The Fibroid Removal in Sterility Treatment ‘‘FIRST’’ Survey: A European Society of Gynecology Online Questionnaire

1. Introduction

Fibroids are the most common benign tumours of the female genital tract, with a prevalence ranging from 4.5% to 68.6% during female reproductive years [1]. Also known as leiomyomas (or myomas), fibroids arise in the myometrium and are stimulated by oestrogen and progesterone; therefore, they may progress following menarche and before menopause, whereas they are more likely to regress in the post-menopausal period [2]. Although the majority of patients with fibroids are asymptomatic [3], patients may also experience a variety of symptoms such as heavy menstrual bleeding (HMB), pelvic pain or pressure symptoms [4]. Certain fibroids may also negatively affect female fertility and increase the risk of recurrent pregnancy loss [5], possibly due to a variety of mechanisms such as increased uterine peristalsis, neuroendocrine actions of the myoma pseudocapsule, and altered gene expression involved in endometrial receptivity [6]. The size and location of the fibroid may influence its impact on fertility [7]. Fibroids are also responsible for a significant financial burden, with direct healthcare costs estimated to range between 4 and 10 billion dollars in the USA [8].

Fibroids may vary greatly in terms of size, number and localisation. Depending on their location in relation to the endometrium, myometrium and uterine serosa, fibroids are commonly subclassified from 0 to 8, according to the widely-used International Federation of Gynaecology and Obstetrics (FIGO) “leiomyoma subclassification system” [9,10]: fibroids 0–2 are ‘‘submucous’’, fibroids 3–8 are ‘‘other’’ (intramural: 3 and 4, subserosal: 5–7, other: 8), while the classification also recognises hybrid fibroids that impact both the serosa and the endometrium (two numbers listed, separated by a hyphen). Given the heterogeneity of the condition and associated clinical picture, a “one size fits all” approach for patients with fibroids would be unrealistic.

In recent years, we have witnessed an undeniable increase in the uptake of minimally invasive, uterus-sparing approaches for the management of fibroids [11]. Although evidence supports the role of myomectomy in improving myoma-related symptoms and quality of life [12], the evidence is less clear regarding the impact of fibroids per se, as well as their removal, on fertility outcomes [5,13]. Following this, considerable variations worldwide have been documented on fibroid management in the context of fertility [14,15,16], while a recent systematic review highlighted the urgent need for high-quality guidelines to guide clinical practice [17].

The aim of our study, an online survey using a 27-question questionnaire distributed to gynaecologists who are members of the European Society of Gynecology (ESG), was to capture their views and clinical practices regarding minimally invasive, fertility-sparing management of fibroids, focusing on fertility outcomes.

2. Materials and Methods

This was a prospective cohort study. The initial questionnaire consisted of 30 questions that, following review by all authors, was reduced to 27 questions in the final form. An anonymous, online survey was subsequently designed on the platform ‘’SurveyPlanet’’ (app.surveyplanet.com), including those 27 questions, which was approved by the board members of the ESG. An invitation link was automatically created by the aforementioned platform and shared with members of the ESG via email. Surveys were electronically completed and answers prospectively collected, while survey administrators had real-time access to data. Institutional Review Board (IRB) approval was not required for this study; however, approval by the ESG board of directors was sought and granted in advance of initiating the online survey.

Questions 1 to 5 related to the participants’ background, aiming to capture their relevant training and surgical experience (Table 1). Questions 6 to 27 related to the clinical management of fibroids (Table 2). Answering all questions, except question 8, was mandatory in order to proceed with the next question and submit the answers. For all questions except question 16, only one answer was possible. For question 16, multiple answers were acceptable.

Sample size calculation in advance was not applicable for this study. The survey was closed by the survey administrators at 3 months following initiation of the survey. Therefore, the size of our availability sample was merely based on the number of participants that responded to our invitation and answered all questions of our online survey. Statistical analysis was performed using simple statistics, namely percentages for each answer. Since answers were anonymous, it was not possible to group answers per country or geographical region.

3. Results

98 participants completed our online survey. This corresponded to 19.6% of the 500 invitations sent. The majority (83%) of participants resided in Europe. Answers to questions 1 to 5 (with numbers and percentages per answer) are shown in Table 3, while answers for questions 6 to 27 are shown in Table 4.

Pie charts for question 6, question 12, question 18, and question 23 are demonstrated in Figure 1, Figure 2, Figure 3 and Figure 4 respectively.

4. Discussion

The results of our online survey among gynaecologists, members of the ESG, reflect the paucity of high-quality evidence and lack of standardised care on many aspects of fertility-sparing management of fibroids. In line with this, a recent Cochrane review of four RCTs revealed uncertainty regarding the benefits of myomectomy over no-intervention, in terms of clinical pregnancy rates and pregnancy loss risk reduction [5].

For FIGO 0–II fibroids, the majority of participants recommended hysteroscopic removal in infertile patients (94%), however, only 27% would remove them in all cases, regardless of size and proportion of submucosal component. Submucous fibroids present a number of unique features compared to outer myometrium fibroids: firstly, they are likely to originate in the junctional zone (JZ) of the myometrium [14]. Furthermore, submucous fibroids appear to have higher numbers of oestrogen and progesterone receptors [18], as well as fewer karyotype aberrations compared to outer myometrium fibroids [19], which may explain why they are less likely to exhibit significant increases in size over time. Submucous fibroids are believed to have a negative effect on fertility through a variety of possible mechanisms, such as anatomical distortion of the uterine cavity [20], impaired junctional zone peristalsis [21], altering levels of inflammation [22], and molecular changes at the level of the endometrium [23]. A systematic review demonstrated that patients with submucous myomas had significantly lower clinical pregnancy and implantation rates compared to infertile controls, while hysteroscopic removal of submucous fibroids led to improved clinical pregnancy rates (but not livebirth rates) compared to submucous fibroids left in situ [24]. According to American Society of Reproductive Medicine (ASRM) clinical guidance, removal of cavity-distorting fibroids (submucous or intramural with submucous component) should be considered in order to improve pregnancy rates even in asymptomatic patients, albeit there is insufficient evidence of its impact on livebirth rates [13]. International Federation of Fertility Societies (IFFS) suggests that removal should be considered in patients presenting with infertility [25]. Although there is insufficient evidence that removal of submucous fibroids reduces the chances of early pregnancy loss in infertile patients [13], it should be acknowledged that patients with recurrent pregnancy losses form a distinct clinical entity. A retrospective cohort study of patients with myoma and recurrent early pregnancy losses observed a reduction in pregnancy losses following laparoscopic myomectomy; however, the number of patients with pregnancy losses was low [26].

With regards to measures to reduce the risk of adhesion formation following hysteroscopic myomectomy, half of the participants never use such measures (49%). A meta-analysis identified no benefit of using gel barriers on clinical or livebirth rate; however, it reduced the presence of intra-uterine adhesions at second-look hysteroscopy [27]. Again, significant heterogeneity was noted among participants on which method should be followed to reduce adhesion formation risk, reflecting the lack of high-quality evidence comparing available methods [28]. Similarly, responses varied on the role of second-look hysteroscopy, with 35% of participants never performing it. The American Association of Gynecologic Laparoscopists (AAGL) practice guidelines on submucosal fibroids state that second-look hysteroscopy may be effective for post-operative adhesions and could reduce the long-term risk of adhesion formation, particularly in cases of multiple submucosal myomectomies [14].

Non-cavity distorting, FIGO III and IV fibroids pose a unique fertility management challenge to the clinician, due to the lack of high-quality evidence guiding practice [29]. 57% (for FIGO III fibroids) and 51% (for FIGO IV fibroids) of participants believe that they have a detrimental impact on fertility, stating a number of different sizes as cut-off values. It needs to be acknowledged, however, that FIGO III fibroids, although anatomically-speaking intramural, abut the JZ and, therefore, may impair mechanisms critical to implantation independent of cavity distortion, likely having a more profound impact on fertility [29]. ASRM practice committee guideline (2017) states there is insufficient evidence that a certain size, number or location of non-cavity distorting fibroids is associated with a reduced likelihood of achieving pregnancy or an increased risk of early pregnancy loss [13]. Similarly, the IFFS standard 10 and Australasian CREI Consensus Expert Panel on Trial evidence (ACCEPT) consensus statement suggest that the impact of multiple fibroids and variation in size is uncertain [25,30]. 37% of participants would not routinely remove FIGO III or IV fibroids in couples trying to conceive. The IFFS Standard 10 states that there is no convincing evidence supporting the routine removal of intramural fibroids and decision to treat should be individualised, taking into account a multitude of factors [25]. Similarly, according to the ACCEPT consensus statement, there is insufficient evidence to determine whether myomectomy for intramural fibroids improves fertility outcomes [30], while the ASRM states that myomectomy is generally not advised to improve pregnancy outcomes in asymptomatic, infertile patients with non-cavity distorting myomas [13]. Considerable variation was noted regarding the fibroid size cut-off to trigger removal prior to IVF, with nearly one fourth of participants stating that the size of FIGO III/IV fibroids is not relevant: despite results of a recent meta-analysis identifying that patients with intramural, non-cavity distorting fibroids of 2–6 centimetres have lower live birth rates (LBR) following IVF compared to controls without fibroids [31], whether removal pre-IVF is indicated remains a matter of debate among experts [32], reflecting the conflicting evidence [5,33].

The preferable modality to diagnose and map fibroids in infertile patients also varied significantly between participants, likely reflecting variations in local availability and protocols. 23% utilise hysteroscopy, while the IFFS standard 10 recommends hysteroscopy in all patients suspected of having a submucous fibroid and those whose cavity is obscured by the presence of an intramural fibroid [25]. The majority utilise conventional laparoscopic myomectomy for FIGO III and IV fibroids, in line with the well-established benefits of minimal access surgery over laparotomy [34], although evidence suggesting superiority in terms of fertility outcomes is currently lacking [5].

The vast majority of participants check the integrity of the uterine cavity intra-operatively, following removal of FIGO III fibroids. Taking into account that such fibroids abut the endometrial cavity and a considerable risk of breaching the cavity during surgery exists, leading to intra-uterine adhesion formation and potentially serious gynaecological and obstetric sequelae [35], this approach may seem reasonable.

Asked about the duration of GnRH-agonist/antagonist treatment before removal of FIGO III and IV fibroids, the most popular answer was “3 months”: relevant guidelines confirm the need for “short-term” use only; however, no guidance on exact course duration is given [25,30]. Of note, half of the participants stated that the distance between the inner portion of the intramural, non-cavity distorting fibroid and the JZ does not affect their decision for removal and the other half stated that it does, with variable cut-off values given. Although fibroids with shorter distance to the JZ may be linked to reduced chances of clinical pregnancy in women undergoing Assisted Reproductive Technology (ART), available guidance does not recommend removal solely based on distance from JZ, nor does it provide cut-off values. Regarding the time period required between myomectomy and attempting natural conception or IVF, most responded that their decision would depend on factors like number, size and surgical route. Although relevant guidelines do not provide a single answer and individualisation appears reasonable, a systematic review identified no relationship between the risk of uterine rupture and the period of time between myomectomy and pregnancy [36].

The majority of participants use barbed sutures in laparoscopic or robotic myomectomy. Although their use may be associated with less operative time and blood loss and ease of use, international society guidelines do not recommend their use over conventional sutures, as no evidence of superior fertility outcomes has been observed [37].

Almost 8 out of 10 participants have never used the robotic approach for minimally-invasive myomectomy, a figure likely secondary to lack of availability and training in certain healthcare settings. No clear guidance exists suggesting that the robotic approach is preferable to conventional laparoscopy for myomectomy, although a number of inherent advantages of the robotic approach need to be recognised [38].

Our study provides a realistic snapshot of fibroid-related care with a focus on fertility. Including a diverse population of participants, both in terms of experience, training and country of practice, it is reflective of the actual heterogeneity in the assessment and management of fibroids internationally. At the same time, a number of limitations need to be acknowledged: firstly, the relatively small number of participants. Furthermore, only half of the participants had undergone specialist training and 4 in 10 performed more than 10 laparoscopic or robot-assisted myomectomies per annum, suggesting that our sample comprised mostly of clinicians with, at least, limited experience in the surgical management of fibroids. However, since the management of fibroids in many countries is undertaken by generalists, this may also be viewed as a potential strength of our study, increasing generalisability of the results. Lastly, our survey was anonymous; therefore, we were unable to group answers according to the participants’ background, with practices likely differing significantly among different levels of expertise and healthcare settings.

5. Conclusions

The results of our online survey among gynaecologists from variable backgrounds, members of ESG, demonstrate a significant heterogeneity of opinion regarding most aspects of the assessment and management of fibroids in the fertility context, reflecting the lack of high-quality evidence and relevant formal society guidance. Evidence from future, high-quality studies is eagerly awaited in order to guide uniform care for fibroids in the context of fertility and sterility.