Pregravidary “thorns” of anti-recurrent pharmacotherapy after myomectomy

• Vadim A. Khorolsky
• Vladislavа A. Novikovа

Abstract

The aim of the study was to assessment of the features of the pregravid lead-up after organ-preserving surgical and anti-recurrence pharmacological therapy for uterine fibroids (UF).

Material and methods. A prospective cohort study was performed. Clinical base: perinatal center of the regional clinical hospital No. 2, perinatal center of the children’s regional clinical hospital. Study period: 2014–2019. The study included 150 women of reproductive age with spontaneous pregnancy after laparoscopic myomectomy (ME) and a course of anti-recurrence therapy. The selection was carried out individually: mifepristone, gonadotropin-releasing hormone agonist (GnRH agonist) or ulipristal acetate.

Results. After removal of myomatous nodes (1–5, maximum diameter 150 mm) and remaining 1 to 5 nodes not removed due to isthmus localization or small size, mifepristone was used as anti-relapse therapy (58%). A 3-month course of anti-recurrence therapy reduced the number of remaining UF nodes up to the complete disappearance of some of them (from 2.25±1.02 to 0.91±0.68, p<0.001). The growth of the remaining myomatous nodes against the background of the subsequent intake of COCs (low-dose, containing a gestagen with antiproliferative activity – drospirenone, dienogest) was not observed, the size of the nodes decreased almost two-fold (from 15.81±2.68 to 8.94±5.49 mm, p<0.001). This provided a significant decrease (p<0.001) in the maximum size of the remaining myomatous nodes in comparison with those after ME. The maximum size of the remaining myomatous nodes before the conditionally fertile cycle did not exceed 10.0 mm on average, and taking ulipristal acetate (n=0.04) made it possible to achieve their smallest size – 7.63±5.70 mm.

Benign breast dysplasia (BBD) accompanied 72% of women in the cohort. The greatest likelihood of BBD is associated with the need to GnRH agonists; more associated with mifepristone than with ulipristal acetate (OR 3.92, 95% CI 1.80–8.55). Taking GnRH agonists was associated with the complete disappearance of signs of DMDM, taking mifepristone or ulipristal acetate – with its debut. Taking COCs in the first 3 months was associated with an increase in clinical and/or ultrasound signs of diffuse mastopathy, the number of small cysts, the frequency of which by the time of COC withdrawal gradually returned to baseline or decreased.

The ultrasound thickness of the endometrium after taking mifepristone and ulipristal acetate significantly exceeded those after taking GnRH agonists; 3 months of taking COCs - led to its normalization. The number of fertile cycles was 3.58±1.61 (from 1 to 8); in 1/2 women, pregnancy occurred in the 2^nd (20%), 3^rd (29.33%) fertile cycles after the completion of COC use. The minimum age of the scar on the uterus was at least 12 months; the maximum was 22 months, on average 15.93±1.83 months. The association of the age of the scar on the uterus after ME with the required anti-recurrence therapy has not been established.

Conclusion. Myomectomy is a stage of personalized pregravid preparation of women with uterine fibroid, which implies not only adherence to modern intraoperative techniques, but targeted choice of anti-recurrent therapy, provision of conditions for myometrium repair for a period of at least 12 months by prescribing COCs. The multi-stage pregravid preparation of women proposed by us seems to be promising for improving the health indicators of women of reproductive age, the outcome of pregnancy and childbirth after organ-preserving treatment with UF.

Keywords:uterine fibroids; myomectomy; anti-recurrence therapy for uterine fibroids; combined oral contraceptives; preconception treatment; benign breast dysplasia; endometrial thickness

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