Fertility outcome following ovarian stimulation in infertile women having pretreatment with levonorgestrel releasing intrauterine system versus dienogest for symptomatic adenomyosis
DOI:
https://doi.org/10.18203/2320-1770.ijrcog20252308Keywords:
Dienogest, Fertility outcome, Levonorgestrel intrauterine system, Ovarian stimulation, Symptomatic adenomyosisAbstract
Background: Adenomyosis is an emerging enigmatic uterine disease that negatively impacts women's fertility. Conservative treatments, including medical management, offer hope to preserve future fertility but remain challenging, especially in low-resource settings. Since 2019, at our center, infertile women diagnosed with symptomatic adenomyosis have been pre-treated with either a Levonorgestrel-Releasing Intrauterine System (LNG-IUS) or Dienogest based on physician preference. Following symptomatic relief, ovarian stimulation protocols were applied to optimize the chances of natural conception without assisted reproductive technologies (ART). This study aimed to compare fertility outcomes following ovarian stimulation in infertile women with symptomatic adenomyosis who had been pre-treated with LNG-IUS versus Dienogest.
Methods: This quasi-experimental study was conducted at Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, from January 2024 to December 2024. Infertile women with previously diagnosed symptomatic adenomyosis, symptomatically relieved by LNG-IUS or Dienogest, were enrolled. Following enrolment, LNG-IUS devices were removed and Dienogest was discontinued. Participants were divided into two groups: Group A (pre-treated with LNG-IUS) and Group B (pre-treated with Dienogest) and both underwent ovarian stimulation using oral ovulogens.
Results: Both groups were comparable in baseline socio demographic, biochemical and biophysical criteria. Ovulation and pregnancy rate in each cycle were higher in LNG-IUS group than Dienogest group though this difference was not statistically significant (p>0.05).
Conclusions: Pre-treatment with LNG-IUS prior to ovarian stimulation may offer better fertility outcomes compared to Dienogest, though larger studies involving more cycles and multicenter collaboration are necessary to confirm these findings.
Metrics
References
Chen Q, Li YW, Wang S, Fan QB, Shi HH, Leng JH, et al. Clinical manifestations of adenomyosis patients with or without pain symptoms. J Pain Res. 2019;14:3127-33. DOI: https://doi.org/10.2147/JPR.S212117
Liang Z, Yin M, Ma M, Wang Y, Kuang Y. Effect of pretreatment with a levonorgestrel-releasing intrauterine system on IVF and vitrified–warmed embryo transfer outcomes in women with adenomyosis. Reproductive Bio Med. 2019;39(1):111-8. DOI: https://doi.org/10.1016/j.rbmo.2019.03.101
Santulli P, Vannuccini S, Bourdon M, Chapron C, Petraglia F. Adenomyosis: the missed disease. Reproductive Bio Med. 2025;50(4):104837. DOI: https://doi.org/10.1016/j.rbmo.2025.104837
Dai Y, Leng J. The Surgical Treatment of Adenomyosis. Adenomyosis: Facts and treatments. 2021:99-111. DOI: https://doi.org/10.1007/978-981-33-4095-4_11
Puente JM, Fabris A, Patel J, Patel A, Cerrillo M, Requena A, et al. Adenomyosis in infertile women: prevalence and the role of 3D ultrasound as a marker of severity of the disease. Reproduct Bio Endocrinol. 2016;14:1-9. DOI: https://doi.org/10.1186/s12958-016-0185-6
Bourdon M, Oliveira J, Marcellin L, Santulli P, Bordonne C, Maitrot Mantelet L, et al. Adenomyosis of the inner and outer myometrium are associated with different clinical profiles. Human Reprod. 2021;36(2):349-57. DOI: https://doi.org/10.1093/humrep/deaa307
Wang WJ, Hao CF, Yin GJ, Bao SH, Qiu LH, Lin QD. Increased prevalence of T helper 17 (Th17) cells in peripheral blood and decidua in unexplained recurrent spontaneous abortion patients. J Reprod Immunol. 2010;84(2):164-70. DOI: https://doi.org/10.1016/j.jri.2009.12.003
Banu J, Sultana S, Alamgir CF. Clinical efficacy of levonorgestrel releasing intrauterine system versus dienogest for women having symptomatic adenomyosis. Scholars International J Obst Gynecol. 2023;6(1):34–40. DOI: https://doi.org/10.36348/sijog.2023.v06i01.006
Feng M, Chen LH, Hsu LT, Wu HM. Segmented in vitro fertilization and frozen embryo transfer in dienogest-treated patient with adenomyosis: A case report and lierature review. Taiwanese J Obstet Gynecol. 2022;61(5):906-8. DOI: https://doi.org/10.1016/j.tjog.2021.09.037
Liang T, Zhang W, Pan N, Han B, Li R, Ma C. Reproductive outcomes of in vitro fertilization and fresh embryo transfer in infertile women with adenomyosis: a retrospective cohort study. Front Endocrinol. 2022;13:865358. DOI: https://doi.org/10.3389/fendo.2022.865358
Schindler AE. Dienogest in long-term treatment of endometriosis. International J Women's Health. 2011;6:175-84. DOI: https://doi.org/10.2147/IJWH.S5633
Yang Y, Li J, Chen H, Feng W. Assessment of risk factors associated with severe endometriosis and establishment of preoperative prediction model. Diagnostics. 2022;28;12(10):2348. DOI: https://doi.org/10.3390/diagnostics12102348
Akhigbe RE, Afolabi OA, Adegbola CA, Akhigbe TM, Oyedokun PA. Comparison of effectiveness of the levonorgestrel intrauterine system and dienogest in the management of adenomyosis: A systematic review and meta-analysis. European J Obstet Gynecol Reprod Biol. 2024;2:439. DOI: https://doi.org/10.1016/j.ejogrb.2024.07.038
Younes G, Tulandi T. Effects of adenomyosis on in vitro fertilization treatment outcomes: a meta-analysis. Fert Ster. 2017;108(3):483-90. DOI: https://doi.org/10.1016/j.fertnstert.2017.06.025
Maheshwari A, Gurunath S, Fatima F, Bhattacharya S. Adenomyosis and subfertility: a systematic review of prevalence, diagnosis, treatment and fertility outcomes. Human Repr. 2012;18(4):374-92. DOI: https://doi.org/10.1093/humupd/dms006
Xiao Y, Li T, Xia E, Yang X, Sun X, Zhou Y. Expression of integrin β3 and osteopontin in the eutopic endometrium of adenomyosis during the implantation window. European J Obst Gynecol Reprod Biol. 2013;170(2):419-22. DOI: https://doi.org/10.1016/j.ejogrb.2013.05.007
Fischer CP, Kayisili U, Taylor HS. HOXA10 expression is decreased in endometrium of women with adenomyosis. Fert Ster. 2011;95(3):1133-6. DOI: https://doi.org/10.1016/j.fertnstert.2010.09.060
Fraser IS. Non-contraceptive health benefits of intrauterine hormonal systems. Contraception. 2010;82(5):396-403. DOI: https://doi.org/10.1016/j.contraception.2010.05.005
Ekin M, Cengiz H, Ayağ ME, Kaya C, Yasar L, Savan K. Effects of the levonorgestrel-releasing intrauterine system on urinary symptoms in patients with adenomyosis. European J Obst Gynecol Reprod Biol. 2013;170(2):517-20. DOI: https://doi.org/10.1016/j.ejogrb.2013.07.019
Fawzy M, Mesbah Y. Comparison of dienogest versus triptorelin acetate in premenopausal women with adenomyosis: a prospective clinical trial. Arch Gynecol Obst. 2015;292:1267-71. DOI: https://doi.org/10.1007/s00404-015-3755-5
Nagata C, Yanagida S, Okamoto A, Morikawa A, Sugimoto K, Okamoto S, et al. Risk factors of treatment discontinuation due to uterine bleeding in adenomyosis patients treated with dienogest. J Obstet Gynaecol Res. 2012;38(4):639-44. DOI: https://doi.org/10.1111/j.1447-0756.2011.01778.x
Aksenenko AA, Ibragimova MK, Gavisova AA, Mishieva NG. Effectiveness of ivf in treating infertility in patients with internal endometriosis (adenomyosis). Obst Gynecol. 2021;15(1):120-5. DOI: https://doi.org/10.18565/aig.2021.1.120-125
Choudhury S, Jena SK, Mitra S, Padhy BM, Mohakud S. Comparison of efficacy between levonorgestrel intrauterine system and dienogest in adenomyosis: a randomized clinical trial. Therap Advan Reproduc Health. 2024;18:2348. DOI: https://doi.org/10.1177/26334941241227401
Hou X, Xing J, Shan H, Mei J, Sun Y, Yan G, et al. The effect of adenomyosis on IVF after long or ultra-long GnRH agonist treatment. Reproductive biomedicine online. 2020;41(5):845-53. DOI: https://doi.org/10.1016/j.rbmo.2020.07.027