Fertility Sparing Procedure using Carbon Dioxide Fiber Laser Vaporization of Ovarian Endometrioma

Podsumowanie

In this protocol, CO₂ fiber laser technique is demonstrated for the surgical treatment of ovarian endometriosis, which represents a viable alternative in terms of fertility preservation with the major advantage of not being dependent on the surgeon's skills and personal experience.

Streszczenie

The surgical management of endometrioma is still a matter of debate. Cystectomy, which is recognized as the standard technique, seems to be associated with a potential reduction in the ovarian reserve due to the inadvertent removal and thermal damage of healthy ovarian tissue. New ablative techniques with reduced tissue penetration depth and less thermal spread to the surrounding parenchyma may represent a viable alternative to cystectomy. For these reasons, the aim of this manuscript is to demonstrate the ablation of the endometrioma capsule using a CO₂ fiber laser technique and discuss the clinical outcomes. Once the cyst has been drained and washed, a biopsy is taken. After cyst eversion, vaporization of the inner surface of the cyst is performed using a CO₂ fiber laser. The technique is simple and reproducible as even young surgeons without any surgical experience were more confident in performing laser CO₂ vaporization instead of cystectomy. The positive effects of CO₂ technology are reported in a randomized controlled trial, where the postoperative changes in the antral follicular count (AFC) and antimullerian hormone (AMH) levels were compared between patients who had their endometrioma excised (cystectomy) and those who had undergone endometrioma vaporization with CO₂ laser. The patients treated with CO₂ laser showed significantly increased AFC without a reduction in serum AMH levels as compared to the cystectomy group, in which both parameters were significantly reduced. The postoperative pregnancy rate was also assessed, and comparable pregnancy rates were found after both treatments. On the contrary, patients treated with the CO₂ fiber laser technique had more favorable in-vitro fertilization (IVF) outcomes compared to cystectomy.

In conclusion, the CO₂ fiber laser technique may represent a viable alternative to cystectomy in the surgical treatment of endometrioma in terms of ovarian preservation, pregnancy rates, and IVF outcomes. Moreover, it has the advantage of being independent of the surgeon's skills and personal experience.

Wprowadzenie

The best surgical treatment for ovarian endometriosis, especially when fertility preservation is a priority for women with a desire for offspring, is still a matter of debate. Although cystectomy is still the recommended technique¹, previous studies have raised some concerns about its possible detrimental effect on ovarian reserve and reproductive outcomes due to the inadvertent removal of healthy ovarian parenchyma^2,3,4.

Indeed, unlike non-endometriotic cysts, endometrioma is a pseudocyst not surrounded by a real anatomic capsule⁵, in which inflammation caused by free iron and reactive oxygen species (ROS) plays a role in the substitution of the surrounding normal ovarian cortical tissue with fibrous tissue⁶. Thus, the absence of a clear cleavage plan may lead to an increased risk of removing healthy ovarian parenchyma, even when cystectomy is performed by experienced surgeons^7,8.

Moreover, cystectomy-mediated injuries could lead to compromised vascularization due to the diffusion of thermal damage to the surrounding healthy ovarian parenchyma during coagulation, as shown by previous findings where adverse changes in the ovarian artery blood flow were reported after cystectomy^9,10,11.

At our institution, concerns about ovarian damage after cystectomy led to the introduction of CO₂ fiber laser technology since in 2015. This surgical procedure, which can deliver energy with a controlled tissue penetration depth and little thermal spread, was inspired by the work of Jacques Donnez more than 20 years ago¹².

Although ablative techniques involving CO₂ fiber laser technology do not represent a novelty in the surgical management of endometrioma, many surgeons may not feel confident with the procedure. Indeed, only a few studies have investigated the impact of this technique on ovarian reserve, pregnancy outcome, and the rate of recurrence of endometriosis. The aim of this protocol is to provide an overview of the promising results obtained using the CO₂ fiber laser technology since its introduction in 2015 and to describe the simplicity and reproducibility of this technique.

Firstly, in order to assess the impact of CO₂ fiber laser vaporization and cystectomy on ovarian reserve markers, a multicenter randomized trial was conducted between 2017 and 2018. A total of 60 patients were randomly assigned either to Group 1 (cystectomy: 30 patients) or Group 2 (CO₂ laser vaporization: 30 patients) at a ratio of 1:1, by using a computer-generated randomization list that used the simple randomization method¹³. To investigate postoperative spontaneous conception, a prospective observational study was conducted between 2015 and 2019 on 142 women, comparing cystectomy and laser vaporization¹⁴. When pregnancy was not achieved after CO₂ fiber laser vaporization, patients were referred to in-vitro fertilization (IVF) clinics and were then included (n = 26) in a prospective observational study to investigate ovarian responsiveness to controlled ovarian stimulation¹⁵. Following this, a retrospective analysis of a larger sample size study population (n = 125, women with or without offspring desire), who were treated between 2015 and 2018 and whose follow-up lasted at least 12 months, was performed to assess the recurrence rate of a cyst and/or pain symptoms after both the surgical techniques¹⁶.

Protokół

All the studies were conducted in compliance with the Declaration of Helsinki, as outlined in the International Conference on Harmonization Guidelines for Good Clinical Practice. Written informed consent for data collection and anonymous publication of disease-related information is routinely obtained at the institution during patient interviews preceding surgical treatment. Women participating in the randomized controlled study signed a specific informed consent form. The Institutional Review Board of the institution approved all the studies. A diagram of the studies' protocols is shown in Figure 1.

1. Patient selection

1. Only include women with primary unilateral or bilateral endometriomas, with the largest cyst diameter between 3-8 cm, of reproductive age, and who have undergone surgery at San Raffaele Scientific Institute for pain or infertility.
2. Additionally, exclude patients aged ≥ 40 years; with previous surgery of the ovaries, unilateral oophorectomy, salpingectomy, or hysterectomy; with endocrine diseases; undergoing hormonal treatment within 3 months of ovarian reserve assessment; or with suspicion of ovarian atypical endometriosis at the pre-operative ultrasound evaluation stage.

2. Patient characteristics

1. Identify the basal patient characteristics as follows. At baseline (before surgery), perform a detailed medical interview and pelvic ultrasound scan. In particular, collect data regarding age, surgical indication, offspring desire, body mass index (BMI), volume (expressed in cm³) and mean diameter (expressed in cm) of unilateral or bilateral endometrioma, and the volume of each ovary.
2. For ovarian reserve analysis, check the antral follicular count (AFC) and antimullerian hormone (AMH) levels. At baseline (during the first 2-3 days of the menstrual cycle), evaluate the AFC by pelvic ultrasound, and collect blood samples to determine AMH levels. Assess the AFC in both ovaries, before and after surgery, by counting the number of follicles with an average diameter of 2-10 mm.

3. Surgical technique

NOTE: A team of surgeons with extensive experience in the treatment of endometriosis is required.

1. First, place the patient on the operating table with their legs placed into stirrups.
2. After administering general anesthesia, place the patient in the lithotomic position, a variation of the supine position in which the legs are separated from the midline in a 30° to 45° abduction with the hips flexed until the thighs form an angle between 80° and 100°.
3. Establish a sterile field by cleaning the following areas with a sponge soaked in antiseptic solution: the apex of the umbilicus, the abdomen, the perineum, and the top third of the thighs. Then, scrub with a gauze drenched in iodine solution the vulva and, when possible, the vaginal interior up to the cervix and discard it. Repeat this step 3x.
4. With a new sponge drenched in iodine solution, swab the anus twice and discard it. Dry the prepared external areas with a sterile towel and place sterile drapes. Insert a urethral catheter for continuous bladder drainage.
5. When possible, with the use of an anterior and posterior vaginal retractor, expose the cervix and insert the uterine manipulator into the cervix. Create a pneumoperitoneum by either a Verres needle inserted at an angle of 45° in non-obese patients to 90° in obese patients) or using the open technique (a small, 1 cm incision is made below the umbilicus on the midline). Keep the insufflation pressure between 12 mmHg and 14 mmHg.
6. Insert a laparoscope and inspect the upper and lower abdomen. After positioning the patient in a slight Trendelenburg position, place the other laparoscopic access (usually two or three). Perform either CO₂ fiber laser ablation or stripping technique as described below.
7. One-step CO₂ fiber laser vaporization
   1. Firstly, mobilize both adnexa to restore the normal anatomy of the pelvis. Then, by using an aspiration or irrigation device, drain the cyst content and irrigate and inspect its inner wall. Take a biopsy of the cyst wall using scissors and send it for routine histological examination to confirm the diagnosis of endometriosis.
   2. Select the basic operation mode and set the device to fiber laser mode with the continuous wave and constant timed-exposure mode at a power density of 13-15 W¹³.
   3. Evert the cyst with grasping forceps in order to expose the inner cystic wall and completely vaporize the inner wall with a CO₂ fiber laser in a radial way, starting from the center to the periphery, keeping the tip of the fiber at a distance of at least 1 cm from the cystic surface (see Table of Materials).
   4. Do not suture the ovary after vaporization. Carefully control any source of bleeding at the end of the procedure using the water test (i.e., washing the bleeding sites to visualize and achieve hemostasis selectively) or by slightly reducing the pneumoperitoneum.
8. Cystectomy
   1. Start with adhesiolysis in order to free the ovaries from the surrounding structures. Make a sharp cortical incision on the thinnest part of the cyst, just enough to identify the correct cleavage plane. Avoid making the incision close to the fallopian tube or fimbriae.
   2. Take the edges of the incision with two grasping forceps and strip out the cyst from the healthy ovarian parenchyma by delicate traction and counter traction maneuvers.
   3. After removal of the cyst, perform selective hemostasis with bipolar coagulation using the water test, mainly on the edges of the ovary, to reduce the risk of ovarian damage¹³.
9. At the end of the surgery, carefully remove the uterine manipulator if positioned. Suture the fascia with a medium absorption rate braided suture size 0 and the skin with a quick absorption rate suture size 3-0. Place patches on all the incisions and remove the urethral catheter the day after the surgical procedure.

4. Post-operative follow-up and testing

1. Identify the endometriosis stage. Perform endometriosis staging according to the revised American Society for Reproductive Medicine (r-ASRM) classification¹⁷. Calculate the lesion score and total score at the end of surgery based on the surgery report, according to the standards of the r-ASRM classification, and report these as the r-ASRM score.
2. Follow-up 30 days after the surgical procedure. After surgery, refer the patient to the endometriosis outpatient clinic for follow-up. In the case of patients with no immediate pregnancy intention, prescribe hormonal therapy (progestins or estroprogestins).
3. Assess recurrence rate.
   NOTE: To assess the recurrence rate, the minimum follow-up duration is 12 months.
   1. Perform periodic gynecological examinations at intervals ranging from 3-12 months, according to patients' offspring desire or onset of symptoms (i.e., dysmenorrhea, chronic pelvic pain, dyspareunia).
   2. At every follow-up, perform a gynecological examination as well as a transvaginal ultrasound to check for recurrence of the endometriotic cyst. In case of the identification of a cyst with a typical sonographic aspect and a diameter of more than 10 mm arising on the operated ovary, confirmed by transvaginal ultrasound, consider it as cyst recurrence. Assess the symptoms of cyst recurrence by interviewing the patient.
4. Assess pregnancy outcomes. Allow patients wishing to conceive to attempt spontaneous conception for a period of 6-9 months in the case of CO₂ fiber laser vaporization and for a period of 12 months after cystectomy. If spontaneous conception fails, refer the patients immediately for assisted reproductive techniques (ART).
   NOTE: Pregnancy is defined as the evidence of a vital embryo in utero by transvaginal ultrasound at 6 weeks of pregnancy. As suggested by usual clinical practice, in case of the absence of fetal cardiac activity at 6 weeks of pregnancy, wait for at least 7-10 days to diagnose a pregnancy loss. The time taken for spontaneous conception is defined as the interval between surgery and spontaneous conception (or the first IVF when natural conception fails). Do not include patients who become pregnant following oocyte donor-IVF.

Wyniki

The details of the outcomes of the included studies are shown in Table 1.

Ovarian reserve after one-step laser vaporization versus cystectomy in the treatment of ovarian endometrioma¹³
The aim of this randomized controlled study was to compare the two surgical procedures for endometrioma treatment (cystectomy versus CO₂ laser vaporization) in terms of their impact on ovarian reserve markers (AFC and serum AMH concentrat...

Dyskusje

The aim of this method is to provide a comprehensive overview of our experience with CO₂ fiber laser technology at San Raffaele Scientific Institute since 2015, when the use of this technique first started for the surgical management of endometriomas. Since endometriosis is a chronic benign gynecological condition affecting women of reproductive age with potential offspring desire, surgical techniques need to be as fertility-sparing as possible.

A Cochrane review^18...

Materiały

Name	Company	Catalog Number	Comments
CO2 fiber laser	UltraPulse Duo system, Lumenis Ltd	AC-1059590
Insufflation Needle	Covidien	10065003
Laparoscopic Forceps	Erbe Elektromedizin GmbH	20195-133
Manipulator	Lumenis Ltd
UltraPulse Duo	Lumenis Ltd	GA-2000000	CO2 laser system
VIO 3	Erbe Elektromedizin GmbH	10160-000	electrosurgical unit
Voluson S8	GE Healthcare	186958SU5	ultrasound scan voluson system 8