Effect of human chorionic gonadotropin injection before frozen embryo transfer on pregnancy outcomes in endometriosis infertility

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Methods We performed a retrospective, database-searched cohort study. The data of endometriosis patients who underwent frozen embryo transfer between 1/1/2009-31/8/2018 were collected. According to the protocols for frozen embryo transfer cycle, these patients were divided into two groups: Control group(n=305), and hCG group(n=362). And clinical pregnancy rate, live birth rate, early abortion rate, late abortion rate and ectopic pregnancy rate were compared between the two groups. Results There was a significant increase in clinical pregnancy rate in hCG group (56.6% vs. 48.2%, p=0.035) compared to the control group. And the live birth rate in hCG group (43.5% vs. 37.4%, p=0.113) also elevated, but the difference is statistically insignificant. Conclusion hCG administration in hormone replacement regime for FET increase the pregnancy rate in women with endometriosis. Internal Medicine Preventive Medicine endometriosis frozen embryo transfer human chorionic gonadotropin Introduction Endometriosis (EM) is a chronic gynecological disease associated with infertility that is characterized by lesion of endometrial-like tissue outside of the uterine cavity [ 1 – 2 ]. Almost half of the women with endometriosis experience infertility [ 3 ]. EM affect the outcome of assisted reproductive technology (ART), which compassing a wide sperm of causes, including the poor oocyte, sperm and embryo quality, impaired receptivity of the endometrium and implantation failure [ 4 – 5 ]. Clinically, there can be little doubt that the endometrium of women with endometriosis is less receptive to embryo implantation, and strong evidence exists to suggest that endometrial changes are associated with decreased cycle fecundity as a result of this disease[ 6 ]. Endometrial biomarkers are differentially expressed in the endometrium of women with endometriosis compared to normal women [ 7 – 8 ]. Seeking an effective approach to improve endometrial receptivity in endometriosis is a difficult issue in clinical. Frozen embryo transfer (FET) is recommended for endometriosis in ART. Mohamed suggested that preparation of the endometrium for FET with gonadotropin-releasing–hormone (GnRH) agonists could improve live birth rate in endometriosis, comparing fresh cycles [ 9 ]. And recently, Xu found that pregnancy rate, clinical pregnancy rate and birth weight were improved in women with endometriosis who underwent intrauterine injection of human chorionic gonadotropin (hCG) before FET[ 10 ]. But these methods are either time-consuming or inconvenient. So we retrospectively analyzed the data of frozen embryo transplantation in patients with endometriosis in an attempt to find a more effective strategy for frozen embryo transplantation. Materials And Methods Subjects The retrospective, database-searched cohort study was conducted in Reproductive Hospital Affiliated Shandong University. This study was reviewed and approved by research ethics committee of our institution. All patients in the study provided written informed consent for use of their data. All patients were diagnosed as endometriosis by a laparoscopy, underwent frozen embryo transfer in our hospital during a nine year period (1/1/2009-31/8/2018) were included. Patents older than 42 years at the onset of the cycle, basal FSH > 12 U/L, women with uterine malformation, chromosomal abnormalities, polycystic ovary syndrome, hydrosalpinx, recurrent spontaneous abortion or intrauterine adhesions were all excluded. Finally, 667 women diagnosed with infertility associated with EM were collected. According to whether injection hCG in the protocols for frozen embryo transfer cycle, these patients were divided into two groups : Control group(n = 305) and hCG group(n = 362)。 Endometrial preparation Patients in control group received hormone replacement (HT) regime for frozen embryo transfer. The protocol was started with oral estradiol valerate (Progynova, Delpharm Lille) at a dose of 4 mg to 8 mg per begin on day 2 or 3 of menstrual cycle. Then the thickness of endometrium was measured by transvaginal ultrasound, and the concentrations of estrogen and LH in seurm were measured after about 10 days estradiol valerate treatment. When the endometrial thickness reached at least 7.5 mm, vaginal progestin (Utrogestan; Besins Manufacturing) at dose of 200 mg per day and oral dydrogesterone (Duphaston, Abbott) at dose of 20 mg twice daily was added. When the patients received frozen embryo transfer earlier than 2011, they will be treated with intramuscular injection of progesterone (Progesterone Injection, Zhejiang Xianju Pharmaceutical Co., Ltd) instead. Up to two day 3 cleavage–stage embryos or blastocysts frozen early were thawed and transferred 3 or 5 days, respectively, after the start of progesterone. Women in hCG group received hCG 8000 IU intramuscular injection before progestin administration, and HT regime was the same as control group. Progestin supplementation continued until 12 weeks of pregnancy. Outcomes The primary outcome was clinical pregnancy, which was defined as the detection of an intrauterine gestational sac by transvaginal ultrasoundgraphy after 3 weeks embryo transfer. The second outcome was live birth, which was defined as the delivery of any viable neonate who was 28 weeks of gestation or older. The early abortion rate was defined as the percentage of miscarriage early than 12 weeks in the group. Late abortion rate was the proportion of miscarriage in between 12 and 28 weeks in the group. Preterm birth rate was defined as the percentage of birth before 34 weeks in live birth women. Live birth rate was the proportion of women who birth at least one living child in the group. Statistical analysis Continuous variables were represented as means and standard deviations; differences in variables were compared by means of Student’s t-test. Categorical variables were described as frequencies and percentages, with the between-group difference tested by means of the chi-square test and by means of Fisher’s exact test when the number of events was less than 5. Two-sides P value of less than 0.05 were considered to indicate statistical significance. Results Patients The baseline characteristics were similar in control group and hCG group (Table 1 ). There is no difference in the terms of age, BMI, basal endocrine hormone levels, AMH and the number of oocytes retrieved in fresh cycle between two groups. Table 1 Basal characteristics of participants Control group HCG group p value N 305 362 Age(Years) 31.85 ± 4.72 31.62 ± 4.42 0.503 BMI(kg/m 2 ) 22.41 ± 3.96 22.92 ± 3.33 0.221 AMH(ng/ml) 4.52 ± 5.66 4.39 ± 4.16 0.506 Basal FSH(U/L) 6.70 ± 2.30 6.56 ± 1.88 0.380 Basal LH(U/L) 5.81 ± 3.37 5.75 ± 3.43 0.813 Basal E2(pg/ml) 43.50 ± 33.17 48.40 ± 43.04 0.453 No. of oocyte retrieved 14.28 ± 7.95 13.87 ± 7.24 0.485 There were no significant differences between hCG group and control group (P > 0.05) in any of the baseline characteristics. Outcomes of FET The thickness of endometrium, the stage of transferred embryo and the concentration of E2 in serum did not differ significantly among the two groups. However, FET outcomes were improved in hCG group. The pregnancy rate in hCG group (56.6% vs. 48.2%, p = 0.035) significantly increased, comparing the control group (Table 2 ). And the live birth rate in hCG group (43.5% vs. 37.4%, p = 0.113) also elevated, but the difference is statistically insignificant (Table 2 ). In addition, there was no significant difference in early abortion rate, late abortion rate, preterm birth rate and ectopic pregnancy rate between control group and hCG group (Table 2 ). Table 2 Outcomes of frozen embryo transfer Control group HCG group p value Endometrium thickness 0.93 ± 0.17 0.92 ± 0.12 0.236 Transferred embryo stage 0.425 Cleavage stage 22(7.2%) 20(5.5%) blastocyte 283(92.8%) 342(94.5%) Estrogen 261.79 ± 290.85 302.54 ± 373.58 0.258 LH 18.36 ± 11.51 15.11 ± 13.54 0.029* Pregnancy rate 48.2% 56.6% 0.035* Live birth rate 37.4% 43.5% 0.113 Preterm birth rate 4.4% 4.3% 0.601 Early abortion rate 9.2% 10.8% 0.52 Late abortion rate 0% 0.8% 0.254 Ectopic pregnancy rate 1.6% 0.3% 0.098 *means p < 0.05,** means p < 0.001 Discussion In our retrospective analysis, we found that the hCG injection could significantly improve pregnancy rate in EM patients undergoing FET. And live birth rate also elevated in hCG group, however, the difference did not reach statically significant. Several studies have reported that endometriosis affects the endometrium and reduce fertility [ 11 – 12 ]. Reduced implantation, clinical pregnancy rate, ongoing pregnancy and live birth rate was found in women with endometriosis placing sibling oocytes from same donor, comparing women without endometriosis [ 13 ]. We also found that higher prevalence of endometrial ployps in infertile patients with endometriosis, implying the special character of eutopic endometrium in endometriosis, which also impair embryo implantation [ 14 ].Animal studies support clinical data suggesting that endometriosis leads to implantation defects, again implicating the endometrium. Induction of endometriosis in animals demonstrates similar phenotypes to human disease [ 15 – 17 ]. And gradual and profound alteration in endometrium over time was found in induction of endometriosis in the baboon, involving the inflammation and immune system changes[ 18 ]. The expression of endometrial biomarkers altered in the eutopic endometrium of endometriosis compared to normal women. Lessey reported that endometrial integrins, which is known as cell-surface receptor for extracellular matrix protein, playing important role in embryo implantation, decreased in women with infertility and endometriosis[ 19 ]. Reduced integrin expression also associated with reduced IVF outcomes [ 20 ]. Integrinβ5 could up-regulated under the influence of hCG in stromal cells from endometriotic lesions in vivo [ 21 ]. Other key molecules that are required for nomal endometrial receptivity such as HOXA10[ 22 ], its expression also reduced in endometriosis, but have been reported to could be induced by hCG[ 23 ]. Therefore, hCG injection may improve endometrium receptivity via regulating key molecules related to embryo implantation. Moreover, endometriosis has been described as a progesterone resistant disease due to the blunted or inadequate response to progesterone of both the eutopic and ectopic endometrial cells and tissue [ 24 – 27 ]. This manifested as low expression of progesterone receptor, blunted expression of progesterone target genes [ 28 – 30 ] and inadequate decidualization response[ 31 ]. However, the decidualization is an indispensible process for embryo implantation, thus aberrant decidualization would lead to unfavorable effects on embryo implannntation and pregnancy. While it was reported to hCG could regulate progesterone expression via the ERK1/2 pathways [ 32 ], and promote human endometrial stromal cell decidulization leading to a significantly stronger induction of decidualization when used in combination with progesterone. [ 33 ]. In addatation, it has been well established that the immune system of women with endometriosis is dysfunctional. T regulatory (Treg) cells are altered in endometriosis patients and have been suggested to play a role in pathogenesis of endometriosis and its associated infertility [ 34 ]. Lower numbers of Treg cells have been detected in the eutopic endometrium of a non-human primate endometriosis model[ 18 ]. And it was reported that hCG-producing trophoblasts could attracted Treg cell [ 35 ], and more importantly, hCG was involved in Treg differentiation [ 36 ]. Furthermore, aberrant subset of uNK cells was found in the eutopic endometrium of women with endometriosis associated infertility [ 37 ]. Immature uNK cells populations exist in infertile women with endometriosis [ 38 ]. And hCG has been reported as a regulator of uNK cell proliferation mediating via the mannose receptor (CD206) [ 39 ]. These findings may suggest hCG could improve endometrial receptivity via regulating immune cells in eutopic endometrium of infertility women associated with endometriosis. In our research, the pregnancy rate significantly elevated after hCG injection in endometriosis, however, the difference of live birth rate could not reach statistical significance. This may be the result of insufficient time or dose of hCG, and may improve by replacing single hCG treatments with a repetitive administration scheme [ 40 ]. Since our research is retrospective design, the power of conclusion is lower. Further evidence is needed to clarify the protocol that would lead to beneficial outcomes. Declarations Ethics approval and consent to participate: This study was approved by research ethics committee of our institution. All patients in the study have provided written informed consent for use of their data. Availability of data and materials: The datasets analysed during the current study are not publicly available due to these are all clinical data which needed protect patients identity and privacy, but are available from the corresponding author on reasonable request. Conflict of Interest: The authors declare that they have no competing interests. Funding: This study was funded by a grant from the National Nature Science Foundation of China (81571414). Authors' contributions: All the authors contributed equally to this manuscript. Rong Tang designed the study; Yanbo Du interpreted the data and drafted the article; Lei Yan revised the manuscript critically and accoute for all aspects of the work; Mei Sun and Yan Sheng collected all the data; Xiufang Li and Zhenhua Feng analysis the data. Acknowledgements: T hanks to other reproductive hospital staff who offered assistance to this study, Qin Gao, Zengxiang Ma, Jingjing Jiang, Hong Liu, Shanshan Gao, Na Yu and Qiaona Yuan. References Senapati S, Sammel MD, Morse C, Barnhart KT. Impact of endometriosis on in vitro fertilization outcomes: an evaluation of the Society for Assisted Reproductive Technologies Database. Fertil Steril. 2016;106(1):164-71 e1. doi:S0015-0282(16)61044-0 [pii] 10.1016/j.fertnstert.2016.03.037. Johnson NP, Hummelshoj L. 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Human chorionic gonadotropin potentially affects pregnancy outcome in women with recurrent implantation failure by regulating the homing preference of regulatory T cells. Am J Reprod Immunol. 2017;77(3). doi:10.1111/aji.12618. Giuliani E, Parkin KL, Lessey BA, Young SL, Fazleabas AT. Characterization of uterine NK cells in women with infertility or recurrent pregnancy loss and associated endometriosis. Am J Reprod Immunol. 2014;72(3):262-9. doi:10.1111/aji.12259. Thiruchelvam U, Wingfield M, O'Farrelly C. Increased uNK Progenitor Cells in Women With Endometriosis and Infertility are Associated With Low Levels of Endometrial Stem Cell Factor. Am J Reprod Immunol. 2016;75(4):493-502. doi:10.1111/aji.12486. Kane N, Kelly R, Saunders PT, Critchley HO. Proliferation of uterine natural killer cells is induced by human chorionic gonadotropin and mediated via the mannose receptor. Endocrinology. 2009;150(6):2882-8. doi:en.2008-1309 [pii] 10.1210/en.2008-1309. Antonis Makrigiannakis TV, Emmanouel Zoumakis,, Jeschke SNKaU. The Role of HCG in Implantation: A Mini-Review of Molecular and Clinical Evidence. International Journal o f Molecular Sciences. 2017;18(6):1305. 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-15724","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":378853,"identity":"b8d6601c-2099-4289-98db-4fd006155897","order_by":1,"name":"Yanbo Du","email":"","orcid":"","institution":"Reproductive Hospital affiiated to Shandong University","correspondingAuthor":false,"prefix":"","firstName":"Yanbo","middleName":"","lastName":"Du","suffix":""},{"id":378854,"identity":"adf69622-72d6-4362-bf57-dd3f5dd1f316","order_by":2,"name":"Lei Yan","email":"","orcid":"","institution":"Reproductive Hospital affiliated to Shandong University","correspondingAuthor":false,"prefix":"","firstName":"Lei","middleName":"","lastName":"Yan","suffix":""},{"id":378855,"identity":"01a35903-29f7-464c-9a8f-906642028d9e","order_by":3,"name":"Mei Sun","email":"","orcid":"","institution":"Reproductive Hospital affiliated to Shandong University","correspondingAuthor":false,"prefix":"","firstName":"Mei","middleName":"","lastName":"Sun","suffix":""},{"id":378856,"identity":"b9df156b-fdb7-4f39-a98f-31ee3adcf972","order_by":4,"name":"Yan Sheng","email":"","orcid":"","institution":"Reproductive Hosptial affiliated to Shandong University","correspondingAuthor":false,"prefix":"","firstName":"Yan","middleName":"","lastName":"Sheng","suffix":""},{"id":378857,"identity":"0f1c12ee-8224-437f-b463-70eaa54862a2","order_by":5,"name":"Xiufang Li","email":"","orcid":"","institution":"Reproductive Hospital affiliated to Shandong University","correspondingAuthor":false,"prefix":"","firstName":"Xiufang","middleName":"","lastName":"Li","suffix":""},{"id":378858,"identity":"6f5900c4-87ba-44d2-836c-9bf00bf6754f","order_by":6,"name":"Zhenhua Feng","email":"","orcid":"","institution":"Reproductive Hospital affiliated to Shandong University","correspondingAuthor":false,"prefix":"","firstName":"Zhenhua","middleName":"","lastName":"Feng","suffix":""},{"id":378859,"identity":"3e357114-aeeb-4947-b0cf-8ad75e2514f8","order_by":7,"name":"Rong Tang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3ElEQVRIie3PvQrCMBDA8QuBTLFdUxB9hbh0kj5LQqGTgmMHh5aIHVT6Ko5upgQ6xb1jfQQ3XfzYFVs3h/zm+3N3AI7zh4ifZ1repxFS/rkV6bI78ZipdEuSGBcU89bW3ckIkrhqiUFFSUlwXuEeh4HlWlCMB2pQpzIj4Bcb8T3B21fCiBcoL2nkYQjMnvY9tnCKJwrCRloCnM27ktkrEQwdDYQLucZ9kkRooTnKFQ2hX8KM1jITMVIkZsLWtPOXcZmryy17RKg01eWaLkd+sfuevKG/jTuO4zgfPQHtdkw8LhE3RgAAAABJRU5ErkJggg==","orcid":"","institution":"Reproductive Hospital affiliated to Shandong University","correspondingAuthor":true,"prefix":"","firstName":"Rong","middleName":"","lastName":"Tang","suffix":""}],"badges":[],"createdAt":"2020-02-27 16:13:37","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-15724/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-15724/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":13491778,"identity":"4ee3211e-81c9-4d44-a430-773ed68c7fff","added_by":"auto","created_at":"2021-09-16 22:29:01","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":252134,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-15724/v1/d85593f2-5d6d-4ca8-af2b-709fa64d4e68.pdf"}],"financialInterests":"","formattedTitle":"Effect of human chorionic gonadotropin injection before frozen embryo transfer on pregnancy outcomes in endometriosis infertility","fulltext":[{"header":"Introduction","content":" \u003cp\u003eEndometriosis (EM) is a chronic gynecological disease associated with infertility that is characterized by lesion of endometrial-like tissue outside of the uterine cavity [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Almost half of the women with endometriosis experience infertility [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. EM affect the outcome of assisted reproductive technology (ART), which compassing a wide sperm of causes, including the poor oocyte, sperm and embryo quality, impaired receptivity of the endometrium and implantation failure [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Clinically, there can be little doubt that the endometrium of women with endometriosis is less receptive to embryo implantation, and strong evidence exists to suggest that endometrial changes are associated with decreased cycle fecundity as a result of this disease[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Endometrial biomarkers are differentially expressed in the endometrium of women with endometriosis compared to normal women [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Seeking an effective approach to improve endometrial receptivity in endometriosis is a difficult issue in clinical.\u003c/p\u003e \u003cp\u003eFrozen embryo transfer (FET) is recommended for endometriosis in ART. Mohamed suggested that preparation of the endometrium for FET with gonadotropin-releasing\u0026ndash;hormone (GnRH) agonists could improve live birth rate in endometriosis, comparing fresh cycles [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. And recently, Xu found that pregnancy rate, clinical pregnancy rate and birth weight were improved in women with endometriosis who underwent intrauterine injection of human chorionic gonadotropin (hCG) before FET[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. But these methods are either time-consuming or inconvenient. So we retrospectively analyzed the data of frozen embryo transplantation in patients with endometriosis in an attempt to find a more effective strategy for frozen embryo transplantation.\u003c/p\u003e "},{"header":"Materials And Methods","content":" \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSubjects\u003c/h2\u003e \u003cp\u003eThe retrospective, database-searched cohort study was conducted in Reproductive Hospital Affiliated Shandong University. This study was reviewed and approved by research ethics committee of our institution. All patients in the study provided written informed consent for use of their data.\u003c/p\u003e \u003cp\u003eAll patients were diagnosed as endometriosis by a laparoscopy, underwent frozen embryo transfer in our hospital during a nine year period (1/1/2009-31/8/2018) were included. Patents older than 42\u0026nbsp;years at the onset of the cycle, basal FSH\u0026thinsp;\u0026gt;\u0026thinsp;12\u0026nbsp;U/L, women with uterine malformation, chromosomal abnormalities, polycystic ovary syndrome, hydrosalpinx, recurrent spontaneous abortion or intrauterine adhesions were all excluded. Finally, 667 women diagnosed with infertility associated with EM were collected. According to whether injection hCG in the protocols for frozen embryo transfer cycle, these patients were divided into two groups : Control group(n\u0026thinsp;=\u0026thinsp;305) and hCG group(n\u0026thinsp;=\u0026thinsp;362)。\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eEndometrial preparation\u003c/h2\u003e \u003cp\u003ePatients in control group received hormone replacement (HT) regime for frozen embryo transfer. The protocol was started with oral estradiol valerate (Progynova, Delpharm Lille) at a dose of 4\u0026nbsp;mg to 8\u0026nbsp;mg per begin on day 2 or 3 of menstrual cycle. Then the thickness of endometrium was measured by transvaginal ultrasound, and the concentrations of estrogen and LH in seurm were measured after about 10 days estradiol valerate treatment. When the endometrial thickness reached at least 7.5\u0026nbsp;mm, vaginal progestin (Utrogestan; Besins Manufacturing) at dose of 200\u0026nbsp;mg per day and oral dydrogesterone (Duphaston, Abbott) at dose of 20\u0026nbsp;mg twice daily was added. When the patients received frozen embryo transfer earlier than 2011, they will be treated with intramuscular injection of progesterone (Progesterone Injection, Zhejiang Xianju Pharmaceutical Co., Ltd) instead. Up to two day 3 cleavage\u0026ndash;stage embryos or blastocysts frozen early were thawed and transferred 3 or 5 days, respectively, after the start of progesterone. Women in hCG group received hCG 8000\u0026nbsp;IU intramuscular injection before progestin administration, and HT regime was the same as control group. Progestin supplementation continued until 12 weeks of pregnancy.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eOutcomes\u003c/h2\u003e \u003cp\u003eThe primary outcome was clinical pregnancy, which was defined as the detection of an intrauterine gestational sac by transvaginal ultrasoundgraphy after 3 weeks embryo transfer. The second outcome was live birth, which was defined as the delivery of any viable neonate who was 28 weeks of gestation or older. The early abortion rate was defined as the percentage of miscarriage early than 12 weeks in the group. Late abortion rate was the proportion of miscarriage in between 12 and 28 weeks in the group. Preterm birth rate was defined as the percentage of birth before 34 weeks in live birth women. Live birth rate was the proportion of women who birth at least one living child in the group.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eContinuous variables were represented as means and standard deviations; differences in variables were compared by means of Student\u0026rsquo;s t-test. Categorical variables were described as frequencies and percentages, with the between-group difference tested by means of the chi-square test and by means of Fisher\u0026rsquo;s exact test when the number of events was less than 5. Two-sides P value of less than 0.05 were considered to indicate statistical significance.\u003c/p\u003e \u003c/div\u003e "},{"header":"Results","content":" \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u003c/h2\u003e \u003cp\u003eThe baseline characteristics were similar in control group and hCG group (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). There is no difference in the terms of age, BMI, basal endocrine hormone levels, AMH and the number of oocytes retrieved in fresh cycle between two groups.\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 \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eBasal characteristics of participants\u003c/span\u003e\u003c/div\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eControl group\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eHCG group\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003ep value\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eN\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e305\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e362\u003c/div\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 \u003cdiv class=\"SimplePara\"\u003eAge(Years)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e31.85\u0026thinsp;\u0026plusmn;\u0026thinsp;4.72\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e31.62\u0026thinsp;\u0026plusmn;\u0026thinsp;4.42\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.503\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eBMI(kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e22.41\u0026thinsp;\u0026plusmn;\u0026thinsp;3.96\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e22.92\u0026thinsp;\u0026plusmn;\u0026thinsp;3.33\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.221\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAMH(ng/ml)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e4.52\u0026thinsp;\u0026plusmn;\u0026thinsp;5.66\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e4.39\u0026thinsp;\u0026plusmn;\u0026thinsp;4.16\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.506\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eBasal FSH(U/L)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e6.70\u0026thinsp;\u0026plusmn;\u0026thinsp;2.30\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e6.56\u0026thinsp;\u0026plusmn;\u0026thinsp;1.88\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.380\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eBasal LH(U/L)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e5.81\u0026thinsp;\u0026plusmn;\u0026thinsp;3.37\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e5.75\u0026thinsp;\u0026plusmn;\u0026thinsp;3.43\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.813\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eBasal E2(pg/ml)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e43.50\u0026thinsp;\u0026plusmn;\u0026thinsp;33.17\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e48.40\u0026thinsp;\u0026plusmn;\u0026thinsp;43.04\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.453\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eNo. of oocyte retrieved\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e14.28\u0026thinsp;\u0026plusmn;\u0026thinsp;7.95\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e13.87\u0026thinsp;\u0026plusmn;\u0026thinsp;7.24\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.485\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eThere were no significant differences between hCG group and control group (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05) in any of the baseline characteristics.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eOutcomes of FET\u003c/h2\u003e \u003cp\u003eThe thickness of endometrium, the stage of transferred embryo and the concentration of E2 in serum did not differ significantly among the two groups. However, FET outcomes were improved in hCG group. The pregnancy rate in hCG group (56.6% vs. 48.2%, p\u0026thinsp;=\u0026thinsp;0.035) significantly increased, comparing the control group (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). And the live birth rate in hCG group (43.5% vs. 37.4%, p\u0026thinsp;=\u0026thinsp;0.113) also elevated, but the difference is statistically insignificant (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). In addition, there was no significant difference in early abortion rate, late abortion rate, preterm birth rate and ectopic pregnancy rate between control group and hCG group (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\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 \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eOutcomes of frozen embryo transfer\u003c/span\u003e\u003c/div\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eControl group\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eHCG group\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003ep value\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eEndometrium thickness\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.93\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.92\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.236\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eTransferred embryo stage\u003c/div\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 \u003cdiv class=\"SimplePara\"\u003e0.425\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eCleavage stage\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e22(7.2%)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e20(5.5%)\u003c/div\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 \u003cdiv class=\"SimplePara\"\u003eblastocyte\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e283(92.8%)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e342(94.5%)\u003c/div\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 \u003cdiv class=\"SimplePara\"\u003eEstrogen\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e261.79\u0026thinsp;\u0026plusmn;\u0026thinsp;290.85\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e302.54\u0026thinsp;\u0026plusmn;\u0026thinsp;373.58\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.258\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eLH\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e18.36\u0026thinsp;\u0026plusmn;\u0026thinsp;11.51\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e15.11\u0026thinsp;\u0026plusmn;\u0026thinsp;13.54\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.029*\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePregnancy rate\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e48.2%\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e56.6%\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.035*\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eLive birth rate\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e37.4%\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e43.5%\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.113\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePreterm birth rate\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e4.4%\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e4.3%\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.601\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eEarly abortion rate\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e9.2%\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e10.8%\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.52\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eLate abortion rate\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0%\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.8%\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.254\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eEctopic pregnancy rate\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e1.6%\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.3%\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.098\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e*means p\u0026thinsp;\u0026lt;\u0026thinsp;0.05,** means p\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e "},{"header":"Discussion","content":" \u003cp\u003eIn our retrospective analysis, we found that the hCG injection could significantly improve pregnancy rate in EM patients undergoing FET. And live birth rate also elevated in hCG group, however, the difference did not reach statically significant.\u003c/p\u003e \u003cp\u003eSeveral studies have reported that endometriosis affects the endometrium and reduce fertility [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Reduced implantation, clinical pregnancy rate, ongoing pregnancy and live birth rate was found in women with endometriosis placing sibling oocytes from same donor, comparing women without endometriosis [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. We also found that higher prevalence of endometrial ployps in infertile patients with endometriosis, implying the special character of eutopic endometrium in endometriosis, which also impair embryo implantation [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].Animal studies support clinical data suggesting that endometriosis leads to implantation defects, again implicating the endometrium. Induction of endometriosis in animals demonstrates similar phenotypes to human disease [\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. And gradual and profound alteration in endometrium over time was found in induction of endometriosis in the baboon, involving the inflammation and immune system changes[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe expression of endometrial biomarkers altered in the eutopic endometrium of endometriosis compared to normal women. Lessey reported that endometrial integrins, which is known as cell-surface receptor for extracellular matrix protein, playing important role in embryo implantation, decreased in women with infertility and endometriosis[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Reduced integrin expression also associated with reduced IVF outcomes [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Integrinβ5 could up-regulated under the influence of hCG in stromal cells from endometriotic lesions in vivo [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Other key molecules that are required for nomal endometrial receptivity such as HOXA10[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], its expression also reduced in endometriosis, but have been reported to could be induced by hCG[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Therefore, hCG injection may improve endometrium receptivity via regulating key molecules related to embryo implantation.\u003c/p\u003e \u003cp\u003eMoreover, endometriosis has been described as a progesterone resistant disease due to the blunted or inadequate response to progesterone of both the eutopic and ectopic endometrial cells and tissue [\u003cspan additionalcitationids=\"CR25 CR26\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. This manifested as low expression of progesterone receptor, blunted expression of progesterone target genes [\u003cspan additionalcitationids=\"CR29\" citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] and inadequate decidualization response[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. However, the decidualization is an indispensible process for embryo implantation, thus aberrant decidualization would lead to unfavorable effects on embryo implannntation and pregnancy. While it was reported to hCG could regulate progesterone expression via the ERK1/2 pathways [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e], and promote human endometrial stromal cell decidulization leading to a significantly stronger induction of decidualization when used in combination with progesterone. [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn addatation, it has been well established that the immune system of women with endometriosis is dysfunctional. T regulatory (Treg) cells are altered in endometriosis patients and have been suggested to play a role in pathogenesis of endometriosis and its associated infertility [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Lower numbers of Treg cells have been detected in the eutopic endometrium of a non-human primate endometriosis model[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. And it was reported that hCG-producing trophoblasts could attracted Treg cell [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e], and more importantly, hCG was involved in Treg differentiation [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Furthermore, aberrant subset of uNK cells was found in the eutopic endometrium of women with endometriosis associated infertility [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. Immature uNK cells populations exist in infertile women with endometriosis [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. And hCG has been reported as a regulator of uNK cell proliferation mediating via the mannose receptor (CD206) [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. These findings may suggest hCG could improve endometrial receptivity via regulating immune cells in eutopic endometrium of infertility women associated with endometriosis.\u003c/p\u003e \u003cp\u003eIn our research, the pregnancy rate significantly elevated after hCG injection in endometriosis, however, the difference of live birth rate could not reach statistical significance. This may be the result of insufficient time or dose of hCG, and may improve by replacing single hCG treatments with a repetitive administration scheme [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. Since our research is retrospective design, the power of conclusion is lower. Further evidence is needed to clarify the protocol that would lead to beneficial outcomes.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEthics approval and consent to participate:\u003c/em\u003e\u003c/strong\u003e This study was approved by research ethics committee of our institution. All patients in the study have provided written informed consent for use of their data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAvailability of data and materials: \u003c/em\u003e\u003c/strong\u003eThe datasets analysed during the current study are not publicly available due to these are all clinical data which needed protect patients identity and privacy, but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eConflict of Interest: \u003c/em\u003e\u003c/strong\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eFunding: \u003c/em\u003e\u003c/strong\u003eThis study was funded by a grant from the National Nature Science Foundation of China (81571414).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAuthors' contributions: \u003c/em\u003e\u003c/strong\u003eAll the authors contributed equally to this manuscript. Rong Tang designed the study; Yanbo Du interpreted the data and drafted the article; Lei Yan revised the manuscript critically and accoute for all aspects of the work; Mei Sun and Yan Sheng collected all the data; Xiufang Li and Zhenhua Feng analysis the data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAcknowledgements: \u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003eT\u003c/strong\u003ehanks to other reproductive hospital staff who offered assistance to this study, Qin Gao, Zengxiang Ma, Jingjing Jiang, Hong Liu, Shanshan Gao, Na Yu and Qiaona Yuan.\u003c/p\u003e"},{"header":"References","content":"1. Senapati S, Sammel MD, Morse C, Barnhart KT. Impact of endometriosis on in vitro fertilization outcomes: an evaluation of the Society for Assisted Reproductive Technologies Database. Fertil Steril. 2016;106(1):164-71 e1. doi:S0015-0282(16)61044-0 [pii]\n10.1016/j.fertnstert.2016.03.037.\n2. Johnson NP, Hummelshoj L. Consensus on current management of endometriosis. Hum Reprod. 2013;28(6):1552-68. doi:det050 [pii]\n10.1093/humrep/det050.\n3. Meuleman C, Vandenabeele B, Fieuws S, Spiessens C, Timmerman D, D'Hooghe T. High prevalence of endometriosis in infertile women with normal ovulation and normospermic partners. Fertil Steril. 2009;92(1):68-74. doi:S0015-0282(08)00975-8 [pii]\n10.1016/j.fertnstert.2008.04.056.\n4. Du YB, Gao MZ, Shi Y, Sun ZG, Wang J. Endocrine and inflammatory factors and endometriosis-associated infertility in assisted reproduction techniques. Arch Gynecol Obstet. 2013;287(1):123-30. doi:10.1007/s00404-012-2567-0.\n5. Miller JE, Ahn SH, Monsanto SP, Khalaj K, Koti M, Tayade C. Implications of immune dysfunction on endometriosis associated infertility. Oncotarget. 2017;8(4):7138-47. doi:12577 [pii]\n10.18632/oncotarget.12577.\n6. Lessey BA, Kim JJ. Endometrial receptivity in the eutopic endometrium of women with endometriosis: it is affected, and let me show you why. Fertil Steril. 2017;108(1):19-27. doi:S0015-0282(17)30414-4 [pii]\n10.1016/j.fertnstert.2017.05.031.\n7. May KE, Villar J, Kirtley S, Kennedy SH, Becker CM. Endometrial alterations in endometriosis: a systematic review of putative biomarkers. Hum Reprod Update. 2011;17(5):637-53. doi:dmr013 [pii]\n10.1093/humupd/dmr013.\n8. Aghajanova L, Velarde MC, Giudice LC. Altered gene expression profiling in endometrium: evidence for progesterone resistance. Semin Reprod Med. 2010;28(1):51-8. doi:10.1055/s-0029-1242994.\n9. Mohamed AM, Chouliaras S, Jones CJ, Nardo LG. Live birth rate in fresh and frozen embryo transfer cycles in women with endometriosis. Eur J Obstet Gynecol Reprod Biol. 2011;156(2):177-80. doi:S0301-2115(11)00073-X [pii]\n10.1016/j.ejogrb.2011.01.020.\n10. Xu Z, Chen W, Chen C, Xiao Y, Chen X. Effect of intrauterine injection of human chorionic gonadotropin before frozen-thawed embryo transfer on pregnancy outcomes in women with endometriosis. J Int Med Res. 2019;47(7):2873-80. doi:10.1177/0300060519848928.\n11. Kim BG, Yoo JY, Kim TH, Shin JH, Langenheim JF, Ferguson SD et al. Aberrant activation of signal transducer and activator of transcription-3 (STAT3) signaling in endometriosis. Hum Reprod. 2015;30(5):1069-78. doi:dev050 [pii]\n10.1093/humrep/dev050.\n12. Vannuccini S, Clifton VL, Fraser IS, Taylor HS, Critchley H, Giudice LC et al. Infertility and reproductive disorders: impact of hormonal and inflammatory mechanisms on pregnancy outcome. Hum Reprod Update. 2016;22(1):104-15. doi:dmv044 [pii]\n10.1093/humupd/dmv044.\n13. Prapas Y, Goudakou M, Matalliotakis I, Kalogeraki A, Matalliotaki C, Panagiotidis Y et al. History of endometriosis may adversely affect the outcome in menopausal recipients of sibling oocytes. Reprod Biomed Online. 2012;25(5):543-8. doi:S1472-6483(12)00469-5 [pii]\n10.1016/j.rbmo.2012.07.020.\n14. Zhang YN, Zhang YS, Yu Q, Guo ZZ, Ma JL, Yan L. 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Antonis Makrigiannakis TV, Emmanouel Zoumakis,, Jeschke SNKaU. The Role of HCG in Implantation: A Mini-Review of Molecular and Clinical Evidence. International Journal o f Molecular Sciences. 2017;18(6):1305. \n\n\n"}],"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":"endometriosis, frozen embryo transfer, human chorionic gonadotropin","lastPublishedDoi":"10.21203/rs.3.rs-15724/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-15724/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003ePurpose To investigate the effect of hCG in hormone replacement regime for frozen thawed embryo transfer in women with endometriosis. Methods We performed a retrospective, database-searched cohort study. The data of endometriosis patients who underwent frozen embryo transfer between 1/1/2009-31/8/2018 were collected. According to the protocols for frozen embryo transfer cycle, these patients were divided into two groups: Control group(n=305), and hCG group(n=362). And clinical pregnancy rate, live birth rate, early abortion rate, late abortion rate and ectopic pregnancy rate were compared between the two groups. Results There was a significant increase in clinical pregnancy rate in hCG group (56.6% vs. 48.2%, p=0.035) compared to the control group. And the live birth rate in hCG group (43.5% vs. 37.4%, p=0.113) also elevated, but the difference is statistically insignificant. Conclusion hCG administration in hormone replacement regime for FET increase the pregnancy rate in women with endometriosis.\u003c/p\u003e","manuscriptTitle":"Effect of human chorionic gonadotropin injection before frozen embryo transfer on pregnancy outcomes in endometriosis infertility","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-03-03 12:56:29","doi":"10.21203/rs.3.rs-15724/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":"23e6b3dd-4825-45f0-bb50-25191fd43027","owner":[],"postedDate":"March 3rd, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":65133,"name":"Internal Medicine"},{"id":65134,"name":"Preventive Medicine"}],"tags":[],"updatedAt":"2020-03-31T13:12:41+00:00","versionOfRecord":[],"versionCreatedAt":"2020-03-03 12:56:29","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-15724","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-15724","identity":"rs-15724","version":["v1"]},"buildId":"WvIrzKhiLBfengagbw6Ux","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}