Effect of local endometrial injury in Follicular vs. luteal phase on implantation and pregnancy outcomes of Frozen Embryo Transfer Cycles in women with repeated in vitro fertilization failure.A randomized clinical trial

Effect of local endometrial injury in Follicular vs. luteal phase on implantation and pregnancy outcomes of Frozen Embryo Transfer Cycles in women with repeated in vitro fertilization failure.A randomized clinical trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effect of local endometrial injury in Follicular vs. luteal phase on implantation and pregnancy outcomes of Frozen Embryo Transfer Cycles in women with repeated in vitro fertilization failure.A randomized clinical trial Ladan Kashani, zahra parsaiyan This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1657996/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction :recurrent implantation failure(RIF)refers to failure to achieve a clinical pregnancy after transferring at least four good quality embryos in a minimum of three fresh or frozen cycles.Endometrial scratch is the newly proposed surgical strategy to improve endometrial receptivity;the healing process following scratch may release cytokines and growth factors which encourage endometrial growth and facilitates implantation.Timing of this procedure is a point that may lead to different outcomes.This study compares follicular versus luteal phase injury due to their different molecular patterns on the outcome of embryo transfer in RIF patients. Study design: This study is a double blinded randomized clinical trial.Patients came into infertility clinic of Arash women’s hospital in years2017and2018are divided into two groups. In one group injury was done with pipelle at4th-6thday of frozen embryo transferring cycle(n = 38)and in the other one it was done at21th- 23thday of the cycle before the FET (n = 40).Then the infertility rates were compared. Results Totally29(41.4%)chemical pregnancies happened,15(51.7%)of them was in follicular group and14(48.3%)in luteal group.28(40%)clinical pregnancies happened totally which were equal in both groups(14 in each one).Ongoing pregnancies happened in 22(31.4%)patients that12(54.5%)of them were in follicular and the other10(45.5%)were in luteal group. Conclusion According to this study,local endometrial injury by pipelle didn’t show any significant differences in both groups pregnancy outcomes.But in the follicular group the IVF cycle time period is decreased and therefore the psychological burden of long time required for luteal phase LEI will decrease and is more acceptable for patients,maybe it’s better to do LEI in follicular phase;more studies with larger sample sizes recommended. repeated IVF failure local endometrial injury Implantation pipelle follicular phase luteal phase Introduction: Infertility defined as one year of unprotected intercourse without conception [ 2 – 3 ]. Major developments have occurred in recent years, in vitro fertilization is one of them that could be used in almost all infertility cases. IVF success rate is about 30 to 40 percent in each cycle [ 4 ]. It depends on factors like woman’s age, infertility cause, treatment protocol, embryo quality, number of transmitted fetuses, transmission technique, sperm quality and endometrial characteristics [ 5 ]. Repeated implantation failure (RIF) is failure of implantation of transferred embryos after several IVF treatment cycles. However, there are no formal criteria defining the number of failed cycles or the total number of embryos transferred in these IVF attempts so, there are various definitions in different infertility centers. usually RIF defines as failure of implantation in at least two or three consecutive IVF attempts, in which 1–2 embryos of high grade quality are transferred in each cycle. [ 6 ]. These failures can cause psychological and financial burden to the patients and community and causes wasting times. Therefor many researchers focus on finding ways to increase the implantation rates. Environmental and feto maternal factors affect pregnancy outcomes. Endometrial cavity abnormalities, inappropriate endometrium, thrombophilias, connective tissue disorders and immunological disorders are examples of the maternal factors that affect pregnancy and genetic disorders are of fetal factors [ 7 – 8 – 9 ]. Embryo quality and receptive endometrium condition are two important factors for successful implantation (10). If the endometrium is not suitable for implantation, regarding the quality of embryo, implantation does not occur. Local endometrial injury could evoke local inflammatory responses by rising in cytokines and growth factors and causing expression of genes that contribute in fetus implantation so it can cause higher pregnancy rate in women with RIF [11- 12 – 13 ]. Many studies reported on contradictory results of endometrial injury in women with RIF. Some studies showed that implantation rates, and clinical pregnancy rates improved by LEI [14–18], and some of them showed no differences [19–20]. Juan et al. studied a systematic review about the Impact of local endometrial injury on in vitro fertilization/intracytoplasmic sperm injection outcomes and found conflicting data [21]. Studies regarding this issue are conflicting results. Endometrial injury in most of studies was performed in either follicular phase or luteal phase, or in both phases. The effects of endometrial injury in follicular vs. luteal phase have been studied only in one study previously. Furthermore, timing of this procedure is a point that may lead to different outcomes (30). This study compares follicular endometrial injury to luteal phase injury due to their different molecular patterns on the outcome of embryo transfer in RIF patients. Because of the long time required in luteal phase local endometrial injury of FET cycles and its consecutive psychological and financial costs, it seems that doing LEI in follicular phase would be helpful for these discomforts rather than luteal phase. This study is going to compare the effect of LEI in follicular phase vs. luteal phase of frozen embryo transferring cycles of IVF in women with RIF. Methods: Study design and participants: This study is a double blinded randomized clinical trial. This study is designed as aclinical trial with a parallel random allocation and a 1: 1 ratio. A total of 78 patients of infertility clinic of Arash women’s hospital with at least one IVF failure in years 2017 and 2018 were concluded in this study. The inclusion criteria were: (i) infertile women with at least one IVF failure; (ii) ≤ 40 years of age; (iii) a normal uterine cavity demonstrated by hysteroscopy or hysterosalpingography done during one year ago; (iiii) not using OCP or GnRh agonists in the previous cycle. The exclusion Criteria were: (i) abnormal uterine cavity like polyp, fibroid or asherman syndrome; (ii) Endometrial hyperplasia or endometrial cancer; (iii) active vaginal or cervical infections (iiii) systemic disease such as diabetes mellitus, hypertension, and systematic lupus erythemato or etc. Recruited participantswere equally randomized into two groups using a table of block randomization: follicular group (group 1: endometrial injury in proliferative phase, n = 38); and luteal group (group 2: injury in luteal phase, n = 40). This study was approved by the Institutional ethics committee Review Board of Tehran medical university (IR.TUMS.MEDICINE.REC.1396.2911) all participating patients recruited to thestudy were fully counseled and signed written informed consent. Techniques: Patients of follicular group were treated with estradiol valerate for 10 to 14 days and simultaneously the endometrial injury was performed by biopsy catheter (Pipelle; de Cornier, Prodimed, Neuilly-en-Thelle, France) in days 4–6 ( if the bleeding stopped) of menstrual cycle before transmitting frozen embryos in uterus. This procedure performed as follows: the Pipelle was inserted through the cervical os and advanced gently until resistance was felt and after scratching, it was brought out of uterus. After 14 days, transvaginal sonography was done and if the triple line endometrium was seen or the echogenic endometrium was ≥ 7 mm, progesterone suppository was prescribed and after 3–4 days, 2 or 3 days frozen fetuses were transmitted in uterus. After 2 weeks serum beta hcg was checked and if it was more than 15 milli International Units per milliliter, trans vaginal sonography was performed for finding gestational sac(s). If it was seen, pregnant women were followed up to 12 weeks. In group 2, the same procedure was done but the endometrial injury with pipelle was performed in days of 21–23 of the menstrual cycle before FET. The outcomes were described as (a) chemical pregnancy: positive serum beta hcg, (b) clinical pregnancy: existence of gestational sac(s), (c) implantation rate: the proportion of gestational sacs to transferred fetuses, and (d) ongoing pregnancy: being pregnant after 12 weeks. Limitations: Long period of following patients was a limitation of the study which was resolved by calling patients and free visits. Data analysis: Stata ver.13 was the analyzing software. The baseline characteristics of the two groups of patients were compared by chi-square and independent T-test. For determining the relationships between the injury time and pregnancy outcomes logistic regression was used. P-value was 5 percent. Results: A total of 78 patients were recruited in this study from 2016 to 2017, 38 patients were in follicular group which pipelle was performed on days 4 to 6 of the FET cycle and 40 patients were in luteal group which pipelle was performed on days 21–23 of the cycle before FET. It was 8 patients’ loss during follow up, 3 from follicular group and 5 from luteal group. They were unavailable to see their outcomes. Therefore, there were 35 participants in each group finally. The average age was 31.37 years in follicular and 31.2 years in luteal group. The average years of infertility and body mass index(BMI) in both groups were about the same. Also the number of retrieved and freezed ovocytes and transferred eggs were compared and there were no significant differences. Mean endometrial thickness at the time of transferring was 9.21 mm in follicular and 9.67 mm in luteal group which they didn’t differ statistically. Both groups were compared from the aspect of infertility causes. Male infertility rate accounts for 51.4% of infertility causes overall which was 47.2% in follicular and 52.8% in luteal group. Unexplained infertility was another cause of infertility (21.4% generally) that was happened 53.3% in follicular and 46.6% in luteal group. Other causes of infertility were PCOD, tubal factor and endometriosis which account for 34.2%, 8.5% and 4.2% of all contributors respectively. Statistically, no differences were seen. Next, infertility types evaluated. Generally primary infertility rate was 78.5% and secondary type was 21.4%. they are shown in the table. In Table 1 basic characteristic of both groups are shown and there is not statistical differences. Table 1 basic characteristics of patients undergoing endometrial local injury in follicular and luteal phases Variables Follicular group Luteal group P value Age(y) 31.37 ± 5.35 31.2 ± 5.51 0.912 BMI(Kg/m 2 ) 24.64 ± 2.69 25.65 ± 3.01 0.387 Duration of sub fertility 6.6 ± 4.55 6.02 ± 4.46 0.942 Oocyte number 17.68 ± 7.91 19.48 ± 5.38 0.24 frozen embryo number 6.17 ± 3.36 6.48 ± 2.46 0.22 Transferred embryo number 2.65 ± 0.68 3.05 ± 0.9 0.489 Endometrial thickness 9.21 ± 1.42 9.67 ± 1.74 0.251 Types of infertility 0.38 Primary 26(74.3%) 1 29(82.85%) secondary 9(25.7%) 6(17.14%) Causes of infertility 0.632 Male factor 17(48.57%) 19(54.28%) Tubal factor 4(11.42%) 2(5.71%) PCO 11(31.42%) 13(37.14%) Endometriosis 3(8.57%) 0 Unexplained 8(22.85%) 7(20%) 1 = percent of the participants in their groups. Finally, both groups evaluated for pregnancy outcomes. 29 cases of successful Chemical pregnancy happened (41.4%) that was 51.7% in follicular and 48.3% in luteal group. In clinical pregnancy, 28 cases were successful, which divided equally in both groups.22 cases of ongoing pregnancy happened that its percentage was 54.5 for follicular and 45.5 for luteal group. Abortion occurred in 10% of participants. 57.1% in follicular and 42.8%in luteal group were seen. Implantation rate generally was 0.19 with SD = 0.28. its rate in follicular group was 0.21 (SD = 0.28) and in luteal group was 0.17 (SD = 0.27). Statistically no significant differences were seen in pregnancy outcomes. In Table 2 the pregnancy outcomes are shown and no significant differences were seen. Table 2 Pregnancy outcomes of patients undergoing endometrial injury in proliferative phase and luteal phase (percent in each group) Outcomes Follicular group Luteal group P value Chemical pregnancy 15(42.85%) 14(40%) 0.808 Clinical pregnancy 14(40%) 14(40%) 1 Ongoing pregnancy 12(34.28%) 10(28.57%) 0.607 Abortion rate 4(11.42%) 3(8.57%) 0.643 Implantation rate 0.21 ± 0.28 0.17 ± 0.27 0.5 In Tables 3 , 4 and 5 the demographic and IVF factors effects on chemical, clinical and ongoing pregnancy is shown. Table 3 demographic and IVF factors effects on chemical pregnancy Factors Successful chemical pregnancy Unsuccessful chemical pregnancy P-value Mean age 31 ± 5.41 31.48 ± 5.44 0.303 Male infertility 15(51.72%) 21(51.21%) 0.967 Female infertility 21(72.41%) 27(65.85%) 0.075 embryo grade A = 21 B = 0 AB = 8 A = 27 B = 2AB = 12 0.463 BMI 24.99 ± 3.1 25.25 ± 2.7 0.706 Endometrial thickness 9.5 ± 1.6 9.39 ± 1.5 0.435 Fetus transferred 2.75 ± 0.6 2.92 ± 0.9 0.403 Table 4 demographic and IVF factors effect on clinical pregnancy Factors Successful clinical pregnancy Unsuccessful clinical pregnancy P-value Mean age 30.82 ± 5.43 31.59 ± 5.42 0.332 Male infertility 15(53.57%) 21(50%) 0.770 Female infertility 20(71.42%) 28(66.66%) 0.099 embryo grade A = 20 B = 0 AB = 8 A = 28 B = 2AB = 12 0.499 BMI 24.89 ± 3.1 25.31 ± 2.6 0.56 Endometrial thickness 9.51 ± 1.6 9.38 ± 1.5 0.78 Fetus transferred 2.82 ± 0.6 2.88 ± 0.9 0.76 Table 5 demographic and IVF factors effect on ongoing pregnancy Factors Successful ongoing pregnancy Unsuccessful ongoin pregnancy P-value Mean age 30.72 ± 5.02 31.54 ± 5.59 0.506 Male infertility 11(50%) 25(52.08%) 0.871 Female infertility 16(72.72%) 32(66.6%) 0.249 embryo grade A = 16 B = 0 AB = 6 A = 32 B = 2AB = 14 0.602 BMI 3.03 ± 24.77 2.83 ± 25.31 0.46 Endometrial thickness 1.7 ± 9.65 1.5 ± 9.33 0.43 embryo transferred 0.63 ± 2.86 0.89 ± 2.85 0.96 None of them were significant. Discussion: In this study, we try to assess whether there is a difference between follicular phase and luteal phase endometrial injury on pregnancy outcomes. In our study there was no difference between injury in the follicular phase or luteal phase on pregnancy and implantation outcomes. There are multiple factors that affect implantation of the embryo other than oocyte or sperm quality, and endometrial receptivity is one of them which is important [21–22]. Kalma et al. reported that endometrial biopsies cause the rise in membranous proteins expression like Uroplakin 1b. Some believe that endometrial injury before embryo transfer could cause decidualization and improves Implantation. Also Inflammatory response and rise of cytokines, interleukins, growth factors, dendritic cells and macrophages could improve plantation. Endometrial injury could improve synchronicity of embryo and uterus [24–25]. The effect of endometrial injury on improving pregnancy outcomes has been studied previously and there are many conflicting results. Barash et al. showed that repeated endometrial biopsies by a Pipelle catheter on days 8, 12, 21, and 26 of the spontaneous menstrual cycle before the IVF-ET treatment doubled clinical pregnancy and live birth rates in women with RIF. They used fresh embryos nut in our study there were frozen embryos which could decrease the implantation rate by itself [ 14 ]. Raziel et al. demonstrated that endometrial injury by pipelle catheter on days 21 and 26 of luteal cycle of women with RIF improved pregnancy outcomes significantly. They used pipelle catheter to obtain multiple biopsies of endometrium in each participant but we used it just to scratch the endometrium and didn't obtain biopsies[26]. Karimzadeh et al. on 2009 reported significantly improved implantation and clinical pregnancy in the group of women with RIF who underwent endometrial biopsy by pipelle in luteal phase of fresh cycles[15]. Narvekar et al. performed endometrial biopsy by pipelle catheter and hysteroscopy on 7th to 10th day of the cycle prior to the fresh embryo transfer cycle and once again between 24th to 25th day of the nontransfer cycle only by pipelle in women with RIF, and they showed that the live birth among this group was significantly higher than the control group [27]. Nastri et al. reported that the live birth and clinical pregnancy in the patients who endometrial injury was performed in follicular phase( on days 7 to 14 of menstrual cycle before fresh embryo transfer) by pipelle catheter were significantly improved, they used oral contraceptive pretreatment before the IVF cycle [28]. Relji et al. performed LEI in the luteal phase of the cycle preceding ovarian stimulation in an office hysteroscopy setting. Multiple endometrial injuries approximately 2 mm in depth and width in the upper part of the uterine cavity were performed using grasping forceps or scissors. They demonstrated that it can improve implantation and pregnancy outcomes [29]. In a recent study Wenjie et al. compared LEI in luteal phase preceding IVF with follicular phase. For patients in proliferative phase group, endometrial injury was performed between cycle day10–12. For patients in luteal phase group, endometrial injury was performed 7–9 days after ovulation. The endometrial injury procedure was performed in a standard approach using a Pipelle catheter (Shanghai Jiabao Medical Healthy Science Company, Shanghai, China). The Pipelle catheter was introduced through the cervix up to the uterine fundus. The piston was drawn back to the end of the sheath to create a negative pressure. The sheath was rotated and moved back and forth within the uterine cavity to ensure adequate endometrial tissue has been obtained. Those patients in control groups had the Pipelle catheter inserted through the cervix but no injury was performed to the endometrium. They reported that there are no significant differences in implantation, pregnancy and live birth rates [30]. But Melnick et al. recently showed that LEI with the pipelle catheter in luteal phase did not increase implantation and clinical pregnancy rates. endometrial biopsies were performed with the use of a Pipelle endometrial suction curette (Cooper Surgical) 5–12 days after detection of an LH surge and they used fresh embryos [20]. The local endometrial injury can be induced by endometrial biopsy (scratch) or hysteroscopy, and it has been shown that endometrial biopsy is twice as effective as opposed to hysteroscopy [31]. We used pipelle catheter to make endometrial scratch because it was inexpensive and having minimal side effects, also it was more acceptable by our patients. These conflicting data probably are because of different phases of endometrial injury, different cycles, different devices used for injury, various numbers of biopsies and many other factors. Previous studies focus on injuries in luteal or follicular phase or both but by the best of our knowledge there are limited studies compare these two phases. Conclusion: There are no significant differences in implantation and pregnancy rates between follicular and luteal phase local endometrial injury with the pipelle catheter. Studies with larger sample sizes are needed. References 1- CoughlanC,Ledger W,Wang Q,et al.Recurrent implantation failuredefinition and management .Reprod Biomed Online.2014a;28:14-38 2- Simón C, Martín JC, Pellicer A. Paracrine regulators of implantation. Baillieres Best Pract Res Clin Obstet Gynaecol. 2000 Oct;14(5):815-26. doi: 10.1053/beog.2000.0121. PMID: 11023802. 3- Vander Borght, M., & Wyns, C. (2018). Fertility and infertility: Definition and epidemiology. Clinical Biochemistry. doi:10.1016/j.clinbiochem.2018.03.012 4- De Geyter C, Calhaz-Jorge C, Kupka MS, Wyns C, Mocanu E, Motrenko T, Scaravelli G, Smeenk J, Vidakovic S, Goossens V 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 2018;9:1586–1601 5- Sim_on C, Moreno C, Remohí J, Pellicer A. Molecular interactions between embryo and uterus in the adhesion phase of human implantation. Hum Reprod1998;13(Suppl 3):219–32, discussion 233–236. 6- Mardanian F, Kazeroonizadeh M, Rashidi B. Evaluation of CD56(dim) and CD56(bright) natural killer cells in peripheral blood of women with IVF failures. 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Australian and New Zealand Journal of Obstetrics and Gynaecology. 2009 Dec 1;49(6):677-80 16- Singh N, Toshyan V, Kumar S, Vanamail P, Madhu M. Does endometrial injury enhances implantation in recurrent in-vitro fertilization failures? A prospective randomized control study from tertiary care center. J Hum Reprod Sci 2015;8:218-23. 17- 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):1166–76. 18- Gibreel A, Badawy AE-AN. Endometrial scratching to improve pregnancy rate in couples with unexplained subfertility: a randomized controlled trial. J Obs Gynaecol Res. 2013;39:680–4. 19- Wing T, Yeung Y, Chai J, Hang R, Li W, Chi V, et al. The effect of endometrial injury on ongoing pregnancy rate in unselected subfertile women undergoing in vitro fertilization : a randomized controlled trial. Hum Reprod. 2014;29(11):2474–81 20- Melnick AP, Murphy EM, Masbou AK, Sapra KJ. Autologous endometrial coculture biopsy : is timing everything ? Fertil Steril. 2013;104(1):104–9. 21- Juan Gui1,2 , Wangming Xu1,2, Jing Yang1,2,et Al." Impact of local endometrial injury on in vitro fertilization/intracytoplasmic sperm injection outcomes: A systematic review and meta-analysis", J. Obstet. Gynaecol. Res. Vol. 45, No. 1: 57–68, January 2019. 22- Yaman C., Ebner T., Sommergruber M., Polz W., TewsG. Role of three-dimensional ultrasonographic measurement of endometrium volume as a predictor of pregnancy outcome in an IVF-ET program: a preliminary study.Fertil Steril. 2000;74(4):797-801 23- Hanna Achache, Ariel Revel, Endometrial receptivity markers, the journey to successful embryo implantation, Human Reproduction Update, Volume 12, Issue 6, November/December 2006, Pages 731–746 24- Kalma, Y., Granot, I., Gnainsky, Y., Or, Y., Czernobilsky, B., Dekel, N., & Barash, A. (2009). 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J human reprod sci 2010;3 (1): 15-9. 28- Nastri CO, Ferriani RA, Raine-Fenning N, Martins WP. Endometrial scratching performed in the non-transfer cycle and outcome of assisted reproduction: randomized controlled trial. Ultrasound Obstet Gynecol 2013;42 (4): 375-82. 29- Relji M, Knez J, Kova V, Kova B. Endometrial injury, the quality of embryos, and blastocyst transfer are the most important prognostic factors for in vitro fertilization success after previous repeated unsuccessful attempts. J Assist Reprod Genet. 2017;6 30- Wenjie Liu, Reshef Tal, He Chao, Minghui Liu and Ying Liu.Effect of local endometrial injury in proliferative vs. luteal phase on IVF outcomes in unselected subfertile women undergoing in vitro fertilization. Reproductive Biology and Endocrinology (2017) 15:75 31- Potdar, N., Gelbaya, T., & Nardo, L. G. (2012). Endometrial injury to overcome recurrent embryo implantation failure: a systematic review and meta-analysis. Reproductive BioMedicine Online, 25(6), 561–571. doi:10.1016/j.rbmo.2012.08.00 Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1657996","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":109602428,"identity":"fbaa513a-9bf9-4250-9dbc-f665d8c1c2f8","order_by":0,"name":"Ladan Kashani","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Ladan","middleName":"","lastName":"Kashani","suffix":""},{"id":109602429,"identity":"a3b7cdfe-47e8-4838-b039-cb5bda94289f","order_by":1,"name":"zahra parsaiyan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8klEQVRIiWNgGAWjYPACCSBmPvgASPLwkaCFLdkApIWNBJt41EAaGQhqkZ/d/OzjjxqLxP7ZPWyVX3PsZNgYmB8+uoFHC+OcY8azeY5JJM64c/bYbdltyUCHsRkb5+DRwiyRYMzMwCaR2HAjL+225DZmoBYeNml8Wtgk0j8z/vgnkTj/Ro5ZseS2esJaeCRyjBl42yQSNwC1MH7cdpiwFgmZM8XMvH0SxhtvpCVLM247zsPGTMAv8rPbNzP++FYnO+9G8sGPP7dV2/OzNz98jE8LOBKBwLEBSDDzgJjM+JQjabEHEYw/CKkeBaNgFIyCEQkAUahD905aSVUAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0003-4092-397X","institution":"Iran University of Medical Sciences: Tehran University of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"zahra","middleName":"","lastName":"parsaiyan","suffix":""}],"badges":[],"createdAt":"2022-05-15 09:55:55","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1657996/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1657996/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":22282818,"identity":"32bd229f-fe3c-424b-8acf-f64253bd6abf","added_by":"auto","created_at":"2022-06-06 07:12:51","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":292293,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1657996/v1/62ca983e-b0a4-458c-8e4c-6425071abea1.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eEffect of local endometrial injury in Follicular vs. luteal phase on implantation and pregnancy outcomes of Frozen Embryo Transfer Cycles in women with repeated in vitro fertilization failure.A randomized clinical trial\u003c/p\u003e","fulltext":[{"header":"Introduction:","content":" \u003cp\u003eInfertility defined as one year of unprotected intercourse without conception [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Major developments have occurred in recent years, in vitro fertilization is one of them that could be used in almost all infertility cases.\u003c/p\u003e \u003cp\u003eIVF success rate is about 30 to 40 percent in each cycle [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. It depends on factors like woman\u0026rsquo;s age, infertility cause, treatment protocol, embryo quality, number of transmitted fetuses, transmission technique, sperm quality and endometrial characteristics [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRepeated implantation failure (RIF) is failure of implantation of transferred\u003c/p\u003e \u003cp\u003eembryos after several IVF treatment cycles. However, there are no formal criteria defining the number of failed cycles or the total number of embryos transferred in these IVF attempts so, there are various definitions in different infertility centers. usually RIF defines as failure of implantation in at least two or three consecutive IVF attempts, in which 1\u0026ndash;2 embryos of high grade quality are transferred in each cycle. [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. These failures can cause psychological and financial burden to the patients and community and causes wasting times. Therefor many researchers focus on finding ways to increase the implantation rates.\u003c/p\u003e \u003cp\u003eEnvironmental and feto maternal factors affect pregnancy outcomes. Endometrial cavity abnormalities, inappropriate endometrium, thrombophilias, connective tissue disorders and immunological disorders are examples of the maternal factors that affect pregnancy and genetic disorders are of fetal factors [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Embryo quality and receptive endometrium condition are two important factors for successful implantation (10). If the endometrium is not suitable for implantation, regarding the quality of embryo, implantation does not occur. Local endometrial injury could evoke local inflammatory responses by rising in cytokines and growth factors and causing expression of genes that contribute in fetus implantation so it can cause higher pregnancy rate in women with RIF [11- \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMany studies reported on contradictory results of endometrial injury in women with RIF. Some studies showed that implantation rates, and clinical pregnancy rates improved by LEI [14\u0026ndash;18], and some of them showed no differences [19\u0026ndash;20].\u003c/p\u003e \u003cp\u003eJuan et al. studied a systematic review about the Impact of local endometrial injury on in vitro fertilization/intracytoplasmic sperm injection outcomes and found conflicting data [21].\u003c/p\u003e \u003cp\u003eStudies regarding this issue are conflicting results. Endometrial injury in most of studies was performed in either follicular phase or luteal phase, or in both phases.\u003c/p\u003e \u003cp\u003eThe effects of endometrial injury in follicular vs. luteal phase have been studied only in one study previously. Furthermore, timing of this procedure is a point that may lead to different outcomes (30). This study compares follicular endometrial injury to luteal phase injury due to their different molecular patterns on the outcome of embryo transfer in RIF patients.\u003c/p\u003e \u003cp\u003eBecause of the long time required in luteal phase local endometrial injury of FET cycles and its consecutive psychological and financial costs, it seems that doing LEI in follicular phase would be helpful for these discomforts rather than luteal phase. This study is going to compare the effect of LEI in follicular phase vs. luteal phase of frozen embryo transferring cycles of IVF in women with RIF.\u003c/p\u003e"},{"header":"Methods:","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and participants:\u003c/h2\u003e \u003cp\u003eThis study is a double blinded randomized clinical trial. This study is designed as aclinical trial with a parallel random allocation and a 1: 1 ratio.\u003c/p\u003e \u003cp\u003eA total of 78 patients of infertility clinic of Arash women\u0026rsquo;s hospital with at least one IVF failure in years 2017 and 2018 were concluded in this study. The inclusion criteria were: (i) infertile women with at least one IVF failure; (ii)\u0026thinsp;\u0026le;\u0026thinsp;40 years of age; (iii) a normal uterine cavity demonstrated by hysteroscopy or\u003c/p\u003e \u003cp\u003ehysterosalpingography done during one year ago; (iiii) not using OCP or GnRh\u003c/p\u003e \u003cp\u003eagonists in the previous cycle.\u003c/p\u003e \u003cp\u003eThe exclusion Criteria were: (i) abnormal uterine cavity like polyp, fibroid or asherman syndrome; (ii) Endometrial hyperplasia or endometrial cancer; (iii) active vaginal or cervical infections (iiii) systemic disease such as diabetes mellitus, hypertension, and systematic lupus erythemato or etc. Recruited participantswere equally randomized into two groups using a table of block randomization: follicular group (group 1: endometrial injury in proliferative phase, n\u0026thinsp;=\u0026thinsp;38); and luteal group (group 2: injury in luteal phase, n\u0026thinsp;=\u0026thinsp;40).\u003c/p\u003e \u003cp\u003e This study was approved by the Institutional ethics committee Review Board of Tehran medical university (IR.TUMS.MEDICINE.REC.1396.2911) all participating patients recruited to thestudy were fully counseled and signed written informed consent.\u003c/p\u003e \u003c/div\u003e"},{"header":"Techniques:","content":"\u003cp\u003ePatients of follicular group were treated with estradiol valerate for 10 to 14 days and simultaneously the endometrial injury was performed by biopsy catheter (Pipelle; de Cornier, Prodimed, Neuilly-en-Thelle, France) in days 4\u0026ndash;6 ( if the bleeding stopped) of menstrual cycle before transmitting frozen embryos in uterus. This procedure performed as follows: the Pipelle was inserted through the cervical os and advanced gently until resistance was felt and after scratching, it was brought out of uterus.\u003c/p\u003e \u003cp\u003eAfter 14 days, transvaginal sonography was done and if the triple line endometrium was seen or the echogenic endometrium was \u0026ge;\u0026thinsp;7 mm, progesterone suppository was prescribed and after 3\u0026ndash;4 days, 2 or 3 days frozen\u003c/p\u003e \u003cp\u003efetuses were transmitted in uterus. After 2 weeks serum beta hcg was checked\u003c/p\u003e \u003cp\u003eand if it was more than 15 milli International Units per milliliter, trans vaginal sonography was performed for finding gestational sac(s). If it was seen, pregnant women were followed up to 12 weeks.\u003c/p\u003e \u003cp\u003eIn group 2, the same procedure was done but the endometrial injury with pipelle was performed in days of 21\u0026ndash;23 of the menstrual cycle before FET.\u003c/p\u003e \u003cp\u003eThe outcomes were described as (a) chemical pregnancy: positive serum beta hcg, (b) clinical pregnancy: existence of gestational sac(s), (c) implantation rate: the proportion of gestational sacs to transferred fetuses, and (d) ongoing pregnancy: being pregnant after 12 weeks.\u003c/p\u003e"},{"header":"Limitations:","content":"\u003cp\u003eLong period of following patients was a limitation of the study which was resolved by calling patients and free visits.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eData analysis:\u003c/h2\u003e \u003cp\u003eStata ver.13 was the analyzing software. The baseline characteristics of the two groups of patients were compared by chi-square and independent T-test. For determining the relationships between the injury time and pregnancy outcomes logistic regression was used. P-value was 5 percent.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results:","content":"\u003cp\u003eA total of 78 patients were recruited in this study from 2016 to 2017, 38 patients were in follicular group which pipelle was performed on days 4 to 6 of the FET cycle and 40 patients were in luteal group which pipelle was performed on days 21\u0026ndash;23 of the cycle before FET. It was 8 patients\u0026rsquo; loss during follow up, 3 from follicular group and 5 from luteal group. They were unavailable to see their outcomes. Therefore, there were 35 participants in each group finally.\u003c/p\u003e \u003cp\u003eThe average age was 31.37 years in follicular and 31.2 years in luteal group. The average years of infertility and body mass index(BMI) in both groups were about the same. Also the number of retrieved and freezed ovocytes and transferred eggs were compared and there were no significant differences. Mean endometrial thickness at the time of transferring was 9.21 mm in follicular and 9.67 mm in luteal group which they didn\u0026rsquo;t differ statistically.\u003c/p\u003e \u003cp\u003eBoth groups were compared from the aspect of infertility causes. Male infertility rate accounts for 51.4% of infertility causes overall which was 47.2% in follicular and 52.8% in luteal group. Unexplained infertility was another cause of infertility (21.4% generally) that was happened 53.3% in follicular and 46.6% in luteal group. Other causes of infertility were PCOD, tubal factor and endometriosis which account for 34.2%, 8.5% and 4.2% of all contributors respectively. Statistically, no differences were seen.\u003c/p\u003e \u003cp\u003eNext, infertility types evaluated. Generally primary infertility rate was 78.5% and secondary type was 21.4%. they are shown in the table.\u003c/p\u003e \u003cp\u003eIn Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e basic characteristic of both groups are shown and there is not statistical differences.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ebasic characteristics of patients undergoing endometrial local injury in follicular and luteal phases\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFollicular group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLuteal group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge(y)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31.37\u0026thinsp;\u0026plusmn;\u0026thinsp;5.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31.2\u0026thinsp;\u0026plusmn;\u0026thinsp;5.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.912\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI(Kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.64\u0026thinsp;\u0026plusmn;\u0026thinsp;2.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.65\u0026thinsp;\u0026plusmn;\u0026thinsp;3.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.387\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of sub fertility\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.6\u0026thinsp;\u0026plusmn;\u0026thinsp;4.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.02\u0026thinsp;\u0026plusmn;\u0026thinsp;4.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.942\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOocyte number\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17.68\u0026thinsp;\u0026plusmn;\u0026thinsp;7.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19.48\u0026thinsp;\u0026plusmn;\u0026thinsp;5.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003efrozen embryo number\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.17\u0026thinsp;\u0026plusmn;\u0026thinsp;3.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.48\u0026thinsp;\u0026plusmn;\u0026thinsp;2.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.22\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTransferred embryo number\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.65\u0026thinsp;\u0026plusmn;\u0026thinsp;0.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.05\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.489\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEndometrial thickness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.21\u0026thinsp;\u0026plusmn;\u0026thinsp;1.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.67\u0026thinsp;\u0026plusmn;\u0026thinsp;1.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.251\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTypes of infertility\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.38\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26(74.3%)\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29(82.85%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003esecondary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9(25.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6(17.14%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCauses of infertility\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.632\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale factor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17(48.57%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19(54.28%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTubal factor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(11.42%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(5.71%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePCO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11(31.42%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13(37.14%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEndometriosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3(8.57%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnexplained\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8(22.85%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7(20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e1\u0026thinsp;=\u0026thinsp;percent of the participants in their groups.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eFinally, both groups evaluated for pregnancy outcomes. 29 cases of successful Chemical pregnancy happened (41.4%) that was 51.7% in follicular and 48.3% in luteal group. In clinical pregnancy, 28 cases were successful, which divided equally in both groups.22 cases of ongoing pregnancy happened that its percentage was 54.5 for follicular and 45.5 for luteal group. Abortion occurred in 10% of participants. 57.1% in follicular and 42.8%in luteal group were seen. Implantation rate generally was 0.19 with SD\u0026thinsp;=\u0026thinsp;0.28. its rate in follicular group was 0.21 (SD\u0026thinsp;=\u0026thinsp;0.28) and in luteal group was 0.17 (SD\u0026thinsp;=\u0026thinsp;0.27). Statistically no significant differences were seen in pregnancy outcomes.\u003c/p\u003e \u003cp\u003eIn Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e the pregnancy outcomes are shown and no significant differences were seen.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePregnancy outcomes of patients undergoing endometrial injury in proliferative phase and luteal phase (percent in each group)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcomes\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFollicular group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLuteal group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemical pregnancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15(42.85%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14(40%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.808\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical pregnancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14(40%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14(40%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOngoing pregnancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12(34.28%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10(28.57%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.607\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbortion rate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(11.42%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(8.57%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.643\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImplantation rate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.21\u0026thinsp;\u0026plusmn;\u0026thinsp;0.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.17\u0026thinsp;\u0026plusmn;\u0026thinsp;0.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn Tables \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e and \u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e the demographic and IVF factors effects on chemical, clinical and ongoing pregnancy is shown.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003edemographic and IVF factors effects on chemical pregnancy\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFactors\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSuccessful chemical pregnancy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUnsuccessful chemical pregnancy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean age\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31\u0026thinsp;\u0026plusmn;\u0026thinsp;5.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31.48\u0026thinsp;\u0026plusmn;\u0026thinsp;5.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.303\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale infertility\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15(51.72%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21(51.21%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.967\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale infertility\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21(72.41%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27(65.85%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.075\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eembryo grade\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA\u0026thinsp;=\u0026thinsp;21 B\u0026thinsp;=\u0026thinsp;0 AB\u0026thinsp;=\u0026thinsp;8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eA\u0026thinsp;=\u0026thinsp;27 B\u0026thinsp;=\u0026thinsp;2AB\u0026thinsp;=\u0026thinsp;12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.463\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.99\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.25\u0026thinsp;\u0026plusmn;\u0026thinsp;2.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.706\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEndometrial thickness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.39\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.435\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFetus transferred\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.75\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.92\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.403\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003edemographic and IVF factors effect on clinical pregnancy\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFactors\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSuccessful clinical pregnancy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUnsuccessful clinical pregnancy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean age\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30.82\u0026thinsp;\u0026plusmn;\u0026thinsp;5.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31.59\u0026thinsp;\u0026plusmn;\u0026thinsp;5.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.332\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale infertility\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15(53.57%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21(50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.770\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale infertility\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20(71.42%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28(66.66%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.099\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eembryo grade\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA\u0026thinsp;=\u0026thinsp;20 B\u0026thinsp;=\u0026thinsp;0 AB\u0026thinsp;=\u0026thinsp;8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eA\u0026thinsp;=\u0026thinsp;28 B\u0026thinsp;=\u0026thinsp;2AB\u0026thinsp;=\u0026thinsp;12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.499\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.89\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.31\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.56\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEndometrial thickness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.51\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.38\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.78\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFetus transferred\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.82\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.88\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.76\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003edemographic and IVF factors effect on ongoing pregnancy\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFactors\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSuccessful ongoing pregnancy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUnsuccessful ongoin pregnancy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean age\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30.72\u0026thinsp;\u0026plusmn;\u0026thinsp;5.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31.54\u0026thinsp;\u0026plusmn;\u0026thinsp;5.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.506\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale infertility\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11(50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25(52.08%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.871\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale infertility\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16(72.72%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32(66.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.249\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eembryo grade\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA\u0026thinsp;=\u0026thinsp;16 B\u0026thinsp;=\u0026thinsp;0 AB\u0026thinsp;=\u0026thinsp;6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eA\u0026thinsp;=\u0026thinsp;32 B\u0026thinsp;=\u0026thinsp;2AB\u0026thinsp;=\u0026thinsp;14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.602\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.03\u0026thinsp;\u0026plusmn;\u0026thinsp;24.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.83\u0026thinsp;\u0026plusmn;\u0026thinsp;25.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.46\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEndometrial thickness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.7\u0026thinsp;\u0026plusmn;\u0026thinsp;9.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.5\u0026thinsp;\u0026plusmn;\u0026thinsp;9.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.43\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eembryo transferred\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.63\u0026thinsp;\u0026plusmn;\u0026thinsp;2.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.89\u0026thinsp;\u0026plusmn;\u0026thinsp;2.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.96\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eNone of them were significant.\u003c/p\u003e"},{"header":"Discussion:","content":"\u003cp\u003eIn this study, we try to assess whether there is a difference between follicular phase and luteal phase endometrial injury on pregnancy outcomes. In our study there was no difference between injury in the follicular phase or luteal phase on pregnancy and implantation outcomes.\u003c/p\u003e \u003cp\u003eThere are multiple factors that affect implantation of the embryo other than oocyte or sperm quality, and endometrial receptivity is one of them which is important [21\u0026ndash;22].\u003c/p\u003e \u003cp\u003eKalma et al. reported that endometrial biopsies cause the rise in membranous proteins expression like Uroplakin 1b. Some believe that endometrial injury before embryo transfer could cause decidualization and improves Implantation. Also Inflammatory response and rise of cytokines, interleukins, growth factors, dendritic cells and macrophages could improve plantation. Endometrial injury could improve synchronicity of embryo and uterus [24\u0026ndash;25].\u003c/p\u003e \u003cp\u003eThe effect of endometrial injury on improving pregnancy outcomes has been studied previously and there are many conflicting results.\u003c/p\u003e \u003cp\u003eBarash et al. showed that repeated endometrial biopsies by a Pipelle catheter on days 8, 12, 21, and 26 of the spontaneous menstrual cycle before the IVF-ET treatment doubled clinical pregnancy and live birth rates in women with RIF. They used fresh embryos nut in our study there were frozen embryos which could decrease the implantation rate by itself [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRaziel et al. demonstrated that endometrial injury by pipelle catheter on days 21 and 26 of luteal cycle of women with RIF improved pregnancy outcomes significantly. They used pipelle catheter to obtain multiple biopsies of endometrium in each participant but we used it just to scratch the endometrium and didn't obtain biopsies[26].\u003c/p\u003e \u003cp\u003eKarimzadeh et al. on 2009 reported significantly improved implantation and clinical pregnancy in the group of women with RIF who underwent endometrial biopsy by pipelle in luteal phase of fresh cycles[15].\u003c/p\u003e \u003cp\u003eNarvekar et al. performed endometrial biopsy by pipelle catheter and hysteroscopy on 7th to 10th day of the cycle prior to the fresh embryo transfer cycle and once again between 24th to 25th day of the nontransfer cycle only by pipelle in women with RIF, and they showed that the live birth among this group was significantly higher than the control group [27].\u003c/p\u003e \u003cp\u003eNastri et al. reported that the live birth and clinical pregnancy in the patients who endometrial injury was performed in follicular phase( on days 7 to 14 of menstrual cycle before fresh embryo transfer) by pipelle catheter were significantly improved, they used oral contraceptive pretreatment before the IVF cycle [28].\u003c/p\u003e \u003cp\u003eRelji et al. performed LEI in the luteal phase of the cycle preceding ovarian stimulation in an office hysteroscopy setting. Multiple endometrial injuries approximately 2 mm in depth and width in the upper part of the uterine cavity were performed using grasping forceps or scissors. They demonstrated that it can improve implantation and pregnancy outcomes [29].\u003c/p\u003e \u003cp\u003eIn a recent study Wenjie et al. compared LEI in luteal phase preceding IVF with follicular phase. For patients in proliferative phase group, endometrial injury was performed between cycle day10\u0026ndash;12. For patients in luteal phase group, endometrial injury was performed 7\u0026ndash;9 days after ovulation. The endometrial injury procedure was performed in a standard approach using a Pipelle catheter (Shanghai Jiabao Medical Healthy Science Company, Shanghai, China). The Pipelle catheter was introduced through the cervix up to the uterine fundus. The piston was drawn back to the end of the sheath to create a negative pressure. The sheath was rotated and moved back and forth within the uterine cavity to ensure adequate endometrial tissue has been obtained. Those patients in control groups had the Pipelle catheter inserted through the cervix but no injury was performed to the endometrium. They reported that there are no significant differences in implantation, pregnancy and live birth rates [30].\u003c/p\u003e \u003cp\u003eBut Melnick et al. recently showed that LEI with the pipelle catheter in luteal phase did not increase implantation and clinical pregnancy rates. endometrial biopsies were performed with the use of a Pipelle endometrial suction curette (Cooper Surgical) 5\u0026ndash;12 days after detection of an LH surge and they used fresh embryos [20].\u003c/p\u003e \u003cp\u003eThe local endometrial injury can be induced by endometrial biopsy (scratch) or hysteroscopy, and it has been shown that endometrial biopsy is twice as effective as opposed to hysteroscopy [31].\u003c/p\u003e \u003cp\u003eWe used pipelle catheter to make endometrial scratch because it was inexpensive and having minimal side effects, also it was more acceptable by our patients.\u003c/p\u003e \u003cp\u003eThese conflicting data probably are because of different phases of endometrial injury, different cycles, different devices used for injury, various numbers of biopsies and many other factors.\u003c/p\u003e \u003cp\u003ePrevious studies focus on injuries in luteal or follicular phase or both but by the best of our knowledge there are limited studies compare these two phases.\u003c/p\u003e"},{"header":"Conclusion:","content":"\u003cp\u003eThere are no significant differences in implantation and pregnancy rates between follicular and luteal phase local endometrial injury with the pipelle catheter. Studies with larger sample sizes are needed.\u003c/p\u003e"},{"header":"References","content":"\u003cp\u003e1-\u0026nbsp;CoughlanC,Ledger W,Wang Q,et al.Recurrent implantation failuredefinition and management\u003c/p\u003e\n\u003cp\u003e.Reprod Biomed Online.2014a;28:14-38\u003c/p\u003e\n\u003cp\u003e2-\u0026nbsp;Sim\u0026oacute;n C, Mart\u0026iacute;n JC, Pellicer A. Paracrine regulators of implantation. Baillieres Best Pract Res Clin Obstet Gynaecol. 2000 Oct;14(5):815-26. doi: 10.1053/beog.2000.0121. PMID: 11023802.\u003c/p\u003e\n\u003cp\u003e3-\u0026nbsp;Vander Borght, M., \u0026amp; Wyns, C. (2018). Fertility and infertility: Definition and epidemiology.\u003c/p\u003e\n\u003cp\u003eClinical Biochemistry. doi:10.1016/j.clinbiochem.2018.03.012\u003c/p\u003e\n\u003cp\u003e4-\u0026nbsp;De Geyter C, Calhaz-Jorge C, Kupka MS, Wyns C, Mocanu E, Motrenko T, Scaravelli G, Smeenk J,\u003c/p\u003e\n\u003cp\u003eVidakovic S, Goossens V et al. ART in Europe,2014: results generated from European registries\u003c/p\u003e\n\u003cp\u003eby ESHRE: the European IVF-monitoring Consortium (EIM) for the European Society of Human\u003c/p\u003e\n\u003cp\u003eReproduction and Embryology (ESHRE). Hum Reprod 2018;9:1586\u0026ndash;1601\u003c/p\u003e\n\u003cp\u003e5- Sim_on C, Moreno C, Remoh\u0026iacute; J, Pellicer A. Molecular interactions between embryo and\u003c/p\u003e\n\u003cp\u003euterus in the adhesion phase of human implantation. Hum Reprod1998;13(Suppl\u003c/p\u003e\n\u003cp\u003e3):219\u0026ndash;32, discussion 233\u0026ndash;236.\u003c/p\u003e\n\u003cp\u003e6-\u0026nbsp;Mardanian F, Kazeroonizadeh M, Rashidi B. Evaluation of CD56(dim) and CD56(bright) natural\u003c/p\u003e\n\u003cp\u003ekiller cells in peripheral blood of women with IVF failures.\u0026nbsp;\u003cem\u003eIran J Reprod Med\u003c/em\u003e. 2015;13(9):577\u0026ndash;\u003c/p\u003e\n\u003cp\u003e582.\u003c/p\u003e\n\u003cp\u003e7- Paulson, R. J., Sauer, M. V., \u0026amp; Lobo, R. A. (1990). Factors affecting embryo implantation\u003c/p\u003e\n\u003cp\u003eafter human in vitro fertilization: A hypothesis. American Journal of Obstetrics and\u003c/p\u003e\n\u003cp\u003eGynecology, 163(6), 2020\u0026ndash;2023. doi:10.1016/0002-9378(90)90790\u003c/p\u003e\n\u003cp\u003e8- Chelsea Fox, Scott Morin, Jae-Wook Jeong et al.\u0026quot; Local and Systemic Factors and\u003c/p\u003e\n\u003cp\u003eImplantation: what is the Evidence?\u0026quot; Fertil Steril. 2016 April ; 105(4): 873\u0026ndash;884.\u003c/p\u003e\n\u003cp\u003edoi:10.1016/j.fertnstert.2016.02.018.\u003c/p\u003e\n\u003cp\u003e9- Younglai EV, Holloway AC, Foster WG. Environmental and occupational factors affecting\u003c/p\u003e\n\u003cp\u003efertility and IVF success. Hum Reprod Update 2005; 11:43.\u003c/p\u003e\n\u003cp\u003e10- im\u0026oacute;n , art\u0026iacute;n , ellicer aracrine regulators of implantation ailliere\u0026rsquo;s est ract\u003c/p\u003e\n\u003cp\u003eRes Clin Obstet Gynaecol. 2000;14(5):815\u0026ndash;26\u003c/p\u003e\n\u003cp\u003e11- Wing T, Yeung Y, Chai J, Hang R, Li W, Chi V, et al. The effect of endometrial injury on\u003c/p\u003e\n\u003cp\u003eongoing pregnancy rate in unselected subfertile women undergoing in vitro fertilization\u003c/p\u003e\n\u003cp\u003e: a randomized controlled trial. Hum Reprod. 2014;29(11):2474\u0026ndash;81\u003c/p\u003e\n\u003cp\u003e12-\u0026nbsp;Rico-Rosillo MG, Vega-Robledo GB. Immunological mechanisms involved in pregnancy.\u003c/p\u003e\n\u003cp\u003eGinecol Obstet Mex. 2012;80(5):332- 40\u003c/p\u003e\n\u003cp\u003e13-\u0026nbsp;Mirkin, S., Arslan, M., Churikov, D., Corica, A., Diaz, J., Williams, S., Bocca, S., Oehninger, S.,\u003c/p\u003e\n\u003cp\u003e2005. In search of candidate genes critically expressed in the human endometrium during the\u003c/p\u003e\n\u003cp\u003ewindow of implantation. Hum. Reprod. 20, 2104\u0026ndash;2117\u003c/p\u003e\n\u003cp\u003e14- Barash A, Dekel N, Fieldust S, Segal I, et al. Local injury to the endometrium doubles the\u003c/p\u003e\n\u003cp\u003eincidence of successful pregnancies in patients undergoing in vitro fertilization\u003c/p\u003e\n\u003cp\u003eCharacteristics of the Subjects. Fertil Steril. 2003;79(6):1317\u0026ndash;22\u003c/p\u003e\n\u003cp\u003e15- Karimzadeh MA, Ayazi Rozbahani M, Tabibnejad N. Endometrial local injury improves\u003c/p\u003e\n\u003cp\u003ethe pregnancy rate among recurrent implantation failure patients undergoing in vitro\u003c/p\u003e\n\u003cp\u003efertilisation/intra cytoplasmic sperm injection: a randomised clinical trial. Australian and\u003c/p\u003e\n\u003cp\u003eNew Zealand Journal of Obstetrics and Gynaecology. 2009 Dec 1;49(6):677-80\u003c/p\u003e\n\u003cp\u003e16- Singh N, Toshyan V, Kumar S, Vanamail P, Madhu M. Does endometrial injury enhances\u003c/p\u003e\n\u003cp\u003eimplantation in recurrent in-vitro fertilization failures? A prospective randomized\u003c/p\u003e\n\u003cp\u003econtrol study from tertiary care center. J Hum Reprod Sci 2015;8:218-23.\u003c/p\u003e\n\u003cp\u003e17- Zhou L, Li R, Wang R, Huang H, Zhong K. Local injury to the endometrium in controlled\u003c/p\u003e\n\u003cp\u003eovarian hyperstimulation cycles improves implantation rates. Fertil Steril.\u003c/p\u003e\n\u003cp\u003e2008;89(5):1166\u0026ndash;76.\u003c/p\u003e\n\u003cp\u003e18- Gibreel A, Badawy AE-AN. Endometrial scratching to improve pregnancy rate in couples\u003c/p\u003e\n\u003cp\u003ewith unexplained subfertility: a randomized controlled trial. J Obs Gynaecol Res.\u003c/p\u003e\n\u003cp\u003e2013;39:680\u0026ndash;4.\u003c/p\u003e\n\u003cp\u003e19- Wing T, Yeung Y, Chai J, Hang R, Li W, Chi V, et al. The effect of endometrial injury on\u003c/p\u003e\n\u003cp\u003eongoing pregnancy rate in unselected subfertile women undergoing in vitro fertilization\u003c/p\u003e\n\u003cp\u003e: a randomized controlled trial. Hum Reprod. 2014;29(11):2474\u0026ndash;81\u003c/p\u003e\n\u003cp\u003e20- Melnick AP, Murphy EM, Masbou AK, Sapra KJ. Autologous endometrial coculture\u003c/p\u003e\n\u003cp\u003ebiopsy : is timing everything ? Fertil Steril. 2013;104(1):104\u0026ndash;9.\u003c/p\u003e\n\u003cp\u003e21- Juan Gui1,2 , Wangming Xu1,2, Jing Yang1,2,et Al.\u0026quot; Impact of local endometrial injury on\u003c/p\u003e\n\u003cp\u003ein vitro fertilization/intracytoplasmic sperm injection outcomes: A systematic review\u003c/p\u003e\n\u003cp\u003eand meta-analysis\u0026quot;, J. Obstet. Gynaecol. Res. Vol. 45, No. 1: 57\u0026ndash;68, January 2019.\u003c/p\u003e\n\u003cp\u003e22- Yaman C., Ebner T., Sommergruber M., Polz W., TewsG. Role of three-dimensional\u003c/p\u003e\n\u003cp\u003eultrasonographic measurement of endometrium volume as a predictor of pregnancy\u003c/p\u003e\n\u003cp\u003eoutcome in an IVF-ET program: a preliminary study.Fertil Steril. 2000;74(4):797-801\u003c/p\u003e\n\u003cp\u003e23-\u0026nbsp;Hanna Achache, Ariel Revel, Endometrial receptivity markers, the journey to successful\u003c/p\u003e\n\u003cp\u003eembryo implantation, Human Reproduction Update, Volume 12, Issue 6,\u003c/p\u003e\n\u003cp\u003eNovember/December 2006, Pages 731\u0026ndash;746\u003c/p\u003e\n\u003cp\u003e24- Kalma, Y., Granot, I., Gnainsky, Y., Or, Y., Czernobilsky, B., Dekel, N., \u0026amp; Barash, A.\u003c/p\u003e\n\u003cp\u003e(2009). Endometrial biopsy-induced gene modulation: first evidence for the expression\u003c/p\u003e\n\u003cp\u003eof bladder-transmembranal uroplakin Ib in human endometrium. Fertility and Sterility,\u003c/p\u003e\n\u003cp\u003e91(4), 1042\u0026ndash;1049.e9. doi:10.1016/j.fertnstert.2008.01.043\u003c/p\u003e\n\u003cp\u003e25- Dimitriadis E, Salmonsen LA, Robb L. Expression of interleukin-11 during the human\u003c/p\u003e\n\u003cp\u003emenstrual cycle: coincidence with stromal cell decidualization and relationship to\u003c/p\u003e\n\u003cp\u003eleukemia inhibitory factor and prolactin. Mol Hum Reprod 2000;6:907\u0026ndash;14.\u003c/p\u003e\n\u003cp\u003e26- Raziel A, Schachter M, Strassburger D, Bern O, Ron-El R, Friedler S. Favorable influence\u003c/p\u003e\n\u003cp\u003eof local injury to the endometrium in intracytoplasmic sperm injection patients with\u003c/p\u003e\n\u003cp\u003ehigh-order implantation failure. Fertil Steril 2007;87 (1): 198-201.\u003c/p\u003e\n\u003cp\u003e27- Narvekar SA, Gupta N, Shetty N, Kottur A, Srinivas M, Rao KA. endometrial injury in the\u003c/p\u003e\n\u003cp\u003enontransfer cycle improve the IVF-ETsubsequent cycle in patients with previous\u003c/p\u003e\n\u003cp\u003eunsuccessful IVF? controlled pilot study. J human reprod sci 2010;3 (1): 15-9.\u003c/p\u003e\n\u003cp\u003e28- Nastri CO, Ferriani RA, Raine-Fenning N, Martins WP. Endometrial scratching performed\u003c/p\u003e\n\u003cp\u003ein the non-transfer cycle and outcome of assisted reproduction: randomized controlled\u003c/p\u003e\n\u003cp\u003etrial. Ultrasound Obstet Gynecol 2013;42 (4): 375-82.\u003c/p\u003e\n\u003cp\u003e29- Relji M, Knez J, Kova V, Kova B. Endometrial injury, the quality of embryos, and\u003c/p\u003e\n\u003cp\u003eblastocyst transfer are the most important prognostic factors for in vitro fertilization\u003c/p\u003e\n\u003cp\u003esuccess after previous repeated unsuccessful attempts. J Assist Reprod Genet. 2017;6\u003c/p\u003e\n\u003cp\u003e30- Wenjie Liu, Reshef Tal, He Chao, Minghui Liu and Ying Liu.Effect of local endometrial\u003c/p\u003e\n\u003cp\u003einjury in proliferative vs. luteal phase on IVF outcomes in unselected subfertile women\u003c/p\u003e\n\u003cp\u003eundergoing in vitro fertilization. Reproductive Biology and Endocrinology (2017) 15:75\u003c/p\u003e\n\u003cp\u003e31- Potdar, N., Gelbaya, T., \u0026amp; Nardo, L. G. (2012). Endometrial injury to overcome recurrent\u003c/p\u003e\n\u003cp\u003eembryo implantation failure: a systematic review and meta-analysis. Reproductive\u003c/p\u003e\n\u003cp\u003eBioMedicine Online, 25(6), 561\u0026ndash;571. doi:10.1016/j.rbmo.2012.08.00\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"repeated IVF failure, local endometrial injury, Implantation, pipelle, follicular phase, luteal phase","lastPublishedDoi":"10.21203/rs.3.rs-1657996/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1657996/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eIntroduction\u003c/h2\u003e \u003cp\u003e:recurrent implantation failure(RIF)refers to failure to achieve a clinical pregnancy after transferring at least four good quality embryos in a minimum of three fresh or frozen cycles.Endometrial scratch is the newly proposed surgical strategy to improve endometrial receptivity;the healing process following scratch may release cytokines and growth factors which encourage endometrial growth and facilitates implantation.Timing of this procedure is a point that may lead to different outcomes.This study compares follicular versus luteal phase injury due to their different molecular patterns on the outcome of embryo transfer in RIF patients.\u003c/p\u003e\u003ch2\u003eStudy design:\u003c/h2\u003e \u003cp\u003eThis study is a double blinded randomized clinical trial.Patients came into infertility clinic of Arash women\u0026rsquo;s hospital in years2017and2018are divided into two groups. In one group injury was done with pipelle at4th-6thday of frozen embryo transferring cycle(n\u0026thinsp;=\u0026thinsp;38)and in the other one it was done at21th- 23thday of the cycle before the FET (n\u0026thinsp;=\u0026thinsp;40).Then the infertility rates were compared.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eTotally29(41.4%)chemical pregnancies happened,15(51.7%)of them was in follicular group and14(48.3%)in luteal group.28(40%)clinical pregnancies happened totally which were equal in both groups(14 in each one).Ongoing pregnancies happened in 22(31.4%)patients that12(54.5%)of them were in follicular and the other10(45.5%)were in luteal group.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eAccording to this study,local endometrial injury by pipelle didn\u0026rsquo;t show any significant differences in both groups pregnancy outcomes.But in the follicular group the IVF cycle time period is decreased and therefore the psychological burden of long time required for luteal phase LEI will decrease and is more acceptable for patients,maybe it\u0026rsquo;s better to do LEI in follicular phase;more studies with larger sample sizes recommended.\u003c/p\u003e","manuscriptTitle":"Effect of local endometrial injury in Follicular vs. luteal phase on implantation and pregnancy outcomes of Frozen Embryo Transfer Cycles in women with repeated in vitro fertilization failure.A randomized clinical trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-05-31 17:07:39","doi":"10.21203/rs.3.rs-1657996/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a85502ed-08ff-4f83-a752-23891b41c1b9","owner":[],"postedDate":"May 31st, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-06-06T07:12:43+00:00","versionOfRecord":[],"versionCreatedAt":"2022-05-31 17:07:39","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1657996","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1657996","identity":"rs-1657996","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}