Impact of adenomyosis and endometriosis on IVF/ICSI pregnancy outcome in patients undergoing gonadotropin-releasing hormone agonist treatment and frozen embryo transfer

Impact of adenomyosis and endometriosis on IVF/ICSI pregnancy outcome in patients undergoing gonadotropin-releasing hormone agonist treatment and frozen 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 Impact of adenomyosis and endometriosis on IVF/ICSI pregnancy outcome in patients undergoing gonadotropin-releasing hormone agonist treatment and frozen embryo transfer Yu Wang, Yu-Chiao Yi, Hwa-Fen Guu, Ya-Fang Chen, Jui-Chun Chang, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1919429/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 Purpose Although numerous studies have attempted to establish the relationship between adenomyosis and infertility, no consensus has emerged. Our aim was to investigate whether adenomyosis and endometriosis affected IVF outcomes in our patients. Methods This was a retrospective study of 1720 patients from January 2016 to December 2019. In total, 1389 cycles were included: 229 cycles in the endometriosis group (group E), 89 cycles in the adenomyosis group (group A), 69 cycles in the endometriosis and adenomyosis group (group EA), and 1002 cycles in the control group (group C). Most patients in groups A and EA received GnRH agonist treatment before FET. Results The 1st FET live birth rates (LBR) were 39.3%, 34.7%, 39% and 17,6% in groups E, A, EA, and C. The miscarriage rates were 19.9%, 34.7%, 39%, and 17.6%. The per retrieval cycle cumulative pregnancy rates (cLBRs) in patients < 38 y/o were 53.8%, 58.1%, 44.8%, and 61.2%. The per retrieval cycle cLBRs in patients ≥ 38 y/o were 25%, 7.3%, 17.2%, and 29%. Among groups A and EA, LBRs were 25.58% and 18.89% in patients with a ≥ 7-fold decrease and a < 7-fold decrease in CA-125 level, respectively, after GnRH agonist treatment. Conclusion Endometriosis was not associated with a poorer pregnancy outcome. Patients with adenomyosis with/without endometriosis had higher miscarriage rates, lower LBRs, and lower cLBRs, especially in patients aged ≥ 38 years, even after GnRH agonist treatment before FET cycles. Patients who have a greater than 7-fold decrease in CA-125 level after GnRH agonist treatment might have better clinical pregnancy outcomes. Adenomyosis endometriosis cumulative live birth rate gonadotropin-releasing hormone agonist treatment In Vitro Fertilization What Does This Study Add To The Clinical Work? 1. Adenomyosis can impact live birth rate even after GnRH agonist treatment before frozen embryo transfer. 2. Patients with adenomyosis have a lower cumulative pregnancy rate compared with control and endometriosis patients. 3. Adenomyosis seems to have a greater impact in patients over 38 years old. 4. No impact of pregnancy rate was seen in patients with endometriosis compared with the control group. 5. Patients who have a greater than 7-fold decrease in CA-125 level after GnRH agonist treatment might have better clinical pregnancy outcomes. Introduction Adenomyosis is usually defined as the occurrence of ectopic rests of endometrium-like tissue and fibrosis resulting in an enlarged uterus. The endometrium resides deeply within the myometrium with both glands and stroma. The prevalence of adenomyosis from hysterectomy in general population is around 20% and about the same prevalence is found by transvaginal sonography (TVS) [ 1 , 2 ]. TVS and magnetic resonance imaging (MRI) obtain equivalent results in the diagnosis of adenomyosis [ 3 , 4 ]. Treatment of adenomyosis includes cyclic NSAID, combined oral contraceptive pills, progestin-only regimens, selective progesterone receptor modulators (SPRMs), levonorgestrel-releasing intrauterine system (LNG-IUS) and GnRH (gonadotropin-releasing hormone) agonists [ 5 – 7 ]. It has been shown that GnRH agonists may help women achieve a better in vitro fertilization (IVF) outcome [ 8 ]. In infertile women, around 24% of women are diagnosed with adenomyosis [ 9 , 10 ]. There are several hypothetical mechanisms in adenomyosis-associated infertility, including dysregulations of the myometrial architecture and function, chronic inflammation, presence of local oxygen, and altered endometrial function, which can cause implantation failure [ 11 , 12 ]. Although numerous studies have attempted to explain the relationship between adenomyosis and infertility, there are still no definitive conclusions [ 10 , 13 ]. Recent studies have shown adenomyosis was related to a lower clinical pregnancy rate (CPR), ongoing pregnancy rate (OGR), live birth rate (LBR) [ 10 , 14 ]. However, some studies showed that adenomyosis did not affect pregnancy outcome [ 8 , 15 , 16 ]. Endometriosis is found in around 40% of infertile women. Although it might affect natural conception rates, it is now believed that ART could bypass the toxic pelvic environment and achieve favorable clinical pregnancy rates [ 17 , 18 ]. As mentioned above, the effect of adenomyosis and/ or endometriosis on pregnancy outcome remains controversial. In this retrospective study, we analyzed patients with endometriosis, adenomyosis, or both, who underwent IVF or intracytoplasmic sperm injection (ICSI). We attempted to determine whether adenomyosis and endometriosis affected IVF outcomes in our patients. Materials And Methods Subjects This was a retrospective study of patients who underwent IVF in Taichung Veterans General Hospital, Taiwan between January 1, 2016, and December 31, 2019. It is standard practice for all of our patients undergoing IVF to receive TVS during their first visit to our hospital. Patients with a diagnosis of endometriosis and/or adenomyosis were included as the potential study group, and patients without endometriosis and/or adenomyosis or other uterine/systemic disorders were categorized as the potential control group. The inclusion criteria for the study were as follows: (1) patients underwent a cycle of IVF or ICSI, (2) endometriosis was confirmed by surgery or sonography examination, (3) adenomyosis was diagnosed by two-dimensional or three-dimensional TVS in the past 12 months. Adenomyosis were diagnosed after visualizing at least three sonographic criteria on TVS, including globular uterus caused by overall increase in myometrial thickness; asymmetrically thickened anterior or posterior myometrial wall; poorly defined endo-myometrial interface; presence of heterogeneous myometrial area; and myometrial cysts. No restriction was made for the number of previous failed cycles. The exclusion criteria were as follows: (1) patients with other uterine anomalies, (2) patients with immune diseases or metabolic diseases, (3) patients receiving donated oocytes, (4) patients with embryos transferred from mixed cycles, (5) patients with uterine leiomyoma, (6) patients receiving preimplantation genetic testing for aneuploidy, (7) patients who underwent adenomyomectomy. We analyzed those patients in the study and control group who had finished their treatment cycles, either as a result of achieving a live birth or ultimately failing after transferring all of their embryos. The cumulative live birth rates (cLBRs) per started cycle were followed until May 31, 2021. In order to simplify the data analysis, transfer cycles with embryos from different cycles were excluded from the study. Adenomyosis status All patients received a CA-125 blood test, except for those who had already received a test previously at our hospital. For those whose CA-125 value exceeded the normal range (35 U/ml), a pre-embryo transfer (ET) GnRH agonist treatment was prescribed. GnRH agonist was prescribed at intervals of 28 to 35 days until the CA-125 was in normal range. Controlled Ovarian Hyperstimulation Protocol Patients in the GnRH agonist group received leuprolide acetate (Leuprolide, 0.5mg/d; Takeda Co., Taiwan) consisting of a daily low dose of GnRH agonist, subcutaneously administered for at least 10 days before the onset of ovarian stimulation. Meanwhile, participants in the antagonist group received the GnRH antagonist cetrorelix acetate (Cetrotide, 0.25 mg/d SC; Merck Serono, German) starting flexibly on stimulation days 5 ~ 7 by ultrasound monitoring 5 days after the onset of COH with gonadotropins. The types and dosages of gonadotropin administration were individualized for each participant according to her age, body mass index, anti-mullerian hormone level (AMH), FSH/LH level, antral follicle counts on cycle day 2~3 and response to previous ovarian stimulation. Doses were adjusted according to the ovarian response as monitored by vaginal ultrasound folliculometry and serum E2 level testing. When two or more follicles reached a mean diameter of 18 mm, 10,000 IU of hCG (Pregnyl, Merck Sharp & Dohme, America; Organon) or 250- 500 ug of recombinant hCG (Ovidrel; Merck Serono, German) was injected for the oocyte retrieval 35~36 hours later. Progesterone 25mg/amp (Astar Co., Taiwan), 1-2 amp/day, was injected intramuscularly starting from the night of oocyte retrieval and was then continued or shifted to topical progesterone (8% Crinone; Merck-Serono, German) 1 tube/day on the day of embryo transfer, which was maintained until the pregnant patients had reached 8 complete weeks of gestation for luteal support (LS). For the frozen-thaw cycle, patients received an artificial hormone replacement regimen (estradiol valerate 2 mg, Synmosa Co., Taiwan) with a step-up from 4-8mg per day for 5 days, to 6-12mg per day for 5 days, followed by twice daily vaginal progesterone (8% Crinone; Merck Serono, German) 90mg plus estradiol valerate 12mg once endometrial thickness exceeded 8 mm on ultrasound assessment. Then the dosage was maintained till the patient reached 10 complete weeks of gestation for luteal support (LS). In addition, 0.1 mg Decapeptyl (Ferring Co., Germany) was also administered on the 6th day after ICSI as a measure of adjuvant LS. The embryo transfers (ET) were carried out on day 2, day 3, or day 5 of culture. Outcome measures Serum βhCG was checked on embryonic age day 14, and measurements over 5 mIU/mL were defined as a biochemical pregnancy if no gestational sac could be identified later. Clinical pregnancy was defined as the presence of a gestational sac under TVS at the gestational age of 4-5 weeks. Live birth rate was defined as the number of deliveries that resulted in a live born neonate. Cumulative live birth rates (cLBR) per retrieval cycle were defined as the percentage of at least one live born neonate from that retrieval cycle. The above results were followed until May 31,2021. Statistical analyses Statistics were conducted by SPSS-PC ver. 22.0. Patient’s characteristics, AMH, oocyte retrieval number, and pregnancy outcomes were analyzed using the two-tailed t test and Chi-squared test among groups, with a p value of less than 0.05 considered statistically significant. Ethical approval The study protocol was approved by the Ethics Committee of Taichung Veterans General Hospital on December 1, 2021 with approval code CE2147, and adhered to relevant ethical guidelines. Results Patient’s characteristics In total, 1720 cycles were reviewed and analyzed in the study period. There were 1179 women and 1389 cycles enrolled in the study using inclusion and exclusion criteria. The cycles were grouped as follows: 229 cycles in the endometriosis group (group E), 89 cycles in the adenomyosis group (group A), 69 cycles in the endometriosis and adenomyosis group (group EA), and 1002 cycles in the control group (group C). Baseline demographics, cycle characteristics, and laboratory culture results of the four groups are summarized in Table 1. The average value of CA-125 before GnRH agonist treatment was 104.8 U/ml in group A and 167.9 U/ml in group EA. The average CA-125 value after treatment was 22.0 U/ml in group A and 26.5 U/ml in group EA before starting hormonal replacement therapy in preparation for embryo transfer. A total of 72 cycles (80.9%) in group A and 54 cycles (85.6%) in group EA received GnRH agonist treatment before embryo transfer. The LBRs of 1 st frozen-thawed embryo transfer cycle (FET) were significantly lower in group A and group AE as compared to those in group E and group C (Table 2). Subgroup analysis also revealed significant differences between groups E and C, and groups EA and C in patients younger than age 38 years. Significantly lower LBRs were also noted in group A compared with group C, and in group EA compared with group C in patients older than age 38 years. The cumulative pregnancy outcomes per retrieval are presented in Table 3. There were significantly lower cLBRs in groups A and EA compared with group C. In the sub-group analyses according to age, the lower average cLBR in groups A and EA was mostly due to older patients (age ≥38 years). The abortion rates were higher in group A and AE without significant differences. Table 4 shows the subgroup analysis of the clinical outcomes in the 1 st FET cycles by the initial serum CA-125 and fold decrease in CA-125 level after treatment in group A and group EA. There were no significant differences in CPR and LBR among the different CA-125 levels, including cut-off values set at 100, 150, or 200 U/ml. The analysis of fold decrease in CA-125 level after treatment revealed that patients who had a greater than 7-fold decrease had a significantly higher CPR. On May 31, 2021, there were still 4 patients in group E, 1 patient in group A, and 12 patients in group C with an ongoing pregnancy who are not included in this study. The follow up before publication showed 1 termination due to fetal anomalies in group A and 1 fetal death in group C. Discussion To the best of our knowledge, no studies have been conducted to determine the cumulative live birth rate of patients with endometriosis and adenomyosis with and without endometriosis under GnRH agonist pre-treatment before FET. Our study compared the effects of these diseases on their respective pregnancy outcomes. We evaluated the live birth rates after first transfer of frozen thawed embryos and the final cumulative live birth rates based on per retrieval cycle basis, with a further sub-analysis of the patients by age. These data showed clearly that in patients with adenomyosis undergoing GnRH agonist pretreatment before FET, cumulative LBRs were not inferior in patients aged <38 years but were significantly lower in those aged ≥38 years, compared with the control and endometriosis groups. Moreover, the endometriosis group achieved a cumulative LBR comparable with that of the control group. There was no clear evidence indicating whether or not adenomyosis impacted the clinical pregnancy rates, and its effect on cumulative pregnancy rates was even less clear. It remains debatable as to what strategy should be adopted for embryo transfer in adenomyosis patients. In Table 5, we have summarized the available studies in the literature which have investigated the impact of adenomyosis and/or endometriosis on pregnancy outcome by IVF/ICSI. Three studies found that adenomyosis had no impact on pregnancy rates [8, 15, 16]. Other studies reported adverse influences of adenomyosis on pregnancy rates [9, 10, 14, 19-21]. In studies with ultralong GnRH agonist protocol before fresh ET, the results found conflicting conclusions [8, 9, 22]. In a study reporting that adenomyosis has a negative effect on pregnancy outcomes, overdiagnosis of adenomyosis was noted as a concern [15]. However, this hypothesis was refuted in a study conducted the following year [21]. An investigation of patients receiving GnRH-agonist treatment reported that adenomyosis had no effect on LBR [8]. In the aforementioned study longer GnRH-agonist treatment (average 5 months) was prescribed compared with our study (2.2 months in group A and 2.5 months in group EA). The pregnancy outcomes of the adenomyosis group in two prior studies were similar to our results (LBR 35%, 29.7%, our study 32.1%) [8, 15]. However, the pregnancy outcomes of the control group were both lower than those in our study, which might be the key reason that led to the different conclusions (LBR 30%, 29.3%, our study 48.1%). Although a recent study reported CRP and LBR in adenomyosis group that were not inferior, the results also showed that FET was related to better pregnancy outcomes compared with fresh ET [20]. In three prior studies, there were no pretreatment CA-125 data available for further comparisons between baseline and changes in the disease severity [8, 15, 20]. For studies showing a negative impact of adenomyosis on pregnancy rates, a 2012 study revealed a similar pregnancy outcome to that found in our study [21]. A retrospective study with a relatively large number of patients revealed a decrease of CPR and LBR in the adenomyosis group under ultra-long GnRH agonist treatment [10]. Although the aforementioned study and our study have similar conclusions, our patients were treated with a different treatment strategy and displayed better pregnancy outcomes (LBR 32% v.s 11.36%) in a relatively older patient population. Our results support the hypothesis that adenomyosis does adversely impact pregnancy outcomes. Our data showed that in patients aged <38 years, cLBRs per retrieval cycle increased around 5-10% per cycle compared with the results of their first ET. Nevertheless, in patients aged ≥38 years, the cLBRs per retrieval cycle in both group A and EA were less than 20%. The lower cLBRs in adenomyosis patients could mostly be explained by patients being aged ≥38 years. Adenomyosis probably irreversibly injures the myometrial architecture and function after years of disease progression [12]. If the damage is severe enough, it might still affect implantation potential even after applying GnRH agonist pre-treatment to achieve a seemingly normal CA-125 value, eventually leading to a lower chance of achieving a live birth chance. Previous studies showed that the impacts of endometriosis on fertility can mostly be overcome by IVF [17, 18, 23]. ART could achieve pregnancy outcomes that are relatively close to those attained in patients with male factor [18]. Our study found the same results, namely, that endometriosis had no negative effects on LBRs in fresh ET, FET, and cLBR per retrieval cycle compared with the control group. Our study findings also suggest that the outcomes of adenomyosis patients were also diagnosed with endometriosis were similar to those of adenomyosis patients. Whether the poor pregnancy outcomes in patients with adenomyosis are due to decreased implantation rates or increased miscarriage rates has not been clearly established [24]. There is a higher spontaneous abortion rate in patients with adenomyosis, which may require enhanced luteal support [25]. In another study, it was reported that donated oocyte cycles showed a miscarriage rate twice that of the endometriosis and control groups [19]. Furthermore, patients receiving PGT-A showed a 3-fold greater rate of miscarriage in the adenomyosis group [14]. In addition, an investigation of GnRH agonist treatment reported decreased live birth rates and increased miscarriage rates [10]. Our study revealed a higher miscarriage rate in adenomyosis patients. The miscarriage rates were similar between our data and the findings of the abovementioned study [10]. More studies are needed to establish whether there is an impact on CPR and, furthermore, to explore the effects in patients under different treatment strategies. GnRH agonist is believed to reduce inflammatory reaction, mitigate the angiogenic response, and induce apoptosis in tissue from patients with adenomyosis [26]. It was reported that among 3 groups (fresh ET with/without GnRH agonist treatment before cycles, GnRH agonist treatment before FET cycles), GnRH agonist treatment before FET cycles showed the best clinical pregnancy rates, compared with fresh ET both with and without GnRH pretreatment [9]. Moreover, it has also been demonstrated that FET cycles with long-term GnRH agonist pretreatment significantly improved pregnancy outcomes [27, 28]. We use GnRH agonist pretreatment before FET as our ET strategy in most of our adenomyosis patients and monitored CA-125 levels to guide the length of treatment duration. Our results showed that under GnRH agonist pretreatment before FET to achieve a relatively normal CA-125 serum level, the live birth rates of patients with adenomyosis approached those of patients under the age of 38 years in groups E and C. However, in patients aged ≥38 years, LBRs and cLBR were still lower than those of the control group. Our subgroup analysis showed that serum CA-125 levels before GnRH agonist treatment were not associated with CPR or LBR at cut-off values of 200, 150, and 100 U/ml. We demonstrated that patients could achieve non inferior pregnancy outcomes after GnRH agonist treatment before FET, even with a high CA-125 level. However, there was no LB in patients with pretreatment CA-125 > 350 U/ml. The subgroup analysis of the fold decrease in CA-125 level after treatment revealed that patients with a 7-fold decrease had significantly higher CPRs. Our study has notable strengths. This is the first study to compare the impact of endometriosis and adenomyosis in patients receiving GnRH pre-treatment on cLBR and to include age in the analysis. The limitation of this retrospective study was that we did not enroll group of adenomyosis patients without GnRH agonist treatment. Due to the lack of fresh ET data, we did not analyze the impact of adenomyosis on the pregnancy outcome between fresh ET and FET. There are also no data on the change in uterus volume after GnRH agonist treatment due to incomplete data. We might have missed some patients with endometriosis in adenomyosis group due to not all patients received laparoscopies. In conclusion, endometriosis was not associated with a poorer pregnancy outcome. Patients with adenomyosis, or both adenomyosis and endometriosis, have a higher miscarriage rate, lower LBRs, and lower cLBRs, especially in patients aged ≥38 years even after GnRH agonist treatment before FET cycles. Patients who have a greater than 7-fold decrease in CA-125 level after GnRH agonist treatment might have better clinical pregnancy outcomes. Declarations Acknowledgements None Competing Interests The authors have no relevant financial or non-financial interests to disclose. Author Contribution Yu Wang: Manuscript writing, project development Yu-Chiao Yi: Data collection Hwa-Fen Guu: Data collection and management Ya-Fang Chen: Project development and data analysis Hsiao-Fan Kung: Data collection and management Jui-Chun Chang: Data collection Li-Yu Chen: Data collection Shih-Ting Chuan: Project development Ming-Jer Chen: Manuscript editing, project development, and data analysis Interest statement The authors have no relevant financial or non-financial interests to disclose. Funding The authors declare that no funds, grants, or other support were received during the preparation of this manuscript Ethical approval The study protocol was approved by the Ethics Committee of Taichung Veterans General Hospital on December 1, 2021 with approval code CE2147, and adhered to relevant ethical guidelines. This manuscript is original, has not been published before and is not currently being considered for publication elsewhere. The manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. The order of authors listed in the manuscript has been approved by all of us. References Ben Hamouda S, Ouerdiane N, Ben Zina H, Masmoudi A, Ennine I, Bouguerra B, Sfar R (2007) [Adenomyosis at hysterectomy]. Tunis Med 85:559–562 Naftalin J, Hoo W, Pateman K, Mavrelos D, Holland T, Jurkovic D (2012) How common is adenomyosis? 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PLoS ONE 13:e0194800. .https://doi.org/10.1371/journal.pone.0194800 Benagiano G, Brosens I, Habiba M (2014) Structural and molecular features of the endomyometrium in endometriosis and adenomyosis. Hum Reprod Update 20:386–402. https://doi.org/10.1093/humupd/dmt052 Chiang CH, Chang MY, Shiau CS, Hou HC, Hsieh TT, Soong YK (1999) Effect of a sonographically diffusely enlarged uterus without distinct uterine masses on the outcome of in vitro fertilization-embryo transfer. J Assist Reprod Genet 16:369–372. https://doi.org/10.1023/a:1020593930366 Khan KN, Kitajima M, Hiraki K, Fujishita A, Sekine I, Ishimaru T, Masuzaki H (2010) Changes in tissue inflammation, angiogenesis and apoptosis in endometriosis, adenomyosis and uterine myoma after GnRH agonist therapy. Hum Reprod 25:642–653. https://doi.org/10.1093/humrep/dep437 Niu Z, Chen Q, Sun Y, Feng Y (2013) Long-term pituitary downregulation before frozen embryo transfer could improve pregnancy outcomes in women with adenomyosis. 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Sci Rep 11:19326. https://doi.org/10.1038/s41598-021-98918-5 Tables Table 1 Baseline demographics, cycle characteristics and culture results of the four groups Parameters Endometriosis (group E) (n=229) Adenomyosis (group A) (n=89) Endometriosis+ adenomyosis (group EA) (n=69) Control (group C) (n=1002) Age (years) 34.8±4 38±3.7 37.6±4.3 37±4.2 AMH (ng/ml) Average 2.6±2.2 1.8±2.0 2.0±1.7 2.9±3.1 <38 (year-old) 2.7±2.1 2.6±2.2 2.2±1.7 3.6±1.7 ≥38 (year-old) 1.8±2.2 1.3±1.7 1.8±1.7 2.0±2.3 Rates of primary / secondary infertility 64.6%/35.4% 51.7%/48.3% 73.9%/26.1% 54.7%/45.3% Induction duration (days) 10.0±2.0 9.8±2.0 10.0±2.0 9.9±1.9 Total dosage of FSH (IU) 3595.13±2158.7 3639±2271.4 3421.4±1728.8 3612±2272.8 Total dosage of LH (IU) 1090.3±658 1126±563 1343.5±632.5 1086.5±614.6 Estradiol on day of hCG administration (pg/mL) 2131.5±1534.9 1538.1±1543.5 1801.5±1697.7 2322.2±1942.5 Progesterone on day of hCG administration (ng/mL) 0.9±1.4 0.7±0.5 0.7±0.4 0.8±0.5 No. of oocyte retrieved 10.3±7.8 7.8±7.6 6.4±5.0 11.2±9.2 No. of mature oocytes 8.0±6.3 5.6±6.4 5.3±4.6 8.7±7.3 No. of oocytes fertilized 7.6±6.3 5.4±5.5 5.2±4.3 7.7±6.8 Fertilization rates 72.1% 70.6% 77.9% 69.4% Rates of good embryos* (at day3) 28% 28.6% 31.8% 32.3% Rates of good blastocyst** (at day 5/6) 30.4% 28.8% 26.4% 33.67% Rates of blastocyte for cleavage (from cleavage stage embryos) 53.7% 50.7% 45.8% 52.4% * Cleavage embryos were defined as good quality embryo if they were composed of at least seven-to-eight cell grade1 or 2 on day 3, according to the Veeck classification system ** Grade according to Gardner classification system of “3BA” or greater was defined as good quality blastocyst Table 2 Pregnancy outcomes of 1st frozen-thawed embryo transfer cycles (FET) of the four groups Pregnancy outcome Endometriosis (group E) (n=229) Adenomyosis (group A) (n=89) Endometriosis+ adenomyosis (group EA) (n=69) Control (group C) (n=1002) P value CPR in 1 st FET cycles 49.1% 49.1% 41% 58.4% EA vs C 0.029 Other: NS LBR in 1 st FET cycles 39.3% 32.1% 25.0% 48.1% EA vs C 0.003 A vs C 0.028 Other: NS Clinical miscarriage rates 19.9% 34.7% 39% 17.6% NS NS, non-significant P-values Table 3 Cumulative live birth rates per retrieval cycle of the four groups Pregnancy outcome Endometriosis (group E) (n=229) Adenomyosis (group A) (n=89) Endometriosis+ adenomyosis (group EA) (n=69) Control (group C) (n=1002) P value per retrieval cycle 46.6% (97/208) 29.2% (21/72) 31.0% (18/58) 46.8% (448/957) E vs EA 0.034 EA vs C 0.019 A vs C 0.004 E vs A 0.01 Other: NS per retrieval cycle, with patients age <38 53.8% (84/156) 58.1% (18/31) 44.8% (13/29) 61.2% (326/533) EA vs C 0.008 Other: NS per retrieval cycle, with patients age ≥38 25.0% (13/52) 7.3% (3/41) 17.2% (5/29) 29.0% (122/424) A vs C 0.003 E vs A 0.028 Other: NS NS, non-significant P-values Table 4 The clinical outcomes of FET cycles by the initial serum CA-125 and fold decreases in CA-125 after treatment in group A and group EA Initial CA-125 ≥100 U/ml Initial CA-125 <100 U/ml P value Clinical pregnancy rates 35.71% (25/70) 31.17% (24/77) 0.678 Live birth rates 24.29% (17/70) 22.08% (17/77) 0.853 CA-125 decrease folds ≥ 7 times CA-125 decrease folds < 7 times P value Clinical pregnancy rates 44.19% (19/43) 26.67% (24/90) 0.043* Live birth rates 25.58% (11/43) 18.89% (17/90) 0.376 * p <0.05 Table 5 Main characteristics of published studies on adenomyosis, endometriosis, and pregnancy outcomes. Study design Number of patients Treatment protocols and IVF characteristics CPR LBR Authors/ year adenomyosis control adenomyosis control adenomyosis control Retrospective cohort study 20 54 long-term (>3 months) GnRH agonist prior to first IVF/ICSI cycle 35% 30% Mijatovic et al., 2010 [8] Retrospective cohort study 37 164 Only fresh ET 35% 31% 29.7% (OGR) 29.3% (OGR) Costello et al., 2011 [15] Retrospective cohort study 38 137 Only D4/5 fresh ET 23.6% 43.6% Thalluri et al., 2012 [21] Prospective multicenter 49 49 Only asymptomatic Adenomyosis patients with fresh ET 43% 29% 35% 18% Benaglia et al., 2014 [16] Retrospective cohort study 34 137 All patients underwent PGS, 79.4% (n = 27) adenomyosis underwent ultra-long GnRH-agonist down regulation 47% 80% Stanekova et al., 2018 [14] Prospective multicenter cohort study 120 (fresh) 79 (FET) 335 (fresh) 170 (FET) 23.1% (fresh) 40.5% (FET) 35.6% (fresh) 40.0% (FET) 11.5% (fresh) 24.1% (FET) 17.0% (fresh) 23.5% (FET) Higgins et al., 2021 [20] Retrospective matched cohort study Adenomyosis/endometriosis/ control: 328/242/331 All received oocytes donation Adenomyosis/endometriosis/ control: 40%/44%/30.8% Adenomyosis/endometriosis/ control: 26.8%/38%/37.1% Martinez-Conejero et al., 2011 [19] Retrospective study Adenomyosis: Fresh ET without GnRH-a pretreatment/ Fresh ET with GnRH-a pretreatment /FET with GnRH-a Pretreatment: 147/105/43 Fresh ET without GnRH-a pretreatment/ Fresh ET with GnRH-a pretreatment /FET with GnRH-a Pretreatment: 25.2%/30.5%/39.5% Park et al., 2016 [9] Retrospective cohort study Adenomyosis/endometriosis/ adenomyosis+endometriosis/control: 64/88/355/466 Adenomyosis group underwent ultra-long down regulation, All D2 or D3 ET Adenomyosis/endometriosis/ adenomyosis+endometriosis/control: 23.44%/36.55%/22.72%/35.55% Adenomyosis/endometriosis/ adenomyosis+endometriosis/control: 12.5%/26.48%/11.36%/27.47% Sharma et al., 2019 [10] Retrospective cohort study Adenomyosis FET pretreatment/without pretreatment: 48/140 Cumulative LBR group pretreatment/without pretreatment: 97/216 All adenomyosis patients, GnRH agonist pretreatment at early follicle phase up to 3 doses Adenomyosis FET pretreatment/without pretreatment: 37.7%/21.2% Cumulative LBR group pretreatment/without pretreatment: 40.5%/27.9% Chen, M et al., 2020 [22] 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. 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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-1919429","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":127682193,"identity":"e4b06bb9-09c6-4ebb-8fa5-653b3bcd13d3","order_by":0,"name":"Yu Wang","email":"","orcid":"https://orcid.org/0000-0003-3828-3723","institution":"Taichung Veterans General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yu","middleName":"","lastName":"Wang","suffix":""},{"id":127682194,"identity":"80b1d9e9-c03a-4495-a408-bf93fbaf8126","order_by":1,"name":"Yu-Chiao Yi","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Yu-Chiao","middleName":"","lastName":"Yi","suffix":""},{"id":127682195,"identity":"8c5e3e19-b6a8-4f65-aaad-7064ab88bfae","order_by":2,"name":"Hwa-Fen Guu","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Hwa-Fen","middleName":"","lastName":"Guu","suffix":""},{"id":127682196,"identity":"bed2a8a9-5da3-4181-be38-230982efd2f9","order_by":3,"name":"Ya-Fang Chen","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Ya-Fang","middleName":"","lastName":"Chen","suffix":""},{"id":127682197,"identity":"419695ce-8f52-42f4-8589-661119bc5fea","order_by":4,"name":"Jui-Chun Chang","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Jui-Chun","middleName":"","lastName":"Chang","suffix":""},{"id":127682198,"identity":"93084c36-329e-4975-919d-7e04ad4d9b90","order_by":5,"name":"Li-Yu Chen","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Li-Yu","middleName":"","lastName":"Chen","suffix":""},{"id":127682199,"identity":"9be49346-af74-4c6e-a337-97ad8cd5302c","order_by":6,"name":"Shih-Ting Chuan","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Shih-Ting","middleName":"","lastName":"Chuan","suffix":""},{"id":127682200,"identity":"a659bb56-055d-4571-8cae-318ab90004e5","order_by":7,"name":"Ming-Jer Chen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA40lEQVRIiWNgGAWjYDACZiCWAGIDBgbGB0Cah48ULcwGIC1sRNsGVM4G0spAUItuO+/hFxYV9+TN2XuPVX7NsZNhY2B++OgGHi1mh/nSLCTOFBvu7DmXdlt2WzLQYWzGxjl4tfCYGUi2JSQY3Mgxuy25jRmohYdNmrCWf0At99+YFUtuqydKi/EDyQaQLTxmjB+3HSbOFgaJYwmGG87kGEszbjvOw8ZMyC/nzxh/lqhJkDc4fsbw489t1fb87M0PH+PTAgRs0hJQFjMPmMSvHKzk4wcoi/EHYdWjYBSMglEwAgEAVKRCXkUvTGMAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-5618-1969","institution":"","correspondingAuthor":true,"prefix":"","firstName":"Ming-Jer","middleName":"","lastName":"Chen","suffix":""}],"badges":[],"createdAt":"2022-08-02 01:28:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1919429/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1919429/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":28246985,"identity":"03a538a7-bf76-4beb-aeac-a305b2faa347","added_by":"auto","created_at":"2022-10-25 19:57:10","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":283938,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1919429/v1/ed9010d2-bb23-4db5-9e25-9296016899f3.pdf"}],"financialInterests":"","formattedTitle":"Impact of adenomyosis and endometriosis on IVF/ICSI pregnancy outcome in patients undergoing gonadotropin-releasing hormone agonist treatment and frozen embryo transfer","fulltext":[{"header":"What Does This Study Add To The Clinical Work? ","content":"\u003cp\u003e1. Adenomyosis can impact live birth rate even after GnRH agonist treatment before frozen embryo transfer.\u003c/p\u003e\n\u003cp\u003e2. Patients with adenomyosis have a lower cumulative pregnancy rate compared with control and endometriosis patients.\u003c/p\u003e\n\u003cp\u003e3. Adenomyosis seems to have a greater impact in patients over 38 years old.\u003c/p\u003e\n\u003cp\u003e4. No impact of pregnancy rate was seen in patients with endometriosis compared with the control group.\u003c/p\u003e\n\u003cp\u003e5. Patients who have a greater than 7-fold decrease in CA-125 level after GnRH agonist treatment might have better clinical pregnancy outcomes.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eAdenomyosis is usually defined as the occurrence of ectopic rests of endometrium-like tissue and fibrosis resulting in an enlarged uterus. The endometrium resides deeply within the myometrium with both glands and stroma. The prevalence of adenomyosis from hysterectomy in general population is around 20% and about the same prevalence is found by transvaginal sonography (TVS) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. TVS and magnetic resonance imaging (MRI) obtain equivalent results in the diagnosis of adenomyosis [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTreatment of adenomyosis includes cyclic NSAID, combined oral contraceptive pills, progestin-only regimens, selective progesterone receptor modulators (SPRMs), levonorgestrel-releasing intrauterine system (LNG-IUS) and GnRH (gonadotropin-releasing hormone) agonists [\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. It has been shown that GnRH agonists may help women achieve a better in vitro fertilization (IVF) outcome [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn infertile women, around 24% of women are diagnosed with adenomyosis [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. There are several hypothetical mechanisms in adenomyosis-associated infertility, including dysregulations of the myometrial architecture and function, chronic inflammation, presence of local oxygen, and altered endometrial function, which can cause implantation failure [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Although numerous studies have attempted to explain the relationship between adenomyosis and infertility, there are still no definitive conclusions [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Recent studies have shown adenomyosis was related to a lower clinical pregnancy rate (CPR), ongoing pregnancy rate (OGR), live birth rate (LBR) [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. However, some studies showed that adenomyosis did not affect pregnancy outcome [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eEndometriosis is found in around 40% of infertile women. Although it might affect natural conception rates, it is now believed that ART could bypass the toxic pelvic environment and achieve favorable clinical pregnancy rates [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAs mentioned above, the effect of adenomyosis and/ or endometriosis on pregnancy outcome remains controversial. In this retrospective study, we analyzed patients with endometriosis, adenomyosis, or both, who underwent IVF or intracytoplasmic sperm injection (ICSI). We attempted to determine whether adenomyosis and endometriosis affected IVF outcomes in our patients.\u003c/p\u003e"},{"header":"Materials And Methods","content":"\u003cp\u003e\u003cstrong\u003eSubjects\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis was a retrospective study of patients who underwent IVF in Taichung Veterans General Hospital, Taiwan between January 1, 2016, and December 31, 2019. It is standard practice for all of our patients undergoing IVF to receive TVS during their first visit to our hospital. Patients with a diagnosis of endometriosis and/or adenomyosis were included as the potential study group, and patients without endometriosis and/or adenomyosis or other uterine/systemic disorders were categorized as the potential control group. The inclusion criteria for the study were as follows: (1) patients underwent a cycle of IVF or ICSI, (2) endometriosis was confirmed by surgery or sonography examination, (3) adenomyosis was diagnosed by two-dimensional or three-dimensional TVS in the past 12 months. Adenomyosis were diagnosed after visualizing at least three sonographic criteria on TVS, including globular uterus caused by overall increase in myometrial thickness; asymmetrically thickened anterior or posterior myometrial wall; poorly defined endo-myometrial interface; presence of heterogeneous myometrial area; and myometrial cysts. No restriction was made for the number of previous failed cycles. The exclusion criteria were as follows: (1) patients with other uterine anomalies, (2) patients with immune diseases or metabolic diseases, (3) patients receiving donated oocytes, (4) patients with embryos transferred from mixed cycles, (5) patients with uterine leiomyoma, (6) patients receiving preimplantation genetic testing for aneuploidy, (7) patients who underwent adenomyomectomy.\u003c/p\u003e\n\u003cp\u003eWe analyzed those patients in the study and control group who had finished their treatment cycles, either as a result of achieving a live birth or ultimately failing after transferring all of their embryos. The cumulative live birth rates (cLBRs) per started cycle were followed until May 31, 2021. In order to simplify the data analysis, transfer cycles with embryos from different cycles were excluded from the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdenomyosis status\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll patients received a CA-125 blood test, except for those who had already received a test previously at our hospital. For those whose CA-125 value exceeded the normal range (35 U/ml), a pre-embryo transfer (ET) GnRH agonist treatment was prescribed. GnRH agonist was prescribed at intervals of 28 to 35 days until the CA-125 was in normal range.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eControlled Ovarian Hyperstimulation Protocol \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients in the GnRH agonist group received leuprolide acetate (Leuprolide, 0.5mg/d; Takeda Co., Taiwan) consisting of a daily low dose of GnRH agonist, subcutaneously administered for at least 10 days before the onset of ovarian stimulation. Meanwhile, participants in the antagonist group received the GnRH antagonist cetrorelix acetate (Cetrotide, 0.25 mg/d SC; Merck Serono, German) starting flexibly on stimulation days 5 ~ 7 by ultrasound monitoring 5 days after the onset of COH with gonadotropins. \u003c/p\u003e\n\u003cp\u003eThe types and dosages of gonadotropin administration were individualized for each participant according to her age, body mass index, anti-mullerian hormone level (AMH), FSH/LH level, antral follicle counts on cycle day 2~3 and response to previous ovarian stimulation. Doses were adjusted according to the ovarian response as monitored by vaginal ultrasound folliculometry and serum E2 level testing. \u003c/p\u003e\n\u003cp\u003eWhen two or more follicles reached a mean diameter of 18 mm, 10,000 IU of hCG (Pregnyl, Merck Sharp \u0026amp; Dohme, America; Organon) or 250- 500 ug of recombinant hCG (Ovidrel; Merck Serono, German) was injected for the oocyte retrieval 35~36 hours later. Progesterone 25mg/amp (Astar Co., Taiwan), 1-2 amp/day, was injected intramuscularly starting from the night of oocyte retrieval and was then continued or shifted to topical progesterone (8% Crinone; Merck-Serono, German) 1 tube/day on the day of embryo transfer, which was maintained until the pregnant patients had reached 8 complete weeks of gestation for luteal support (LS). \u003c/p\u003e\n\u003cp\u003eFor the frozen-thaw cycle, patients received an artificial hormone replacement regimen (estradiol valerate 2 mg, Synmosa Co., Taiwan) with a step-up from 4-8mg per day for 5 days, to 6-12mg per day for 5 days, followed by twice daily vaginal progesterone (8% Crinone; Merck Serono, German) 90mg plus estradiol valerate 12mg once endometrial thickness exceeded 8 mm on ultrasound assessment. Then the dosage was maintained till the patient reached 10 complete weeks of gestation for luteal support (LS).\u003c/p\u003e\n\u003cp\u003eIn addition, 0.1 mg Decapeptyl (Ferring Co., Germany) was also administered on the 6th day after ICSI as a measure of adjuvant LS. The embryo transfers (ET) were carried out on day 2, day 3, or day 5 of culture. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOutcome measures\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSerum \u0026beta;hCG was checked on embryonic age day 14, and measurements over 5 mIU/mL were defined as a biochemical pregnancy if no gestational sac could be identified later. \u003c/p\u003e\n\u003cp\u003eClinical pregnancy was defined as the presence of a gestational sac under TVS at the gestational age of 4-5 weeks. Live birth rate was defined as the number of deliveries that resulted in a live born neonate. \u003c/p\u003e\n\u003cp\u003eCumulative live birth rates (cLBR) per retrieval cycle were defined as the percentage of at least one live born neonate from that retrieval cycle. The above results were followed until May 31,2021.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analyses\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStatistics were conducted by SPSS-PC ver. 22.0. Patient\u0026rsquo;s characteristics, AMH, oocyte retrieval number, and pregnancy outcomes were analyzed using the two-tailed t test and Chi-squared test among groups, with a p value of less than 0.05 considered statistically significant.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol was approved by the Ethics Committee of Taichung Veterans General Hospital on December 1, 2021 with approval code CE2147, and adhered to relevant ethical guidelines. \u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003ePatient\u0026rsquo;s characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn total, 1720 cycles were reviewed and analyzed in the study period. There were 1179 women and 1389 cycles enrolled in the study using inclusion and exclusion criteria. The cycles were grouped as follows: 229 cycles in the endometriosis group (group E), 89 cycles in the adenomyosis group (group A), 69 cycles in the endometriosis and adenomyosis group (group EA), and 1002 cycles in the control group (group C). Baseline demographics, cycle characteristics, and laboratory culture results of the four groups are summarized in Table 1.\u003c/p\u003e\n\u003cp\u003eThe average value of CA-125 before GnRH agonist treatment was 104.8 U/ml in group A and 167.9 U/ml in group EA. The average CA-125 value after treatment was 22.0 U/ml in group A and 26.5 U/ml in group EA before starting hormonal replacement therapy in preparation for embryo transfer. A total of 72 cycles (80.9%) in group A and 54 cycles (85.6%) in group EA received GnRH agonist treatment before embryo transfer.\u003c/p\u003e\n\u003cp\u003eThe LBRs of 1\u003csup\u003est\u003c/sup\u003e frozen-thawed embryo transfer cycle (FET) were significantly lower in group A and group AE as compared to those in group E and group C (Table 2). Subgroup analysis also revealed significant differences between groups E and C, and groups EA and C in patients younger than age 38 years. Significantly lower LBRs were also noted in group A compared with group C, and in group EA compared with group C in patients older than age 38 years.\u003c/p\u003e\n\u003cp\u003eThe cumulative pregnancy outcomes per retrieval are presented in Table 3. There were significantly lower cLBRs in groups A and EA compared with group C. In the sub-group analyses according to age, the lower average cLBR in groups A and EA was mostly due to older patients (age \u0026ge;38 years). The abortion rates were higher in group A and AE without significant differences.\u003c/p\u003e\n\u003cp\u003eTable 4 shows the subgroup analysis of the clinical outcomes in the 1\u003csup\u003est\u003c/sup\u003e FET cycles by the initial serum CA-125 and fold decrease in CA-125 level after treatment in group A and group EA. There were no significant differences in CPR and LBR among the different CA-125 levels, including cut-off values set at 100, 150, or 200 U/ml. The analysis of fold decrease in CA-125 level after treatment revealed that patients who had a greater than 7-fold decrease had a significantly higher CPR.\u003c/p\u003e\n\u003cp\u003eOn May 31, 2021, there were still 4 patients in group E, 1 patient in group A, and 12 patients in group C with an ongoing pregnancy who are not included in this study. The follow up before publication showed 1 termination due to fetal anomalies in group A and 1 fetal death in group C.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eTo the best of our knowledge, no studies have been conducted to determine the cumulative live birth rate of patients with endometriosis and adenomyosis with and without endometriosis under GnRH agonist pre-treatment before FET. Our study compared the effects of these diseases on their respective pregnancy outcomes. We evaluated the live birth rates after first transfer of frozen thawed embryos and the final cumulative live birth rates based on per retrieval cycle basis, with a further sub-analysis of the patients by age. These data showed clearly that in patients with adenomyosis undergoing GnRH agonist pretreatment before FET, cumulative LBRs were not inferior in patients aged \u0026lt;38 years but were significantly lower in those aged \u0026ge;38 years, compared with the control and endometriosis groups. Moreover, the endometriosis group achieved a cumulative LBR comparable with that of the control group.\u003c/p\u003e\n\u003cp\u003eThere was no clear evidence indicating whether or not adenomyosis impacted the clinical pregnancy rates, and its effect on cumulative pregnancy rates was even less clear. It remains debatable as to what strategy should be adopted for embryo transfer in adenomyosis patients. In Table 5, we have summarized the available studies in the literature which have investigated the impact of adenomyosis and/or endometriosis on pregnancy outcome by IVF/ICSI. Three studies found that adenomyosis had no impact on pregnancy rates [8, 15, 16]. Other studies reported adverse influences of adenomyosis on pregnancy rates [9, 10, 14, 19-21]. In studies with ultralong GnRH agonist protocol before fresh ET, the results found conflicting conclusions [8, 9, 22].\u003c/p\u003e\n\u003cp\u003eIn a study reporting that adenomyosis has a negative effect on pregnancy outcomes, overdiagnosis of adenomyosis was noted as a concern [15]. However, this hypothesis was refuted in a study conducted the following year [21]. An investigation of patients receiving GnRH-agonist treatment reported that adenomyosis had no effect on LBR [8]. In the aforementioned study longer GnRH-agonist treatment (average 5 months) was prescribed compared with our study (2.2 months in group A and 2.5 months in group EA). The pregnancy outcomes of the adenomyosis group in two prior studies were similar to our results (LBR 35%, 29.7%, our study 32.1%) [8, 15]. However, the pregnancy outcomes of the control group were both lower than those in our study, which might be the key reason that led to the different conclusions (LBR 30%, 29.3%, our study 48.1%). Although a recent study reported CRP and LBR in adenomyosis group that were not inferior, the results also showed that FET was related to better pregnancy outcomes compared with fresh ET [20]. In three prior studies, there were no pretreatment CA-125 data available for further comparisons between baseline and changes in the disease severity [8, 15, 20].\u003c/p\u003e\n\u003cp\u003eFor studies showing a negative impact of adenomyosis on pregnancy rates, a 2012 study revealed a similar pregnancy outcome to that found in our study [21]. A retrospective study with a relatively large number of patients revealed a decrease of CPR and LBR in the adenomyosis group under ultra-long GnRH agonist treatment [10]. Although the aforementioned study and our study have similar conclusions, our patients were treated with a different treatment strategy and displayed better pregnancy outcomes (LBR 32% v.s 11.36%) in a relatively older patient population.\u003c/p\u003e\n\u003cp\u003eOur results support the hypothesis that adenomyosis does adversely impact pregnancy outcomes. Our data showed that in patients aged \u0026lt;38 years, cLBRs per retrieval cycle increased around 5-10% per cycle compared with the results of their first ET. Nevertheless, in patients aged \u0026ge;38 years, the cLBRs per retrieval cycle in both group A and EA were less than 20%. The lower cLBRs in adenomyosis patients could mostly be explained by patients being aged \u0026ge;38 years. Adenomyosis probably irreversibly injures the myometrial architecture and function after years of disease progression [12]. If the damage is severe enough, it might still affect implantation potential even after applying GnRH agonist pre-treatment to achieve a seemingly normal CA-125 value, eventually leading to a lower chance of achieving a live birth chance.\u003c/p\u003e\n\u003cp\u003ePrevious studies showed that the impacts of endometriosis on fertility can mostly be overcome by IVF [17, 18, 23]. ART could achieve pregnancy outcomes that are relatively close to those attained in patients with male factor [18]. Our study found the same results, namely, that endometriosis had no negative effects on LBRs in fresh ET, FET, and cLBR per retrieval cycle compared with the control group. Our study findings also suggest that the outcomes of adenomyosis patients were also diagnosed with endometriosis were similar to those of adenomyosis patients.\u003c/p\u003e\n\u003cp\u003eWhether the poor pregnancy outcomes in patients with adenomyosis are due to decreased implantation rates or increased miscarriage rates has not been clearly established [24]. There is a higher spontaneous abortion rate in patients with adenomyosis, which may require enhanced luteal support [25]. In another study, it was reported that donated oocyte cycles showed a miscarriage rate twice that of the endometriosis and control groups [19]. Furthermore, patients receiving PGT-A showed a 3-fold greater rate of miscarriage in the adenomyosis group [14]. In addition, an investigation of GnRH agonist treatment reported decreased live birth rates and increased miscarriage rates [10]. Our study revealed a higher miscarriage rate in adenomyosis patients. The miscarriage rates were similar between our data and the findings of the abovementioned study [10]. More studies are needed to establish whether there is an impact on CPR and, furthermore, to explore the effects in patients under different treatment strategies.\u003c/p\u003e\n\u003cp\u003eGnRH agonist is believed to reduce inflammatory reaction, mitigate the angiogenic response, and induce apoptosis in tissue from patients with adenomyosis [26]. It was reported that among 3 groups (fresh ET with/without GnRH agonist treatment before cycles, GnRH agonist treatment before FET cycles), GnRH agonist treatment before FET cycles showed the best clinical pregnancy rates, compared with fresh ET both with and without GnRH pretreatment [9]. Moreover, it has also been demonstrated that FET cycles with long-term GnRH agonist pretreatment significantly improved pregnancy outcomes [27, 28]. We use GnRH agonist pretreatment before FET as our ET strategy in most of our adenomyosis patients and monitored CA-125 levels to guide the length of treatment duration. Our results showed that under GnRH agonist pretreatment before FET to achieve a relatively normal CA-125 serum level, the live birth rates of patients with adenomyosis approached those of patients under the age of 38 years in groups E and C. However, in patients aged \u0026ge;38 years, LBRs and cLBR were still lower than those of the control group.\u003c/p\u003e\n\u003cp\u003eOur subgroup analysis showed that serum CA-125 levels before GnRH agonist treatment were not associated with CPR or LBR at cut-off values of 200, 150, and 100 U/ml. We demonstrated that patients could achieve non inferior pregnancy outcomes after GnRH agonist treatment before FET, even with a high CA-125 level. However, there was no LB in patients with pretreatment CA-125 \u0026gt; 350 U/ml. The subgroup analysis of the fold decrease in CA-125 level after treatment revealed that patients with a 7-fold decrease had significantly higher CPRs.\u003c/p\u003e\n\u003cp\u003eOur study has notable strengths. This is the first study to compare the impact of endometriosis and adenomyosis in patients receiving GnRH pre-treatment on cLBR and to include age in the analysis. The limitation of this retrospective study was that we did not enroll group of adenomyosis patients without GnRH agonist treatment. Due to the lack of fresh ET data, we did not analyze the impact of adenomyosis on the pregnancy outcome between fresh ET and FET. There are also no data on the change in uterus volume after GnRH agonist treatment due to incomplete data. We might have missed some patients with endometriosis in adenomyosis group due to not all patients received laparoscopies.\u003c/p\u003e\n\u003cp\u003eIn conclusion, endometriosis was not associated with a poorer pregnancy outcome. Patients with adenomyosis, or both adenomyosis and endometriosis, have a higher miscarriage rate, lower LBRs, and lower cLBRs, especially in patients aged \u0026ge;38 years even after GnRH agonist treatment before FET cycles. Patients who have a greater than 7-fold decrease in CA-125 level after GnRH agonist treatment might have better clinical pregnancy outcomes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYu Wang: Manuscript writing, project development\u003c/p\u003e\n\u003cp\u003eYu-Chiao Yi: Data collection\u003c/p\u003e\n\u003cp\u003eHwa-Fen Guu: Data collection and management\u003c/p\u003e\n\u003cp\u003eYa-Fang Chen: Project development and data analysis\u003c/p\u003e\n\u003cp\u003eHsiao-Fan Kung: Data collection and management\u003c/p\u003e\n\u003cp\u003eJui-Chun Chang: Data collection\u003c/p\u003e\n\u003cp\u003eLi-Yu Chen: Data collection\u003c/p\u003e\n\u003cp\u003eShih-Ting Chuan: Project development\u003c/p\u003e\n\u003cp\u003eMing-Jer Chen: Manuscript editing, project development, and data analysis\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInterest statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol was approved by the Ethics Committee of Taichung Veterans General Hospital on December 1, 2021 with approval code CE2147, and adhered to relevant ethical guidelines.\u003c/p\u003e\n\u003cp\u003eThis manuscript is original, has not been published before and is not currently being considered for publication elsewhere. The manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. The order of authors listed in the manuscript has been approved by all of us.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBen Hamouda S, Ouerdiane N, Ben Zina H, Masmoudi A, Ennine I, Bouguerra B, Sfar R (2007) [Adenomyosis at hysterectomy]. Tunis Med 85:559\u0026ndash;562\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNaftalin J, Hoo W, Pateman K, Mavrelos D, Holland T, Jurkovic D (2012) How common is adenomyosis? A prospective study of prevalence using transvaginal ultrasound in a gynaecology clinic. 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Hum Reprod Update 20:386\u0026ndash;402. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/humupd/dmt052\u003c/span\u003e\u003cspan address=\"10.1093/humupd/dmt052\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChiang CH, Chang MY, Shiau CS, Hou HC, Hsieh TT, Soong YK (1999) Effect of a sonographically diffusely enlarged uterus without distinct uterine masses on the outcome of in vitro fertilization-embryo transfer. 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Sci Rep 11:19326. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41598-021-98918-5\u003c/span\u003e\u003cspan address=\"10.1038/s41598-021-98918-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1\u0026nbsp;\u003c/strong\u003eBaseline demographics, cycle characteristics and culture results of the four groups\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003eParameters\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003eEndometriosis (group E)\u003c/p\u003e\n \u003cp\u003e(n=229)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003eAdenomyosis (group A)\u003c/p\u003e\n \u003cp\u003e(n=89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003eEndometriosis+ adenomyosis (group EA)\u003c/p\u003e\n \u003cp\u003e(n=69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003eControl (group C)\u003c/p\u003e\n \u003cp\u003e(n=1002)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e34.8\u0026plusmn;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e38\u0026plusmn;3.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e37.6\u0026plusmn;4.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e37\u0026plusmn;4.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003eAMH (ng/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003eAverage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e2.6\u0026plusmn;2.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e1.8\u0026plusmn;2.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e2.0\u0026plusmn;1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e2.9\u0026plusmn;3.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e\u0026lt;38 (year-old)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e2.7\u0026plusmn;2.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e2.6\u0026plusmn;2.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e2.2\u0026plusmn;1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e3.6\u0026plusmn;1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e\u0026ge;38 (year-old)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e1.8\u0026plusmn;2.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e1.3\u0026plusmn;1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e1.8\u0026plusmn;1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e2.0\u0026plusmn;2.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003eRates of primary / secondary infertility\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e64.6%/35.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e51.7%/48.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e73.9%/26.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e54.7%/45.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003eInduction duration (days)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e10.0\u0026plusmn;2.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e9.8\u0026plusmn;2.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e10.0\u0026plusmn;2.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e9.9\u0026plusmn;1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003eTotal dosage of FSH (IU)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e3595.13\u0026plusmn;2158.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e3639\u0026plusmn;2271.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e3421.4\u0026plusmn;1728.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e3612\u0026plusmn;2272.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003eTotal dosage of LH (IU)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e1090.3\u0026plusmn;658\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e1126\u0026plusmn;563\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e1343.5\u0026plusmn;632.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e1086.5\u0026plusmn;614.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003eEstradiol on day of hCG administration (pg/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e2131.5\u0026plusmn;1534.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e1538.1\u0026plusmn;1543.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e1801.5\u0026plusmn;1697.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e2322.2\u0026plusmn;1942.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003eProgesterone on day of hCG administration (ng/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e0.9\u0026plusmn;1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e0.7\u0026plusmn;0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e0.7\u0026plusmn;0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e0.8\u0026plusmn;0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003eNo. of oocyte retrieved\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e10.3\u0026plusmn;7.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e7.8\u0026plusmn;7.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e6.4\u0026plusmn;5.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e11.2\u0026plusmn;9.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003eNo. of mature oocytes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e8.0\u0026plusmn;6.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e5.6\u0026plusmn;6.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e5.3\u0026plusmn;4.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e8.7\u0026plusmn;7.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003eNo. of oocytes fertilized\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e7.6\u0026plusmn;6.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e5.4\u0026plusmn;5.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e5.2\u0026plusmn;4.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e7.7\u0026plusmn;6.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003eFertilization rates\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e72.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e70.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e77.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e69.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003eRates of good embryos* (at day3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e28%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e28.6%\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e31.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e32.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003eRates of good blastocyst** (at day 5/6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e30.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e28.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e26.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e33.67%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003eRates of blastocyte for cleavage (from cleavage stage embryos)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e53.7%\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e50.7%\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e45.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e52.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e* Cleavage embryos were defined as good quality embryo if they were composed of at least seven-to-eight cell grade1 or 2 on day 3, according to the Veeck classification system\u003c/p\u003e\n\u003cp\u003e** Grade according to Gardner classification system of \u0026ldquo;3BA\u0026rdquo; or greater was defined as good quality blastocyst\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2 \u003c/strong\u003ePregnancy outcomes of 1st frozen-thawed embryo transfer cycles (FET) of the four groups\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.457960644007155%\"\u003e\n \u003cp\u003ePregnancy outcome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.457960644007155%\"\u003e\n \u003cp\u003eEndometriosis (group E)\u003c/p\u003e\n \u003cp\u003e(n=229)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.457960644007155%\"\u003e\n \u003cp\u003eAdenomyosis (group A)\u003c/p\u003e\n \u003cp\u003e(n=89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.71019677996422%\"\u003e\n \u003cp\u003eEndometriosis+ adenomyosis (group EA)\u003c/p\u003e\n \u003cp\u003e(n=69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.457960644007155%\"\u003e\n \u003cp\u003eControl (group C)\u003c/p\u003e\n \u003cp\u003e(n=1002)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.457960644007155%\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.457960644007155%\"\u003e\n \u003cp\u003eCPR in 1\u003csup\u003est\u003c/sup\u003e FET cycles\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.457960644007155%\"\u003e\n \u003cp\u003e49.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.457960644007155%\"\u003e\n \u003cp\u003e49.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.71019677996422%\"\u003e\n \u003cp\u003e41%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.457960644007155%\"\u003e\n \u003cp\u003e\u0026nbsp;58.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.457960644007155%\"\u003e\n \u003cp\u003eEA vs C 0.029\u003c/p\u003e\n \u003cp\u003eOther: NS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.457960644007155%\"\u003e\n \u003cp\u003eLBR in 1\u003csup\u003est\u003c/sup\u003e FET cycles\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.457960644007155%\"\u003e\n \u003cp\u003e39.3%\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.457960644007155%\"\u003e\n \u003cp\u003e32.1%\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.71019677996422%\"\u003e\n \u003cp\u003e25.0%\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.457960644007155%\"\u003e\n \u003cp\u003e48.1%\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.457960644007155%\"\u003e\n \u003cp\u003eEA vs C 0.003\u003c/p\u003e\n \u003cp\u003eA vs C 0.028\u003c/p\u003e\n \u003cp\u003eOther: NS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.457960644007155%\"\u003e\n \u003cp\u003eClinical miscarriage rates\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.457960644007155%\"\u003e\n \u003cp\u003e19.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.457960644007155%\"\u003e\n \u003cp\u003e34.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.71019677996422%\"\u003e\n \u003cp\u003e39%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.457960644007155%\"\u003e\n \u003cp\u003e17.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.457960644007155%\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNS, non-significant P-values\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u003c/strong\u003e Cumulative live birth rates per retrieval cycle of the four groups\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.2748643761302%\"\u003e\n \u003cp\u003ePregnancy outcome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.636528028933093%\"\u003e\n \u003cp\u003eEndometriosis (group E)\u003c/p\u003e\n \u003cp\u003e(n=229)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.636528028933093%\"\u003e\n \u003cp\u003eAdenomyosis (group A)\u003c/p\u003e\n \u003cp\u003e(n=89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.90235081374322%\"\u003e\n \u003cp\u003eEndometriosis+ adenomyosis (group EA)\u003c/p\u003e\n \u003cp\u003e(n=69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.455696202531644%\"\u003e\n \u003cp\u003eControl (group C)\u003c/p\u003e\n \u003cp\u003e(n=1002)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.09403254972875%\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.2748643761302%\"\u003e\n \u003cp\u003eper retrieval cycle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.636528028933093%\"\u003e\n \u003cp\u003e46.6%\u003c/p\u003e\n \u003cp\u003e(97/208)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.636528028933093%\"\u003e\n \u003cp\u003e29.2%\u003c/p\u003e\n \u003cp\u003e(21/72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.90235081374322%\"\u003e\n \u003cp\u003e31.0%\u003c/p\u003e\n \u003cp\u003e(18/58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.455696202531644%\"\u003e\n \u003cp\u003e46.8%\u003c/p\u003e\n \u003cp\u003e(448/957)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.09403254972875%\"\u003e\n \u003cp\u003eE vs EA 0.034\u003c/p\u003e\n \u003cp\u003eEA vs C 0.019\u003c/p\u003e\n \u003cp\u003eA vs C 0.004\u003c/p\u003e\n \u003cp\u003eE vs A 0.01\u003c/p\u003e\n \u003cp\u003eOther: NS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.2748643761302%\"\u003e\n \u003cp\u003eper retrieval cycle, with patients age \u0026lt;38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.636528028933093%\"\u003e\n \u003cp\u003e53.8%\u003c/p\u003e\n \u003cp\u003e(84/156)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.636528028933093%\"\u003e\n \u003cp\u003e58.1%\u003c/p\u003e\n \u003cp\u003e(18/31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.90235081374322%\"\u003e\n \u003cp\u003e44.8%\u003c/p\u003e\n \u003cp\u003e(13/29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.455696202531644%\"\u003e\n \u003cp\u003e61.2%\u003c/p\u003e\n \u003cp\u003e(326/533)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.09403254972875%\"\u003e\n \u003cp\u003eEA vs C 0.008\u003c/p\u003e\n \u003cp\u003eOther: NS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.2748643761302%\"\u003e\n \u003cp\u003eper retrieval cycle, with patients age \u0026ge;38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.636528028933093%\"\u003e\n \u003cp\u003e25.0%\u003c/p\u003e\n \u003cp\u003e(13/52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.636528028933093%\"\u003e\n \u003cp\u003e7.3%\u003c/p\u003e\n \u003cp\u003e(3/41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.90235081374322%\"\u003e\n \u003cp\u003e17.2%\u003c/p\u003e\n \u003cp\u003e(5/29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.455696202531644%\"\u003e\n \u003cp\u003e29.0%\u003c/p\u003e\n \u003cp\u003e(122/424)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.09403254972875%\"\u003e\n \u003cp\u003eA vs C 0.003\u003c/p\u003e\n \u003cp\u003eE vs A 0.028\u003c/p\u003e\n \u003cp\u003eOther: NS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNS, non-significant P-values\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4\u003c/strong\u003e The clinical outcomes of FET cycles by the initial serum CA-125 and fold decreases in CA-125 after treatment in group A and group EA\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.71480144404332%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25.451263537906136%\"\u003e\n \u003cp\u003eInitial CA-125 \u0026ge;100 U/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25.451263537906136%\"\u003e\n \u003cp\u003eInitial CA-125 \u0026lt;100 U/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"22.382671480144403%\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.71480144404332%\"\u003e\n \u003cp\u003eClinical pregnancy rates\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25.451263537906136%\"\u003e\n \u003cp\u003e35.71% (25/70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25.451263537906136%\"\u003e\n \u003cp\u003e31.17% (24/77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"22.382671480144403%\"\u003e\n \u003cp\u003e0.678\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.71480144404332%\"\u003e\n \u003cp\u003eLive birth rates\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25.451263537906136%\"\u003e\n \u003cp\u003e24.29% (17/70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25.451263537906136%\"\u003e\n \u003cp\u003e22.08% (17/77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"22.382671480144403%\"\u003e\n \u003cp\u003e0.853\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.71480144404332%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25.451263537906136%\"\u003e\n \u003cp\u003eCA-125 decrease folds \u0026ge; 7 times\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25.451263537906136%\"\u003e\n \u003cp\u003eCA-125 decrease folds \u0026lt; 7 times\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"22.382671480144403%\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.71480144404332%\"\u003e\n \u003cp\u003eClinical pregnancy rates\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25.451263537906136%\"\u003e\n \u003cp\u003e44.19% (19/43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25.451263537906136%\"\u003e\n \u003cp\u003e26.67% (24/90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"22.382671480144403%\"\u003e\n \u003cp\u003e0.043*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.71480144404332%\"\u003e\n \u003cp\u003eLive birth rates\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25.451263537906136%\"\u003e\n \u003cp\u003e25.58% (11/43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25.451263537906136%\"\u003e\n \u003cp\u003e18.89% (17/90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"22.382671480144403%\"\u003e\n \u003cp\u003e0.376\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*\u003cem\u003ep\u003c/em\u003e\u0026lt;0.05\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5 \u003c/strong\u003eMain characteristics of published studies on adenomyosis, endometriosis, and pregnancy outcomes.\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.962640099626402%\"\u003e\n \u003cp\u003eStudy design\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"23.910336239103362%\"\u003e\n \u003cp\u003eNumber of patients\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.336239103362391%\"\u003e\n \u003cp\u003eTreatment protocols and IVF characteristics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"23.910336239103362%\"\u003e\n \u003cp\u003eCPR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"23.910336239103362%\"\u003e\n \u003cp\u003eLBR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.970112079701121%\"\u003e\n \u003cp\u003eAuthors/ year\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.962640099626402%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.947696139476962%\"\u003e\n \u003cp\u003eadenomyosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.962640099626402%\"\u003e\n \u003cp\u003econtrol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.336239103362391%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.947696139476962%\"\u003e\n \u003cp\u003eadenomyosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.962640099626402%\"\u003e\n \u003cp\u003econtrol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.947696139476962%\"\u003e\n \u003cp\u003eadenomyosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.962640099626402%\"\u003e\n \u003cp\u003econtrol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.970112079701121%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.962640099626402%\"\u003e\n \u003cp\u003eRetrospective \u0026nbsp; cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.947696139476962%\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.962640099626402%\"\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.336239103362391%\"\u003e\n \u003cp\u003elong-term (\u0026gt;3 months) GnRH agonist prior to first IVF/ICSI cycle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.947696139476962%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.962640099626402%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.947696139476962%\"\u003e\n \u003cp\u003e35%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.962640099626402%\"\u003e\n \u003cp\u003e30%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.970112079701121%\"\u003e\n \u003cp\u003eMijatovic et al., 2010\u0026nbsp;[8]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.962640099626402%\"\u003e\n \u003cp\u003eRetrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.947696139476962%\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.962640099626402%\"\u003e\n \u003cp\u003e164\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.336239103362391%\"\u003e\n \u003cp\u003eOnly fresh ET\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.947696139476962%\"\u003e\n \u003cp\u003e35%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.962640099626402%\"\u003e\n \u003cp\u003e31%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.947696139476962%\"\u003e\n \u003cp\u003e29.7% (OGR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.962640099626402%\"\u003e\n \u003cp\u003e29.3% (OGR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.970112079701121%\"\u003e\n \u003cp\u003eCostello et al., 2011\u0026nbsp;[15]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.962640099626402%\"\u003e\n \u003cp\u003eRetrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.947696139476962%\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.962640099626402%\"\u003e\n \u003cp\u003e137\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.336239103362391%\"\u003e\n \u003cp\u003eOnly D4/5 fresh ET\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.947696139476962%\"\u003e\n \u003cp\u003e23.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.962640099626402%\"\u003e\n \u003cp\u003e43.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.947696139476962%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.962640099626402%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.970112079701121%\"\u003e\n \u003cp\u003eThalluri\u0026nbsp;et al., 2012\u0026nbsp;[21]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.962640099626402%\"\u003e\n \u003cp\u003eProspective multicenter\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.947696139476962%\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.962640099626402%\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.336239103362391%\"\u003e\n \u003cp\u003eOnly asymptomatic Adenomyosis patients with fresh ET\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.947696139476962%\"\u003e\n \u003cp\u003e43%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.962640099626402%\"\u003e\n \u003cp\u003e29%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.947696139476962%\"\u003e\n \u003cp\u003e35%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.962640099626402%\"\u003e\n \u003cp\u003e18%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.970112079701121%\"\u003e\n \u003cp\u003eBenaglia\u0026nbsp;et al., 2014\u0026nbsp;[16]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.962640099626402%\"\u003e\n \u003cp\u003eRetrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.947696139476962%\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.962640099626402%\"\u003e\n \u003cp\u003e137\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.336239103362391%\"\u003e\n \u003cp\u003eAll patients underwent PGS, 79.4% (n = 27) adenomyosis underwent ultra-long GnRH-agonist down regulation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.947696139476962%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.962640099626402%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.947696139476962%\"\u003e\n \u003cp\u003e47%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.962640099626402%\"\u003e\n \u003cp\u003e80%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.970112079701121%\"\u003e\n \u003cp\u003eStanekova\u0026nbsp;et al., 2018\u0026nbsp;[14]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.962640099626402%\"\u003e\n \u003cp\u003eProspective multicenter cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.947696139476962%\"\u003e\n \u003cp\u003e120 (fresh)\u003c/p\u003e\n \u003cp\u003e79\u003c/p\u003e\n \u003cp\u003e(FET)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.962640099626402%\"\u003e\n \u003cp\u003e335 (fresh)\u003c/p\u003e\n \u003cp\u003e170\u003c/p\u003e\n \u003cp\u003e(FET)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.336239103362391%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.947696139476962%\"\u003e\n \u003cp\u003e23.1% (fresh)\u003c/p\u003e\n \u003cp\u003e40.5% (FET)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.962640099626402%\"\u003e\n \u003cp\u003e35.6% (fresh)\u003c/p\u003e\n \u003cp\u003e40.0% (FET)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.947696139476962%\"\u003e\n \u003cp\u003e11.5% (fresh)\u003c/p\u003e\n \u003cp\u003e24.1% (FET)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.962640099626402%\"\u003e\n \u003cp\u003e17.0% (fresh)\u003c/p\u003e\n \u003cp\u003e23.5% (FET)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.970112079701121%\"\u003e\n \u003cp\u003eHiggins et al., 2021\u0026nbsp;[20]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.962640099626402%\"\u003e\n \u003cp\u003eRetrospective matched cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"23.910336239103362%\"\u003e\n \u003cp\u003eAdenomyosis/endometriosis/ control: 328/242/331\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.336239103362391%\"\u003e\n \u003cp\u003eAll received oocytes donation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"23.910336239103362%\"\u003e\n \u003cp\u003eAdenomyosis/endometriosis/ control: 40%/44%/30.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"23.910336239103362%\"\u003e\n \u003cp\u003eAdenomyosis/endometriosis/ control: 26.8%/38%/37.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.970112079701121%\"\u003e\n \u003cp\u003eMartinez-Conejero\u0026nbsp;et al., 2011\u0026nbsp;[19]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.962640099626402%\"\u003e\n \u003cp\u003eRetrospective study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"23.910336239103362%\"\u003e\n \u003cp\u003eAdenomyosis:\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eFresh ET without GnRH-a pretreatment/ Fresh ET with GnRH-a pretreatment /FET with GnRH-a\u003c/p\u003e\n \u003cp\u003ePretreatment: 147/105/43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.336239103362391%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"23.910336239103362%\"\u003e\n \u003cp\u003eFresh ET without GnRH-a pretreatment/ Fresh ET with GnRH-a pretreatment /FET with GnRH-a\u003c/p\u003e\n \u003cp\u003ePretreatment: 25.2%/30.5%/39.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"23.910336239103362%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.970112079701121%\"\u003e\n \u003cp\u003ePark et al., 2016\u0026nbsp;[9]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.962640099626402%\"\u003e\n \u003cp\u003eRetrospective cohort study\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"23.910336239103362%\"\u003e\n \u003cp\u003eAdenomyosis/endometriosis/ adenomyosis+endometriosis/control: 64/88/355/466\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.336239103362391%\"\u003e\n \u003cp\u003eAdenomyosis group underwent ultra-long down regulation, All D2 or D3 ET\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"23.910336239103362%\"\u003e\n \u003cp\u003eAdenomyosis/endometriosis/ adenomyosis+endometriosis/control: 23.44%/36.55%/22.72%/35.55%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"23.910336239103362%\"\u003e\n \u003cp\u003eAdenomyosis/endometriosis/ adenomyosis+endometriosis/control: 12.5%/26.48%/11.36%/27.47%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.970112079701121%\"\u003e\n \u003cp\u003eSharma et al., 2019\u0026nbsp;[10]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"9.962640099626402%\"\u003e\n \u003cp\u003eRetrospective cohort study\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"23.910336239103362%\"\u003e\n \u003cp\u003eAdenomyosis\u003c/p\u003e\n \u003cp\u003eFET pretreatment/without pretreatment: 48/140\u003c/p\u003e\n \u003cp\u003eCumulative LBR group\u003c/p\u003e\n \u003cp\u003epretreatment/without pretreatment: 97/216\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.336239103362391%\"\u003e\n \u003cp\u003eAll adenomyosis patients, GnRH agonist pretreatment at early follicle phase up to 3 doses\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"23.910336239103362%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"23.910336239103362%\"\u003e\n \u003cp\u003eAdenomyosis\u003c/p\u003e\n \u003cp\u003eFET pretreatment/without pretreatment: 37.7%/21.2%\u003c/p\u003e\n \u003cp\u003eCumulative LBR group\u003c/p\u003e\n \u003cp\u003epretreatment/without pretreatment: 40.5%/27.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.970112079701121%\"\u003e\n \u003cp\u003eChen, M et al., 2020 [22]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Adenomyosis, endometriosis, cumulative live birth rate, gonadotropin-releasing hormone agonist treatment, In Vitro Fertilization","lastPublishedDoi":"10.21203/rs.3.rs-1919429/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1919429/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eAlthough numerous studies have attempted to establish the relationship between adenomyosis and infertility, no consensus has emerged. Our aim was to investigate whether adenomyosis and endometriosis affected IVF outcomes in our patients.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis was a retrospective study of 1720 patients from January 2016 to December 2019. In total, 1389 cycles were included: 229 cycles in the endometriosis group (group E), 89 cycles in the adenomyosis group (group A), 69 cycles in the endometriosis and adenomyosis group (group EA), and 1002 cycles in the control group (group C). Most patients in groups A and EA received GnRH agonist treatment before FET.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe 1st FET live birth rates (LBR) were 39.3%, 34.7%, 39% and 17,6% in groups E, A, EA, and C. The miscarriage rates were 19.9%, 34.7%, 39%, and 17.6%. The per retrieval cycle cumulative pregnancy rates (cLBRs) in patients\u0026thinsp;\u0026lt;\u0026thinsp;38 y/o were 53.8%, 58.1%, 44.8%, and 61.2%. The per retrieval cycle cLBRs in patients\u0026thinsp;\u0026ge;\u0026thinsp;38 y/o were 25%, 7.3%, 17.2%, and 29%. Among groups A and EA, LBRs were 25.58% and 18.89% in patients with a\u0026thinsp;\u0026ge;\u0026thinsp;7-fold decrease and a\u0026thinsp;\u0026lt;\u0026thinsp;7-fold decrease in CA-125 level, respectively, after GnRH agonist treatment.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eEndometriosis was not associated with a poorer pregnancy outcome. Patients with adenomyosis with/without endometriosis had higher miscarriage rates, lower LBRs, and lower cLBRs, especially in patients aged\u0026thinsp;\u0026ge;\u0026thinsp;38 years, even after GnRH agonist treatment before FET cycles. Patients who have a greater than 7-fold decrease in CA-125 level after GnRH agonist treatment might have better clinical pregnancy outcomes.\u003c/p\u003e","manuscriptTitle":"Impact of adenomyosis and endometriosis on IVF/ICSI pregnancy outcome in patients undergoing gonadotropin-releasing hormone agonist treatment and frozen embryo transfer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-08-11 17:20:49","doi":"10.21203/rs.3.rs-1919429/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"873d7e34-dd3d-4ba2-8b0f-d3bbf67ed1eb","owner":[],"postedDate":"August 11th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-10-25T19:57:00+00:00","versionOfRecord":[],"versionCreatedAt":"2022-08-11 17:20:49","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1919429","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1919429","identity":"rs-1919429","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}