{"paper_id":"54ba2c54-f270-4282-b0bc-d375d1facea8","body_text":"Efficacy of Natural Cycle versus GnRH-a Down Regulation Cycle of Endometrial Preparation in Minimal and Mild endometriosis Patients Undergoing Frozen-Thawed Embryo Transfer | 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 Efficacy of Natural Cycle versus GnRH-a Down Regulation Cycle of Endometrial Preparation in Minimal and Mild endometriosis Patients Undergoing Frozen-Thawed Embryo Transfer Ya Li, Jing Zhong, Songyuan Tang, Lili Wang, Ying Zhong This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-122904/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 Background Minimal and mild endometriosis patients with infertility are treated by in vitro fertilization and embryo transfer/intracytoplasmic sperm injection (IVF-ET/ICSI) in recent years. However, inconsistencies in findings within and across individual studies raise concerns as to determine which method is the best treatment, especially in the frozen-thawed embryo transfer cycle (FET). We hope to compare the efficacy of natural cycle versus GnRH-a down regulation cycle endometrial preparations in minimal and mild endometriosis patients undergoing FET. Methods We retrospectively analyzed a cohort of 1170 minimal and mild endometriosis patients receiving FET at the Reproductive Medicine Centre from Chengdu Jinjiang Hospital for Maternal and Child Health Care from January 1, 2016 to December 31, 2018. They were assigned to the natural cycle group and the GnRH-a down regulation cycle group based on endometrial preparation protocols. Baseline characteristics, frozen-thawed embryo transfer cycle and pregnancy outcomes were compared between the two groups. Results There were nonsignificant differences in baseline characteristics including age, BMI, types of infertility, the duration of infertility and the delivery history between the natural cycle group and the GnRH-a down regulation cycle group ( P >0.05). The biochemical pregnancy rate (63.62% v.s. 53.83%), clinical pregnancy rate (56.10% v.s. 47.49%), implantation rate (43.19% v.s. 34.88%) and live birth rate (44.31% v.s. 35.84%) in the natural cycle group were significantly higher than those in the GnRH-a down regulation cycle group ( P <0.05). However, there were nonsignificant differences in the multiple birth rate, abortion rate, ectopic pregnancy rate, premature birth rate, neonatal weight and length between the two groups ( P >0.05). The multivariate regression analysis showed that age, anti-Müllerian hormone (AMH), the number of transplanted high-quality blastocysts and endometrial preparation protocols were associated with the live birth rate in minimal and mild endometriosis women undergoing FET ( P <0.05). Conclusion Compared with GnRH-a down regulation cycle, natural cycle endometrial preparation of FET is a prominent endometrial preparation method for improving the implantation rate, clinical pregnancy rate, and live birth rate in minimal and mild endometriosis patients, which is more cost-effective in clinical practice. Maternal & Fetal Medicine minimal and mild endometriosis frozen-thawed embryo transfer natural cycle GnRH-a down regulation cycle clinical pregnancy rate live birth rate Figures Figure 1 Background Endometriosis is a benign chronic gynecological disease featuring chronic pelvic pain and infertility in reproductive-age females, associated with the pathogenesis of the implantation of the endometrium outside the uterine cavity [ 1 ] . While the prevalence of endometriosis in women of childbearing age is about 10–15%, those with minimal and mild endometriosis combined with infertility comprise 25–50% of all endometriosis cases [ 2 ] . In a cohort study recruiting childbearing-age women with endometriosis, women younger than 35 years of age doubled the risk of infertility compared with those without endometriosis [ 3 ] . According to the American Society for Reproductive Medicine Stage (ASRM) score, endometriosis can be classified as minimal (I), mild (II), moderate (III) and severe (IV) [ 4 ] , and the incidence of minimal to mild minimal and mild endometriosis is much higher than that of moderate and severe endometriosis. Though the exact pathogenesis of infertility in patients with minimal or mild endometriosis has not yet been fully explored, it may attribute to anatomical changes in the pelvis, ovarian dysfunction, pelvic micro environment and inflammatory factors or cytokines that influence endometrial receptivity and egg / embryo quality [ 5 – 7 ] . In recent years, in vitro fertilization and embryo transfer/intracytoplasmic sperm injection (IVF-ET/ICSI) has been applied for minimal and mild endometriosis patients combined with infertility, especially for those who are still not pregnant undergoing surgery. However, previous studies about the efficacy of IVF-ET/ICSI in minimal and mild endometriosis women have yielded inconsistent results [ 8 ] . A meta-analysis uncovered that the diminished pregnancy rate, ovarian response, implantation rate and clinical pregnancy rate following IVF in endometriosis patients combined with infertility compared with infertile women due to fallopian tubal factors, which may attribute to decreased endometrial receptivity and damaged mitochondrial structure and function in oocytes in minimal and mild endometriosis [ 9 ] . However, another relevant study only reported non-significant differences in pregnancy outcomes between endometriosis patients combined with infertility and infertile women due to fallopian tubal factors after IVF-ET/ICSI [ 10 ] , which is supported by another meta-analysis conducted in 2015 that there are similar pregnancy outcomes between endometriosis patients and pregnant women without severe diseases [ 11 ] . Compared with fresh embryo transfer during controlled ovarian hyperstimulation (COH), FET contributes to an improved cumulative clinical pregnancy rate and persistent pregnancy rate in minimal and mild endometriosis patients as it minimizes the influence of high-level estrogen on endometrial receptivity during controlled ovarian hyperstimulation [ 12 ] . Although current studies emphasizing the optimal endometrial preparation protocols for minimal and mild endometriosis patients receiving FET have not reached a consensus [ 13 , 14 ] , GnRH-a down regulation and natural cycle of endometrial preparation in FETs are still the two major endometrial preparation methods for minimal and mild endometriosis patients. Numerous evidences show that GnRH-a could be able to decrease the influence of minimal and mild endometriosis on adverse pregnancy outcomes and to improve endometrial receptivity [ 15 ] , and that down regulated FET using long-term GnRH-a might improve pregnancy outcomes, despite a concern for probability of resultant implantation failure owing to adverse reactions of exogenous hormones and inappropriate endometrial thickness [ 10 ] . As natural cycle endometrial preparation of FET does not require exogenous hormones, the natural physiological status of the endometrium can be largely preserved with merely a negligible influence [ 16 ] . Current studies about the influences of down regulation cycle and natural cycle of endometrial preparation in FETs on clinical outcomes of minimal and mild endometriosis women are rarely reported. So the aim of this study was to retrospectively analyze possible influences of the two main endometrial preparation protocols for minimal and mild endometriosis. Methods 1.1 Subjects Medical records of 1170 minimal and mild endometriosis patients undergoing FET in the Reproductive Medicine Centre from Chengdu Jinjiang Hospital for Maternal and Child Health Care from January 1, 2016 to December 31, 2018 were retrospectively analyzed. Minimal and mild endometriosis was pathologically confirmed after laparoscopic or open surgery. Patients were assigned to the natural cycle group and the GnRH-a down regulation cycle group according to specific endometrial preparation protocols. Subjects were included if ( i ) they were diagnosed as ASRM I-II after laparoscopic or open surgery; ( ii ) aged 20–40 years; and ( iii ) they received blastocyst transfer. Subjects were excluded if ( i ) infertility was caused by other factors; ( ii ) chromosomal abnormalities were found in one or both spouses; ( iii ) patients reported other endocrine diseases; (iv) they reported organic diseases of the uterus (e.g., adenomyosis, scar uterus and intrauterine adhesions); ( v ) malformation of the reproductive system was detected; or ( vi ) the spouse reported severe oligoasthenospermia, asthenospermia and teratozoospermia. c were compared between the two groups. The eligibility flow chart was depicted in Fig. 1 . The study was approved by the institutional research ethics committee of Chengdu Jinjiang Hospital for Maternal and Child Health Care, and written informed consent was obtained from each subject. 1.2 Methods 1.2.1 Endometrial preparation protocols Transvaginal ultrasonography was performed and basal hormone levels were determined on day 2 or day 3 of the menstrual cycle for all patients. For women in the natural cycle group, the follicular size, endometrial thickness, the morphology of the endometrium and endometrial blood flow were monitored by transvaginal ultrasonography on day 8 to day 10 of the menstrual cycle. Serum levels of estradiol (E2), progesterone (P) and luteinizing hormone (LH) were detected once the dominant follicle size was up to 18–20 mm, and patients were administered by intramuscular injection of 6,000 U human chorionic gonadotropin (HCG; LIVZON, China) on the same day. After ascertaining the time of ovulation, they received the oral administration of dydrogesterone 20 mg bid (Abbott, Holland). Blastocyst thawed and transplanted were performed on day 5 of dydrogesterone administration. For women in the GnRH-a down regulation cycle group, they accepted the intramuscular administration of 3.75 mg diphereline (Ipsen, France) on day 2 or day 3 of the menstrual cycle, and the endometrium was monitored by vaginal ultrasonography and basal hormone levels were re-examined on day 28th. For patients with E2 < 40 pg/ml, LH < 10mIU/mL, FSH < 10mIU/mL, endometrium < 5 mm on day 28th during GnRH-a down regulation cycles, endometrial preparation was undertaken with the oral administration of Femoston (red) 1 pill tid (Abbott, Holland) for 12 days. The levels of E2 and P in serum were determined, and the thickness and blood flow of the endometrium was detected by transvaginal ultrasonography on the 13th day. On the same day, subjects also received the oral administration of Femoston (yellow) 2 pills bid (Abbott, Holland) and the vaginal administration of Crinone 90 mg qd (MERCK SEROND, Germany) if their endometrial condition was suitable for FET. Blastocysts thawed and transplanted were performed on day 5 of the oral and vaginal administrations. Estrogens could be supplemented (controlled in 20 days) if the endometrium was not appropriate. The funding from the Sichuan Science and Technology Program played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript. 1.2.2 Blastocyst frozen-thawed embryo transfer The quality of embryos was rated based on the Gardner system [ 17 ] . frozen-thawed embryo transfer of blastocyst were performed in accordance with standard process. Based on the patients’ conditions, 1–2 cultured blastocysts was/were transferred and guided by the vaginal ultrasound. Dydrogesterone and/or Crinone was administrated for luteal phase support. 1.2.3 Luteal-phase support and pregnancy confirmation Medications for luteal-phase support were given continuously after blastocyst transplantation. On day 14th after transplantation, biochemical pregnancy was positive if the serum level of HCG was more than 25 U/L, while clinical pregnancy was confirmed with the presence of the gestational sac using transvaginal ultrasound on day 28th and day 38th after transplantation. Medications for luteal-phase support were given until 10–12 weeks of gestation. 1.3 Measurements Baseline clinical and demographic characteristics of both groups were recorded, encompassing age, the duration of infertility, types of infertility, body mass index (BMI), antral follicle count (AFC), Anti-mullerian hormone (AMH), the number of transplanted blastocysts and the number of transplanted high-quality blastocysts. Clinical pregnancy outcomes consisted of the biochemical pregnancy rate (the percentage of subjects with a serum HCG level > 25 U/L on day 14 after transplantation in all transplanted subjects), the clinical pregnancy rate (the proportion of subjects with the presence of the gestation sac in all transplanted subjects), the implantation rate (the proportion of the number of the gestation sac in all transplanted blastocysts), the multiple pregnancy rate(the proportion of the subjects of the multiple gestation sacs in all subjects of clinical pregnancy), the miscarriage rate (the percentage of women with miscarriage in all subjects of clinical pregnancy), the ectopic pregnancy rate (the proportion of women with ectopic pregnancy in all subjects of clinical pregnancy), the live birth rate (the percentage of women giving birth to live-born infants in all transplanted subjects), the normal delivery rate (the percentage of women with normal vaginal delivery in all pregnant subjects), the cesarean section rate (the percentage of women with cesarean section in all pregnant subjects), newborn birth weight and length. 1.4 Statistical Analysis Statistical analyses were performed using the SPSS 22.0 software (IBM SPSS). Measurement data were expressed as \\(\\stackrel{-}{x}\\) ±s. Differences between the two groups were compared using the independent t test if the data were normally distributed; otherwise, the Mann-Whitney U test was employed. Results of clinical pregnancy outcomes of the two groups were expressed as percentages, and compared using the Chi-square test or Fisher’s exact test. Multivariate regression analysis was employed to assess influences of age, BMI, the duration of infertility, types of infertility, AMH, AFC, the number of transplanted blastocysts, the number of transplanted high-quality blastocysts, endometrial thickness on the day of transplantation and endometrial preparation protocols on the live birth rate of minimal and mild endometriosis patients. A P value < 0.05 was considered as statistically significant. Results 2.1 Baseline characteristics of minimal and mild endometriosis women in natural cycle group v.s. GnRH-a down regulation cycle groups A total of 1170 eligible subjects in their FET cycles were recruited, consisting of 492 subjects in the natural cycle group and 678 in the GnRH-a down regulation cycle group. No significant differences in age, the duration of infertility, types of infertility, BMI, delivery history and endometrial thickness on the day of transplantation were found between the two groups ( P > 0.05). However, the AFC and AMH levels in the natural cycle group were significantly higher than those in the GnRH-a down regulation cycle group, while the numbers of transplanted blastocysts and transplanted high-quality blastocysts were lower in the natural cycle group ( P < 0.05) (Table 1 ). Table 1 Baseline characteristics of minimal and mild endometriosis women in natural cycle group v.s. GnRH-a down regulation cycle group Natural cycle group GnRH-a down regulation cycle group P value FET cycles 492 678 Age (years) 0.951 < 35 312 (63.41%) 428 (63.17%) ≥ 35 180 (36.59%) 250 (36.87%) BMI (kg/m 2 ) 22.68 ± 3.22 22.88 ± 3.73 0.567 Duration of infertility 3.42 ± 2.22 3.52 ± 2.43 0.466 Types of infertility 0.814 Primary infertility 155 (31.50%) 218 (32.15%) Secondary infertility 337 (68.50%) 460 (67.85%) AMH 3.71 ± 3.01 3.11 ± 3.73 0.006 AFC 11.73 ± 6.48 9.57 ± 7.29 < 0.001 Delivery history 0.455 None 411 (83.54%) 555 (81.86%) Yes 81 (16.46%) 123 (18.14%) Number of transplanted blastocysts 1.72 ± 0.45 1.78 ± 0.42 0.028 Number of transplanted high-quality blastocysts 1.34 ± 0.66 1.60 ± 0.49 < 0.001 Endometrial thickness on the day of transplantation 10.00 ± 1.86 10.03 ± 1.79 0.820 2.2 Better Pregnancy Outcomes In Natural Cycle Of Fet The biochemical pregnancy rate, clinical pregnancy rate, implantation rate and live birth rate were significantly higher in the natural cycle group than those in the GnRH-a down regulation cycle group ( P < 0.05). There were nonsignificant differences in the multiple pregnancy rate, miscarriage rate, ectopic pregnancy rate, premature birth rate, normal delivery rate and cesarean section rate between the two groups, neither was newborn birth weight nor newborn birth length between the two groups ( P > 0.05) (Table 2 ). There were no birth defects in both groups. Table 2 Pregnancy outcomes of minimal and mild endometriosis women in natural cycle group v.s. GnRH-a down regulation cycle groups Natural cycle group GnRH-a down regulation cycle group P value FET cycles 492 678 Biochemical pregnancy rate 313 (63.62%) 365 (53.83%) < 0.001 Clinical pregnancy rate 276 (56.10%) 322 (47.49%) 0.004 Implantation rate 43.19% 34.88% < 0.001 Multiple pregnancy rate 62 (28.44%) 51 (20.99%) 0.063 Miscarriage rate 46 (16.67%) 58 (18.01%) 0.942 Ectopic pregnancy rate 3 (1.09%) 8 (2.48%) 0.238 Live birth rate 218 (44.31%) 243 (35.84%) 0.003 Premature birth rate 55 (25.23%) 73 (30.04%) 0.249 Normal delivery rate 20 (9.48%) 14 (5.81%) 0.14 Cesarean section rate 191 (90.52%) 227 (94.19%) 0.14 Newborn birth weight 2.82 ± 0.63 2.85 ± 0.63 0.515 Newborn birth length 48.13 ± 2.79 48.35 ± 2.65 0.382 2.3 Potential factors influencing the live birth rate in minimal and mild endometriosis women undergoing FET Age, AMH, the number of transplanted high-quality blastocysts and endometrial preparation protocols were significantly associated with the live birth rate in minimal and mild endometriosis subjects undergoing FET ( P < 0.05). However, BMI, the duration of infertility, types of infertility, AFC, the number of transplanted blastocysts and endometrial thickness on the day of transplantation were not associated with the live birth rate following FET ( P > 0.05) (Table 3 ). Table 3 Potential factors affecting live birth rate outcomes in minimal and mild endometriosis women undergoing FET Potential factors OR 95%CI P value Age (years) 0.92 (0.89, 0.94) < 0.001 BMI (kg/m 2 ) 0.99 (0.95, 1.03) 0.634 Duration of infertility 1.01 (0.95, 1.07) 0.820 Types of infertility 0.089 Primary infertility 1 Secondary infertility 1.30 (0.96, 1.76) AMH 1.08 (1.01, 1.14) 0.014 AFC 1.01 (0.98, 1.03) 0.640 Number of transplanted blastocysts 1.24 (0.84, 1.83) 0.280 Number of transplanted high-quality blastocysts 2.59 (1.98, 3.38) < 0.001 Endometrial thickness on the day of transplantation 1.00 (0.93, 1.08) 0.905 FET cycles 0.025 Natural cycle endometrial preparation 1 GnRH-a down regulation cycle endometrial preparation 0.71 (0.53, 0.96) Discussion Endometriosis is an estrogen dependent inflammatory disease classically characterized by infertility and secondary progressively dysmenorrhea, which is becoming more prevalent in childbearing-age women. Endometriosis is closely related to infertility, about 10–25% of women with endometriosis have undergone IVF/ICSI [ 18 ] , however whether minimal and mild endometriosis are associated with infertility and the outcomes of IVF/ICSI are still unclear. So more assisted reproductive technology for effectively improving the pregnancy rate for minimal and mild endometrios women are still needed. Though previous studies about the two major endometrial preparation protocols analyzed the correlations between fresh embryo transfer or FET and pregnancy outcomes in the population, their results are inconsistent. Therefore, in this study we aimed to compare the effects of natural cycle endometrial preparation versus long-term GnRH-a down regulation cycle endometrial preparation of FET on the live birth rate in minimal and mild endometriosis women. In this study, all subjects were pathologically confirmed as I-II endometriosis of ASRM after laparoscopic or open surgery, and they were assigned to the natural cycle and GnRH-a down regulation cycle groups according to specific endometrial preparation protocols. Their baseline characteristics were comparable. The biochemical pregnancy rate, clinical pregnancy rate, implantation rate and live birth rate were significantly higher in the natural cycle group than those in the GnRH-a down regulation cycle group. Besides, there were nonsignificant differences in the multiple pregnancy rate, miscarriage rate, ectopic pregnancy rate, premature birth rate, normal delivery rate and cesarean section rate between the two groups. By contrast, van de Houwen LE et al. [ 19 ] concluded that GnRH-a down regulation cycle of FET improved ongoing pregnancy rates compared with natural cycle of FET in severe endometriosis patients. However,another study has assessed the influence of endometrial peristalsis on embyros/blastocysts implantation and has reported that natural cycle of FET is instrumental to a high pregnancy rate [ 20 ] . Nevertheless, they did not take into consideration different endometrial preparations. Levron et al. demonstrated that the implantation rate and clinical pregnancy rate were improved after natural cycle of FET, which is consistent with our findings. In addition, in long-term GnRH-a down regulation cycle, minimal and mild endometriosis patients in the present study were supplemented with exogenous estrogens before the placental function was established. Due to no using of exogenous estrogens, natural cycle of FET do not alter endometrial receptivity, and there were a more natural effect of luteal support for blatocyst development; moreover, it is cost-saving during a short period of treatment. Embryo quality and endometrial receptivity are the major factors that influence outcomes following FET. In our study, both blastocyst culture and cryopreservation during the controlled ovarian hyperstimulation cycle contribute to a high pregnancy rate and live birth rate after FET. To obtain higher developmental potential [ 21 ] , we eliminated blastocysts with poor quality or chromosomal abnormalities, and we kept high-quality blastocysts during blastocyst culture, and then performed the vitrification for good quality blastocysts. And we discover that more high-quality transplanted blastocysts is what matters to a higher live birth rate after FET, rather than the number of transplanted blastocysts, which is also supported by the study by Bourdon M et al. [ 22 ] In the present study we confirmed that age and AMH levels were associated with the live birth rate following FET. Evidences show that age is an independent risk for the live birth rate. With the increasing age, diminished quality of oocytes alongside mitochondrial dysfunction and oxidative stress increases the risk of embryo chromosome abnormalities, often manifesting as the presence of aneuploid embryo and a low blastulation rate [ 23 ] . Decreases in AMH levels and the AFC indicate a reduced ovarian reserve, which further influences the numbers of eggs, embryos and high-quality embryos. It is reported that minimal and mild endometriosis may have a certain impact on low newborn birth weight [ 24 ] . Although no significant differences in newborn birth weight and length were identified between the natural cycle and GnRH-a down regulation cycle groups, a higher premature rate and lower newborn birth weight in both groups were consistent with previous studies [ 19 , 25 ] . As a result, further research is required to clarify the correlation between minimal and mild endometriosis and low newborn birth weight. It is reported that IVF treatment in severe minimal and mild endometriosis patients may enhance susceptibilities to congenital cardiovascular and skeletal muscle diseases in neonates [ 26 ] . After we screened fetal malformation, although there were early and late abortions in both groups during pregnancy, no birth defects were detected, which can be explained by the inclusion of minimal and mild endometriosis patients, high-quality blastocysts transplantation, comprehensive prenatal examinations of the abnormal fetus, or a small sample size. This is a retrospective non-randomized controlled trial, so a potential selection bias may influence the research quality. A prospective randomized controlled trial at multi-centers is required to validate our findings. Summarily, this study demonstrates that natural cycle endometrial preparation is superior to GnRH-a down regulation cycle endometrial preparation in terms of the implantation rate, clinical pregnancy rate and live birth rate, which also improves the cost-effectiveness of FET for women with minimal and mild endometriosis. A large sample size is still required to re-verify the influence of endometrial preparations on pregnancy outcomes of Chinese minimal and mild endometriosis women undergoing FET. Abbreviations FET: frozen-thawed embryo transfer; IVF-ET/ICSI: in vitro fertilization and embryo transfer/intracytoplasmic sperm injection; COH: controlled ovarian hyperstimulation; GnRH-a: gonadotropin-releasing hormone agonist; AMH: anti-Müllerian hormone; AFC: antral follicle count. Declarations Ethics approval and consent to participate: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the institutional research ethics committee of Chengdu Jinjiang Hospital for Maternal and Child Health Care. Informed consent was obtained from all individual participants included in the study. Consent for publication ： Not applicable. Availability of Data and Materials: The data that support the findings of this study are available from the Reproductive Medicine Centre from Chengdu Jinjiang Hospital for Maternal and Child Health Care but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of the Reproductive Medicine Centre from Chengdu Jinjiang Hospital for Maternal and Child Health Care. Competing interests: The authors have no competing interests to declare. Funding: This study was funded by the Sichuan Science and Technology Program (grant number 2018JY0295). Authors’ contributions: YL and JZ were responsible for the study inception and design. YL and LW performed the data extraction. YL, ST and YZ interpreted the data, and YL wrote the manuscript. All authors have read, critiqued and approved the final manuscript. Acknowledgements: Not applicable. References Giudice LC, Kao LC. minimal and mild endometriosis[J]. Lancet. 2004;364(9447):1789–99. Macer ML, Taylor HS. minimal and mild endometriosis and infertility: a review of the pathogenesis and treatment of minimal and mild endometriosis-associated infertility. Obstet Gynecol Clin North Am. 2012;39(4):535–49. 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Blastocyst culture and transfer in clinically assisted reproduction: a committee opinion. Fertil Steril. 2018;110(7):1246–52. Bourdon M, Pocate-Cheriet K, Finet de Bantel A, et al. Day 5 versus Day 6 blastocyst transfers: a systematic review and meta-analysis of clinical outcomes. Hum Reprod. 2019;34(10):1948–64. Ubaldi FM, Cimadomo D, Vaiarelli A, et al. Advanced Maternal Age in IVF: Still a Challenge? The Present and the Future of Its Treatment. Front Endocrinol (Lausanne). 2019;10:94. Borghese B, Sibiude J, Santulli P, et al. Low birth weight is strongly associated with the risk of deep infiltrating minimal and mild endometriosis: results of a 743 case-control study. PLoS One. 2015;10(2):e0117387. Kuivasaari P, Hippeläinen M, Anttila M, Heinonen S. Effect of minimal and mild endometriosis on IVF/ICSI outcome: stage III/IV minimal and mild endometriosis worsens cumulative pregnancy and live-born rates. Hum Reprod. 2005;20(11):3130–5. Liang Z, Yin M, Ma M, Wang Y, Kuang Y. Effect of Maternal Advanced minimal and mild endometriosis on Risk of Congenital Malformations for Infants Born After in vitro Fertilization and Frozen-Thawed Embryo Transfer: Analysis of 28,600 Newborns[J]. Front Endocrinol (Lausanne), 2019,10:763. 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-122904\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Research article\",\"associatedPublications\":[],\"authors\":[{\"id\":5931295,\"identity\":\"af4cad53-7821-4b63-8401-c118f9303a74\",\"order_by\":0,\"name\":\"Ya Li\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Chengdu Jinjiang Hospital for Womens and Childrens Health\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Ya\",\"middleName\":\"\",\"lastName\":\"Li\",\"suffix\":\"\"},{\"id\":5931296,\"identity\":\"164094ce-c194-4e45-82ac-7f9cdf705da8\",\"order_by\":1,\"name\":\"Jing Zhong\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Chengdu Jinjiang Hospital for Womens and Childrens Health\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Jing\",\"middleName\":\"\",\"lastName\":\"Zhong\",\"suffix\":\"\"},{\"id\":5931297,\"identity\":\"2042dd45-f68c-4720-a58d-bbc60e053fef\",\"order_by\":2,\"name\":\"Songyuan Tang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Kunming Medical University - Pingzheng Campus\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Songyuan\",\"middleName\":\"\",\"lastName\":\"Tang\",\"suffix\":\"\"},{\"id\":5931298,\"identity\":\"b86ca88b-7073-401d-a3e8-c82bf78b67cf\",\"order_by\":3,\"name\":\"Lili Wang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Chengdu Jinjiang Hospital for Womens and Childrens Health\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Lili\",\"middleName\":\"\",\"lastName\":\"Wang\",\"suffix\":\"\"},{\"id\":5931299,\"identity\":\"059c10e2-07f2-42cf-a131-15ad7093279a\",\"order_by\":4,\"name\":\"Ying Zhong\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAz0lEQVRIiWNgGAWjYBACPgbGxgcfeCTs+JmZDxCnhY2BudlwhoxNsmQ7WwKxWtjbpHls0hg3nOcxIFKLRGKb5Iycw8wMh3k+3njDYCen20BYS7PFhzOH+RibeTdbzmFINjY7QFhL482ZPYeZmZl5t0nzMBxI3EaElgZp3n+HGduYeZ4RraVJmocnjbGHmYeNSC08D4GBzGOTLMHMZmw5x4AIv/Czpz8ER6X9+cMPb7ypsJMjqIVBIAHBliAuaviRDJXgIUbHKBgFo2AUjDgAAGsnPWSqLcs8AAAAAElFTkSuQmCC\",\"orcid\":\"https://orcid.org/0000-0002-8161-7429\",\"institution\":\"Chengdu Jinjiang Hospital for Womens and Childrens Health\",\"correspondingAuthor\":true,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Ying\",\"middleName\":\"\",\"lastName\":\"Zhong\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2020-12-06 13:34:08\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-122904/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-122904/v1\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":4132796,\"identity\":\"f7123780-de32-411c-bab0-4ed6420f6f2f\",\"added_by\":\"auto\",\"created_at\":\"2020-12-09 17:35:40\",\"extension\":\"png\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":28025,\"visible\":true,\"origin\":\"\",\"legend\":\"The eligibility flowchart of subjects in this study\",\"description\":\"\",\"filename\":\"1.PNG\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-122904/v1/bffa201a519b9d67ba333c66.PNG\"},{\"id\":13631562,\"identity\":\"23c0b93f-712b-4902-9a44-f74153959693\",\"added_by\":\"auto\",\"created_at\":\"2021-09-17 08:17:17\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":434511,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-122904/v1/13534451-7758-42f0-a022-d1f4c3735bed.pdf\"}],\"financialInterests\":\"\",\"formattedTitle\":\"Efficacy of Natural Cycle versus GnRH-a Down Regulation Cycle of Endometrial Preparation in Minimal and Mild endometriosis Patients Undergoing Frozen-Thawed Embryo Transfer\",\"fulltext\":[{\"header\":\"Background\",\"content\":\" \\u003cp\\u003eEndometriosis is a benign chronic gynecological disease featuring chronic pelvic pain and infertility in reproductive-age females, associated with the pathogenesis of the implantation of the endometrium outside the uterine cavity\\u003csup\\u003e[\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e]\\u003c/sup\\u003e. While the prevalence of endometriosis in women of childbearing age is about 10\\u0026ndash;15%, those with minimal and mild endometriosis combined with infertility comprise 25\\u0026ndash;50% of all endometriosis cases\\u003csup\\u003e[\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e]\\u003c/sup\\u003e. In a cohort study recruiting childbearing-age women with endometriosis, women younger than 35\\u0026nbsp;years of age doubled the risk of infertility compared with those without endometriosis\\u003csup\\u003e[\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e]\\u003c/sup\\u003e. According to the American Society for Reproductive Medicine Stage (ASRM) score, endometriosis can be classified as minimal (I), mild (II), moderate (III) and severe (IV)\\u003csup\\u003e[\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e]\\u003c/sup\\u003e, and the incidence of minimal to mild minimal and mild endometriosis is much higher than that of moderate and severe endometriosis. Though the exact pathogenesis of infertility in patients with minimal or mild endometriosis has not yet been fully explored, it may attribute to anatomical changes in the pelvis, ovarian dysfunction, pelvic micro environment and inflammatory factors or cytokines that influence endometrial receptivity and egg / embryo quality\\u003csup\\u003e[\\u003cspan additionalcitationids=\\\"CR6\\\" citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e]\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eIn recent years, \\u003cem\\u003ein vitro\\u003c/em\\u003e fertilization and embryo transfer/intracytoplasmic sperm injection (IVF-ET/ICSI) has been applied for minimal and mild endometriosis patients combined with infertility, especially for those who are still not pregnant undergoing surgery. However, previous studies about the efficacy of IVF-ET/ICSI in minimal and mild endometriosis women have yielded inconsistent results\\u003csup\\u003e[\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e]\\u003c/sup\\u003e. A meta-analysis uncovered that the diminished pregnancy rate, ovarian response, implantation rate and clinical pregnancy rate following IVF in endometriosis patients combined with infertility compared with infertile women due to fallopian tubal factors, which may attribute to decreased endometrial receptivity and damaged mitochondrial structure and function in oocytes in minimal and mild endometriosis\\u003csup\\u003e[\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e]\\u003c/sup\\u003e. However, another relevant study only reported non-significant differences in pregnancy outcomes between endometriosis patients combined with infertility and infertile women due to fallopian tubal factors after IVF-ET/ICSI\\u003csup\\u003e[\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e]\\u003c/sup\\u003e, which is supported by another meta-analysis conducted in 2015 that there are similar pregnancy outcomes between endometriosis patients and pregnant women without severe diseases\\u003csup\\u003e[\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e]\\u003c/sup\\u003e. Compared with fresh embryo transfer during controlled ovarian hyperstimulation (COH), FET contributes to an improved cumulative clinical pregnancy rate and persistent pregnancy rate in minimal and mild endometriosis patients as it minimizes the influence of high-level estrogen on endometrial receptivity during controlled ovarian hyperstimulation\\u003csup\\u003e[\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e]\\u003c/sup\\u003e. Although current studies emphasizing the optimal endometrial preparation protocols for minimal and mild endometriosis patients receiving FET have not reached a consensus\\u003csup\\u003e[\\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e]\\u003c/sup\\u003e, GnRH-a down regulation and natural cycle of endometrial preparation in FETs are still the two major endometrial preparation methods for minimal and mild endometriosis patients. Numerous evidences show that GnRH-a could be able to decrease the influence of minimal and mild endometriosis on adverse pregnancy outcomes and to improve endometrial receptivity\\u003csup\\u003e[\\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e]\\u003c/sup\\u003e, and that down regulated FET using long-term GnRH-a might improve pregnancy outcomes, despite a concern for probability of resultant implantation failure owing to adverse reactions of exogenous hormones and inappropriate endometrial thickness\\u003csup\\u003e[\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e]\\u003c/sup\\u003e. As natural cycle endometrial preparation of FET does not require exogenous hormones, the natural physiological status of the endometrium can be largely preserved with merely a negligible influence \\u003csup\\u003e[\\u003cspan citationid=\\\"CR16\\\" class=\\\"CitationRef\\\"\\u003e16\\u003c/span\\u003e]\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eCurrent studies about the influences of down regulation cycle and natural cycle of endometrial preparation in FETs on clinical outcomes of minimal and mild endometriosis women are rarely reported. So the aim of this study was to retrospectively analyze possible influences of the two main endometrial preparation protocols for minimal and mild endometriosis.\\u003c/p\\u003e \"},{\"header\":\"Methods\",\"content\":\" \\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003e1.1 Subjects\\u003c/h2\\u003e \\u003cp\\u003eMedical records of 1170 minimal and mild endometriosis patients undergoing FET in the Reproductive Medicine Centre from Chengdu Jinjiang Hospital for Maternal and Child Health Care from January 1, 2016 to December 31, 2018 were retrospectively analyzed. Minimal and mild endometriosis was pathologically confirmed after laparoscopic or open surgery. Patients were assigned to the natural cycle group and the GnRH-a down regulation cycle group according to specific endometrial preparation protocols. Subjects were included if (\\u003cem\\u003ei\\u003c/em\\u003e) they were diagnosed as ASRM I-II after laparoscopic or open surgery; (\\u003cem\\u003eii\\u003c/em\\u003e) aged 20\\u0026ndash;40 years; and (\\u003cem\\u003eiii\\u003c/em\\u003e) they received blastocyst transfer. Subjects were excluded if (\\u003cem\\u003ei\\u003c/em\\u003e) infertility was caused by other factors; (\\u003cem\\u003eii\\u003c/em\\u003e) chromosomal abnormalities were found in one or both spouses; (\\u003cem\\u003eiii\\u003c/em\\u003e) patients reported other endocrine diseases; (iv) they reported organic diseases of the uterus (e.g., adenomyosis, scar uterus and intrauterine adhesions); (\\u003cem\\u003ev\\u003c/em\\u003e) malformation of the reproductive system was detected; or (\\u003cem\\u003evi\\u003c/em\\u003e) the spouse reported severe oligoasthenospermia, asthenospermia and teratozoospermia. c were compared between the two groups. The eligibility flow chart was depicted in Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e.\\u003c/p\\u003e \\u003cp\\u003eThe study was approved by the institutional research ethics committee of Chengdu Jinjiang Hospital for Maternal and Child Health Care, and written informed consent was obtained from each subject.\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec4\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003e1.2 Methods\\u003c/h2\\u003e \\u003cp\\u003e \\u003cb\\u003e1.2.1 Endometrial preparation protocols\\u003c/b\\u003e \\u003c/p\\u003e \\u003cp\\u003eTransvaginal ultrasonography was performed and basal hormone levels were determined on day 2 or day 3 of the menstrual cycle for all patients. For women in the natural cycle group, the follicular size, endometrial thickness, the morphology of the endometrium and endometrial blood flow were monitored by transvaginal ultrasonography on day 8 to day 10 of the menstrual cycle. Serum levels of estradiol (E2), progesterone (P) and luteinizing hormone (LH) were detected once the dominant follicle size was up to 18\\u0026ndash;20\\u0026nbsp;mm, and patients were administered by intramuscular injection of 6,000 U human chorionic gonadotropin (HCG; LIVZON, China) on the same day. After ascertaining the time of ovulation, they received the oral administration of dydrogesterone 20\\u0026nbsp;mg bid (Abbott, Holland). Blastocyst thawed and transplanted were performed on day 5 of dydrogesterone administration.\\u003c/p\\u003e \\u003cp\\u003eFor women in the GnRH-a down regulation cycle group, they accepted the intramuscular administration of 3.75\\u0026nbsp;mg diphereline (Ipsen, France) on day 2 or day 3 of the menstrual cycle, and the endometrium was monitored by vaginal ultrasonography and basal hormone levels were re-examined on day 28th. For patients with E2\\u0026thinsp;\\u0026lt;\\u0026thinsp;40\\u0026nbsp;pg/ml, LH\\u0026thinsp;\\u0026lt;\\u0026thinsp;10mIU/mL, FSH\\u0026thinsp;\\u0026lt;\\u0026thinsp;10mIU/mL, endometrium\\u0026thinsp;\\u0026lt;\\u0026thinsp;5\\u0026nbsp;mm on day 28th during GnRH-a down regulation cycles, endometrial preparation was undertaken with the oral administration of Femoston (red) 1 pill tid (Abbott, Holland) for 12 days. The levels of E2 and P in serum were determined, and the thickness and blood flow of the endometrium was detected by transvaginal ultrasonography on the 13th day. On the same day, subjects also received the oral administration of Femoston (yellow) 2 pills bid (Abbott, Holland) and the vaginal administration of Crinone 90\\u0026nbsp;mg qd (MERCK SEROND, Germany) if their endometrial condition was suitable for FET. Blastocysts thawed and transplanted were performed on day 5 of the oral and vaginal administrations. Estrogens could be supplemented (controlled in 20 days) if the endometrium was not appropriate. The funding from the Sichuan Science and Technology Program played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.\\u003c/p\\u003e \\u003cdiv id=\\\"Sec5\\\" class=\\\"Section3\\\"\\u003e \\u003ch2\\u003e1.2.2 Blastocyst frozen-thawed embryo transfer\\u003c/h2\\u003e \\u003cp\\u003eThe quality of embryos was rated based on the Gardner system\\u003csup\\u003e[\\u003cspan citationid=\\\"CR17\\\" class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e]\\u003c/sup\\u003e. frozen-thawed embryo transfer of blastocyst were performed in accordance with standard process. Based on the patients\\u0026rsquo; conditions, 1\\u0026ndash;2 cultured blastocysts was/were transferred and guided by the vaginal ultrasound. Dydrogesterone and/or Crinone was administrated for luteal phase support.\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec6\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003e1.2.3 Luteal-phase support and pregnancy confirmation\\u003c/h2\\u003e \\u003cp\\u003eMedications for luteal-phase support were given continuously after blastocyst transplantation. On day 14th after transplantation, biochemical pregnancy was positive if the serum level of HCG was more than 25\\u0026nbsp;U/L, while clinical pregnancy was confirmed with the presence of the gestational sac using transvaginal ultrasound on day 28th and day 38th after transplantation. Medications for luteal-phase support were given until 10\\u0026ndash;12 weeks of gestation.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec7\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003e1.3 Measurements\\u003c/h2\\u003e \\u003cp\\u003eBaseline clinical and demographic characteristics of both groups were recorded, encompassing age, the duration of infertility, types of infertility, body mass index (BMI), antral follicle count (AFC), Anti-mullerian hormone (AMH), the number of transplanted blastocysts and the number of transplanted high-quality blastocysts. Clinical pregnancy outcomes consisted of the biochemical pregnancy rate (the percentage of subjects with a serum HCG level\\u0026thinsp;\\u0026gt;\\u0026thinsp;25\\u0026nbsp;U/L on day 14 after transplantation in all transplanted subjects), the clinical pregnancy rate (the proportion of subjects with the presence of the gestation sac in all transplanted subjects), the implantation rate (the proportion of the number of the gestation sac in all transplanted blastocysts), the multiple pregnancy rate(the proportion of the subjects of the multiple gestation sacs in all subjects of clinical pregnancy), the miscarriage rate (the percentage of women with miscarriage in all subjects of clinical pregnancy), the ectopic pregnancy rate (the proportion of women with ectopic pregnancy in all subjects of clinical pregnancy), the live birth rate (the percentage of women giving birth to live-born infants in all transplanted subjects), the normal delivery rate (the percentage of women with normal vaginal delivery in all pregnant subjects), the cesarean section rate (the percentage of women with cesarean section in all pregnant subjects), newborn birth weight and length.\\u003c/p\\u003e \\u003c/div\\u003e \\n\\u003ch2\\u003e1.4 Statistical Analysis\\u003c/h2\\u003e\\n \\u003cp\\u003eStatistical analyses were performed using the SPSS 22.0 software (IBM SPSS). Measurement data were expressed as \\u003cspan class=\\\"InlineEquation\\\"\\u003e\\u003cspan class=\\\"mathinline\\\"\\u003e\\\\(\\\\stackrel{-}{x}\\\\)\\u003c/span\\u003e\\u003c/span\\u003e\\u0026plusmn;s. Differences between the two groups were compared using the independent \\u003cem\\u003et\\u003c/em\\u003e test if the data were normally distributed; otherwise, the Mann-Whitney \\u003cem\\u003eU\\u003c/em\\u003e test was employed. Results of clinical pregnancy outcomes of the two groups were expressed as percentages, and compared using the Chi-square test or Fisher\\u0026rsquo;s exact test. Multivariate regression analysis was employed to assess influences of age, BMI, the duration of infertility, types of infertility, AMH, AFC, the number of transplanted blastocysts, the number of transplanted high-quality blastocysts, endometrial thickness on the day of transplantation and endometrial preparation protocols on the live birth rate of minimal and mild endometriosis patients. A \\u003cem\\u003eP\\u003c/em\\u003e value\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05 was considered as statistically significant.\\u003c/p\\u003e \"},{\"header\":\"Results\",\"content\":\" \\u003cp\\u003e \\u003cb\\u003e2.1 Baseline characteristics of minimal and mild endometriosis women in natural cycle group\\u003c/b\\u003e \\u003cspan type=\\\"BoldItalic\\\" class=\\\"BoldItalic\\\" name=\\\"Emphasis\\\"\\u003ev.s.\\u003c/span\\u003e \\u003cb\\u003eGnRH-a down regulation cycle groups\\u003c/b\\u003e\\u003c/p\\u003e \\u003cp\\u003eA total of 1170 eligible subjects in their FET cycles were recruited, consisting of 492 subjects in the natural cycle group and 678 in the GnRH-a down regulation cycle group. No significant differences in age, the duration of infertility, types of infertility, BMI, delivery history and endometrial thickness on the day of transplantation were found between the two groups (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;\\u0026gt;\\u0026thinsp;0.05). However, the AFC and AMH levels in the natural cycle group were significantly higher than those in the GnRH-a down regulation cycle group, while the numbers of transplanted blastocysts and transplanted high-quality blastocysts were lower in the natural cycle group (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05) (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e).\\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\\u003eBaseline characteristics of minimal and mild endometriosis women in natural cycle group \\u003cem\\u003ev.s.\\u003c/em\\u003e GnRH-a down regulation cycle group\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"5\\\"\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c2\\\" namest=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003eNatural cycle group\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eGnRH-a down regulation cycle group\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eP\\u003c/em\\u003e value\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eFET cycles\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c3\\\" namest=\\\"c2\\\"\\u003e \\u003cp\\u003e492\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e678\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eAge (years)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c3\\\" namest=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.951\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u0026lt;\\u0026thinsp;35\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c3\\\" namest=\\\"c2\\\"\\u003e \\u003cp\\u003e312 (63.41%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e428 (63.17%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u0026ge;\\u0026thinsp;35\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c3\\\" namest=\\\"c2\\\"\\u003e \\u003cp\\u003e180 (36.59%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e250 (36.87%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\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\\\" colspan=\\\"2\\\" nameend=\\\"c3\\\" namest=\\\"c2\\\"\\u003e \\u003cp\\u003e22.68\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;3.22\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e22.88\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;3.73\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.567\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eDuration of infertility\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c3\\\" namest=\\\"c2\\\"\\u003e \\u003cp\\u003e3.42\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;2.22\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e3.52\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;2.43\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.466\\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\\\" colspan=\\\"2\\\" nameend=\\\"c3\\\" namest=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.814\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003ePrimary infertility\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c3\\\" namest=\\\"c2\\\"\\u003e \\u003cp\\u003e155 (31.50%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e218 (32.15%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eSecondary infertility\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c3\\\" namest=\\\"c2\\\"\\u003e \\u003cp\\u003e337 (68.50%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e460 (67.85%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eAMH\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c3\\\" namest=\\\"c2\\\"\\u003e \\u003cp\\u003e3.71\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;3.01\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e3.11\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;3.73\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003e0.006\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eAFC\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c3\\\" namest=\\\"c2\\\"\\u003e \\u003cp\\u003e11.73\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;6.48\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e9.57\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;7.29\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003e\\u0026lt;\\u0026thinsp;0.001\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eDelivery history\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c3\\\" namest=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.455\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eNone\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c3\\\" namest=\\\"c2\\\"\\u003e \\u003cp\\u003e411 (83.54%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e555 (81.86%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eYes\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c3\\\" namest=\\\"c2\\\"\\u003e \\u003cp\\u003e81 (16.46%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e123 (18.14%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eNumber of transplanted blastocysts\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c3\\\" namest=\\\"c2\\\"\\u003e \\u003cp\\u003e1.72\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.45\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e1.78\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.42\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003e0.028\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eNumber of transplanted high-quality blastocysts\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c3\\\" namest=\\\"c2\\\"\\u003e \\u003cp\\u003e1.34\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.66\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e1.60\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.49\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003e\\u0026lt;\\u0026thinsp;0.001\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eEndometrial thickness on the day of transplantation\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c3\\\" namest=\\\"c2\\\"\\u003e \\u003cp\\u003e10.00\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.86\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e10.03\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.79\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.820\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\n\\u003ch2\\u003e2.2 Better Pregnancy Outcomes In Natural Cycle Of Fet\\u003c/h2\\u003e\\n \\u003cp\\u003eThe biochemical pregnancy rate, clinical pregnancy rate, implantation rate and live birth rate were significantly higher in the natural cycle group than those in the GnRH-a down regulation cycle group (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05). There were nonsignificant differences in the multiple pregnancy rate, miscarriage rate, ectopic pregnancy rate, premature birth rate, normal delivery rate and cesarean section rate between the two groups, neither was newborn birth weight nor newborn birth length between the two groups (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;\\u0026gt;\\u0026thinsp;0.05) (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e). There were no birth defects in both groups.\\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\\u003e Pregnancy outcomes of minimal and mild endometriosis women in natural cycle group \\u003cem\\u003ev.s.\\u003c/em\\u003e GnRH-a down regulation cycle groups\\u003c/p\\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 \\u003cp\\u003eNatural cycle group\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003eGnRH-a down regulation cycle group\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eP\\u003c/em\\u003e value\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eFET cycles\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e492\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e678\\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\\u003eBiochemical pregnancy rate\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e313 (63.62%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e365 (53.83%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003e\\u0026lt;\\u0026thinsp;0.001\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eClinical pregnancy rate\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e276 (56.10%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e322 (47.49%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003e0.004\\u003c/b\\u003e\\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\\u003e43.19%\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e34.88%\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003e\\u0026lt;\\u0026thinsp;0.001\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eMultiple pregnancy rate\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e62 (28.44%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e51 (20.99%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.063\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eMiscarriage rate\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e46 (16.67%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e58 (18.01%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.942\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eEctopic pregnancy rate\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e3 (1.09%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e8 (2.48%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.238\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eLive birth rate\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e218 (44.31%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e243 (35.84%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003e0.003\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003ePremature birth rate\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e55 (25.23%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e73 (30.04%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.249\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eNormal delivery rate\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e20 (9.48%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e14 (5.81%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.14\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eCesarean section rate\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e191 (90.52%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e227 (94.19%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.14\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eNewborn birth weight\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e2.82\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.63\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e2.85\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.63\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.515\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eNewborn birth length\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e48.13\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;2.79\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e48.35\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;2.65\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.382\\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 \\u003cb\\u003e2.3 Potential factors influencing the live birth rate in minimal and mild endometriosis women undergoing FET\\u003c/b\\u003e \\u003c/p\\u003e \\u003cp\\u003eAge, AMH, the number of transplanted high-quality blastocysts and endometrial preparation protocols were significantly associated with the live birth rate in minimal and mild endometriosis subjects undergoing FET (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05). However, BMI, the duration of infertility, types of infertility, AFC, the number of transplanted blastocysts and endometrial thickness on the day of transplantation were not associated with the live birth rate following FET (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;\\u0026gt;\\u0026thinsp;0.05) (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab3\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e).\\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\\u003ePotential factors affecting live birth rate outcomes in minimal and mild endometriosis women undergoing FET\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"4\\\"\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003ePotential factors\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eOR\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e95%CI\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eP\\u003c/em\\u003e 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 (years)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.92\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e(0.89, 0.94)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003e\\u0026lt;\\u0026thinsp;0.001\\u003c/b\\u003e\\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\\u003e0.99\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e(0.95, 1.03)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.634\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eDuration of infertility\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1.01\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e(0.95, 1.07)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.820\\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=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.089\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003ePrimary infertility\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\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 infertility\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1.30\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e(0.96, 1.76)\\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\\u003eAMH\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1.08\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e(1.01, 1.14)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003e0.014\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eAFC\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1.01\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e(0.98, 1.03)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.640\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eNumber of transplanted blastocysts\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1.24\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e(0.84, 1.83)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.280\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eNumber of transplanted high-quality blastocysts\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e2.59\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e(1.98, 3.38)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003e\\u0026lt;\\u0026thinsp;0.001\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eEndometrial thickness on the day of transplantation\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1.00\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e(0.93, 1.08)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.905\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eFET cycles\\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=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003e0.025\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eNatural cycle endometrial preparation\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\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\\u003eGnRH-a down regulation cycle endometrial preparation\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.71\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e(0.53, 0.96)\\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 \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \"},{\"header\":\"Discussion\",\"content\":\" \\u003cp\\u003eEndometriosis is an estrogen dependent inflammatory disease classically characterized by infertility and secondary progressively dysmenorrhea, which is becoming more prevalent in childbearing-age women. Endometriosis is closely related to infertility, about 10\\u0026ndash;25% of women with endometriosis have undergone IVF/ICSI\\u003csup\\u003e[\\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e]\\u003c/sup\\u003e, however whether minimal and mild endometriosis are associated with infertility and the outcomes of IVF/ICSI are still unclear. So more assisted reproductive technology for effectively improving the pregnancy rate for minimal and mild endometrios women are still needed. Though previous studies about the two major endometrial preparation protocols analyzed the correlations between fresh embryo transfer or FET and pregnancy outcomes in the population, their results are inconsistent. Therefore, in this study we aimed to compare the effects of natural cycle endometrial preparation versus long-term GnRH-a down regulation cycle endometrial preparation of FET on the live birth rate in minimal and mild endometriosis women.\\u003c/p\\u003e \\u003cp\\u003eIn this study, all subjects were pathologically confirmed as I-II endometriosis of ASRM after laparoscopic or open surgery, and they were assigned to the natural cycle and GnRH-a down regulation cycle groups according to specific endometrial preparation protocols. Their baseline characteristics were comparable. The biochemical pregnancy rate, clinical pregnancy rate, implantation rate and live birth rate were significantly higher in the natural cycle group than those in the GnRH-a down regulation cycle group. Besides, there were nonsignificant differences in the multiple pregnancy rate, miscarriage rate, ectopic pregnancy rate, premature birth rate, normal delivery rate and cesarean section rate between the two groups. By contrast, van de Houwen LE et al.\\u003csup\\u003e[\\u003cspan citationid=\\\"CR19\\\" class=\\\"CitationRef\\\"\\u003e19\\u003c/span\\u003e]\\u003c/sup\\u003e concluded that GnRH-a down regulation cycle of FET improved ongoing pregnancy rates compared with natural cycle of FET in severe endometriosis patients. However,another study has assessed the influence of endometrial peristalsis on embyros/blastocysts implantation and has reported that natural cycle of FET is instrumental to a high pregnancy rate\\u003csup\\u003e[\\u003cspan citationid=\\\"CR20\\\" class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e]\\u003c/sup\\u003e. Nevertheless, they did not take into consideration different endometrial preparations. Levron et al. demonstrated that the implantation rate and clinical pregnancy rate were improved after natural cycle of FET, which is consistent with our findings. In addition, in long-term GnRH-a down regulation cycle, minimal and mild endometriosis patients in the present study were supplemented with exogenous estrogens before the placental function was established. Due to no using of exogenous estrogens, natural cycle of FET do not alter endometrial receptivity, and there were a more natural effect of luteal support for blatocyst development; moreover, it is cost-saving during a short period of treatment.\\u003c/p\\u003e \\u003cp\\u003eEmbryo quality and endometrial receptivity are the major factors that influence outcomes following FET. In our study, both blastocyst culture and cryopreservation during the controlled ovarian hyperstimulation cycle contribute to a high pregnancy rate and live birth rate after FET. To obtain higher developmental potential\\u003csup\\u003e[\\u003cspan citationid=\\\"CR21\\\" class=\\\"CitationRef\\\"\\u003e21\\u003c/span\\u003e]\\u003c/sup\\u003e, we eliminated blastocysts with poor quality or chromosomal abnormalities, and we kept high-quality blastocysts during blastocyst culture, and then performed the vitrification for good quality blastocysts. And we discover that more high-quality transplanted blastocysts is what matters to a higher live birth rate after FET, rather than the number of transplanted blastocysts, which is also supported by the study by Bourdon M et al.\\u003csup\\u003e[\\u003cspan citationid=\\\"CR22\\\" class=\\\"CitationRef\\\"\\u003e22\\u003c/span\\u003e]\\u003c/sup\\u003e\\u003c/p\\u003e \\u003cp\\u003eIn the present study we confirmed that age and AMH levels were associated with the live birth rate following FET. Evidences show that age is an independent risk for the live birth rate. With the increasing age, diminished quality of oocytes alongside mitochondrial dysfunction and oxidative stress increases the risk of embryo chromosome abnormalities, often manifesting as the presence of aneuploid embryo and a low blastulation rate\\u003csup\\u003e[\\u003cspan citationid=\\\"CR23\\\" class=\\\"CitationRef\\\"\\u003e23\\u003c/span\\u003e]\\u003c/sup\\u003e. Decreases in AMH levels and the AFC indicate a reduced ovarian reserve, which further influences the numbers of eggs, embryos and high-quality embryos.\\u003c/p\\u003e \\u003cp\\u003eIt is reported that minimal and mild endometriosis may have a certain impact on low newborn birth weight\\u003csup\\u003e[\\u003cspan citationid=\\\"CR24\\\" class=\\\"CitationRef\\\"\\u003e24\\u003c/span\\u003e]\\u003c/sup\\u003e. Although no significant differences in newborn birth weight and length were identified between the natural cycle and GnRH-a down regulation cycle groups, a higher premature rate and lower newborn birth weight in both groups were consistent with previous studies\\u003csup\\u003e[\\u003cspan citationid=\\\"CR19\\\" class=\\\"CitationRef\\\"\\u003e19\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR25\\\" class=\\\"CitationRef\\\"\\u003e25\\u003c/span\\u003e]\\u003c/sup\\u003e. As a result, further research is required to clarify the correlation between minimal and mild endometriosis and low newborn birth weight. It is reported that IVF treatment in severe minimal and mild endometriosis patients may enhance susceptibilities to congenital cardiovascular and skeletal muscle diseases in neonates\\u003csup\\u003e[\\u003cspan citationid=\\\"CR26\\\" class=\\\"CitationRef\\\"\\u003e26\\u003c/span\\u003e]\\u003c/sup\\u003e. After we screened fetal malformation, although there were early and late abortions in both groups during pregnancy, no birth defects were detected, which can be explained by the inclusion of minimal and mild endometriosis patients, high-quality blastocysts transplantation, comprehensive prenatal examinations of the abnormal fetus, or a small sample size.\\u003c/p\\u003e \\u003cp\\u003eThis is a retrospective non-randomized controlled trial, so a potential selection bias may influence the research quality. A prospective randomized controlled trial at multi-centers is required to validate our findings. Summarily, this study demonstrates that natural cycle endometrial preparation is superior to GnRH-a down regulation cycle endometrial preparation in terms of the implantation rate, clinical pregnancy rate and live birth rate, which also improves the cost-effectiveness of FET for women with minimal and mild endometriosis. A large sample size is still required to re-verify the influence of endometrial preparations on pregnancy outcomes of Chinese minimal and mild endometriosis women undergoing FET.\\u003c/p\\u003e \"},{\"header\":\"Abbreviations\",\"content\":\"\\u003cp\\u003eFET: frozen-thawed embryo transfer; IVF-ET/ICSI: \\u003cem\\u003ein vitro\\u003c/em\\u003e fertilization and embryo transfer/intracytoplasmic sperm injection; COH: controlled ovarian hyperstimulation; GnRH-a: gonadotropin-releasing hormone agonist; AMH: anti-M\\u0026uuml;llerian hormone; AFC: antral follicle count.\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eEthics approval and consent to participate: \\u003c/strong\\u003eAll procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the institutional research ethics committee of Chengdu Jinjiang Hospital for Maternal and Child Health Care. Informed consent was obtained from all individual participants included in the study.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConsent for publication\\u003c/strong\\u003e\\u003cstrong\\u003e：\\u003c/strong\\u003eNot applicable.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAvailability of Data and Materials: \\u003c/strong\\u003eThe data that support the findings of this study are available from the Reproductive Medicine Centre from Chengdu Jinjiang Hospital for Maternal and Child Health Care but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of the Reproductive Medicine Centre from Chengdu Jinjiang Hospital for Maternal and Child Health Care.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCompeting interests: \\u003c/strong\\u003eThe authors have no competing interests to declare.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eFunding:\\u003c/strong\\u003e This study was funded by the\\u0026nbsp;Sichuan\\u0026nbsp;Science and Technology Program\\u0026nbsp;(grant number 2018JY0295).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAuthors\\u0026rsquo; contributions: \\u003c/strong\\u003eYL and JZ were responsible for the study inception and design. YL and LW performed the data extraction. YL, ST and YZ interpreted the data, and YL wrote the manuscript. All authors have read, critiqued and approved the final manuscript.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAcknowledgements: \\u003c/strong\\u003eNot applicable.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\u003cli\\u003e\\u003cspan\\u003eGiudice LC, Kao LC. minimal and mild endometriosis[J]. Lancet. 2004;364(9447):1789\\u0026ndash;99.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eMacer ML, Taylor HS. minimal and mild endometriosis and infertility: a review of the pathogenesis and treatment of minimal and mild endometriosis-associated infertility. Obstet Gynecol Clin North Am. 2012;39(4):535\\u0026ndash;49.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003ePrescott J, Farland LV, Tobias DK, Gaskins AJ, Spiegelman D, Chavarro JE, Rich-Edwards JW, Barbieri RL, Missmer SA. A prospective cohort study of minimal and mild endometriosis and subsequent risk of infertility[J]. Hum Reprod. 2016;31(7):1475\\u0026ndash;82.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eRevised American Society for Reproductive. Medicine classification of minimal and mild endometriosis: 1996[J]. Fertil Steril. 1997;67(5):817\\u0026ndash;21.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003ede Ziegler D, Borghese B, Chapron C. minimal and mild endometriosis and infertility: pathophysiology and management. Lancet. 2010;376(9742):730\\u0026ndash;8.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eBurney RO, Giudice LC. Pathogenesis and pathophysiology of minimal and mild endometriosis[J]. Fertil Steril. 2012;98(3):511\\u0026ndash;9.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eZhang T, De Carolis C, Man G, Wang CC. The link between immunity, autoimmunity and minimal and mild endometriosis: a literature update[J]. Autoimmun Rev. 2018;17(10):945\\u0026ndash;55.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eDaniilidis A, Pados G. Comments on the ESHRE recommendations for the treatment of minimal minimal and mild endometriosis in infertile women[J]. Reprod Biomed Online. 2018;36(1):84\\u0026ndash;7.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eXu B, Guo N, Zhang XM, Shi W, Tong XH, Iqbal F, Liu YS. Oocyte quality is decreased in women with minimal or mild minimal and mild endometriosis[J]. Sci Rep. 2015;5:10779.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eOp\\u0026oslash;ien HK, Fedorcsak P, Omland AK, et al. In vitro fertilization is a successful treatment in minimal and mild endometriosis-associated infertility. Fertil Steril. 2012;97(4):912\\u0026ndash;8.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eHamdan M, Dunselman G, Li TC, Cheong Y. The impact of endometrioma on IVF/ICSI outcomes: a systematic review and meta-analysis[J]. Hum Reprod Update. 2015;21(6):809\\u0026ndash;25.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eBourdon M, Santulli P, Maignien C, Gayet V, Pocate-Cheriet K, Marcellin L, Chapron C. The deferred embryo transfer strategy improves cumulative pregnancy rates in minimal and mild endometriosis-related infertility: A retrospective matched cohort study[J]. PLoS One. 2018;13(4):e0194800.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eKuang Y, Hong Q, Chen Q, et al. Luteal-phase ovarian stimulation is feasible for producing competent oocytes in women undergoing in vitro fertilization/intracytoplasmic sperm injection treatment, with optimal pregnancy outcomes in frozen-thawed embryo transfer cycles. Fertil Steril. 2014;101(1):105\\u0026ndash;11.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003ePrieto L, Quesada JF, Cambero O, et al. Analysis of follicular fluid and serum markers of oxidative stress in women with infertility related to minimal and mild endometriosis. Fertil Steril. 2012;98(1):126\\u0026ndash;30.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eTamura H, Takasaki A, Nakamura Y, Numa F, Sugino N. A pilot study to search possible mechanisms of ultralong gonadotropin-releasing hormone agonist therapy in IVF-ET patients with minimal and mild endometriosis. J Ovarian Res. 2014;7:100.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eLevron J, Yerushalmi GM, Brengauz M, Gat I, Katorza E. Comparison between two protocols for thawed embryo transfer: natural cycle versus exogenous hormone replacement. Gynecol Endocrinol. 2014;30(7):494\\u0026ndash;7.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eGardner DK, Lane M, Stevens J, Schlenker T, Schoolcraft WB. Reprint of: Blastocyst score affects implantation and pregnancy outcome: towards a single blastocyst transfer. Fertil Steril. 2019;112(4 Suppl1):e81\\u0026ndash;4.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003ePractice Committee of the American Society for Reproductive Medicine. minimal and mild endometriosis and infertility: a committee opinion. Fertil Steril. 2012;98(3):591\\u0026ndash;8.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003evan der Houwen LE, Mijatovic V, Leemhuis E, et al. Efficacy and safety of IVF/ICSI in patients with severe minimal and mild endometriosis after long-term pituitary down-regulation. Reprod Biomed Online. 2014;28(1):39\\u0026ndash;46.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eBergendal A, Naffah S, Nagy C, Bergqvist A, Sj\\u0026ouml;blom P, Hillensj\\u0026ouml; T. Outcome of IVF in patients with minimal and mild endometriosis in comparison with tubal-factor infertility. J Assist Reprod Genet. 1998;15(9):530\\u0026ndash;4.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003ePractice Committee of the American Society for Reproductive Medicine, Practice Committee of the Society for Assisted Reproductive Technology. Electronic address: asrm@asrm.org. Blastocyst culture and transfer in clinically assisted reproduction: a committee opinion. Fertil Steril. 2018;110(7):1246\\u0026ndash;52.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eBourdon M, Pocate-Cheriet K, Finet de Bantel A, et al. Day 5 versus Day 6 blastocyst transfers: a systematic review and meta-analysis of clinical outcomes. Hum Reprod. 2019;34(10):1948\\u0026ndash;64.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eUbaldi FM, Cimadomo D, Vaiarelli A, et al. Advanced Maternal Age in IVF: Still a Challenge? The Present and the Future of Its Treatment. Front Endocrinol (Lausanne). 2019;10:94.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eBorghese B, Sibiude J, Santulli P, et al. Low birth weight is strongly associated with the risk of deep infiltrating minimal and mild endometriosis: results of a 743 case-control study. PLoS One. 2015;10(2):e0117387.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eKuivasaari P, Hippel\\u0026auml;inen M, Anttila M, Heinonen S. Effect of minimal and mild endometriosis on IVF/ICSI outcome: stage III/IV minimal and mild endometriosis worsens cumulative pregnancy and live-born rates. Hum Reprod. 2005;20(11):3130\\u0026ndash;5.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eLiang Z, Yin M, Ma M, Wang Y, Kuang Y. Effect of Maternal Advanced minimal and mild endometriosis on Risk of Congenital Malformations for Infants Born After in vitro Fertilization and Frozen-Thawed Embryo Transfer: Analysis of 28,600 Newborns[J]. Front Endocrinol (Lausanne), 2019,10:763.\\u003c/span\\u003e\\u003c/li\\u003e\\u003c/ol\\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\":\"info@researchsquare.com\",\"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\":\"minimal and mild endometriosis, frozen-thawed embryo transfer, natural cycle, GnRH-a down regulation cycle, clinical pregnancy rate, live birth rate\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-122904/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-122904/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003e\\u003cstrong\\u003eBackground \\u003c/strong\\u003eMinimal and mild endometriosis patients with infertility are treated by in vitro fertilization and embryo transfer/intracytoplasmic sperm injection (IVF-ET/ICSI) in recent years. However, inconsistencies in findings within and across individual studies raise concerns as to determine which method is the best treatment, especially in the frozen-thawed embryo transfer cycle (FET). We hope to compare the efficacy of natural cycle versus GnRH-a down regulation cycle endometrial preparations in minimal and mild endometriosis patients undergoing FET. \\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eMethods\\u003c/strong\\u003e We retrospectively analyzed a cohort of 1170 minimal and mild endometriosis patients receiving FET at the Reproductive Medicine Centre from Chengdu Jinjiang Hospital for Maternal and Child Health Care from January 1, 2016 to December 31, 2018. They were assigned to the natural cycle group and the GnRH-a down regulation cycle group based on endometrial preparation protocols. Baseline characteristics, frozen-thawed embryo transfer cycle and pregnancy outcomes were compared between the two groups. \\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eResults\\u003c/strong\\u003e There were nonsignificant differences in baseline characteristics including age, BMI, types of infertility, the duration of infertility and the delivery history between the natural cycle group and the GnRH-a down regulation cycle group (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026gt;0.05). The biochemical pregnancy rate (63.62% \\u003cem\\u003ev.s.\\u003c/em\\u003e 53.83%), clinical pregnancy rate (56.10% \\u003cem\\u003ev.s.\\u003c/em\\u003e 47.49%), implantation rate (43.19% \\u003cem\\u003ev.s.\\u003c/em\\u003e 34.88%) and live birth rate (44.31% \\u003cem\\u003ev.s.\\u003c/em\\u003e 35.84%) in the natural cycle group were significantly higher than those in the GnRH-a down regulation cycle group (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026lt;0.05). However, there were nonsignificant differences in the multiple birth rate, abortion rate, ectopic pregnancy rate, premature birth rate, neonatal weight and length between the two groups (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026gt;0.05). The multivariate regression analysis showed that age, anti-Müllerian hormone (AMH), the number of transplanted high-quality blastocysts and endometrial preparation protocols were associated with the live birth rate in minimal and mild endometriosis women undergoing FET (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026lt;0.05). \\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eConclusion \\u003c/strong\\u003eCompared with GnRH-a down regulation cycle, natural cycle endometrial preparation of FET is a prominent endometrial preparation method for improving the implantation rate, clinical pregnancy rate, and live birth rate in minimal and mild endometriosis patients, which is more cost-effective in clinical practice. \\u003c/p\\u003e\",\"manuscriptTitle\":\"Efficacy of Natural Cycle versus GnRH-a Down Regulation Cycle of Endometrial Preparation in Minimal and Mild endometriosis Patients Undergoing Frozen-Thawed Embryo Transfer\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2020-12-09 17:35:39\",\"doi\":\"10.21203/rs.3.rs-122904/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"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\":\"0a053fb2-d350-4f25-8465-97d6f190ccfc\",\"owner\":[],\"postedDate\":\"December 9th, 2020\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[{\"id\":1393573,\"name\":\"Maternal \\u0026 Fetal Medicine\"}],\"tags\":[],\"updatedAt\":\"2021-01-18T14:56:38+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2020-12-09 17:35:39\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-122904\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-122904\",\"identity\":\"rs-122904\",\"version\":[\"v1\"]},\"buildId\":\"ehx78VzkSd0WSzXnipQa-\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC0","license_restricted":false}