drugset / Trial / NCT05937490
Adenomyosis and ART
Phase 4
Unknown
500 enrolled
University Hospital of Modena
Ministero della Salute, Italy · collabUniversity of Modena and Reggio Emilia · collab
RandomizedParallel-groupOpen-labelTreatment
Summary
The goal of this clinical trial is to: * Prospectively investigate the association of Adenomyosis with fertility outcomes in relation to COH protocols for ART (long or ultra- long protocol) with a preventive high-dose anti-inflammatory progestin such as DNG and to assess their association with pregnancy and neonatal outcomes (preterm delivery,pre-eclampsia,Caesarean section,fetal malpresentation,small for gestational age,low birth weight and postpartum hemorrhage). * Understand how the endometrial interface by studying the response of progesterone and DNG stimulated decidualization markers, correlating them with the success of ART protocol stimulation and to pregnancy specific outcomes * Evaluate the immune changes during the implantation period and in the different trimesters of the pregnancies after ART conception.
Timeline
- Start
- 2023-03-27
- Primary completion
- 2025-03
- Completion
- 2025-03
Publications
- Background Abbott JA. Adenomyosis and Abnormal Uterine Bleeding (AUB-A)-Pathogenesis, diagnosis, and management. Best Pract Res Clin Obstet Gynaecol. 2017 Apr;40:68-81. doi: 10.1016/j.bpobgyn.2016.09.006. Epub 2016 Sep 30.
- Background Chapron C, Vannuccini S, Santulli P, Abrao MS, Carmona F, Fraser IS, Gordts S, Guo SW, Just PA, Noel JC, Pistofidis G, Van den Bosch T, Petraglia F. Diagnosing adenomyosis: an integrated clinical and imaging approach. Hum Reprod Update. 2020 Apr 15;26(3):392-411. doi: 10.1093/humupd/dmz049.
- Background Burney RO, Giudice LC. Pathogenesis and pathophysiology of endometriosis. Fertil Steril. 2012 Sep;98(3):511-9. doi: 10.1016/j.fertnstert.2012.06.029. Epub 2012 Jul 20.
- Background Lalani S, Choudhry AJ, Firth B, Bacal V, Walker M, Wen SW, Singh S, Amath A, Hodge M, Chen I. Endometriosis and adverse maternal, fetal and neonatal outcomes, a systematic review and meta-analysis. Hum Reprod. 2018 Oct 1;33(10):1854-1865. doi: 10.1093/humrep/dey269.
- Background Koot YE, van Hooff SR, Boomsma CM, van Leenen D, Groot Koerkamp MJ, Goddijn M, Eijkemans MJ, Fauser BC, Holstege FC, Macklon NS. An endometrial gene expression signature accurately predicts recurrent implantation failure after IVF. Sci Rep. 2016 Jan 22;6:19411. doi: 10.1038/srep19411.
- Background Peng Y et al. Biol Reprod. 2021 Feb 2:ioab017.
- Background Nirgianakis K, Kalaitzopoulos DR, Schwartz ASK, Spaanderman M, Kramer BW, Mueller MD, Mueller M. Fertility, pregnancy and neonatal outcomes of patients with adenomyosis: a systematic review and meta-analysis. Reprod Biomed Online. 2021 Jan;42(1):185-206. doi: 10.1016/j.rbmo.2020.09.023. Epub 2020 Oct 4.
- Background Grandi G, Barra F, Ferrero S, Sileo FG, Bertucci E, Napolitano A, Facchinetti F. Hormonal contraception in women with endometriosis: a systematic review. Eur J Contracept Reprod Health Care. 2019 Feb;24(1):61-70. doi: 10.1080/13625187.2018.1550576. Epub 2019 Jan 21.
- Background Grandi G, Mueller MD, Bersinger NA, Facchinetti F, McKinnon BD. The association between progestins, nuclear receptors expression and inflammation in endometrial stromal cells from women with endometriosis. Gynecol Endocrinol. 2017 Sep;33(9):712-715. doi: 10.1080/09513590.2017.1314458. Epub 2017 Apr 17.
- Background Grandi G, Mueller M, Bersinger N, Papadia A, Nirgianakis K, Cagnacci A, McKinnon B. Progestin suppressed inflammation and cell viability of tumor necrosis factor-alpha-stimulated endometriotic stromal cells. Am J Reprod Immunol. 2016 Oct;76(4):292-8. doi: 10.1111/aji.12552. Epub 2016 Aug 12.
- Background Grandi G, Mueller MD, Papadia A, Kocbek V, Bersinger NA, Petraglia F, Cagnacci A, McKinnon B. Inflammation influences steroid hormone receptors targeted by progestins in endometrial stromal cells from women with endometriosis. J Reprod Immunol. 2016 Sep;117:30-8. doi: 10.1016/j.jri.2016.06.004. Epub 2016 Jun 17.
- Background Grandi G, Mueller M, Bersinger NA, Cagnacci A, Volpe A, McKinnon B. Does dienogest influence the inflammatory response of endometriotic cells? A systematic review. Inflamm Res. 2016 Mar;65(3):183-92. doi: 10.1007/s00011-015-0909-7. Epub 2015 Dec 9.
- Background Grandi G, Xholli A, Napolitano A, Palma F, Cagnacci A. Pelvic pain and quality of life of women with endometriosis during quadriphasic estradiol valerate/dienogest oral contraceptive: a patient-preference prospective 24-week pilot study. Reprod Sci. 2015 May;22(5):626-32. doi: 10.1177/1933719114556488. Epub 2014 Nov 13.
- Background Grandi G, Ferrari S, Xholli A, Cannoletta M, Palma F, Romani C, Volpe A, Cagnacci A. Prevalence of menstrual pain in young women: what is dysmenorrhea? J Pain Res. 2012;5:169-74. doi: 10.2147/JPR.S30602. Epub 2012 Jun 20.
- Background Grandi G, Xholli A, Ferrari S, Cannoletta M, Volpe A, Cagnacci A. Intermenstrual pelvic pain, quality of life and mood. Gynecol Obstet Invest. 2013;75(2):97-100. doi: 10.1159/000343997. Epub 2012 Nov 23.
- Background Nirgianakis K, Grandi G, McKinnon B, Bersinger N, Cagnacci A, Mueller M. Dienogest mediates midkine suppression in endometriosis. Hum Reprod. 2016 Sep;31(9):1981-6. doi: 10.1093/humrep/dew180. Epub 2016 Jul 13.
- Background Barra F, Romano A, Grandi G, Facchinetti F, Ferrero S. Future directions in endometriosis treatment: discovery and development of novel inhibitors of estrogen biosynthesis. Expert Opin Investig Drugs. 2019 Jun;28(6):501-504. doi: 10.1080/13543784.2019.1618269. Epub 2019 May 17. No abstract available.
- Background Barra F, Grandi G, Tantari M, Scala C, Facchinetti F, Ferrero S. A comprehensive review of hormonal and biological therapies for endometriosis: latest developments. Expert Opin Biol Ther. 2019 Apr;19(4):343-360. doi: 10.1080/14712598.2019.1581761. Epub 2019 Feb 27.
- Background Kocbek V, Grandi G, Blank F, Wotzkow C, Bersinger NA, Mueller MD, Kyo S, McKinnon BD. TNFalpha-induced IKKbeta complex activation influences epithelial, but not stromal cell survival in endometriosis. Mol Hum Reprod. 2016 Nov;22(11):768-777. doi: 10.1093/molehr/gaw054. Epub 2016 Aug 19.
- Background Cagnacci A, Bellafronte M, Xholli A, Palma F, Carbone MM, Di Carlo C, Grandi G. Impact of laparoscopic cystectomy of endometriotic and non-endometriotic cysts on ovarian volume, antral follicle count (AFC) and ovarian doppler velocimetry. Gynecol Endocrinol. 2016;32(4):298-301. doi: 10.3109/09513590.2016.1142523. Epub 2016 Feb 5.
- Background Pinzauti S, Lazzeri L, Tosti C, Centini G, Orlandini C, Luisi S, Zupi E, Exacoustos C, Petraglia F. Transvaginal sonographic features of diffuse adenomyosis in 18-30-year-old nulligravid women without endometriosis: association with symptoms. Ultrasound Obstet Gynecol. 2015 Dec;46(6):730-6. doi: 10.1002/uog.14834.
- Background Berkhout RP, Lambalk CB, Repping S, Hamer G, Mastenbroek S. Premature expression of the decidualization marker prolactin is associated with repeated implantation failure. Gynecol Endocrinol. 2020 Apr;36(4):360-364. doi: 10.1080/09513590.2019.1650344. Epub 2019 Aug 7.
- Background Berneau SC, Ruane PT, Brison DR, Kimber SJ, Westwood M, Aplin JD. Characterisation of Osteopontin in an In Vitro Model of Embryo Implantation. Cells. 2019 May 9;8(5):432. doi: 10.3390/cells8050432.
- Background Park CW, Choi MH, Yang KM, Song IO. Pregnancy rate in women with adenomyosis undergoing fresh or frozen embryo transfer cycles following gonadotropin-releasing hormone agonist treatment. Clin Exp Reprod Med. 2016 Sep;43(3):169-73. doi: 10.5653/cerm.2016.43.3.169. Epub 2016 Sep 22.
- Background Niu Z, Chen Q, Sun Y, Feng Y. Long-term pituitary downregulation before frozen embryo transfer could improve pregnancy outcomes in women with adenomyosis. Gynecol Endocrinol. 2013 Dec;29(12):1026-30. doi: 10.3109/09513590.2013.824960. Epub 2013 Sep 5.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Dienogest | Small molecule | 2 mg | — |
| Subject | Leuprolide | Other / unclassified | 3.75 mg | — |