Endometrial scratch vs no intervention in egg donation cycles: the ENDOSCRATCH trial protocol

Alexandra Izquierdo, Laura de la Fuente, Katharina Spies, Jennifer Rayward, Lourdes López, David Lora, Alberto Galindo, Alexandra Izquierdo, Laura de la Fuente, Katharina Spies, Jennifer Rayward, Lourdes López, David Lora, Alberto Galindo

Abstract

Background: The effects of endometrial scratching (ES) on embryo implantation have been studied for many years. Several studies have shown better outcomes when performed on patients undergoing intrauterine insemination and in vitro fertilization (IVF) cycles, but many other reports have not been able to find these differences. As far as cycles with donor eggs are concerned, reported evidence is scarce. Our aim in this trial is to determine if ES is useful for those patients undergoing IVF cycles with donor eggs, in order to assure a greater homogeneity in embryo quality and endometrial preparation.

Methods: This single centre randomized controlled trial will include patients undergoing an egg donation cycle, meeting the inclusion criteria and who accept to participate in the study. Once informed consent is signed, patients will be randomly allocated to the study arm (group A) and then receive ES in the luteal phase of the cycle prior to embryo transfer, or the control arm (group B) without any intervention. All cycle data will be collected and analyzed to obtain the clinical pregnancy and the live birth rates in the two groups.

Discussion: Several studies have tried to determine the effectiveness of an ES in IVF cycles, but it is still unclear due to the heterogeneity of these reports. The aim of this study is to determine if there are differences in clinical pregnancy rate and live birth rate in egg donor cycles, when comparing an ES performed in the preceding luteal phase versus no intervention, given that embryo quality and endometrial preparation protocols will be comparable.

Trial registration: Ethical approval of version 2.0 of this trial was obtained on the 13th January 2017. It was retrospectively registered on the 5th April 2017 as the ENDOSCRATCH Trial (NCT03108157) in ClinicalTrials.gov.

Keywords: Egg donation; Endometrial injury; Endometrial receptivity; Endometrial scratching; Hysteroscopy; In vitro fertilization; Recurrent implantation failure.

Conflict of interest statement

The authors declare that they have no competing interests.

References

    1. De Geyter C, Calhaz-Jorge C, Kupka MS, Wyns C, Mocanu E, Motrenko T, et al. ART in Europe, 2014: results generated from European registries by ESHRE: The European IVF-monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE) Hum Reprod Oxf Engl. 2018;33(9):1586–1601. doi: 10.1093/humrep/dey242.
    1. Cakmak H, Taylor HS. Implantation failure: molecular mechanisms and clinical treatment. Hum Reprod Update. 2011;17(2):242–253. doi: 10.1093/humupd/dmq037.
    1. Gnainsky Y, Granot I, Aldo PB, Barash A, Or Y, Schechtman E, et al. Local injury of the endometrium induces an inflammatory response that promotes successful implantation. Fertil Steril. 2010;94(6):2030–2036. doi: 10.1016/j.fertnstert.2010.02.022.
    1. Nastri CO, Lensen S, Polanski L, Raine-Fenning N, Farquhar CM, Martins WP. Endometrial injury and reproductive outcomes: there’s more to this story than meets the horse’s blind eye. Hum Reprod Oxf Engl. 2015;30(3):749. doi: 10.1093/humrep/deu365.
    1. Kalma Y, Granot I, Gnainsky Y, Or Y, Czernobilsky B, Dekel N, et al. Endometrial biopsy-induced gene modulation: first evidence for the expression of bladder-transmembranal uroplakin Ib in human endometrium. Fertil Steril. 2009;91(4):1042–1049. doi: 10.1016/j.fertnstert.2008.01.043.
    1. Lensen SF, Manders M, Nastri CO, Gibreel A, Martins WP, Templer GE, et al. Endometrial injury for pregnancy following sexual intercourse or intrauterine insemination. Cochrane Database Syst Rev. 2016;6:CD011424.
    1. Senocak GC, Yapca OE, Borekci B. Comparison of pregnancy rates between patients with and without local endometrial scratching before intrauterine insemination. J Gynecol Obstet Hum Reprod. 2017;46(9):687–690. doi: 10.1016/j.jogoh.2017.09.003.
    1. Vitagliano A, Noventa M, Saccone G, Gizzo S, Vitale SG, Laganà AS, et al. Endometrial scratch injury before intrauterine insemination: is it time to re-evaluate its value? Evidence from a systematic review and meta-analysis of randomized controlled trials. Fertil Steril. 2018;109(1):84–96. doi: 10.1016/j.fertnstert.2017.09.021.
    1. Barash A, Dekel N, Fieldust S, Segal I, Schechtman E, Granot I. Local injury to the endometrium doubles the incidence of successful pregnancies in patients undergoing in vitro fertilization. Fertil Steril. 2003;79(6):1317–1322. doi: 10.1016/S0015-0282(03)00345-5.
    1. Raziel A, Schachter M, Strassburger D, Bern O, Ron-El R, Friedler S. Favorable influence of local injury to the endometrium in intracytoplasmic sperm injection patients with high-order implantation failure. Fertil Steril. 2007;87(1):198–201. doi: 10.1016/j.fertnstert.2006.05.062.
    1. Zhou L, Li R, Wang R, Huang H, Zhong K. Local injury to the endometrium in controlled ovarian hyperstimulation cycles improves implantation rates. Fertil Steril. 2008;89(5):1166–1176. doi: 10.1016/j.fertnstert.2007.05.064.
    1. Karimzadeh MA, Ayazi Rozbahani M, Tabibnejad N. Endometrial local injury improves the pregnancy rate among recurrent implantation failure patients undergoing in vitro fertilisation/intra cytoplasmic sperm injection: a randomised clinical trial. Aust N Z J Obstet Gynaecol. 2009;49(6):677–680. doi: 10.1111/j.1479-828X.2009.01076.x.
    1. Frantz S, Parinaud J, Kret M, Rocher-Escriva G, Papaxanthos-Roche A, Creux H, et al. Decrease in pregnancy rate after endometrial scratch in women undergoing a first or second in vitro fertilization. A multicenter randomized controlled trial. Hum Reprod Oxf Engl. 2019;34(1):92–99. doi: 10.1093/humrep/dey334.
    1. Lensen S, Osavlyuk D, Armstrong S, Stadelmann C, Hennes A, Napier E, et al. A Randomized Trial of Endometrial Scratching before In Vitro Fertilization. N Engl J Med. 2019;380(4):325–334. doi: 10.1056/NEJMoa1808737.
    1. Yeung TWY, Chai J, Li RHW, Lee VCY, Ho PC, Ng EHY. The effect of endometrial injury on ongoing pregnancy rate in unselected subfertile women undergoing in vitro fertilization: a randomized controlled trial. Hum Reprod Oxf Engl. 2014;29(11):2474–2481. doi: 10.1093/humrep/deu213.
    1. Eskew AM, Reschke LD, Woolfolk C, Schulte MB, Boots CE, Broughton DE, et al. Effect of endometrial mechanical stimulation in an unselected population undergoing in vitro fertilization: futility analysis of a double-blind randomized controlled trial. J Assist Reprod Genet. 2019;36(2):299–305. doi: 10.1007/s10815-018-1356-5.
    1. Baum M, Yerushalmi GM, Maman E, Kedem A, Machtinger R, Hourvitz A, et al. Does local injury to the endometrium before IVF cycle really affect treatment outcome? Results of a randomized placebo controlled trial. Gynecol Endocrinol Off J Int Soc Gynecol Endocrinol. 2012;28(12):933–936. doi: 10.3109/09513590.2011.650750.
    1. Gibreel A, El-Adawi N, Elgindy E, Al-Inany H, Allakany N, Tournaye H. Endometrial scratching for women with previous IVF failure undergoing IVF treatment. Gynecol Endocrinol Off J Int Soc Gynecol Endocrinol. 2015;31(4):313–316. doi: 10.3109/09513590.2014.994603.
    1. Nastri C, Ferriani R, Raine-Fenning N, Martins W. Endometrial scratching performed in the non-transfer cycle and outcome of assisted reproduction: a randomized controlled trial. Ultrasound Obstet Gynecol. 2013;42(4):375–382.
    1. Potdar N, Gelbaya T, Nardo LG. Endometrial injury to overcome recurrent embryo implantation failure: a systematic review and meta-analysis. Reprod BioMed Online. 2012;25(6):561–571. doi: 10.1016/j.rbmo.2012.08.005.
    1. Nastri CO, Lensen SF, Gibreel A, Raine-Fenning N, Ferriani RA, Bhattacharya S, et al. Endometrial injury in women undergoing assisted reproductive techniques. Cochrane Database Syst Rev. 2015;3:CD009517.
    1. Dain L, Ojha K, Bider D, Levron J, Zinchenko V, Walster S, et al. Effect of local endometrial injury on pregnancy outcomes in ovum donation cycles. Fertil Steril. 2014;102(4):1048–1054. doi: 10.1016/j.fertnstert.2014.06.044.
    1. Narvekar SA, Gupta N, Shetty N, Kottur A, Srinivas M, Rao KA. Does local endometrial injury in the nontransfer cycle improve the IVF-ET outcome in the subsequent cycle in patients with previous unsuccessful IVF? A randomized controlled pilot study. J Hum Reprod Sci. 2010;3(1):15–19. doi: 10.4103/0974-1208.63116.
    1. Seval MM, Şükür YE, Özmen B, Kan Ö, Sönmezer M, Berker B, et al. Does adding endometrial scratching to diagnostic hysteroscopy improve pregnancy rates in women with recurrent in-vitro fertilization failure? Gynecol Endocrinol Off J Int Soc Gynecol Endocrinol. 2016;32(12):957–960. doi: 10.1080/09513590.2016.1190818.
    1. Maged AM, Rashwan H, AbdelAziz S, Ramadan W, Mostafa WAI, Metwally AA. et al. Randomized controlled trial of the effect of endometrial injury on implantation and clinical pregnancy rates during the first ICSI cycle. Int J Gynaecol Obstet Off Organ Int Fed Gynaecol Obstet. 2018;140(2):211–6. doi: 10.1002/ijgo.12355.
    1. Lensen S, Sadler L, Farquhar C. Endometrial scratching for subfertility: everyone’s doing it. Hum Reprod Oxf Engl. 2016;31(6):1241–1244. doi: 10.1093/humrep/dew053.
    1. Santamaria X, Katzorke N, Simón C. Endometrial “scratching”: what the data show. Curr Opin Obstet Gynecol. 2016;28(4):242–249. doi: 10.1097/GCO.0000000000000279.

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