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During surgical resection of the ovarian cyst, a clinician with experience of ultrasound and laparoscopy will perform an ultrasound scan during surgery to resect cyst tissue only and preserve healthy ovarian tissue.

A laparoscopic ovarian cystectomy will be performed without ultrasound guidance. This is currently standard clinical practice.

Laparoscopic ovarian cystectomy to be performed under intra-operative ultrasound guidance.

Ultrasound guided laparoscopic ovarian cystectomy

Laparoscopic Ovarian Cystectomy will be performed as standard clinical practice.

Laparoscopic Ovarian Cystectomy

Joseph Yazbek, MD

Lorraine S Kasaven, MBChB

Lorraine Kasaven, MRCOG

Title:

Intra-operative ultrasound guided laparoscopic ovarian cystectomy (UGLOC) as a method of fertility preservation in the management of benign ovarian cysts.

Background:

Approximately 10% of women in the United Kingdom (UK) will undergo surgery for the presence of an ovarian mass during their lifetime. Ovarian surgery, however, is not without risks and can potentially harm healthy ovarian tissue surrounding the cyst, resulting in reduced reproductive potential (the ability of the ovary to produce eggs for fertilisation). Surgical methods to preserve healthy ovarian tissue and improve the chances of successful pregnancy post-operatively are known as Fertility Preserving Surgery (FPS). Evidence suggests that a novel approach of FPS involving the removal of an ovarian cyst performed under ultrasound guidance improves the differentiation between the healthy ovarian tissue and the ovarian cyst. As such, the surgeon can remove the cyst alone, whilst limiting disruption to the healthy surrounding ovarian tissue.

Aim:

The purpose of this study is to assess if surgical removal of an ovarian cyst performed under ultrasound guidance improves the reproductive potential of the ovaries, when compared to surgery performed without ultrasound guidance.

Eligibility

All patients of reproductive age (18-45 years old) with ultrasound features suggestive of a benign ovarian cyst requiring surgical treatment (removal of the cyst). Patients diagnosed with benign ovarian cysts, deemed to be non -harmful to the patient if left untreated, of the following classifications can be included in the study: dermoid, simple cyst, serous cystadenoma, mucinous cystadenoma or endometrioma.

Design:

A multicentre randomised controlled trial. Women across Imperial College London Healthcare and University College London Trusts will be allocated to a surgical treatment group at random: 1) laparoscopic ovarian cystectomy performed without ultrasound guidance (control group) or 2) ultrasound guided laparoscopic ovarian cystectomy performed with ultrasound guidance (fertility preservation surgery: intervention group).

Duration:

3 years

Background:

The use of intra-operative ultrasound has been widely implemented amongst other specialties. However, within gynaecological surgery, it is not as commonly recognized, despite evidence that it can be used as an adjunct to improving minimally invasive surgical techniques. This is primarily due to the improved visualization of the operative field, which can assist more technically difficult surgical procedures, thus minimizing intra-operative complications. The application of ultrasound guidance within gynaecological procedures have included predominantly ovarian cyst aspiration, in vitro fertilization and removal or insertion of intra-uterine devices. Although pre-operative imaging provides procedural planning, it cannot compare to the information gained from real time imaging. For example, in previous studies, intra-operative ultrasound detected more myomas during myomectomy than pre-operative transvaginal imaging. Furthermore, it provides the potential to assess lesion margins, ensuring resection of pathology is complete with negligible damage to surrounding healthy tissues. This is consistent with a recent systematic review, which also demonstrated that albeit a novel technique, amongst various case series, pathology can be safely resected without incurring injury to healthy reproductive tissue. Therefore, intra-operative ultrasound has the potential to improve surgical accuracy, reduce complications and improve patient safety. The application of intra-operative ultrasound as an adjunct to fertility sparing surgery has not been widely researched, with only a few case series reporting surgical outcomes on patients undergoing treatment for pre-malignant or malignant pathology. The aim of this study therefore, is to determine the efficacy of this surgical technique in the management of benign pathology, including the surgical resection of ovarian cysts.

Hypothesis:

Intra-operative ultrasound will prove a significant method of fertility preservation surgery, as measured by a significantly reduced decrease in Anti-Mullerian Hormone (AMH) and antral follicle count (AFC) at 3 and 6 months post-operatively, when compared to the control group.

Study Design:

This will be a multi-centre prospective cohort study carried out as a non-blinded randomised controlled trial. Women will be allocated to either a control group of laparoscopic ovarian cystectomy performed without ultrasound guidance, or to the experimental ultrasound guided laparoscopic ovarian cystectomy (UGLOC) group. All surgeons operating and women recruited to the study will be aware of which group they have been allocated to from the beginning of their participation to the study. The research team aims for equal sample sizes in both groups.

Recruitment:

Women referred to the outpatient gynaecology clinic with a suspected ovarian cyst will be asked about their clinical history and undergo a pelvic transvaginal ultrasound scan (2D and 3D ultrasonography) as part of routine clinical care. If an ovarian cyst is seen on ultrasound, it will be assessed according to local protocols based on simple descriptors and International Ovarian Tumour Analysis (IOTA) simple rules. Depending on the severity of symptoms, nature of the cyst and fulfilment of the inclusion criteria and if the woman is suitable for surgical management, she will then be invited to participate in the study. Participants will be recruited from various general gynaecology clinics, as well as specialist clinics including: ovarian cyst clinic, the IOTA and Rapid access clinics across Imperial and University College London Hospital.

Following consent of participation, the woman will be assigned to either a control or experimental group. A separate research group, not directly affiliated with the project will perform the randomisation process. The research group will print x "control group" labels and x "experimental group," in which each label is then sealed into an individual envelope. All envelopes will be numbered and issued in sequence. During the recruitment process, once the participant has given consent to participate in the trial, a member of the research team will select the envelope in sequence, which will then assign the participant to a group. This will prevent the person performing the randomisation from selecting another envelope if they are not happy with the group allocation.

For this study, it will not be necessary to postpone diagnostic procedures or treatment, and participation will not influence normal treatment.

Surgical Intervention:

The same surgeons will operate on women in both the control and experimental group. This will aim to exclude bias which may otherwise attribute findings to the surgeon operating. Surgery will be performed at Imperial Healthcare NHS Trusts and at the University College London Hospitals NHS Foundation Trust by an experienced clinician.

Data Collection:

The research team will collect the following data: Participant demographics including age, BMI, gravida, parity and gynaecological surgical history. Pre-operative data will include findings from the diagnostic transvaginal scan and measure of ovarian reserve: AMH and AFC. Intra-operative data will include transvaginal findings during surgery (in the experimental group only), such as cyst location and size or any new lesions noted. Residual ovarian volume post cystectomy will also be measured intraoperatively. Histology data will include the histological diagnosis of the ovarian cyst and volume of normal ovarian tissue excised during the cystectomy measured as per margins in mm. Outcomes following surgery including duration of surgery (mins), length of hospital stay (days) and post operative complications will be recorded.

Follow up:

Post-operatively, participants will return to their respective hospital gynaecology clinic responsible for the care and management of the ovarian cyst for follow up at 3 and 6 months. During the appointment a blood test will be taken to assess ovarian reserve by measuring the AMH level. The outpatient gynaecology nurse in clinic or research staff will be responsible for taking the blood sample and will only require one EDTA bottle (yellow top) to be filled (20-40mls). The blood samples will be processed by Imperial College Healthcare Trust laboratories or University College London Hospitals NHS Foundation Trust, depending on the site taken, and will be discarded as per local protocol once the AMH has been determined. There are no specific storage or transfer requirements outside of normal practice. Therefore, samples will be 'podded' to the labs once taken in the usual way. In addition, an ultrasound will be performed during the follow up appointment by an experienced gynaecology specialist trainee or Consultant to assess the AFC and preserved ovarian volume of tissue remaining. Any incidental findings identified on ultrasound scan of gynaecological pathology, will be managed by the responsible clinician and the participants GP will be informed by letter. Follow up appointments should take approximately 20 minutes. The two blood tests and two ultrasound scans carried out during the follow up process are considered standard clinical practice, and therefore not considered additional investigations for the purpose of this research study.

The majority of participants are likely to be discharged following their 2nd clinic appointment 6 months post- surgery, whereby no further involvement in the study is required. If a participant becomes pregnant during the follow up period, clinic appointments will be deferred to 3 and 6 months post-partum.

Intra-operative Ultrasound Guided Laparoscopic Ovarian Cystectomy as a Method of Fertility Preservation

Intra-operative Ultrasound Guided Laparoscopic Ovarian Cystectomy (UGLOC) as a Method of Fertility Preservation in the Management of Benign Ovarian Cysts: Randomised Controlled Trial

It will not be necessary to share individual participant data (IPD) with other researchers outside of the immediate research team. The only members with access to the information will be the PI (Joseph Yazbek) and the tudy Co-ordinator (Lorraine Kasaven).

Post operative AMH level will be measured at 3 and 6 months post surgery.

Post operative AFC will be measured at 3 and 6 months post surgery.

Surgical outcomes will be determined such as the length of hospital stay measured in days in the control and experimental group.

During the procedure, it will be determined whether or not there has been a cyst rupture, whereby cyst contents have dispersed into the abdominal cavity in the control and experimental group.

The duration of surgery will be measured in the control and experimental group

University College London Hospitals

Imperial College London

Pathological Conditions, Anatomical

Anti-Infective Agents

Pharmaceutical Solutions

Tetracycline

Polidocanol

Sclerosing Solutions

injection of sclerosing agent (tetracycline or polidocanol) into ovarian cyst after aspiration of its contents

sclerotherapy

Khaled Abdallah

The aim of this study was to evaluate the role of sclerotherapy (injection of tetracycline or injection of Polidocanol - 95% hydroxypolyethoxydodecane and 5% ethanol -) in treatment of non-neoplastic ovarian cysts by, percutaneous trans-abdominal approach or trans-vaginal approach.

Ovarian cysts are fluid-filled sacs that form in or on an ovary. Such cysts are relatively common. Most are non-cancerous (benign) and disappear on their own. Ovarian cancer is more likely to occur in women over 50.

Most of the patients with ovarian cyst are symptomless and resolves spontaneously. If untreated, complications such as rupture, torsion, malignant transformation may occur.

Cyst rupture can lead to peritoneal signs, abdominal distension and bleeding, irregularity of the menstrual cycle and abnormal vaginal bleeding, dull bilateral pelvic pain may result from the lutein cysts.

Until recent times, surgery in the form of laparotomy or laparoscopy has been the first choice. However, ultrasonography guided aspiration of the cysts as an alternative treatment is the fast catching up and may even be procedure of choice in the management of ovarian cysts in a selected group of women as it has low recurrence rate, low risk, less cost and in most cases no hospital stay.

There are various types of ovarian cysts, such as functional cysts, follicular cysts, corpus luteum cysts, hemorrhagic cysts, theca-lutein cysts, peritoneal inclusion cysts or pseudo-cysts, polycystic ovaries and endometriomas.

Functional cysts do not regress when treated with combined oral contraceptives that they do with expectant management.

Ovarian cysts are common, affecting 20% of women at some point in their lives . Unlike unilocular cysts including septations, solid irregular wall, or internal plaques, the simple ovarian cyst is defined as an anechoic round or oval lesion. The maximum diameter of simple ovarian cysts in premenopausal women is less than 5 cm, they often disappear during the menstrual cycle and do not require further intervention. Larger cysts (5-7 cm) should be followed using ultrasonography. Cysts larger than 7 cm may require advanced imaging or surgery.

Differential diagnosis in the management of an adnexal mass is complex because of the scope of the disorders that may have caused it and the numerous therapies that may be appropriate. It is the risk of malignancy that propels protocols and procedures, as well as the fundamental concept that early diagnosis and treatment in cancer are related to lesser mortality and morbidity. Non neoplastic ovarian cysts in women with menstrual cycles are the most frequently detected masses involving the adnexa. Many of these cysts are functional and resolve spontaneously within a few days to 2 weeks, but they can persist longer.

The management of women with benign ovarian cysts remains controversial. Various treatment protocols use medical treatment (mainly oral contraceptives), ultrasound-guided aspiration, laparoscopy (cystectomy or drainage and ablation of the cystic wall) and laparotomy (cystectomy) Sclerotherapy of ovarian cysts has been attempted to decrease the probability of recurrence. Although ultrasound-guided aspiration is simple and safe, the recurrence rate is high, ranging from 28.5% to 100%. In order to reduce this rate, ultrasound-guided ethanol sclerotherapy for ovarian cysts was first introduced in 1988, and it has been reported by several authors to be simple and safe.

Tetracycline, methotrexate, and ethanol are the most common agents used for sclerotherapy. When compared to women without cysts, sclerotherapy applied to infertile women with ovarian cysts has been shown to reduce pelvic pain without affecting the number of follicles, term pregnancy and abortion rates, the number of obtained oocytes, embryo quality, or hormonal levels.

We chose either tetracycline or Polidocanol as sclerosing agents. Tetracycline because of its antibacterial effect, which may help to control infections. Tetracyclines (tetracycline, doxycycline, minocycline) have been used as sclerosing agent in various clinical settings such as pleural effusions, pneumothoraxes, hydroceles, benign lymphoepithelial cysts of the parotid gland and lymphoceles after renal transplantation.

Polidocanol is a nonionic surfactant sclerosing agent, which consists of 95% hydroxypolyethoxydodecane and 5% ethanol. Polidocanol was invented as an anesthetic agent. Polidocanol is a liquid surfactant having endothelial cell lytic properties.

The mechanism underlying the sclerosing effect was generally attributed to the results of local chemical irritation or inflammatory response. Ethanol induces a combination of cytotoxic damage, dehydration of cells, and production of mediators for inflammation and fibrosis.

Role of Sclerotherapy in Treatment of Non-neoplastic Ovarian Cyst

The main outcome measure was the disappearance of the cyst and the avoidance of surgery. The cyst was considered resolved if follow-up revealed either no cystic lesion or only a follicle-like cyst no more than 30 mm in diameter.

Al-Azhar University

Resident Doctor

Endometriosis

Coagulants

Hemostatics

Thrombin

Fibrin Tissue Adhesive

During laparoscopic ovarian cystectomy, bleeding will be controlled by using a hemostatic agent (EVICEL® Fibrin Sealant, Ethicon, USA), which consist of thrombin and coagulating proteins, mainly fibrinogen and fibronectin. If hemostasis is not fulfilled enough by using it, a additional intervention such as electrocoagulation with bipolar forceps and barbed suture is required to stop bleeding.

During operation, barbed suture will be applied to the inner surface of ovarian parenchyme where ovarian endometriosis was attached. In this group, if bleeding is continued after suturing, additional electrocoagulation with bipolar forceps will be conducted.

During laparoscopic ovarian cystectomy, bleeding will be controlled by using a hemostatic agent (EVICEL®)

Hemostatic agent (EVICEL®) application during laparoscopic ovarian cystectomy

During laparoscopic ovarian cystectomy, suturing of ovarian inner surface will be conducted to stop bleeding

suturing with barbed sutures during laparoscopic ovarian cystectomy

Hyunji Lim, MD

Hee seung Kim, MD/PhD

Ga Won Yim, MD/PhD

Chae Hyeong Lee, MD/PhD

Hee Seung Kim, MD/PhD

This study aims to evaluate the efficacy of preservation of ovarian function, hemostasis, and safety of a hemostatic agent versus suturing during laparoscopic ovarian cystectomy for ovarian endometriosis.

In women with endometrioma who plan to undergo laparoscopic ovarian cystectomy, surgical technique can influence postoperative ovarian function because of removal of normal ovarian tissue with ovarian cyst and damage to ovarian tissue during bleeding control after stripping of endometrioma. This study is designed to compare hemostatic sealant to suturing in terms of hemostatic function, safety and preservation of ovarian function.

Ovarian function of all patients will be evaluated on pre op, post op 12 weeks, post op 48 weeks by measuring AMH and ovarian volume. And Hemostatic function will be evaluated by measuring serum hemoglobin, blood loss during operation, etc.

Comparison of Hemostatic Agent to Suture in Terms of Hemostatic Function and Preservation of Ovarian Function

A Multi-center, Randomized, Investigator-initiated Trial to Evaluate the Efficacy of PRreservation of ovArian Function, Hemostasis, and sAfety of a Hemostatic Agent Versus Suturing During Laparoscopic Ovarian Cystectomy for Endometrioma

Reduction rate of AMH level in serum 12 weeks after surgery

Reduction rate of AMH level in serum 48 weeks after surgery

Stop-watch will be operated right after finishing stripping endometrioma. It will be evaluated how long the time have been spent for bleeding control

Stop-watch will be operated right after finishing stripping endometrioma. It will be evaluated whether hemostasis is finished within 10 minutes

The volume of blood loss will be estimated by using simple visual assessment technique referring to gauze count and irrigation bottle

whether patients are transfused during admission period

any adverse events during admission period

time from anesthesia start to delivery of patient to recovery room

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Intra-operative Ultrasound Guided Laparoscopic Ovarian Cystectomy as a Method of Fertility Preservation	NCT05032846	Benign Ovarian ...	Ultrasound guid... Laparoscopic Ov...	18 Years - 50 Years	Imperial College London
Role of Sclerotherapy in Treatment of Non-neoplastic Ovarian Cyst	NCT06399744	Benign Ovarian ...	sclerotherapy	15 Years - 48 Years	Al-Azhar University
Comparison of Hemostatic Agent to Suture in Terms of Hemostatic Function and Preservation of Ovarian Function	NCT04643106	Benign Ovarian ...	Hemostatic agen... suturing with b...	19 Years - 45 Years	Seoul National University Hospital
Intra-operative Ultrasound Guided Laparoscopic Ovarian Cystectomy as a Method of Fertility Preservation	NCT05032846	Benign Ovarian ...	Ultrasound guid... Laparoscopic Ov...	18 Years - 50 Years	Imperial College London
Role of Sclerotherapy in Treatment of Non-neoplastic Ovarian Cyst	NCT06399744	Benign Ovarian ...	sclerotherapy	15 Years - 48 Years	Al-Azhar University

Spots Global Cancer Trial Database for benign ovarian cyst