Fibromas and Infertility. What is the Role of Myomectomy in the Improvement of Fertility?

Abstract

Introduction: Uterine fibroids, also known as myomas, are benign tumors that develop from the smooth muscle cells of the uterus. Fibroids are estimated to occur predominantly in 20% to 40% of women of reproductive age, in whom they can cause symptoms like pressure, discomfort and excessive hemorrhage.

Evidence acquisition: Precise assessment of fibroid size, number and location is crucial for selecting the appropriate treatment for the patient. Treatment options include medical management, interventional radiology and surgery, depending on the patient's symptoms and fertility desires.

Evidence synthesis: Gynecologists must create personalized plans based on fibroid characteristics and their potential impact on fertility. Hysteroscopic myomectomy has been shown to improve pregnancy rates in certain cases. However, myomectomy is not always recommended for asymptomatic women with fibroids that do not distort the uterine cavity. It may be considered when pelvic anatomy is significantly affected, because it hinders procedures like oocyte retrieval. The relationship between specific number, size and position of myomas (excluding submucosal myomas or intramural myomas that distort the endometrial cavity) with the outcomes of pregnancy has not been verified.

Conclusion: Considering the lack of current randomized controlled trials (RCTs) investigating the effects of myomectomy, it is advisable to conduct future multicenter prospective studies.

Keywords:: fibroma, myoma, fertility, myomectomy.

INTRODUCTION

Uterine fibroids, also referred to as myomas, are benign tumors that arise from the myometrial smooth muscle cells of the uterus (1). These growths are indicative of a highly frequent health issue that significantly impacts women of reproductive age on a global scale. Uterine myomas, which can range from asymptomatic cases to producing significant morbidity, necessitate thorough examination due to their capacity to affect nearly every aspect of women's health, including their fertility (2).

Uterine myomas are a prevalent pathology which is estimated to occur in 20% to 40% of women of reproductive age (3). Symptoms directly associated with these benign tumors are the primary cause for laparotomy in non-pregnant women in the United States (3). Fibromas are believed to originate from a mutation occurring in a single myometrial cell; therefore, they are frequently characterized as clonal (4). Females with fibromas may experience a variety of serious symptoms, such as hemorrhage pressure, abdominal discomfort and excessive bleeding. Symptoms may also be caused by distortion of adjacent organs like the bladder (urinary frequency) or rectum (tenesmus). In contrast, there are females with fibromas which are asymptomatic (5). Furthermore, fibromas are classified by the International Federation of Gynecology and Obstetrics (FIGO) into subtypes based on their location within the uterus. These are categorized from type 0 to type 8 (6).

MATERIALS AND METHODS

In conducting this review, the authors performed a comprehensive search across PubMed and Scopus. The search strategy was designed to capture relevant studies, focusing on keywords such as "fibromas," "myomectomy," "infertility" and "fertility outcomes." Inclusion criteria were limited to peer-reviewed articles, clinical trials, observational studies and reviews that specifically addressed the role of myomectomy in fertility enhancement. Only English language studies were included. Exclusion criteria were case reports, editorials and studies unrelated to fertility outcomes post-myomectomy. This selection process ensured that the articles included provided a solid foundation of clinical evidence and were relevant to the focus of this review.

Fibromas and fertility

The therapy of fibroids should not only be focused toward improving symptomatology, but also affected by the patient's desire for future fertility, wish to keep the uterus and overall health status. Medical therapies, interventional radiology and surgical operations are available as treatments for fibroids. Many international obstetric and gynecological societies advocate for a step-up approach, starting with pharmaceutical and minimally invasive treatments and progressing to surgery, for the management of uterine myomas (7). The main goal of medical treatment for fibroids is to reduce abnormal uterine hemorrhage using agents such as oral contraceptives, gonadotropin-releasing hormone analogues, danazol, aromatase inhibitors or levonorgestrel intrauterine system (LNG-IUS).

On the other hand, surgical removal of leiomyomas (myomectomy) is indicated in cases of infertility, pelvic pain, irregular uterine bleeding and recurrent miscarriage. Myomectomy is chosen by women who wither want to preserve their reproductivity for future childbearing or prefer to avoid a hysterectomy. Laparoscopy, laparotomy, vaginal or hysteroscopic myomectomy can be used as surgical techniques in order to remove the fibromas (8).

Infertility is defined as the inability to maintain a clinical pregnancy after 12 months of regular unprotected intercourses and affects 8 to 12% of reproductive-aged couples globally (9). Anatomical abnormalities of the female reproductive tract, both congenital and acquired, such as polyps, leiomyomas and intrauterine adhesions may have an impact in fertility (10).

Uterine fibroids can alter the uterine anatomy, with submucosal leiomyomas potentially impacting embryo implantation and development. Large fibroids may cause symptoms like pelvic pressure or pain and can affect fertility and pregnancy maintenance. Infertile patients often have a higher prevalence of fibroids, with over one-fourth of women undergoing assisted reproductive techniques having them, despite fibroids representing only 2-3% of infertility cases (11).

Does the size of fibroids matter?

In the majority of studies women with small intramural myomas were included, most likely because women with a previous history of myomectomy or other factors were excluded from studies. There were a few articles that attempted to demonstrate the impact that the size of the fibroids has on infertility. In 19 studies, women with intramural fibroids measuring 1-8 cm were compared with control women without fibroids regarding the outcomes of in vitro fertilization (IVF) and showed that implantation and clinical pregnancy rates decreased significantly, while miscarriage rates increased (12).

Uterine fibroids that were equal to or less than four centimeters in mean diameter had IVF or intracytoplasmic sperm injection (ICSI) outcomes that were comparable to those of the control group (13). On the other hand, the rate of pregnancy was lower in patients who had intramural fibroids with a diameter of more than four centimeters than it was in patients who had intramural fibroids with a smaller diameter (13). In addition, there was a tendency of lower implantation rates in patients with intramural fibroids that were bigger than four centimeters in size as compared to patients who had intramural fibroids that were smaller (13). The study excluded women with myomas larger than seven centimeters due to their consultation to seek treatment before considering assisted reproductive techniques.

In the study by Somigliana et al (14), patients with asymptomatic intramural or subserosal myomas smaller than 5 cm were compared with women without myomas. The researchers discovered comparable live birth rates in both groups, leading to the conclusion that the existence of small myomas did not affect the IVF outcomes (14).

Moreover, Yan et al (15) observed that woman with intramural fibroids measuring over 2.85 cm had notably lower delivery rates following IVF treatment compared to those without myomas. It appears that the size is likely a crucial autonomous factor for the intramural myomas that have no impact on endometrial cavity. Furthermore, a retrospective study conducted in UK observed that women who had fibroids with a diameter of 3 cm or more had noticeably lower rates of clinical pregnancy and live birth rate, even if their uterine cavity was not distorted (16).

Does myomectomy improve fertility?

It seems logical to assume that if all the reported results are accurate, proceeding to myomectomy could resolve the infertility problem and restore the patient's fertility after the procedure. Performing surgical excision of myomas always involves myometrial trauma, which is then repaired through suturing and scar healing. This process can lead to functional issues caused by defective myometrium and adhesion formation. Therefore, the surgical management of myomas is not straightforward, presenting gynecologists and fertility specialists with a profoundly challenging clinical dilemma.

In an extensive review of prospective and retrospective studies, Donnez and Jadoul (17) found a pregnancy rate of 45% among patients who underwent hysteroscopy and 49% among those who were subjected to laparoscopic/abdominal myomectomy. These rates of pregnancy following myomectomy were additionally validated by more recent extensive studies. Somigliana et al (14) investigated the success rate subsequent to abdominal myomectomy in prospective studies; they found a postoperative pregnancy rate of 57%, which was reported to reach 61% in women with otherwise unexplained infertility.

The impact of myomectomy of submucosal or intramural fibroids that distort the endometrial cavity on in vitro fertilization-embryo transfer was assessed in a retrospective case-controlled study. Patients who underwent laparotomy or hysteroscopic resection of fibroids prior to IVF achieved comparable outcomes to the control group in terms of ongoing pregnancy, implantation and early pregnancy loss (18).

In a comparative analysis of 106 patients with fibroids who underwent laparoscopic removal and 106 patients with unexplained infertility without myomas, Bulletti et al (19) examined the effect of myomectomy on infertility. The group of laparoscopically treated subjects had a significantly higher delivery rate (42%) compared to the groups of non-treated patients with fibroids (11%) and patients without myomas (25%). Five years later, the same authors compared the outcomes of myomectomy to expectant management prior to IVF (20). After being informed of the benefits and risks of myomectomy, patients with at least one intramural–subserosal fibroid larger than 5 cm were split into two groups based on their choice, with one group receiving myomectomy and the other receiving expectant management (20). A total of 84 patients who underwent surgical laparascopy removal of myomas prior to IVF achieved a 25% delivery rate and a cumulative success rate of 33%. In contrast, patients who underwent IVF without prior surgery achieved a 15% clinical pregnancy rate and a 12% delivery rate (20).

In a prospective randomized control trial, Casini et al (21) compared the rates of pregnancy in women with submucosal fibroids who underwent laparoscopic and/or hysteroscopic myomectomy to those of subjects who did not undergo these procedures. The pregnancy rates of women who underwent surgical treatment for submucous myomas were found to be significantly higher than those who did not receive such treatment (43.3% vs. 27.2%, respectively), as were those with submucosal/intramural myomas (36.4% vs. 15%, respectively) (21).

DISCUSSION

Gynecologists should develop a comprehensive individualized strategy that takes into account the age, quantity, size and location of the fibroids. The expected effect of the lesion on the patient's ability to conceive, the efficacy of the surgical intervention and any additional clinical signs related to the presence of myoma should all be considered before deciding whether to proceed to myomectomy. There is substantial evidence indicating that myomectomy does not have a negative impact on reproductive outcomes, such as clinical pregnancy rates and live birth rates, after assisted reproductive technology (ART) (26). Tables at the end of the discussion section summarize the key points and findings from the articles referenced in the present article.

Subserosal fibroids

The concept that subserosal fibroids do not have any effect on fertility is supported by currently available data which refers to the affect that they have on fertility, as previously mentioned. In addition, there was no evidence that myomectomy had any positive effects on fertility (14, 24). For these reason, surgical excision of subserosal fibroids is not recommended in terms of fertility. Subserosal fibroids of 4.1 to 6.9 cm in women experiencing IVF/ICSI were linked with lower clinical pregnancy rates in comparison to women with no fibroids or fibroids less than 4 cm (13). Nonetheless, if a subserosal myoma is linked to symptoms because of its size or position, if its volume expansion could cause problems during pregnancy, or if there is another form of concurrent myoma, then surgical treatment may be required (Table 1).

Submucosal fibroids

In contrast, the notion that submucosal fibroids have an adverse impact on fertility in comparison to women without fibroids is generally accepted. Women who have submucosal myomas have considerably lower rates of live births and clinical pregnancy but significantly higher miscarriage rates, regardless of the method of conception (14, 24). Also, multiple retrospective cohort studies provide evidence in favor of the hypothesis that women undergoing surgical resection of submucosal myomas have greater chances for clinical pregnancy (18, 22) (Table 2). Hysteroscopic removal of submucosal fibroids significantly improves fertility outcomes by correcting endometrial distortion and enhancing implantation potential. Therefore, it is justifiable to advise women desiring pregnancy to undergo surgical removal of myoma. Moreover, abnormal uterine bleeding is frequently observed in conjunction with submucosal myomas, playing a typical independent indication for their excision (27).

Independent of indication (primarily bleeding and infertility), hysteroscopic excision is the gold standard for type 0, 1 and 2 myomas (28).

Intramural fibroids

The role of intramural fibroids in fertility and reproductive outcomes has long been a subject of uncertainty. Studies and meta-analyses agree that intramural myomas that do not distort the uterine cavity have an adverse impact on IVF outcomes (17), especially those that are larger than 4 cm in diameter (13, 14, 24, 29).

Myomectomy prior to IVF-ICSI does not appear to improve outcomes for intramural leiomyomas <4 cm that do not distort the uterine cavity (13). Thus, it is not recommended to perform myomectomy in order to enhance pregnancy outcomes for asymptomatic infertile women who have non-cavity-distorting myomas (13) (Table 3). The optimal approach for managing patients with bigger intramural fibroids of 4-7 cm in mean diameter, which do not invade the uterine cavity, remains uncertain.

The laparoscopic excision of intramural fibroids leads to the formation of scars in the uterus, which can have an impact on future pregnancies (30). On the other hand, hysteroscopy is the most effective treatment for restoring the uterine cavity in patients with abnormalities that are linked to infertility due to its limitation to the pseudocapsule causing no harm to the normal myometrium (30).

Type 3 fibroids are a subtype of intramural fibroids that have a significant impact on the pregnancy outcomes of ART. Hysteroscopy is currently the most effective method for performing myomectomy on this type of fibroids (30). It has the potential to enhance the clinical pregnancy rate and live birth rate in individuals diagnosed with type 3 fibroids. The proximity to the endometrium enables better preservation of myometrial fibers in comparison to laparoscopic, laparotomic and vaginal methods (31). The use of loop hysteroscopic myomectomy has been proven to be a secure and efficient method, enabling the removal of uterine leiomyomas in a single procedure with a little chance of postoperative adhesions (32).

The main aim of managing type 3 myoma by hysteroscopic resection is to prevent the need for open or laparoscopic myomectomy, as these procedures have been shown to negatively impact fertility when compared to hysteroscopic myomectomy (28).

CONCLUSION

Considerable debate has arisen concerning the influence of fibromas on fertility. The efficacy of myomectomy in women with asymptomatic myomas, in terms of increasing the chances of conception and live birth while reducing the risk of pregnancy loss, remains questionable (24, 25). After conducting a thorough examination of reliable studies, it has been determined that there is not enough evidence to support the claim that myomas decrease the chances of successfully attaining and sustaining pregnancy. There is substantial evidence that hysteroscopic myomectomy enhances the rates of clinical pregnancy (13, 18, 22). However, there is not enough information to determine the effect of this technique on the chance of early pregnancy loss or live birth. Myomectomy is typically not recommended to enhance pregnancy outcomes in asymptomatic infertile females with non-cavity-distorting myomas (13). Nevertheless, myomectomy may be a viable option in certain situations, such as when there is significant deformation of the pelvic anatomy that makes it difficult to access the ovaries for oocyte retrieval.

The relationship between specific number, size and position of myomas (excluding submucosal myomas or intramural myomas that distort the endometrial cavity) with the outcomes of pregnancy has not been verified.

However, RCTs do not include individuals with submucosal fibroids or intramural tumors that deform the cavity. As a result, the effect of this specific group of myomas on the rates of conception, pregnancy loss and live birth has not been efficiently studied. Moreover, the presence of diverse study populations and approaches, inconsistent implementation of control groups, varying terminology for categorizing location, inconsistent selection of primary outcomes, inadequate consideration of factors that may influence pregnancy outcomes and insufficient representation of different racial and ethnic groups have impacted our ability to accurately analyze the available data. Therefore, it is necessary to further investigate the correlation between myomas and pregnancy outcomes, including both spontaneous pregnancies and those achieved through assisted reproductive techniques. Additionally, it is important to determine whether myomectomy provides any advantages in terms of fertility and pregnancy outcomes.

Thus, once surgical treatment is deemed necessary, the approach should be carefully selected based on the size, location and number of fibroids. Minimally invasive techniques such as laparoscopy are generally preferred for their reduced morbidity and faster recovery, while laparotomy is selected for complex cases involving large or numerous fibroids. Rational decisionmaking in fibroid management is essential to avoid overtreatment and optimize patient outcomes. The evaluation and management of myomas in patients with infertility should be conducted by gynecologists with expertise in reproductive medicine. Gynecologists specializing in fertility are uniquely positioned to apply evidence-based criteria and tailor management strategies to the individual needs of patients, prioritizing optimal reproductive outcomes while minimizing overtreatment. This specialized approach ensures that both the evaluation and treatment are aligned with the patient’s fertility goals.

Conflicts of interest: none declared.

Financial support: none declared.

Authors’ contribution: KN conceptualized the review and wrote it; SK and PT performed the literature search, collected relevant articles; DC and NG, corrected the manuscript; EK and AG responsible for analyzing the information from the literature, identifying key themes, and interpreting the data; NN and AD supervised the work, guided the review, and approved the final version of the manuscript for submission.

TABLE 1.

Key findings from studies on subserosal fibroids and their impact on fertility and pregnancy outcomes

TABLE 2.

Key findings from studies on submucosal fibroids and their impact on fertility and pregnancy outcomes

TABLE 3.

Key findings from studies on intramural fibroids and their impact on fertility and pregnancy outcomes