Chapter 11 – Fibroids and Fertility




Abstract




Uterine fibroids are the most common pelvic tumours, occurring in 30% of women over the age of 30 years. Their incidence increases with age, and they are more common in certain ethnic populations. The frequency of fibroids reported in literature varies widely due to differences in diagnostic tests used, populations studied and study design. The largest study to date, prospectively followed up 95,061 female nurses in America aged between 25 and 44 years with questionnaires every two years, to determine the incidence of fibroids among premenopausal women by age and race [1]. The diagnosis of fibroids was self reported and confirmed for a sample of cases. The crude incidence rate in this study was 12.8 per 1,000 woman years. The standardised rates were much higher in black women than in white women, 30.6 and 8.9 per 1,000 woman years respectively. Even after adjusting for variables such as body mass index, infertility and contraception, the rates among black women were significantly higher than those amongst white women (RR 3.25; 95% CI 2.71–3.88). Another large American survey included 1,364 women aged between 35 and 49 years who were randomly selected from an urban health plan. All recruited women underwent transvaginal ultrasonography. The cumulative incidence of fibroids at 50 years of age was 70 and >80% for whites and African Americans respectively. The prevalence of fibroids is lower in Europe, although still remarkable from the healthcare point of view. An Italian cohort study documented an incidence of ultrasonographically detectable fibroids of 21% in a series of 341 unselected women residing in an urban zone aged between 30 and 60 years [2]. A Swedish study recruiting 335 unselected subjects from an urban district and who accepted to undergo transvaginal ultrasonography showed a prevalence of 3% in women aged between 25 and 32 years and 8% in those aged between 33 and 40 years [3].





Chapter 11 Fibroids and Fertility


Yakoub Khalaf and Sesh K. Sunkara



1 Introduction


Uterine fibroids are the most common pelvic tumours, occurring in 30% of women over the age of 30 years. Their incidence increases with age, and they are more common in certain ethnic populations. The frequency of fibroids reported in literature varies widely due to differences in diagnostic tests used, populations studied and study design. The largest study to date, prospectively followed up 95,061 female nurses in America aged between 25 and 44 years with questionnaires every two years, to determine the incidence of fibroids among premenopausal women by age and race [1]. The diagnosis of fibroids was self reported and confirmed for a sample of cases. The crude incidence rate in this study was 12.8 per 1,000 woman years. The standardised rates were much higher in black women than in white women, 30.6 and 8.9 per 1,000 woman years respectively. Even after adjusting for variables such as body mass index, infertility and contraception, the rates among black women were significantly higher than those amongst white women (RR 3.25; 95% CI 2.71–3.88). Another large American survey included 1,364 women aged between 35 and 49 years who were randomly selected from an urban health plan. All recruited women underwent transvaginal ultrasonography. The cumulative incidence of fibroids at 50 years of age was 70 and >80% for whites and African Americans respectively. The prevalence of fibroids is lower in Europe, although still remarkable from the healthcare point of view. An Italian cohort study documented an incidence of ultrasonographically detectable fibroids of 21% in a series of 341 unselected women residing in an urban zone aged between 30 and 60 years [2]. A Swedish study recruiting 335 unselected subjects from an urban district and who accepted to undergo transvaginal ultrasonography showed a prevalence of 3% in women aged between 25 and 32 years and 8% in those aged between 33 and 40 years [3].



2 Classification of Fibroids


Numerous classifications of fibroids can be found in the literature. They are traditionally classified according to their anatomical location and divided into submucous, intramural or subserous. Submucous fibroids are those that distort the uterine cavity and are further divided into three subtypes: pedunculated (type 0); sessile with less than 50% intramural extension of the fibroid (type I); and sessile with 50% or greater intramural extension (type II). The FIGO classification describes eight fibroid locations (0–7; 0 = pedunculated intracavitary, 1 = submucosal with <50% intramural, 2 = submucosal with ≥50% intramural, 3 = 100% intramural and contact with endometrium, 4 = intramural, 5 = subserosal with ≥50% intramural, 6 = subserosal with <50% intramural, 7 = pedunculated subserosal) as well as other forms which include cervical and parasitic fibroids [4].



3 Clinical Presentation of Uterine Fibroids


Symptoms associated with the presence of uterine fibroids include heavy and prolonged periods, pelvic pressure (from large fibroids), pain (resulting from torsion of a pedunculated fibroid or degeneration), urinary symptoms and constipation resulting from pressure by anterior and posterior fibroids. Whether they cause infertility is the subject of considerable speculation. Although most women with fibroids are fertile, fibroids may interfere with fertility secondary to anatomical distortion and alterations to the uterine environment [5]. For those women afflicted with fibroids, the risk of miscarriage [6] and pregnancy complications such as pain are also increased.



4 Do Fibroids Impair Fertility?


A decreased risk of fibroids in parous women when compared with nulliparous women has been repeatedly reported. The observation that parity is associated with a reduction in the risk of fibroids could be interpreted in two ways. Parity may be a protective factor or, alternatively, fertility may be partly compromised in women with fibroids. Studies investigating the association between fibroids and history of infertility may be of help in clarifying this issue, but unfortunately evidence on this regard is scarce. Overall, the question therefore remains about causality of the association. Does pregnancy protect from fibroid development or, conversely, do fibroids affect fertility?



5 How Could Fibroids Impair Fertility?


Whilst fibroids are associated with infertility in 5–10% of cases, they are estimated to be the sole cause of infertility in 2–3% of cases [7]. Fibroids can impair fertility through several possible mechanisms such as: anatomic distortion of the uterine cavity and subsequent alterations to endometrial function, functional changes such as increased uterine peristalsis and impairment of the endometrial and myometrial blood supply and changes to the local hormone milieu and paracrine molecular changes induced by fibroids, which could impair gamete transport [5,8]. The effect of fibroids on fertility is dictated largely by the location and size of the fibroid.



6 Effect of Fibroids on Embryo Implantation


The advent of assisted reproductive techniques (ART) and, in particular, of in vitro fertilisation (IVF) treatment has offered a useful tool to elucidate the relationship between fibroids and fertility. Results from IVF treatment provide precious information on the impact of uterine fibroids on embryo implantation.


There have been meta-analyses that have aimed to assess the impact of fibroids in IVF cycles. A meta-analysis of studies investigating the influence of fibroids located at different sites in IVF cycles showed that myomas negatively affect pregnancy rates [8]. Although based on a small number of studies, submucous fibroids appeared to strongly interfere with the chance of pregnancy: OR (95% CI) for conception and delivery being 0.3 (0.1–0.7) and 0.3 (0.1–0.8) respectively. The impact of intramural fibroids was less dramatic although still statistically significant: OR (95% CI) for conception and delivery being 0.8 (0.6–0.9) and 0.7 (0.5–0.8) respectively. In a follow-up study, intramural fibroids were shown to have an adverse effect on live birth rate after three consecutive cycles of IVF treatment [9]. In general, these effects appeared to be more relevant when considering the delivery rate compared to the clinical pregnancy rate. Conversely, subserosal fibroids did not seem to affect pregnancy rates.


A systematic review evaluated the effects on fertility by location of fibroids [10]. The results demonstrated that women with submucous fibroids, compared with infertile women without fibroids, demonstrated a significantly lower clinical pregnancy rate (RR 0.36; 95% CI 0.17–0.73), implantation rate (RR 0.28; 95% CI 0.12–0.64) and ongoing pregnancy/ live birth rate (RR 0.31; 95% CI 0.11–0.85) and a significantly higher miscarriage rate (RR 1.67; 95% CI 1.37–2.05). Women with intramural fibroids also had a significantly lower clinical pregnancy rate, implantation rate and ongoing pregnancy/ live birth rate and a significantly higher miscarriage rate. When women with subserous fibroids were compared with women without fibroids, no difference was observed for any outcome measure.


There is controversy on the impact of intramural fibroids that do not distort the uterine cavity on IVF treatment outcome. The first prospective observational study reported an adverse effect of such fibroids on outcome of IVF [11]. This was further addressed in a comprehensive systematic review that looked at 19 observational studies comprising a total of 6,087 IVF cycles. Meta-analysis of these studies showed a significant decrease in live birth (RR 0.79; 95% CI 0.70–0.88) and clinical pregnancy rates (RR 0.85; 95% CI 0.77–0.94) in women with non-cavity distorting intramural fibroids compared to those without fibroids, following IVF treatment [12]. However, there is currently lack of evidence from randomised controlled trials whether any intervention in this group of women would improve the outcome of IVF treatment and restore live birth rates to the levels expected in women without fibroids.



7 Fibroids and Miscarriage


An early review comprising reports on women with symptomatic, palpable fibroids published from 1957 to 1980 identified a reduction in miscarriage from 41% to 19%, in a cohort of women with symptomatic fibroids who underwent myomectomy [7]. A small, uncontrolled series of 19 asymptomatic women who conceived with fibroids reported a reduction in miscarriage post myomectomy compared to the pre-myomectomy rate (24% vs 60%) [13].


A study involving 143 women with ultrasonographically identified fibroids in the first trimester reported a nearly two-fold increase in miscarriage rate, when compared to 715 age-matched controls without fibroids (14% vs 7.6%, P < 0.5) [6]. Although the fibroid size was not associated with the spontaneous loss rate, the presence of multiple fibroids was a significant predictor of spontaneous loss and among the 88 patients with only a single fibroid, there was no increased risk of miscarriage compared with controls. A meta-analysis of controlled studies of intramural fibroids and IVF outcome which reported on miscarriage showed a miscarriage rate of 22% in women with intramural fibroids compared with 15.4% in the control group [14]. Data are currently unavailable to evaluate the risk of miscarriage in women with submucosal fibroids. Another observational study reported miscarriages in 5 of 9 (53%) pregnant women with submucosal fibroids and 9 out of 21 women (43%) who underwent prior myomectomy [15].



8 Fertility after Myomectomy


Before the advent of less invasive options, hysterectomy was the standard treatment for women troubled with fibroid-associated symptoms. This option is understandably unacceptable for women wishing to conserve their fertility. Myomectomy which involves the removal of the fibroid with conservation of the uterus is the alternative surgical treatment option for women wishing to conceive. The procedure may be performed abdominally, laparoscopically or hysteroscopically. Several reviews of literature on pregnancy rates following myomectomy have been published. One of the early reviews focussing on studies published between 1933 and 1980 by Buttram and Reiter [7] reported a 40% pregnancy rate following abdominal myomectomy (480 out of 1,202 cases). This rate was 54% when patients with other causes of infertility were excluded. Another review by Vercellini et al [16] confirmed this rate of success following myomectomy. They reported a post-surgical pregnancy rate of 57% across prospective studies. When including women with unexplained infertility, this rate was 61%. The advent of endoscopic surgery did not seem to modify this result. In a review by Donnez and Jadoul [5] the pregnancy rate among women undergoing hysteroscopic and laparoscopic myomectomy was reported as 45% and 49% respectively. These findings have further been confirmed by more recent and larger studies.

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Oct 26, 2020 | Posted by in GYNECOLOGY | Comments Off on Chapter 11 – Fibroids and Fertility
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