Fibroids and fertility
Many hypotheses have been proposed to explain the mechanisms by which fibroids affect fertility. Some of these theories include a reduction in perfusion of the endometrium, local inflammatory changes that inhibit implantation, and alterations in normal uterine contractility that limit gamete and embryo migration.6-8 However, fibroids alone are often not the only identifiable cause of infertility. Indeed, one recent analysis suggested that when all other causes of infertility are excluded, fibroids are found in only 1-2% of remaining patients.9
Furthermore, many patients with fibroids achieve pregnancy without difficulty. Thus, counseling an individual patient about how her fibroids may affect reproduction can be challenging. The literature, however, does provide clear answers in some clinical scenarios. An abundance of data demonstrate that patients with submucosal myomas are less likely to become pregnant (RR 0.363, 95% CI 0.179-0.737, P=0.005) and more likely to experience spontaneous abortion (RR 1.678, 95% CI: 1.373-2.051, P=0.22) than are women who have intramural or subserosal fibroids.10 Conversely, many studies have demonstrated that patients with subserosal fibroids are not at increased risk of infertility or pregnancy loss.11 Controversy still exists, however, regarding the effect on fertility of intramural myomas that have no impact on the uterine cavity. The majority of studies comparing patients with intramural fibroids and those without fibroids have demonstrated no difference in pregnancy rates. However, 2 recent meta-analyses both observed that after pooling the results of individual studies, patients with non-cavity-distorting intramural fibroids were less likely to become pregnant (RR 0.88, 95% CI 0.77–0.94, P=0.002)12 and more likely to miscarry (RR 1.891, 95% CI 1.473–2.428, P<0.001).10
While fibroid location has received significant scrutiny in the literature, fibroid size and number have received relatively less attention. The limited expert opinion that does exist generally supports the notion that only intramural myomas >4 cm significantly affect pregnancy rates.13 However, the available literature does not provide data regarding whether 10-cm fibroids produce similar untoward effects on pregnancy rates and outcomes as 4-cm fibroids. While it seems logical that larger fibroids and an increased number of intramural fibroids would be more likely to cause poor outcomes, more data addressing these questions are needed.
While information comparing the likelihood of a pregnancy between women with and without fibroids is helpful from a counseling standpoint, it does not address whether treating those fibroids improves outcomes. Multiple studies compare the outcomes of patients with submucosal fibroids who underwent myomectomy to those who did not. Only one of these studies was performed prospectively and demonstrated that hysteroscopic myomectomy improved the chances of pregnancy over no treatment (43% vs 27%, P<0.05) in patients with submucosal myomas.14 A meta-analysis of the remaining retrospective studies also found an apparent benefit of hysteroscopic myomectomy for submucosal myomas (RR 2.034, 95% CI 1.081–3.826, P=0.028).10
The picture for non-cavity-distorting fibroids is less clear. Pooled data from multiple observational studies have reported post-myomectomy pregnancy rates for infertile patients with intramural myomas that approach 50%.15 However, there are relatively few studies that have prospectively compared pregnancy rates in patients with non-cavity-distorting fibroids after myomectomy versus expectant management. Those studies have produced conflicting results. Bulletti et al. found that myomectomy prior to in vitro fertilization (IVF) for patients with at least one non-cavity-distorting myoma >5 cm improved delivery rates over expectant management (25% vs 12%, P<0.05).16
Conversely, Casini et al. observed no significant difference in pregnancy rates whether myomectomy for non-cavity-distorting fibroids was performed or not.14 An important distinction between these 2 studies was that pregnancy was attempted via IVF in the Bulletti study. This bypasses one potential side effect of abdominal myomectomy—pelvic adhesions—which may affect a patient’s ability to naturally conceive following surgery.
Additionally, when considering this literature, it is especially important to note that all studies that reported a negative effect of intramural myomas on fertility and all studies that demonstrated an improvement in outcomes following myomectomy for intramural myomas utilized traditional TVUS to establish the diagnosis, an approach known to be limited in its accuracy. In fact, the only study that confirmed a lack of cavity involvement of intramural myomas via hysteroscopy found no negative impact of intramural myomas on IVF outcomes.17 Thus, it is possible that studies observing a negative impact of intramural myomas on fertility may have missed a submucosal component to those fibroids.18
Thus, given that 1) the evidence to support myomectomy for non-cavity-distorting myomas is debatable and 2) the implications of abdominal surgery (risk of adhesions, surgical risk of bleeding or infection, increased likelihood of requiring a cesarean section) are significant, it seems prudent to allow patients to attempt pregnancy on their own without surgery before offering intervention for intramural fibroids. For patients who do not conceive after a reasonable amount of time and whose workup has yielded no other likely source for infertility, it is reasonable to offer myomectomy for large intramural myomas with adequate counseling regarding the associated risks and implications for future pregnancies.
Reassuring ovarian reserve testing and an active plan for pursuing pregnancy is also a prerequisite in these patients prior to undergoing myomectomy for fertility optimization given the controversy surrounding the value of surgery in improving a patient’s chances of pregnancy.