the influence of the number of punctures made at LOD on the clinical outcome in 161 women with PCOS. Three punctures (450 joules) per ovary seemed to be the plateau dose for LOD. Deeper penetration with the specially designed diathermy needle allows reduction of the amount of thermal energy delivered to the ovary without affecting the success rates. Making seven or more punctures per ovary appears to deliver an excessive amount of thermal energy to the ovary. This offers no advantage over the lower doses of energy in terms of success rates, and may potentially cause excessive ovarian damage. There is a need for a prospective dose-finding study in order to estimate the optimal amount of thermal energy required for LOD.
![]() |
Notes |
---|
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Armar, N.A., McGarrigle, H.H.G., Honour, J., Holownia, P., Jacobs, H.S. and Lachelin, G.C.L. (1990) Laparoscopic ovarian diathermy in the management of anovulatory infertility in women with polycystic ovaries: endocrine changes and clinical outcome. Fertil. Steril., 53, 4549.[ISI][Medline]
Balen, A.H., Conway, G.S., Kaltsas, G., Techatrasak, K., Manning, P.J., West, C. and Jacobs, H.S. (1995) Polycystic ovary syndrome: the spectrum of the disorder in 1741 patients. Hum. Reprod., 10, 21072111.[Abstract]
Carmina, E.C. and Lobo, R.A. (1999) Do hyperandrogenic women with normal menses have polycystic ovarian syndrome? Fertil. Steril., 71, 319322.[ISI][Medline]
Carter, G.D., Holland, S.M., Alaghband-Zadeh, J., Rayman, G., Dorrington-Ward, P. and Wise P.H. (1983) Investigation of hirsutism: testosterone is not enough. Ann. Clin. Biochem., 20, 262263.[ISI][Medline]
Dabirashrafi, H. (1989) Complications of laparoscopic ovarian cauterization. Fertil. Steril., 52, 878879.[ISI][Medline]
Eden, J.A., Place, J., Carter, G.D., Jones, J., Alaghband-Zadeh, J. and Pawson, M.E. (1989) The diagnosis of polycystic ovaries in subfertile women. Br. J. Obstet. Gynaecol., 96, 809815.[ISI][Medline]
Felemban, A., Tan, S.L. and Tulandi, T. (2000) Laparoscopic treatment of polycystic ovaries with insulated needle cautery: a reappraisal. Fertil. Steril., 73,266269.
Franks, S. (1995) Polycystic ovarian syndrome. N. Engl. J. Med., 333, 853861.
Gjonnaess, H. (1984) Polycystic ovarian syndrome treated by ovarian electrocautery through the laparoscope. Fertil. Steril., 41, 2025.[ISI][Medline]
Goldzieher, J.W. and Axelrod, L.R. (1963) Clinical and biochemical features of polycystic ovarian disease. Fertil Steril., 4,631653.
Judd, H.L., Rigg, L.A., Anderson, D.C. and Yen, S.S. (1976) The effects of ovarian wedge resection on circulating gonadotrophin and ovarian steroid levels in patients with polycystic ovary syndrome. J. Clin. Endocrinol. Metab., 43, 347355.[Abstract]
Li, T.C., Saravelos, H., Chow, M.S., Chisabingo, R. and Cooke, I.D. (1998) Factors affecting the outcome of laparoscopic ovarian drilling for polycystic ovarian syndrome in women with anovulatory infertility. Br. J. Obstet. Gynaecol., 105, 338344.[ISI][Medline]
Loppöhn, R.E. and Bogchelman, D.H. (1989) The relation of fertility and ovarian histology after bilateral ovarian wedge resection. Fertil. Steril., 52, 221226.[ISI][Medline]
Merchant, R.N. (1996) Treatment of polycystic ovary disease with laparoscopic low-watt bipolar electrocoagulation of the ovaries. J. Am. Assoc. Gynecol. Laparosc., 3, 503508.[ISI][Medline]
Naether, O.G.J., Baukloh, V., Fischer, R. and Kowalczyk, T. (1994) Long-term follow-up in 206 infertility patients with polycystic ovarian syndrome after laparoscopic electrocautery of the ovarian surface. Hum. Reprod., 9,23422349.
Naether, O.G.J., Fischer, R., Weise, H.C., Geiger-Kotzler, L., Delfs, T. and Rudolf, K. (1993) Laparoscopic electrocoagulation of the ovarian surface in infertile patients with polycystic ovarian disease. Fertil. Steril., 60, 8894.[ISI][Medline]
Rossmanith, W.G., Keckstein, J., Spatzier, K. and Lauritzen, C. (1991) The impact of ovarian laser surgery on the gonadotrophin secretion in women with polycystic ovarian disease. Clin. Endocrinol. (Oxf.), 34, 223230.[ISI][Medline]
Stein, I.F. (1964) Duration of fertility following ovarian wedge resectionSteinLeventhal syndrome. West. J. Surg. Obstet. Gynecol., 78, 124127.
Tulandi, T. (1999) Laparoscopic treatment of polycystic ovarian syndrome. In Tulandi, T. (ed.) Atlas of Laparoscopic and Hysteroscopic Techniques for Gynecologists. W.B.Saunders, London, pp. 9395.
Weise, H.C., Naether, O., Fischer, R., Berger-Bispink, S. and Delfs, T. (1991) Behandlungsergebnisse mit der oberflachenkuaterisierung polyzystischer Ovarien bei Sterilitatspatientinnen. Geburtshilfe Frauenheilkunde, 51, 920924.[ISI]
Submitted on August 13, 2001; accepted on November 19, 2001.