Does Adenomyosis Influence ICSI Clinical Outcome? A Systematic Analysis and Impact of GnRH Agonist Pretreatment for Women with Adenomyosis in ICSI-FET Cycle: A Retrospective Cohort Study

Objective To evaluate the impact of adenomyosis on pregnancy outcome in ICSI/FET cycles and the beneficial effect of GnRH agonist pretreatment, conservative surgery or combination therapy on pregnancy outcome.

This is a retrospective cohort study where 613 ICSI cycles done in the period from Jan 2018 to Dec 2020 in Sudha infertility centre, Erode were analyzed. Study populations include 235 women with adenomyosis undergoing ICSI/FET cycle.

Overall, the outcome in terms of clinical pregnancy rate, miscarriage rate, live birth date and ongoing pregnancy rate was lower in women with adenomyosis following ICSI/FET cycles. We found significant improvement in clinical pregnancy rate who had pretreatment with GnRH agonist, conservative surgery or combination therapy.

Adenomyosis as such has detrimental effect on ICSI clinical outcome. Pretreatment with GnRH agonist and conservative surgery and GnRH agonist long protocol could be beneficial. Further large scale prospective comparative studies are needed to confirm this result. Similar content being viewed by others

Costello MF, Lindsay K, McNally G. The effect of adenomyosis on in vitro fertilisation and intra-cytoplasmic sperm injection treatment outcome. Eur J Obstet Gynecol Reprod Biol. 2011;58(2):229–34. https://doi.org/10.1016/j.ejogrb.2011.04.030 (Epub 2011 Jun 12 PMID: 21664029). Salim R, Riris S, Saab W, Abramov B, Khadum I, Serhal P. Adenomyosis reduces pregnancy rates in infertile women undergoing IVF. Reprod Biomed Online. 2012;25(3):273–7. https://doi.org/10.1016/j.rbmo.2012.05.003 (Epub 2012 May 23 PMID: 22832421). Thalluri V, Tremellen KP. Ultrasound diagnosed adenomyosis has a negative impact on successful implantation following GnRH antagonist IVF treatment. Hum Reprod. 2012;27(12):3487–92. https://doi.org/10.1093/humrep/des305 (Epub 2012 Sep 20 PMID: 22997247). Vercellini P, Consonni D, Dridi D, Bracco B, Frattaruolo MP, Somigliana E. Uterine adenomyosis and in vitro fertilization outcome: a systematic review and meta-analysis. Hum Reprod. 2014;29(5):964–77. https://doi.org/10.1093/humrep/deu041 (Epub 2014 Mar 12 PMID: 24622619). Khan KN, Kitajima M, Hiraki K, Fujishita A, Sekine I, Ishimaru T, Masuzaki H. Changes in tissue inflammation, angiogenesis and apoptosis in endometriosis, adenomyosis and uterine myoma after GnRH agonist therapy. Hum Reprod. 2010;25(3):642–53. https://doi.org/10.1093/humrep/dep437. Ota H, Igarashi S, Hatazawa J, Tanaka T. Immunohistochemical assessment of superoxide dismutase expression in the endometrium in endometriosis and adenomyosis. Fertil Steril. 1999;72(1):129–34. https://doi.org/10.1016/s0015-0282(99)00152-1 (PMID: 10428161). Mijatovic V, Florijn E, Halim N, Schats R, Hompes P. Adenomyosis has no adverse effects on IVF/ICSI outcomes in women with endometriosis treated with long-term pituitary down-regulation before IVF/ICSI. Eur J Obstet Gynecol Reprod Biol. 2010;151(1):62–5. https://doi.org/10.1016/j.ejogrb.2010.02.047 (Epub 2010 Apr 21 PMID: 20409633). Harada T, Khine YM, Kaponis A, Nikellis T, Decavalas G, Taniguchi F. The impact of adenomyosis on women’s fertility. Obstet Gynecol Surv. 2016;71(9):557–68. https://doi.org/10.1097/OGX.0000000000000346. Kunz G, Beil D, Huppert P, Leyendecker G. Structural abnormalities of the uterine wall in women with endometriosis and infertility visualized by vaginal sonography and magnetic resonance imaging. Hum Reprod. 2000;15(1):76–82. https://doi.org/10.1093/humrep/15.1.76 (PMID: 10611192). Barroso RP, Osuamkpe C, Nagamani M, et al. Nitric oxide inhibits development of embryos and implantation in mice. Mol Hum Reprod. 1998;4:503–7. Broer SL, van Disseldorp J, Broeze KA, Dolleman M, Opmeer BC, Bossuyt P, Eijkemans MJC, Mol B-WJ, Broekmans FJM, on behalf of the IMPORT study group, Broer SL, van Disseldorp J, Broeze KA, Dolleman M, Opmeer BC, Anderson RA, Ashrafi M, Bancsi L, Caroppo LE, Copperman A, Ebner T, Eldar Geva M, Erdem M, Greenblatt EM, Jayaprakasan K, Fenning R, Klinkert ER, Kwee J, Lambalk CB, La Marca A, McIlveen M, Merce LT, Muttukrishna S, Nelson SM, Ng HY, Popovic-Todorovic B, Smeenk JMJ, Tomás C, Van der Linden PJQ, van Rooij IA, Vladimirov IK, Bossuyt PB, Eijkemans MJC, Mol BW, Frank B. Added value of ovarian reserve testing on patient characteristics in the prediction of ovarian response and ongoing pregnancy: an individual patient data approach. Hum Reprod Update. 2013;19(1):26–36. https://doi.org/10.1093/humupd/dms041. Jeve YB. The combined use of antimullerian hormone and age to predict the ovarian response to controlled ovarian hyperstimulation in poor responders: a novel approach. J Hum Reprod Sci. 2013;6(4):259–62. https://doi.org/10.4103/0974-1208.126298.PMID:24672166;PMCID:PMC3963310. Broekmans FJ, Kwee J, Hendriks DJ, Mol BW, Lambalk CB. A systematic review of tests predicting ovarian reserve and IVF outcome. Hum Reprod Update. 2006;12(6):685–718. https://doi.org/10.1093/humupd/dml034. Kishi Y, Yabuta M, Taniguchi F. Who will benefit from uterus-sparing surgery in adenomyosis-associated subfertility? Fertil Steril. 2014;102(3):802.e1-807.e1. https://doi.org/10.1016/j.fertnstert.2014.05.028 (Epub 2014 Jun 19 PMID: 24954774). Younes G, Tulandi T. Effects of adenomyosis on in vitro fertilization treatment outcomes: a meta-analysis. Fertil Steril. 2017;108(3):483.e3-490.e3. https://doi.org/10.1016/j.fertnstert.2017.06.025 (PMID: 28865548). Naftalin J, Hoo W, Pateman K, Mavrelos D, Holland T, Jurkovic D. How common is adenomyosis? A prospective study of prevalence using transvaginal ultrasound in a gynaecology clinic. Hum Reprod. 2012;27(12):3432–9. https://doi.org/10.1093/humrep/des332. Silva PD, Perkins HE, Schauberger CW. Live birth after treatment of severe adenomyosis with a gonadotropin-releasing hormone agonist. Fertil Steril. 1994;61:171–2. Wang PH, Fuh JL, Chao HT, Liu WM, Cheng MH, Chao KC. Is the surgical approach beneficial to subfertile women with symptomatic extensive adenomyosis? J Obstet Gynaecol Res. 2009;35(3):495–502. https://doi.org/10.1111/j.1447-0756.2008.00951.x (PMID: 19527389). Van den Bosch T, de Bruijn AM, de Leeuw RA, Dueholm M, Exacoustos C, Valentin L, Bourne T, Timmerman D, Huirne JAF. Sonographic classification and reporting system for diagnosing adenomyosis. Ultrasound Obstet Gynecol. 2019;53(5):576–82. https://doi.org/10.1002/uog.19096 (PMID: 29790217). Sharma S, Bathwal S, Agarwal N, Chattopadhyay R, Saha I, Chakravarty B. Does presence of adenomyosis affect reproductive outcome in IVF cycles? A retrospective analysis of 973 patients. Reprod Biomed Online. 2019;38(1):13–21. https://doi.org/10.1016/j.rbmo.2018.09.014 (Epub 2018 Oct 26 PMID: 30446308). Chiang CH, Chang MY, Shiau CS, et al. Effect of a sonographically diffusely enlarged uterus without distinct uterine masses on the outcome of in vitro fertilization-embryo transfer. J Assist Reprod Genet. 1999;16:369–72. Author information Authors and Affiliations Corresponding author Ethics declarations Conflict of interest The authors declare that they have no conflict of Interest. Ethical Statement Hereby, I Dr Pradeepa Sudhakar consciously assure that the for the manuscript submitted above where in accordance with the ethical standards and informed consent was obtained from all the patients being included in the study, Prior ethical approval was obtained from the Sudha Hospital Ethical Committee. Informed Consent Informed consent was obtained from all the patients for being included in the study. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Pradeepa Sudhakar is a Senior Consultant IVF and Reproductive Medicine, Department of Obstetrics and Gynecology, Sudha Hospital, Erode, Tamil Nadu, India; Saranya Manivannan is a Consultant IVF and Reproductive Medicine, Department of Obstetrics and Gynecology, Sudha Hospital, Erode, Tamil Nadu, India; Dhanabagyam Kandasamy is a Director, Department of Reproductive Medicine, Sudha Hospital, Coimbatore, Tamil Nadu, India. Rights and permissions About this article Cite this article Sudhakar, P., Manivannan, S., Kandasamy, D. et al. Does Adenomyosis Influence ICSI Clinical Outcome? A Systematic Analysis and Impact of GnRH Agonist Pretreatment for Women with Adenomyosis in ICSI–FET Cycle: A Retrospective Cohort Study. J Obstet Gynecol India 72, 236–242 (2022). https://doi.org/10.1007/s13224-021-01504-y Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s13224-021-01504-y