Ethanol Sclerotherapy Prior to ART (START)

The Impact of Ethanol Sclerotherapy Before ART (Assisted Reproductive Technology) Cycle on Cumulative Live Birth Rate in Infertile Women With Endometrioma: A Randomized Controlled Trial

The goal of this randomized controlled trial is to assess the impact of ethanol sclerotherapy on ART cycle outcomes. The main questions it aims to answer are: Does ethanol sclerotherapy before ART cycle has any impact on cumulative live birth rate in patients with endometrioma? Does ethanol sclerotherapy improve chronic pelvic pain, dysmenorrhea, complications during oocyte retrieval, response to ovarian stimulation (number of mature oocytes retrieved), and pregnancy loss rates? Infertile patients with endometrioma between 4-10 cm who are scheduled for ART within 2 cycles will be randomized to ethanol sclerotherapy or no intervention.

The effect of ethanol sclerotherapy before assisted reproductive technology (ART) cycle in patients with endometrioma on reproductive outcomes will be investigated. While endometrioma may result in technical difficulties in the ART process, the superiority of ethanol sclerotherapy has yet to be examined before the ART procedure in randomized controlled studies and meta-analyses. The negative effect of ethanol sclerotherapy on ovarian reserve was found to be less than other existing interventions such as cyst stripping. However, randomized controlled studies did not determine its direct effect on ART outcome. Our current study aimed to assess the effect of ethanol sclerotherapy on ART outcomes. Infertile patients aged 18-40 years with at least one endometrioma 4-10 cm and scheduled for ART will be included in the study. Patients with any untreated thyroid dysfunction or additional disease, such as hyperprolactinemia, those who did not accept the study information and consent, and patients younger than 18 or older than 40 will not be included. Those who underwent surgery for endometrioma within 3 months before ART will be excluded. In addition, patients with an anti-mullerian hormone value below 0.3 ng/ml will not be included in the study.

endometrioma, ethanol sclerotherapy, assisted reproductive technology, in vitro fertilization, cumulative live birth rate

In eligible patients allocated to study group, endometrioma/s will be aspirated and treated with ethanol for 10 minutes 1-2 cycles before ART.

2 gr IV cefazolin sodium will be administered 30 minutes before the procedure. The endometrioma cyst content will be aspirated by a single lumen needle, and the total aspirated volume calculation will be done. The endometrioma will then be washed with saline until the color of the cyst content becomes clear. Then, 96% ethanol will be injected into the cyst. The volume of injected ethanol will be 60% of the first aspirated volume (maximum 100 ml). After 10 minutes all ethanol will be aspirated.

Visual Analog Pain Scale scores related to dysmenorrhea, dyspareunia, and/or pelvic pain will be measured before and after procedure

Inclusion Criteria: AMH>0.3 ng/ml unilateral/bilateral endometrioma Endometrioma diameter 40-100 mm Exclusion Criteria: 3 or more IVF/embryo transfer failure Menstrual cycle abnormalities Male Factor infertility Presence of uterine fibroids Presence of hydrosalpinx Presence of uterine abnormalities Suspicion of malignancy according to International Ovarian Tumor Analysis criteria

Akamatsu N, Hirai T, Masaoka H, Sekiba K, Fujita T. [Ultrasonically guided puncture of endometrial cysts--aspiration of contents and infusion of ethanol]. Nihon Sanka Fujinka Gakkai Zasshi. 1988 Feb;40(2):187-91. Japanese.

Alborzi S, Ravanbakhsh R, Parsanezhad ME, Alborzi M, Alborzi S, Dehbashi S. A comparison of follicular response of ovaries to ovulation induction after laparoscopic ovarian cystectomy or fenestration and coagulation versus normal ovaries in patients with endometrioma. Fertil Steril. 2007 Aug;88(2):507-9. doi: 10.1016/j.fertnstert.2006.11.134. Epub 2007 Apr 11.

Benaglia L, Busnelli A, Biancardi R, Vegetti W, Reschini M, Vercellini P, Somigliana E. Oocyte retrieval difficulties in women with ovarian endometriomas. Reprod Biomed Online. 2018 Jul;37(1):77-84. doi: 10.1016/j.rbmo.2018.03.020. Epub 2018 Apr 13.

Benaglia L, Somigliana E, Vercellini P, Abbiati A, Ragni G, Fedele L. Endometriotic ovarian cysts negatively affect the rate of spontaneous ovulation. Hum Reprod. 2009 Sep;24(9):2183-6. doi: 10.1093/humrep/dep202. Epub 2009 Jun 5.

Cohen A, Almog B, Tulandi T. Sclerotherapy in the management of ovarian endometrioma: systematic review and meta-analysis. Fertil Steril. 2017 Jul;108(1):117-124.e5. doi: 10.1016/j.fertnstert.2017.05.015. Epub 2017 Jun 1.

Dunselman GA, Vermeulen N, Becker C, Calhaz-Jorge C, D'Hooghe T, De Bie B, Heikinheimo O, Horne AW, Kiesel L, Nap A, Prentice A, Saridogan E, Soriano D, Nelen W; European Society of Human Reproduction and Embryology. ESHRE guideline: management of women with endometriosis. Hum Reprod. 2014 Mar;29(3):400-12. doi: 10.1093/humrep/det457. Epub 2014 Jan 15.

Garcia-Velasco JA, Somigliana E. Management of endometriomas in women requiring IVF: to touch or not to touch. Hum Reprod. 2009 Mar;24(3):496-501. doi: 10.1093/humrep/den398. Epub 2008 Dec 4.

Hart RJ, Hickey M, Maouris P, Buckett W. Excisional surgery versus ablative surgery for ovarian endometriomata. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD004992. doi: 10.1002/14651858.CD004992.pub3.

Horton J, Sterrenburg M, Lane S, Maheshwari A, Li TC, Cheong Y. Reproductive, obstetric, and perinatal outcomes of women with adenomyosis and endometriosis: a systematic review and meta-analysis. Hum Reprod Update. 2019 Sep 11;25(5):592-632. doi: 10.1093/humupd/dmz012.

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 Jul;92(1):68-74. doi: 10.1016/j.fertnstert.2008.04.056. Epub 2008 Aug 5.

Miquel L, Preaubert L, Gnisci A, Netter A, Courbiere B, Agostini A, Pivano A. Transvaginal ethanol sclerotherapy for an endometrioma in 10 steps. Fertil Steril. 2021 Jan;115(1):259-260. doi: 10.1016/j.fertnstert.2020.08.1422. Epub 2020 Oct 8.

Miquel L, Preaubert L, Gnisci A, Resseguier N, Pivano A, Perrin J, Courbiere B. Endometrioma ethanol sclerotherapy could increase IVF live birth rate in women with moderate-severe endometriosis. PLoS One. 2020 Sep 28;15(9):e0239846. doi: 10.1371/journal.pone.0239846. eCollection 2020.

Roustan A, Perrin J, Debals-Gonthier M, Paulmyer-Lacroix O, Agostini A, Courbiere B. Surgical diminished ovarian reserve after endometrioma cystectomy versus idiopathic DOR: comparison of in vitro fertilization outcome. Hum Reprod. 2015 Apr;30(4):840-7. doi: 10.1093/humrep/dev029. Epub 2015 Mar 3.

Rubod C, Jean Dit Gautier E, Yazbeck C. [Surgical management of endometrioma: Different alternatives in term of pain, fertility and recurrence. CNGOF-HAS Endometriosis Guidelines]. Gynecol Obstet Fertil Senol. 2018 Mar;46(3):278-289. doi: 10.1016/j.gofs.2018.02.013. Epub 2018 Mar 3. French.

Somigliana E, Benaglia L, Paffoni A, Busnelli A, Vigano P, Vercellini P. Risks of conservative management in women with ovarian endometriomas undergoing IVF. Hum Reprod Update. 2015 Jul-Aug;21(4):486-99. doi: 10.1093/humupd/dmv012. Epub 2015 Mar 6.

Sukur YE, Ozmen B, Yakistiran B, Atabekoglu CS, Berker B, Aytac R, Sonmezer M. Endometrioma surgery is associated with increased risk of subsequent assisted reproductive technology cycle cancellation; a retrospective cohort study. J Obstet Gynaecol. 2021 Feb;41(2):259-262. doi: 10.1080/01443615.2020.1754366. Epub 2020 Jun 4.

Yazbeck C, Madelenat P, Ayel JP, Jacquesson L, Bontoux LM, Solal P, Hazout A. Ethanol sclerotherapy: a treatment option for ovarian endometriomas before ovarian stimulation. Reprod Biomed Online. 2009 Jul;19(1):121-5. doi: 10.1016/s1472-6483(10)60055-7.

Yazbeck C, Koskas M, Cohen Scali S, Kahn V, Luton D, Madelenat P. [How I do... ethanol sclerotherapy for ovarian endometriomas]. Gynecol Obstet Fertil. 2012 Oct;40(10):620-2. doi: 10.1016/j.gyobfe.2012.07.029. Epub 2012 Sep 5. No abstract available. French.