Currently there are four therapies recognized or approved by the US Food and Drug Administration (FDA) for the treatment of uterine fibroids: (1) preoperative therapy with Leuprolide acetate (Lupron) and ferrous sulfate; (2) various embolic agents for uterine artery embolization; (3) hardware for magnetic resonance imaging-guided high-energy focused ultrasound; and (4) surgery [2].

Uterine leiomyomas are believed to influence reproduction in several ways. The incidence of infertility and uterine leiomyomas increases with advancing maternal age, and no specific data exist to ascertain if the proportion of infertile women with leiomyomas is greater than the proportion of fertile women with leiomyomas. Yet the indirect evidence is substantial. In one review, annual pregnancy rates among women with leiomyomas distorting and not distorting the uterine cavity were 9% and 35%, respectively, as compared to 40% among age-matched controls with no leiomyomas [3]. Furthermore, multiple reports of successful pregnancies among infertile women following myomectomy strongly suggest a connection [4–6].

Though the exact physiologic mechanisms for reproductive dysfunction from leiomyomas are unclear, many plausible theories exist. There is a potential for reduced fecundity if a myoma occurs in the cornual region of the uterus due to mechanical occlusion of a fallopian tube [7]. It is also possible that large leiomyomas may impair the rhythmic uterine contractions that facilitate sperm motility [8]. It has further been documented that endometrial histology may vary in relation to the location of the leiomyoma. Submucosal leiomyomas may be associated with localized endometrial atrophy as well as alterations in the vascular blood flow, which may impede the implantation of an embryo; delivery of hormones or growth factors involved in implantation such as HOXA10, HOXA11, leukemia inhibitory factor (LIF), and BTEB1 protein; or interference with the normal immune response to pregnancy [9–11]. Submucosal leiomyomas, which distort the uterine cavity, are associated with first-trimester pregnancy loss, preterm delivery, abruption, abnormal presentations in labor, and postpartum hemorrhage [12].

In regard to the effectiveness of assisted reproductive technology , the presence of submucous or intramural leiomyomas is generally thought to reduce the effectiveness of assisted reproductive procedures. Early evidence demonstrated that both pregnancy and implantation rates were significantly lower in patients with intramural or submucosal leiomyomas [13, 14]. In one study, the presence of an intramural leiomyoma decreased the chances of an ongoing pregnancy by 50% following in vitro fertilization [15]. Evidence however suggests that patients with subserosal leiomyomas generally have assisted reproductive technology outcomes consistent with patients without leiomyomas [14–16]. The standard of care worldwide is to perform a removal of any submucous leiomyoma prior to the performance of in vitro fertilization (IVF).

Treatment planning about how to best treat patient’s uterine fibroids depends on the patient’s symptoms, the precise size and location of the fibroids, and the patient’s immediate and future fertility plans. For women who want to preserve their fertility, myomectomy is always clearly indicated when fibroids result in any distortion of the endometrial cavity (Fig. 18.3) and should be strongly considered with the presence of large (>4 cm diameter) intramural fibroids. In the case described above, this woman has tubal factor infertility as the primary reason for her infertility along with a type 1 submucous leiomyoma resulting in heavy vaginal bleeding and mild anemia which should be removed to best promote her fertility with IVF therapy, reduce potential future pregnancy complications, and assist in the immediate correction of her symptomatic heavy uterine bleeding.

In patients who unlike our case have patent fallopian tubes, the removal of submucosal fibroids clearly increases the chance of spontaneous and assisted conception [17]. The universal recommendation to remove any submucous leiomyoma prior to assisted reproductive technology has been linked to early studies and initial clinical experience demonstrating that submucosal fibroids that distort the uterine cavity have been found to carry a relative risk of 0.3 for pregnancy and 0.28 for implantation after ART [18]. Women with submucous leiomyomas or large uterine fibroids in any location within the uterus >5 cm in pregnancy are at significantly increased risk for delivery at an earlier gestational age as compared to women with small or no fibroids, as well as obstetric complications including excess blood loss and increased frequency of postpartum blood transfusion [19].

In the case presented above, due to the significantly enlarged size of the submucous leiomyoma, this patient was prepared for surgery with a 3 months’ preoperative treatment with leuprolide acetate (Lupron, Abbvie Pharmaceuticals). GnRH agonist (GnRHa) therapy induces apoptosis in leiomyoma cells and stops angiogenesis [20, 21]. GnRHa therapy also facilitates hysteroscopic resection of large submucous myomas via less operative blood loss due to decreased vascularity of the leiomyoma, decreased blood flow to the uterus, and a smaller lesion for resection [22]. The disadvantages of GnRHa include the cost of the medication, menopausal symptoms during administration, and bone demineralization with prolonged therapy for periods over 6 months [22]. Short-term preoperative treatment with letrozole 2.5 mg daily for 3 months used as an alternative to GnRHa has been shown to decrease hysteroscopic operative time and the volume of fluid absorbed during hysteroscopic resection of uterine submucosal myomas [22].

Surgical resection of this submucous leiomyoma was performed with a hysteroscopic resectoscope using a bipolar loop electrode and normal saline as the distending medium (Fig. 18.4). The use of a bipolar loop electrode and the use of isotonic fluid virtually eliminate the risk of hyponatremia associated with the use of nonionic solutions such as glycine required for unipolar cutting electrodes, thus greatly increasing the safety of the procedure. The submucous myoma is resected in strips with tissue fragments removed piece by piece through the scope, via periodic aspiration using a straight suction D&C curette or via a hysteroscopic morcellation device (Fig. 18.5). Care must be taken to keep track of fluid intake and output carefully so that any excess fluid absorption can be detected. Any suspicion that an imbalance exists suggesting that the patient may have absorbed 2.5 L of normal saline should prompt immediate cessation of the procedure and evaluation of the patient with the assistance of anesthesia for any clinical evidence of fluid overload or compromise. In healthy reproductive-age women, placement of a Foley catheter to monitor urinary output and the prompt use of diuretics such as Lasix can manage most cases of mild fluid overload with a rapid return to baseline. Resection of large fibroids may need to be stopped if significant fluid overload is noted in the middle of the case and staged with a return to the OR at a later date to complete the resection of the leiomyoma.