Date
Treatment of anovulatory infertility in PCOS
1930
Bilateral ovarian wedge resection (Stein and Leventhal [9])
1961
Clomiphene citrate (Greenblatt [10])
1967
Laparoscopic ovarian biopsies (Palmer and de Brux [12])
1978
Laparoscopic ovarian diathermy (Gjonnaess [13])
1990
Laparoscopic ovarian drilling [Laser] (Huber et al. [15])
The Current Role of Laparoscopic Ovarian Diathermy in PCOS
According to the Thessaloniki PCOS Consensus on infertility treatment related to PCOS, all overweight and obese PCOS women should first be encouraged to loose weight through life style measures before any medical treatment [8]. Whilst CC remains the standard first-line treatment in anovulatory PCOS women, the second line treatment has been the subject of much debate, with competition between LOD, gonadotrophin and metformin to be the preferred choice (Fig. 6.1). Perhaps, with the increasing awareness of the predictors of success/failure of each of these treatments, it may now be possible to apply an individually tailored treatment according to each patient’s pre-treatment characteristics e.g., metformin may be the treatment of choice for overweight/obese women. However, emerging evidence from large RCTs on metformin does not support its routine use for ovulation induction in PCOS [16, 17]. On the other hand, LOD and gonadotrophins have been shown to be equally effective in inducing ovulation and producing high pregnancy and livebirth rates in women with PCOS (Tables 6.2 and 6.3 ) [18, 19]. LOD has been recommended by many authors as the preferred choice after CC-resistance/failure as it offers several advantages over gonadotrophins (Table 6.4). Importantly, in contrast to gonadotrophin therapy, LOD results in mono-ovulation, with no risk of ovarian hyperstimulation syndrome (OHSS) and with an incidence of multiple pregnancies no higher than background rates. Moreover, LOD is less costly and does not require complex monitoring. In an economic evaluation of LOD versus gonadotrophin therapy, Farquhar and co workers estimated the cost per term pregnancy to be €14,489 for gonadotrophin and €11,301 for LOD (22 % lower) [20]. Furthermore, a recent long-term economic study by Nahuis and co-workers reported significantly lower costs per live birth after LOD compared to gonadotrophins therapy in CC-resistant PCOS women [21]. In addition, with LOD, a single treatment leads to repeated physiological ovulatory cycles and potentially repeated pregnancies without the need for repeated courses of medical treatment. The main drawback of LOD is the need for general anaesthetic and surgery. Other complications, such as iatrogenic adhesion formation and premature ovarian failure are rare and appear to be of little clinical significance. Advantages and disadvantages of LOD are summarised in Table 6.4.
Fig. 6.1
Management options for anovulatory infertility associated with PCOS. Weight reduction should be considered before any medical induction of ovulation in all overweight/obese PCOS women. Clomifene citrate is the standard first-line medical ovulation induction in non-obese PCOS women. The second line treatment after clomifene citrate -resistance/failure is still uncertain with competition between LOD, gonadotrophin and metformin to be the preferred choice
Table 6.2
LOD vs . rFSH in CC-resistant PCOS women
LOD (n = 83) | rFSH (n = 85) | |
|---|---|---|
Ovulation (per cycles) | 70 % | 69 % |
Conception at 12/12 | 76 % | 75 % |
Multiple pregnancies | 1 (>2 %) | 9 (14 %) |
Miscarriage rate | 11 % | 11 % |
Livebirth rate | 64 % | 60 % |
Table 6.3
LOD vs. rFSH rFSH in CC-resistant PCOS women
OR (95 % CI) | |
|---|---|
Cumulative pregnancy | 1.04 (0.74, 1.99) |
Livebirth | 1.08 (0.67, 1.75) |
Multiple pregnancy | 0.13 (0.03, 0.59) |
Miscarriage rates | 0.81 (0.36, 1.86) |
Table 6.4
Advantages and disadvantages of LOD
A. Advantages |
1. At least as effective as gonadotrophin treatment |
2. Less Costly |
3. Avoids intensive, inconvenient and complex monitoring |
4. Single treatment produces repeated ovulatory cycles and potentially repeated pregnancies |
5. Avoids OHSS |
6. No increase in muliple pregnanccies |
B. Disadvantages |
1. The need for surgery under general anaesthetic |
2. Iatrogenic adhesion formation |
3. Theoretical risk of premature ovarian failure |
We have recently conducted a randomised controlled trial investigating the potential role of LOD as a first line treatment in preference to CC for anovulatory PCOS [22]. Although, the success rates were not significantly different between LOD and CC, there was a trend towards a higher pregnancy rate with CC treatment. Furthermore, the study provided evidence that LOD is more effective in CC-resistant PCOS patients compared to CC responsive patients. It was therefore concluded that LOD should remain as a second line treatment for anovulatory PCOS.
Techniques of Laparoscopic Ovarian Drilling
Numerous techniques of laparoscopic ovarian surgery to induce ovulation in PCOS women have been developed over the years. Most of the techniques involve either taking ovarian biopsies or making multiple punctures on the surface of the ovary using electrocautery or laser. More recently, there have been several attempts to use a transvaginal route to perform the ovarian surgery utilizing either a fertiloscopy or an ultrasound guided approach. Currently, the most widely used technique for ovarian surgery is laparoscopic ovarian drilling (LOD) using electrocautery due to its simplicity, effectiveness, relative safety and low cost. A detailed description of the technique follows.
LOD Using Electrocautery
Three-Puncture laparoscopy is established and the pelvis is thoroughly inspected for any pathology and the ovaries examined for the features of PCO. The utero-ovarian ligament is grasped with a pair of atraumatic grasping forceps and the ovary is lifted up and stabilized in position away from the bowel (Fig. 6.2a). This is essential to avoid direct or indirect thermal injury to the bowel. A laparoscopic monopolar diathermy needle is used to penetrate the ovarian capsule at a number of points. The active distal part of the needle should measure 7–8 mm in length and 2 mm in diameter and project from an insulated solid cone with a wider diameter. When the needle penetrates the capsule of the ovary, the insulated cone controls the depth of penetration and minimizes thermal damage to the ovarian surface. The needle should be applied to the anti-mesenteric surface of the ovary at right angle to avoid slippage and to minimize surface damage (Fig. 6.2a). The site of application should be away from the ovarian hilum and the fallopian tube. This is necessary to avoid damage of the hilum (which can lead to ovarian atrophy) and the fallopian tube (which can cause mechanical infertility). After insertion of the needle through the ovarian capsule, monopolar coagulation electricity current is activated for 5 s with a power setting of 30w (Fig. 6.2b). Electricity should not be activated before penetrating the surface of the ovary to avoid arcing and to minimize the damage to the ovarian surface due to the charring effect, which may later cause adhesion formation. However, it may be necessary to facilitate the needle insertion by a short burst of diathermy. The ovary is then cooled down by irrigation using Hartmann’s solution before releasing it to its normal position. The techniques are summarized in Table 6.5.
Fig. 6.2
Laparoscopic ovarian drilling with monopolar electrocautery. (a) The utero-ovarian ligament is grasped with atraumatic grasping forceps and the ovary is lifted up away from the bowel. With the ovary stabilized in position, the needle is applied to the anti-mesenteric surface at right angle. (b) The full length of the needle is pushed into the ovarian capsule and electricity is activated for 5 s. This is repeated at 4 separate points
Table 6.5
Techniques of LOD using electrocautery
1. Three – Puncture technique |
2. Utero-ovarian ligament is grasped with a pair of atraumatic forceps |
3. The ovary is lifted up away from the bowel and stabilized |
4. A specially designed monopolar electrocautery needle probe is used |
5. The needle applied at right angle to the anti-mesenteric surface of the ovary |
6. The needle should be away from ovarian hilum and the Fallopian tube |
7. Power is set at 30 W (coagulating) |
8. The full length of the needle is pushed into the capsule to a depth of 6–8 mm |
9. Electricity is activated for 5 s |
10. Four punctures are made in each ovary |
11. The ovary is cooled with saline at the end of the drilling procedure |
12. A crystalloid solution is instilled at the end of the procedure |
How Much Energy Should Be Used for LOD?
The amount of thermal energy used and number of punctures made in each ovary varied considerably in different studies. Between 3 and 25 punctures have been reported with power settings between 30 and 400 W [13, 23–25]. In a retrospective review of 161 women who underwent LOD, we found that two punctures resulted in poor outcome and three punctures (450 J/ovary) seemed to represent a plateau dose, above which no further improvement of the outcome was observed. Seven or more punctures seemed to be associated with reduction of the ovarian reserve suggesting excessive ovarian destruction [25]. In a prospective dose finding study utilizing an “up-and-down design” and involving 30 women with anovulatory PCOS undergoing LOD, we have found four punctures (600 J) per ovary at 30 W for 5 s (150 J) per puncture to represent the optimum number required to achieve the best result [26].
Depth of Needle Insertion into the Ovary
It has now been established that deep insertion of the needle into the ovarian stroma during LOD is necessary to achieve optimal results with the lowest amount of thermal energy. The rational for this approach is that deep penetration allows the direct delivery of thermal energy into to the ovarian stroma resulting in more effective destruction of the androgen producing tissue. This effect is thought to be the main mechanism of action of LOD. Deep penetration also helps to avoid ovarian surface charring, which is a cause of postoperative adhesion formation. The theoretical benefits of deep needle insertion has been supported by previous research by our group as well as others, which showed that a needle insertion of about 8 mm into ovarian stroma resulted in good clinical outcomes with a relatively small amount of energy [14, 25, 26]. On the other hand, Gjonnaess who made shallow craters of 2–4 mm depth on the ovarian surface, delivered a very high amount of thermal energy (>3,750 J/ovary) to achieve successful outcomes [13].
Other Techniques of Ovarian Electrocautery
Several authors applied the techniques described by Gjonnaess making craters on the ovarian surface using biopsy or sterilization forceps pressed against ovarian surface for 2–4 s delivering monopolar current (200–300 W) [13, 24, 27–29]. Pelosi and Pelosi used monopolar diathermy needle to create 4–6 linear incisions into the ovarian tissue to a depth of 5–7 mm, extending from one end of the ovary to the other along the axis [30]. Merchant used low-watt (25 W) bipolar current to penetrate the ovarian capsule and coagulate all the visible cysts [31]. The overall results of these techniques are comparable and encouraging.
Laser Ovarian Surgery
Four lasers have been used including Nd: YAG, CO2, argon and KTP. Nd:YAG laser is delivered via a fine quartz fibre and can be used in the contact and non-contact mode. In the non-contact mode, the laser fibre is applied at a distance of 5–10 mm of the anti-mesenteric surface of the ovary with a power setting of 30–100 W. It has been used to make incisions [15] or punctures [32] or to coagulate a wedge-like area [33]. In the contact mode, with a sapphire tip screwed on the flexible laser fibre, the probe can be introduced into the ovarian capsule to create punctures [34] or to cut out a wedge-shaped portion (0.5 cm) of the ovary [35] CO2 laser has been used to drill 10–40 craters in the ovarian tissue and to vaporize the visible subcapsular follicles. With power setting of 10–30 W in a continuous mode, the laser beam is focused to a spot size of 0.2 mm for 5–10 s per puncture. Argon and Potassium-titanyl-phosphate (KTP) lasers are delivered by flexible fibres, which are used in the contact mode without special tips. With a power setting of 6–16 W all the visible subcapsular cysts can be vaporized and 20–40 punctures can be made in each ovary (Fig. 6.3).
Fig. 6.3
Laparoscopic ovarian drilling with argon laser. The argon laser fibre is introduced through a suction irrigation probe and is applied to the anti-mesenteric surface of the ovary. The fibre is pushed into the ovarian capsule and laser is activated for 1 s with power setting at 6–16 W. Twenty to forty punctures are usually made
Laser Versus Electrocautery
It appears that electrocautery is superior to laser for LOD for a number of reasons. Firstly, electrocautery is more effective than laser in achieving ovulation and pregnancy [32, 36, 37]. Secondly, laser, especially CO2 laser, may be associated with a higher risk of adhesion formation because it produces more surface injury than electrocautery. Thirdly, electrocautery is less costly and easier to set up. In addition, the effect of diathermy may last longer than the laser effect [37]
Transvaginal Ovarian Surgery
In search for less invasive ovarian surgery for PCOS, some authors have described transvaginal approach to apply diathermy, laser or hydrocoagulation to the ovarian stroma. Other authors used transvaginal mini-laparoscopy (fertiloscopy) to perform ovarian drilling. Mio and co-workers were the first to report on the efficacy of transvaginal ultrasound (TVS) guided follicular aspiration in women with PCOS [38]. Syritsa performed TVS-guided ovarian drilling using a specially designed monopolar needle, which has a polyester coating except the 2-mm tip [39]. More recently, Zhu and co-workers described TVS-guided ovarian interstitial YAG-laser-coagulation [40]. They introduced the YAG fibre through an egg-pickup needle (used for in-vitro fertilization [IVF]) into the ovarian substance under sedation to coagulate 3–5 points. Fernandez and co-workers described the use fertiloscopy to perform ovarian drilling [41]. Ramzy and co-workers injected warm saline (75oC) into the ovarian stroma using IVF pickup needle under TVS-guidance [42]. These early reports have shown encouraging results, although the efficacy and safety of these new techniques need to be adequately assessed before they can be recommended for clinical use. The main concern of any transvaginal approach applying any form of energy e.g., electrocautery or laser, is the risk of causing thermal injury to adjacent organs such as the bowel. Two severe adverse events have been reported following fertiloscopic ovarian drilling [43].
Endocrine Effects of LOD
Immediate Effects
After LOD the main hormonal changes include a rapid and persistent fall of androgens (testosterone & androstenedione) with a transient increase of gonadotrophins (LH and FSH) during the first 24–48 h followed later by a gradual fall [26, 24, 44–48]. Preliminary data suggest that insulin sensitivity and lipoprotein abnormalities associated with PCOS are not improved by LOD [28]. In a previous study involving 50 women with anovulatory PCOS, we reported that serum inhibin B concentrations did not change after LOD [49]. This finding makes it unlikely that the action of LOD is mediated via inhibin B.
Long-Term Effects
Naether and co-workers demonstrated that the effects of LOD lasted for 6 years in most of the cases [37]. In another study, Gjonnaess showed that the endocrine effects of LOD seem to be stable for 18–20 years in 50 women with anovulatory PCOS [50]. However, Elting and co-workers demonstrated that women with PCOS gain regular menstrual cycles as they become older [51]. It is therefore possible that the favourable late endocrine effects demonstrated by Gjonnaess could be the effect of age rather than LOD. More recently and in order to investigate this further we compared the results of long-term follow-up of 116 women with anovulatory PCOS who underwent LOD with that of a comparison group of age matched women (n = 38) with PCOS, who did not undergo LOD. We confirmed the long-term beneficial endocrine effects of LOD. In addition, we showed that these long term endocrine improvements were produced by LOD rather than the effect of advancing age alone [52].
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
