Experience of using ovarian stimulation protocol with dienogest in patients with infertility and endometriosis

BACKGROUND: Endometriosis is most often characterized by two main clinical symptoms, namely, pelvic pain and infertility. Hormonal therapy may be prescribed to reduce the recurrence of the disease after surgical treatment and to relieve pain. It in most cases is incompatible with pregnancy planning and infertility treatment in in vitro fertilization programs. Currently, a protocol with various gestagens has been described for ovarian stimulation applicable in programs with cryopreservation of all embryos. However, there is scarce data on the use of such a protocol with dienogest that is widely used in the treatment of endometriosis.

AIM: The aim of this study was to assess the effectiveness and safety of using a protocol of assisted reproductive technology with dienogest in patients with endometriosis and infertility.

METHODS: This retrospective single-center cohort study included patients aged 18 to 45 years with infertility and endometriosis confirmed by surgical treatment or imaging methods (magnetic resonance imaging and ultrasound). The included couples underwent cycles of assisted reproductive technology with ovarian stimulation: with dienogest 2 mg/day continuously, with gonadotropin-releasing hormone agonists, and with gonadotropin-releasing hormone antagonists. All obtained blastocysts were cryopreserved by vitrification. Transfer of thawed embryos was performed in a modified natural cycle or with hormone replacement therapy. We assessed the frequency of obtaining embryos suitable for cryopreservation and euploid (according to the results of preimplantation genetic testing), as well as the frequency of pregnancy and its outcome. When assessing safety, side effects of the drugs used and the frequency of complications were monitored.

RESULTS: 49 couples underwent 80 cycles of assisted reproductive technology with ovarian stimulation: dienogest was used in group 1 (n = 29); protocol with gonadotropin-releasing hormone agonists in group 2 (n = 9); and protocol with gonadotropin-releasing hormone antagonists in group 3 (n = 42). All obtained blastocysts were cryopreserved by vitrification (162 embryos in total). The average age of the patients was 37.99 ± 4.50 years. In group 3, women more often reported local adverse reactions after the introduction of gonadotropin-releasing hormone antagonists (p = 0.021). The study groups did not differ in the frequency of other adverse reactions such as abdominal pain, gastrointestinal symptoms, and headache (p = 0.823). The results of ovarian stimulation were comparable between all the study groups. In total, 31 embryo transfers were performed. The clinical pregnancy rate was 35.5% (95% confidence interval 19.2–54.6): 75.0% in group 1, 33.3% in group 2, and 20.0% in group 3 (p = 0.023). No differences were found in the analysis of pregnancy outcomes between the study groups (p = 0.118). The groups did not differ in the frequency of preimplantation genetic testing (p = 0.153) and embryo quality (p = 0.82).

CONCLUSION: The ovarian stimulation protocol with dienogest allows for effective treatment of infertility in patients with endometriosis without discontinuing drug therapy for a long time.