Combined Treatment Techniques
Developed in 1996 by Donnez et al., the three-stage technique consists of laparoscopic cyst drainage followed by gonadotropin-releasing hormone (GnRH) agonist treatment for 3 months to reduce cyst diameter, and then a second laparoscopic procedure for vaporization of the cyst wall by CO2. This combination technique is potentially more beneficial than cystectomy because normal ovarian tissue is not removed and it causes less thermal damage. In a prospective randomized control trial comparing cystectomy and the three-stage technique, Tsolakidis et al. found cystectomy patients had lower AMH levels after surgery, which suggests that ovarian reserve is less compromised with the three-stage technique ( Table 7 ). The study also found that the AFC was significantly higher in the patients who underwent the three-stage technique ( Table 3 ). However, as previously outlined, thermal damage is still a risk. A drawback to the three-stage technique is the length of time that is needed before IVF can be started. More research is needed to determine if this procedure increases IVF outcomes as compared with expectant management.
Combined Ablation & Cystectomy
In 2010, Donnez et al. developed a surgical technique that combines cystectomy and CO2 ablation. A surgeon removes 80–90% of the cyst with the cystectomy technique and uses the laser to ablate the remaining cyst wall. A GnRH agonist is then used for 3 months following surgery. This technique reduces the risk associated with cystectomy and recurrence associated with ablation alone. 6 months after surgery, the ovarian volume and AFC in the operated ovary and contralateral ovary were not significantly different ( Table 3 ). The pregnancy rate was 41% after a mean follow up of 8.3 months ( Table 6 ). Recurrence was noted in one case (2%) ( Table 5 ). IVF rates were not reported by Donnez et al., and more research is needed in order to assess the benefits of combined ablation and cystectomy on infertile women who do not achieve spontaneous pregnancy following surgery. The benefit of this surgery over traditional laparoscopic procedures is that recurrence rates are low, although a longitudinal randomized control trial study is needed to fully assess recurrence rates. For both the three-stage technique and combined ablation and cystectomy, more research is needed on the potential of using the KTP or plasma laser to maximize fertility outcomes. A potential disadvantage to this procedure is that it can remove healthy cortex and cause thermal damage.
Cystectomy With Vasopressin
In a technique proposed by Saeki et al., vasopressin was injected into the cyst to reduce the amount of bipolar coagulation needed for hemostasis and the amount of healthy tissue that is accidentally removed, since the injection of vasopressin improves the view of the plane of cleavage between the cyst and the ovary. Saeki et al. reported a significant reduction in the number of procedures requiring coagulation to achieve hemostasis. Saline was injected to help reduce the risk of brachacardia and also to assist in hydrodissection. Saeki et al. recommended vasopressin as a beneficial technique in treating endometriomas to reduce the potential loss of ovarian reserve. The study, published in 2010, is the only known study to assess vasopressin, and more research is needed to determine if the vasopressin technique could help improve pregnancy rates, both spontaneous and after IVF.
Cystectomy With Gelantine-thrombin Matrix Seal
In 2009, two research groups evaluated the use of a gelantine-thrombin matrix seal (FloSeal®, Baxter Inc., IL, USA) for hemostasis as a replacement for coagulation. Both research groups found FloSeal to be useful following cystectomy. However, longitudinal studies and studies including IVF outcomes following the procedure are needed in order to assess the benefits of FloSeal in endometrioma patients.[66,67] A clinical trial recently examined AMH levels following cystectomy with a hemostatic matrix versus bipolar coagulation, but the results have yet to be reported.
Aspiration With Sclerotherapy
Ovarian sclerotherapy uses ultrasound-guided aspiration with a sclerosing agent such as 95% ethanol (EST) or methotrexate. The purpose of the sclerosing agent is to prevent cyst regrowth by chemically destroying the wall of the cyst. This treatment option is less invasive than laparoscopic surgery and takes approximately 20–30 min to perform. Sclerotherapy, unlike other treatment options, is less likely to damage healthy ovarian tissue and, thus, is less likely to reduce ovarian reserve. Risks associated with sclerotherapy include infection, internal bleeding, and irritation from the sclerosing agent. To reduce irritation, the agent is removed after 10 min, and the pelvic area is rinsed with saline.
Endometrioma patients treated with EST had significantly higher ongoing pregnancy rates after one IVF cycle than patients with moderate to severe endometriosis but no ovarian endometrioma ( Table 4 ). The endometriosis-only group also had a significantly reduced ovarian reserve, as measured by FSH and AMH levels, compared with the EST group ( Table 2 & Table 7 ). In a prospective controlled clinical trial, patients were divided into an aspiration with 95% EST followed by IVF–intracytoplasmic sperm injection (ICSI) group or a control group of only IVF–ICSI. Although significance levels were not reported, the number of oocytes retrieved, fertilization rate, embryos available, implantation rate, pregnancy rate and continued pregnancy rate were all higher in the aspiration with ethanol group ( Table 1 ). This study suggests that ethanol sclerotherapy may improve ART outcomes, but more research is needed to determine if these differences are significant.
Methotrexate is a folate antagonist that prevents DNA synthesis and is believed to suppress cells in the endometrioma cyst wall. A randomized control trial by Shawki et al. compared cyst recurrence rates in women with endometriomas treated with aspiration or aspiration with methotrexate. A significant difference was noticed in the persistence of the cysts – only 14% of women had a cyst remaining after three treatments in the methotrexate group, compared with 45.3% of women in the aspiration-only group ( Table 5 ). Methotrexate is used in ectopic pregnancies and, therefore, potential risks such as increased oocyte damage, spontaneous abortion and congenital abnormalities may be associated with its use in women trying to achieve pregnancy. However, in a case–control study of unilateral endometriomas, the AFC, number of oocytes retrieved, fertilization rate and embryo quality were not different between the ovary treated with methotrexate and the unaffected contralateral ovary ( Table 3 & Table 4 ). The researchers used methotrexate 30 mg diluted with 3 ml of saline, which is one-third of the dose normally used with ectopic pregnancies. The researchers suggested that the low dose was less toxic, and the results demonstrated that methotrexate did not negatively affect oocyte quality and future pregnancy outcomes. Twenty-one out of the 65 women using ART became pregnant, and 14 of these pregnancies resulted in a live birth – none of the neonates had post delivery congenital abnormalities ( Table 4 ). These results further demonstrate that a low dose is a plausible treatment option. One potential downside to aspiration with methotrexate is the amount of waiting time needed until an IVF cycle can be started. In this particular study, the authors waited for a minimum of 3 months to begin COH. More research is needed to determine if this treatment is plausible in women with bilateral endometriomas and if methotrexate improves IVF outcomes compared with expectant management.
Overall, newer combined techniques seem to not be as damaging to the ovary as traditional surgical techniques, but recurrence rates are high and more research is needed on IVF outcomes.
Expert Rev of Obstet Gynecol. 2013;8(1):29-55. © 2013 Expert Reviews Ltd.