Preoperative relugolix combination therapy in laparoscopic myomectomy: a case series evaluating impact on surgical planes and operative outcomes

Surgical management remains a key treatment for symptomatic uterine fibroids, with myomectomy being the preferred option for patients aiming to preserve fertility or retain their uterus. While open myomectomy has traditionally been the mainstay, advancements in minimally invasive techniques mean that laparoscopic myomectomy is the gold standard in carefully selected women [1]. Together with robotics, these modalities have significantly transformed the surgical landscape, offering reduced recovery times, lower complication rates, and enhanced precision [2].

To ensure successful outcomes, minimise complications, and reduce the need for blood transfusions, optimising patients before surgery is crucial. Therefore, medical therapy plays a vital role in improving preoperative haemoglobin levels and potentially reducing fibroid size. This optimisation helps to create favourable surgical conditions that can allow the enucleation of large or multiple fibroids while also aiming to reduce blood loss and operative time [3]. Gonadotropin-releasing hormone (GnRH) agonists, such as leuprolide acetate, have been extensively utilised to optimise surgical outcomes through reducing fibroid size, improving anaemia, and decreasing vascularity [3]. However, GnRH agonists induce a hypoestrogenic state associated with vasomotor symptoms and bone loss, which can limit their tolerability. The use of GnRH agonists has also been associated with challenges in developing surgical planes as a result of adherence of the pseudocapsule and fibroid necrosis, which may complicate the procedure and prolong operative times [4, 5].

Other alternatives, such as selective progesterone receptor modulators (SPRM), including Ulipristal Acetate (UPA), have been shown to significantly reduce fibroid size and improve symptoms, such as heavy menstrual bleeding (HMB) and pelvic pain. Studies report around 25% fibroid volume reduction after 3 months of therapy [6]. This shrinkage can be particularly beneficial in cases of large or multiple fibroids, where reducing the uterine size can facilitate laparoscopic myomectomy [7]. Previous small studies specifically looking at UPA and myomectomy showed no compromise in patient outcomes [4]. However, although it was effective [5], this drug was withdrawn in most countries due to liver toxicity.

Recent options include GnRH receptor antagonists combined with hormonal add-back therapy, such as Relugolix combination therapy (Relugolix–CT), which can offer a promising option for preoperative optimisation in patients with symptomatic fibroids. While these agents may provide benefits in symptom control and surgical optimisation, their impact on surgical tissue has not yet been studied.

Relugolix–CT (40 mg relugolix, 1 mg oestradiol, and 0.5 mg norethindrone acetate [NETA] once daily) has been approved for the management of uterine fibroid-associated HMB and moderate-to-severe uterine fibroid symptoms [8]. Clinical trials have demonstrated significant reductions in menstrual blood loss [9] and 24 weeks of treatment demonstrated a significant improvement in quality-of-life metrics among patients treated with Relugolix–CT [10]. The combination of relugolix with oestradiol and norethisterone acetate as add-back therapy helps to mitigate hypoestrogenic symptoms and maintains BMD [11].

Optimal treatment duration for Relugolix–CT is not yet known, but reduction in menstrual blood loss has been demonstrated by 4 weeks of therapy, and was sustained until 24 weeks of treatment [12].

Early reports suggest a 12–17% fibroid volume shrinkage with Relugolix–CT [13], which may provide a more favourable surgical field when compared to preoperative GnRH agonist treatment by reducing fibroid and uterine size without compromising tissue dissection [14].

While there is substantial evidence supporting the symptom control and size reduction benefits of both GnRH agonists and Relugolix–CT, their relative impact on laparoscopic myomectomy outcomes remains unclear. Most existing studies focus on open myomectomy, limiting the applicability of findings to minimally invasive procedures [14]. In addition, the influence of Relugolix–CT on surgical dissection and operative parameters, such as operative time and blood loss, warrants further investigation.

This paper presents three cases to explore the operative effects, both positive and negative, of pretreatment with Relugolix–CT on laparoscopic myomectomy compared to no pretreatment.

This study was a retrospective case series of prospectively collected data from patients who underwent laparoscopic myomectomy at Whipps Cross University Hospital, London, over a 6-month period. Patients were identified from surgical records, and relevant clinical data were retrieved from electronic medical records. Women aged 18–50 years with symptomatic uterine fibroids undergoing laparoscopic myomectomy were included if complete preoperative and intraoperative data were available. Patients with a history of fibroid surgery in the preceding 12 months were excluded. The study population was divided into two groups: those who received preoperative Relugolix–CT therapy, and those who underwent surgery without medical pretreatment. Surgeons were not blinded to use of preoperative therapy.

Demographic and clinical characteristics, including age, body mass index (BMI), fibroid size, number of fibroids, and presenting symptoms, were collected. Operative parameters assessed included total operative time, estimated blood loss (EBL), fibroid characteristics, intraoperative findings, such as surgical plane integrity, and postoperative outcomes, including hospital length of stay and complications. Blood loss was estimated by a combination of visual assessment and measurement of volume in suction canisters, adjusted for irrigation fluid.

A standardised surgical protocol was followed across all cases. Abdominal entry was via an intraumbilical incision, or at Palmer’s point in instances, where the uterus exceeded 14 weeks in size. This was followed by placement of two 5-mm lateral ports and one suprapubic port. Haemostatic measures included the administration of 800 mcg rectal misoprostol and intramyometrial injection of vasopressin. Uterine positioning was facilitated using the ClearView™ uterine manipulator (Clinical Innovations). In most cases, the Thunderbeat™ ultrasonic device (Olympus) was the primary energy source, with a 5-mm myoma screw and grasping forceps employed to provide traction and countertraction. Laparoscopic myomectomy was performed using the intracapsular technique [15] to detect, expose, and open the myoma pseudocapsule for enucleation.

Closure of the uterine defect was performed in two or three layers using STRATAFIX™ barbed sutures (Ethicon), and Interceed™ (Gynecare) was applied to minimise adhesion formation. Electromechanical in-bag morcellation was carried out through the suprapubic port, and myoma fragments were retrieved and sent for histopathological evaluation. All histology reports confirmed benign pathology.

Statistical analysis was performed using descriptive statistics to summarise baseline characteristics and surgical outcomes. Continuous variables were expressed as mean ± standard deviation. Ethical approval was not required for this retrospective service evaluation, and all data were anonymised in accordance with institutional guidelines.

A total of 24 patients who underwent laparoscopic myomectomy during the study period were included. Of these, three patients received a preoperative course of Relugolix–CT for 3, 6, and 9 months, respectively, while 21 patients underwent surgery without pretreatment. Baseline demographic and clinical characteristics, including age, body mass index (BMI), and fibroid size, were comparable between the two groups (Table 1). The most common indications for surgery were HMB, bulk-related symptoms, and fertility concerns.

This is the first case series providing an initial evaluation of the impact of preoperative Relugolix–CT therapy on laparoscopic myomectomy outcomes. Relugolix–CT use for symptom relief as part of the medical management of uterine fibroids is well-established [10], but its role in surgical optimisation has remained uncertain. Our findings suggest that pretreatment with Relugolix–CT does not negatively impact intraoperative blood loss or overall surgical outcomes, supporting its use without concern for worsening operative conditions.

A key observation was that fibroid capsule integrity was preserved in all Relugolix–CT-pretreated cases, indicating that Relugolix–CT does not distort surgical planes or hinder myomectomy. This is an important consideration, as some medical therapies for fibroids have been associated with increased fibrosis or altered tissue consistency, potentially complicating surgical dissection [4]. The absence of such effects with Relugolix–CT suggests that it does not interfere with standard laparoscopic myomectomy techniques.

However, it is important to acknowledge that surgical plane integrity was assessed subjectively by operating surgeons and not through histological confirmation. In addition, surgeons were not blinded to the pretreatment status, which may have introduced observational bias.

Although blood loss was lower in the Relugolix–CT group, this difference was not statistically significant, indicating that while Relugolix–CT may contribute to reduced vascularity, it does not dramatically alter intraoperative bleeding. Likewise, operative time and length of hospital stay were comparable between the Relugolix–CT and control groups. These findings further support the conclusion that Relugolix–CT does not negatively affect the technical aspects of myomectomy and are consistent with previous studies showing pre-surgical Relugolix–CT to be effective for HMB and safe intra-operatively [14].

Importantly, there were no complications in either group, reinforcing the safety of laparoscopic myomectomy regardless of preoperative Relugolix–CT use. The lack of adverse surgical effects suggests that Relugolix–CT remains a useful preoperative option for uterine fibroid symptom control without introducing additional surgical challenges.

This study has several limitations. The statistical power of our findings is limited by the small sample size, particularly in the Relugolix–CT group. As this was a retrospective study, the decision to initiate Relugolix–CT was made on clinical grounds rather than by random allocation, introducing the possibility of selection bias. In our cohort, pretreatment was typically initiated in patients with symptomatic anaemia to optimise haemoglobin prior to surgery. In this very small, non-blinded treatment group, baseline characteristics such as severity of symptoms and size of fibroids could not be controlled for, which could potentially confound results.

In addition, non-blinding of surgeons to preoperative treatments, together with variability in surgical technique, may also influence the results by introducing observational bias in assessment of surgical planes and capsule integrity. Intraoperative observations were consistent across cases, and used the technique described by Tinelli et al. [15]. However, the lack of objective or histological assessment of surgical plane integrity limits the robustness of these findings, as capsule integrity was based solely on descriptive observation. Future studies, ideally involving randomised controlled trials, are needed to confirm these findings and further explore Relugolix–CT’s role in surgical planning.

Relugolix–CT pretreatment did not negatively impact surgical planes, blood loss, or overall surgical outcomes in this laparoscopic myomectomy case series. These findings suggest that its use for preoperative symptom control does not compromise the surgical approach, supporting its safety and feasibility in patients undergoing myomectomy. Further high-quality studies are required to validate these early findings.