Possibilities of a combined approach to treating endometriosis-associated infertility
Objective. To assess the clinical and socio-hygienic characteristics of patients with endometriosis-associated infertility and to comparatively evaluate the effectiveness and compliance of a combined approach to its treatment using gestagen (dienogest) and a gonadotropin-releasing hormone (GnRH) agonist.Artymuk N.V., Danilova L.N., Tachkova O.A.
Subjects and methods. The investigation enrolled 150 patients with histologically confirmed endometriosis-associated infertility, by excluding other causes of infertility. Study design: a randomized, open-label, monocentric trial. Group 1 consisted of 75 women who, after surgical treatment for endometriosis (ablation and/or excision), took the GnRH agonist buserelin or diphereline at a dose of 3.75 mg once every 28 days for 3 months intramuscularly (subcutaneously). Group 2 included 75 women who were postoperatively prescribed gestagen (dienogest) at a dose of 2 mg daily for 6 months continuously.
Results. The combined treatment of endometriosis-associated infertility via surgery, followed by the administration of both the GnRH agonist and dienogest, was highly effective in reducing the clinical manifestations of endometriosis, such as pelvic pains, dysmenorrhea, dyspareunia, and bleeding. The spontaneous pregnancy rate in both groups was similar (53.3% and 54.7%, respectively; p = 0.870). The patients receiving dienogest versus those taking the GnRH agonist were recorded to have a significantly lower frequency of adverse effects (16% and 92%, respectively), a tendency toward lower rates of undeveloped pregnancy (9.3% and 17.3%). and a higher rate of live births (90.7% and 82.7%; p = 0.489).
Conclusion. The use of gestagen in the combined therapy of patients with endometriosis-associated infertility and pelvic pain has advantages over that of the GnRH agonist due to their similar efficacy and the lower frequency of adverse effects.
Keywords
endometriosis-associated infertility
endometriosis
dienogest
gonadotropin-releasing hormone agonists
combined treatment for endometriosis
References
- Senapati S., Barnhart K. Managing endometriosis associated infertility. Clin. Obstet. Gynecol. 2011; 54(4): 720-6. https://doi.org/10.1097/GRF.0b013e3182353e06.
- Mettler L., Alkatout I., Keckstein J., Meinhold-Heerlein I., eds. Endometriosis: a concise practical guide to current diagnosis and treatment. Endo Press; 2018.
- Khine Y.M., Taniguchi F., Harada T. Clinical management of endometriosis-associated infertility. Reprod. Med. Biol. 2016; 15(4): 217-25. https://doi.org/10.1007/s12522-016-0237-9.
- Pantou A., Simopoulou M., Sfakianoudis K., Giannelou P., Rapani A., Maziotis E. et al. The role of laparoscopic investigation in enabling natural conception and avoiding in vitro fertilization overuse for infertile patients of unidentified aetiology and recurrent implantation failure following in vitro fertilization. J. Clin. Med. 2019; 8(4). pii: E548. https://doi.org/10.3390/jcm8040548.
- Hwang H., Chung Y.J., Lee S.R., Park H.T., Song J.Y., Kim H. et al. Clinical evaluation and management of endometriosis: guideline for Korean patients from Korean Society of Endometriosis. Obstet. Gynecol. Sci. 2018; 61(5): 553-64. https://doi.org/10.5468/ogs.2018.61.5.553.
- Centers for Disease Control and Prevention, American Society for Reproductive Medicine, Society for Assisted Reproductive Technology. 2013 assisted reproductive technology national summary report [Internet]. Atlanta (GA): US Department of Health and Human Services; 2015. Available at: http://www.cdc.gov/art/pdf/2013-report/art_2013_national_summary_report.pdf Accessed December 1, 2016.
- Yu H., Li B., Li T., Zhang S., Lin X. Combination of noninvasive methods in diagnosis of infertile women with minimal or mild endometriosis, a retrospective study in China. Medicine (Baltimore). 2019; 98(31): e16695.https://doi.org/10.1097/MD.0000000000016695.
- Management of women with endometriosis. Guideline of the European Society of Human Reproduction and Embryology. September 2013.
- Pahlajani G., Falcone T. Laparoscopic surgery for endometriosis associated infertility: a pathophysiologic approach. Gynecol. Surg. 2010; 7: 319-28.
- Hughes E., Brown J., Collins J.J., Farquhar C., Fedorkow D.M., Vandekerckhove P. Ovulation suppression for endometriosis. Cochrane Database Syst. Rev. 2007; (3): CD000155.
- Lessey B.A. Medical management of endometriosis and infertility. Fertil. Steril. 2000; 73(6): 1089-96. http://dx.doi.org/10.1016/s0015-0282(00)00519-7.
- Pritts E.A., Taylor R.N. An evidence-based evaluation of endometriosis-associated infertility. Endocrinol. Metab. Clin. North Am. 2003; 32(3): 653-67.http://dx.doi.org/10.1016/s0889-8529(03)00045-8.
- Endometriosis: diagnosis and management. NICE guideline. 6 September 2017.
- Collinet P., Fritel X., Revel-Delhom C., Ballester M., Bolze P.A., Borghese B. et al. Management of endometriosis: CNGOF/HAS clinical practice guidelines – Short version. J. Gynecol. Obstet. Hum. Reprod. 2018; 47(7): 265-74.
- Meuleman C., Vandenabeele B., Fieuws S., Spiessens C., Timmerman D., D’Hooghe T. High prevalence of endometriosis in infertile women with normal ovulation and normospermic partners. Fertil. Steril. 2009; 92(1): 68-74.
- The Effect of Surgery for Endometriomas on Fertility. Scientific Impact Paper No. 55. September 2017.
- He L.Q., Cai X.Z., Wang Y., Wang X.F. Effect of GnRHa therapy following conservative laparoscopic surgery for endometriosis on clinical pregnant rate in patients with endometriosis-associated infertility. Nan Fang Yi Ke Da Xue Xue Bao. 2018; 38(5): 596-600.
- Yang Y., Zhu W., Chen S., Zhang G., Chen M., Zhuang Y. Laparoscopic surgery combined with GnRH agonist in endometriosis. J. Coll. Physicians Surg. Pak. 2019; 29(4): 313-6. https://doi.org/10.29271/jcpsp.2019.04.313.
- Артымук Н.В., Данилова Л.Н., Червов В.О., Рыбников Д., Тачкова О.А., Черняева В.И. Комбинированное лечение пациенток с эндометриозом и бесплодием с применением агонистов гонадотропин-рилизинг-гормона и диеногеста. Проблемы репродукции. 2016; 22(5): 93-7. [Artymuk N.V., Danilova L.N., Chervov V.O., Rybnikov S.V., Tachkova O.A., Chernyaeva V.I. Combined treatment of endometriosis in infertile patients with gonadotropin-releasing hormone agonist or dienogest. Problemy reproduktsii / Russian Journal of Human Reproduction. 2016; 22(5): 93-7. (In Russian). https://doi.org/10.17116/repro201622593-97
- Артымук Н.В., Данилова Л.Н., Червов В.О., Рыбников С.В., Тачкова О.А., Черняева В.И. Сравнительная оценка комбинированного лечения пациенток, страдающих эндометриозом и бесплодием, с применением агонистов гонадотропин-рилизинг-гормона и диеногеста. Проблемы репродукции. 2017; 23(2): 61-5. [Artymuk N.V., Danilova L.N., Chervov V.O., Rybnikov S.V., Tachkova O.A., Chernyaeva V.I. Comparison of the gonadotropin-releasing hormone agonist and dienogest in the combined treatment of infertile patients with endometriosis. Problemy reproduktsii/ Russian Journal of Human Reproduction. 2017; 23(2): 61-65. https://doi.org/10.17116/repro201723261-65
- Muller V., Kogan I., Yarmolinskaya M., Niauri D., Gzgzyan A., Aylamazyan E. Dienogest treatment after ovarian endometrioma removal in infertile women prior to IVF. Gynecol. Endocrinol. 2017; 33(Suppl. 1): 18-21. https://doi.org/10.1080/09513590.2017.1415676.
- Xue H., Liu M., Hao W., Li Y. Clinical evaluation of laparoscopic surgery combined with triptorelin acetate in patients with endometriosis and infertility. Pak. J. Med. Sci. 2018; 34(5): 1064-9. https://doi.org/10.12669/pjms.345.15574.
- Somigliana E., Vigano P., Filippi F., Papaleo E., Benaglia L., Candiani M., Vercellini P. Fertility preservation in women with endometriosis: for all, for some, for none? Hum. Reprod. 2015; 30(6): 1280-6.
- Somigliana E., Vigano P., Benaglia L., Busnelli A., Berlanda N., Vercellini P. Management of endometriosis in the infertile patient. Semin. Reprod. Med. 2017; 35(1): 31-5.
Received 01.10.2019
Accepted 04.10.2019
About the Authors
Natalya V. Artymuk, MD, professor, head of the Department of Obstetrics and Gynecology named after Professor G.A. Ushakova of the Kemerovo State Medical University, chief freelance specialist of the Russian Ministry of Health in Obstetrics and Gynecology in the Siberian Federal District, president of the Kemerovo regional public organization “Association of Obstetricians and Gynecologists”, member of the Presidium of the Board of the Russian Society of Obstetricians and Gynecologists, 22a,tel.: + 7 (3843) 734856, artymuk@gmail.com ORCID: 0000-0001-7014-6492
650056, Kemerovo, Voroshilov street, d.22a.
Larisa N. Danilova, Head of the Gynecological Department of the Kemerovo Regional Clinical Emergency Hospital named after M.A. Podgorbunsky. Phone: + 7 (3842) 392222, e-mail: lar.danilova@mail.ru, ORCID: 0000-0002-1272-401X
650000, Kemerovo, Ostrovsky street, 22.
Olga A. Tachkova, candidate of medical sciences, associate professor of the Department of Hospital Therapy and Clinical Pharmacology of Kemerovo State Medical University. Phone: +7 (3843) 734856 E-mail: ol.an.t@yandex.ru, ORCID 0000-0002-6537-3460
650056, Kemerovo, Voroshilov street, d.22a.
For citation: Artymuk N.V., Danilova L.N., Tachkova O.A. Possibilities of a combined approach to treating endometriosis-associated infertility.
Akusherstvo i Ginekologiya / Obstetrics and gynecology. 2019; 10: 148-56. (In Russian).
https://dx.doi.org/10.18565/aig.2019.10.148-156