There are several medical and surgical treatments for patients with symptomatic uterine fibroids and pregnancy desire. Choosing the most optimal therapy in each case is sometimes controversial [1]. Myomectomy may improve fertility outcomes in women with submucous and intramural fibroids [1]. Nevertheless, there is still insufficient evidence from randomised controlled trials to establish the effect of myomectomy to improve fertility [1, 3].
Alternative medical treatment with UPA causes decrease of excessive menstrual bleeding and reduced total fibroid volume [4]. UPA was not inferior to LPA in terms of menstrual bleeding control in women with symptomatic fibroids before surgery [5]. It has been reported that repeated 12-week courses of 5 mg a day of UPA is effective and safe for bleeding and pain control, fibroid volume reduction, and restoration of quality of life in patients with symptomatic fibroids [1, 6]. UPA has also shown fibroid size reduction and can induce myoma migration, leading to the normalization of the uterine cavity in patients with previous distortion due to submucous fibroids [6]. In these cases, medical management could replace surgery. The optimal moment to conception following a treatment course with UPA is not clear [7]. Decreased endometrial receptivity due to PAECs should be considered [7, 8] although it is a reversible pharmacological response and it has been reported that endometrium returns to normal spontaneously after finishing UPA [5].
In a systematic review of Gasperis et al [7], a total of 71 pregnancies were followed after UPA treatment. 39% patients achieved 27 (38%) pregnancies following UPA treatment without interval myomectomies. The majority of pregnancies occurred more than 3 months after finishing UPA treatment course. 10 patients conceived within 3 months of stopping treatment, achieving 70% of live births.
In the available bibliography four cases of IVF were performed after UPA treatment and two pregnancies ended in a live birth [9, 10]. Embryo transfer was performed three months after finishing UPA therapy in both cases. Spontaneous first trimester abortion ocurred in the other two [7].
Khaw et al [11], in a recent systematic review compared pregnancy outcomes after fertility-preserving treatment of uterine fibroids. They analyzed live birth and miscarriage rates after four treatment modalities: UPA therapy, myomectomy surgery and radiological approach with uterine artery embolization (UAE) or thermal ablation. It is important to consider that results after UPA therapy were not included in the statistical analysis due to the limited number of cases. They conclude that myomectomy appears to be, so far, the mainstay fertility preservation treatment for fibroids and seems to have better pregnancy outcomes compared to UPA, UAE or ablation theraphy [10]. However, myomectomy has specific surgical risks including pelvic or intrauterine adhesions depending on the surgical approach [12]. The risk of hysterectomy has to be taken into account in women without reproductive wishes fulfilled. The rates of appearance of new myomas after five and eight years after myomectomy have been established in 53 and 84 percent respectively [13]. There is also a remarkable percentage of patients, around 15–20% [14] (both in laparoscopy and in laparotomy access) with an incomplete resection of all of the fibroids.
To improve fertility outcomes in advance-age patients, Orvieto et al [15] propose ovarian stimulating cycle, aiming the embryo cryopreservation [16], followed by myomectomy or 12 weeks course of UPA treatment.
Submucosal fibroids have a detrimental impact on the chances of success with IVF [17] and it is recommended to treat them in sterile patients. Regardless of the treatment applied, the proven restoration of uterine cavity maximizes the chances of a successful IVF [12]. Expectant management in asymptomatic subserous fibroids is also accepted. However, the management of noncavity-distorting intramural fibroids prior to IVF/ICSI is under debate. Their presence could hinder pregnancy and the vascularization distortion caused by surgery could provoke negative effects in subsequent pregnancies. Current evidence suggests a detrimental impact of the presence of these fibroids [17].
On the other hand, there is a large bibliography available about IVF after myomectomy. The cumulative incidence of clinical pregnancy improves significantly after myomectomy in women undergoing IVF [18].
Further studies are needed to clarify the role of UPA in IVF, which patients could be suitable and what real percentage could avoid ending up in a surgical procedures [12]. However, this can be hampered because in 2018, European Medicines Agency (EMA) has informed rare but serious cases of liver injury during UPA treatment. They recommended liver monitoring to minimize this risk. Recently, on 12 March 2020, EMA’s safety committee (PRAC), recommended to stop all UPA treatments for uterine fibroids until its benefit-risk ratio is reevaluated, motivated by the appearance of a new case of severe liver failure.