Comparison of Pregnancy and Neonatal Outcomes of Single Frozen Blastocyst Transfer Between Letrozole-induction and HRT Cycles in Patients With Abnormal Ovulation

Comparison of Pregnancy and Neonatal Outcomes of Single Frozen Blastocyst Transfer Between Letrozole-induction and HRT Cycles in Patients With Abnormal Ovulation | 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 Help Center Sign In Submit a Preprint Cite Share Download PDF Research Comparison of Pregnancy and Neonatal Outcomes of Single Frozen Blastocyst Transfer Between Letrozole-induction and HRT Cycles in Patients With Abnormal Ovulation Junwei Zhang, Zhen Li, Lijun Sun, Yichun Guan, Mingze Du This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-204446/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: The use of frozen embryo transfer (FET) cycles has dramatically risen. The optimal endometrial preparation method for women undergoing FET is of utmost importance to provide the optimal chances of pregnancy. For patients with abnormal ovulation in particular, there have been few studies on FET protocols; notably, most of these studies focus only on the clinical pregnancy rate or live birth rate (LBR) and pay little attention to the regimen’s safety for offspring. Methods: It was a retrospective cohort study. First FET cycle with a single blastocyst from whole embryo frozen IVF/ICSI at the Reproductive Center of Third Affiliated Hospital of Zhengzhou University between January 2016 and January 2020. The LBR was the primary outcome of interest. The secondary outcome measures were miscarriage rate and offspring safety, including preterm birth, low birthweight (LBW), small-for-gestational age (SGA), macrosomia and large-for-gestational age (LGA). Results: In total, 2782 FET cycles met the eligibility criteria for analysis. Additionally, there were 1178 singleton births from FET cycles. The clinical pregnancy rate was 58.4% in the L-FET group and 54.5% in the HRT group, with no statistical significance (P=.116). The miscarriage rate was higher in the HRT group than in the L-FET group (21.7% vs. 14.3%, P=.005). The LBR was significantly higher in the L-FET group than in the HRT group (49.6% vs. 41.7%, P=.001). Neonatal outcomes were similar between the two groups. After adjustments for confounding factors, the LBR was higher in the L-FET group (aOR 1.30, 95% CI 1.06-1.58). The rate of miscarriage was lower in the L-FET group (aOR 0.63, 95% CI 0.44-0.90). Conclusion: For patients with abnormal ovulation, the L-FET regimen has a higher LBR and lower miscarriage rate than HRT. The neonatal outcomes were similar between the two groups. Endocrinology & Metabolism Letrozole frozen embryo transfer live birth rate miscarriage neonatal outcomes Background Over the past decade, the use of frozen embryo transfer (FET) cycles has dramatically risen with the development of vitrification technology, and a rapid rise in single embryo transfer (ET), combined with the development of preimplantation genetic screening (PGS) and preimplantation genetic diagnosis (PGD), has increased the number of embryos available for freezing[ 1 – 3 ]. FET increases the cumulative live birth rate (LBR), reduces cost, is relatively simple to undertake and can be accomplished in a shorter time period than repeated in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles with fresh ET. Currently, for every 2 embryos transferred, one is a FET[ 4 ]. In some countries, the number of FET cycles far exceeds the number of fresh ET cycles[ 5 ]. The optimal endometrial preparation method for women undergoing FET is of utmost importance to provide the optimal chances of pregnancy. There are different FET cycle regimens used to prepare the endometrium, including natural cycles, hormone replacement therapy (HRT) with estrogen and progesterone, cycles in which ovulation is induced by drugs, and gonadotrophin-releasing hormone agonist (GnRH-a) cycles. Although there are many options for the preparation of the endometrium, there is still no uniform recommendation for the preparation of the FET endometrium for different groups of women to date[ 6 , 7 ]. For patients with abnormal ovulation in particular, there have been few studies on FET protocols; notably, most of these studies focus only on the clinical pregnancy rate or LBR[ 8 – 10 ] and pay little attention to the regimen’s safety for offspring. The most frequently used regimens for patients with abnormal ovulation are ovulation induction by letrozole and HRT. Letrozole is a third-generation aromatase inhibitor that is used mainly for the treatment of postmenopausal breast cancer. Recent studies have shown that letrozole can be used effectively for ovulation induction. Letrozole has a short half-life and has both peripheral and central effects[ 11 , 12 ]. Similar to clomiphene, Letrozole has no antiestrogen effect, is effective at promoting ovulation and has little effect on the cervical mucus, endometrium and sex hormone levels[ 12 , 13 ]. Furthermore, there are no obvious teratogenic effects on the fetus[ 14 , 15 ]. HRT can be used to prepare the endometrium, and then, the date of transplantation can be arranged and the number of monitoring procedures reduced; additionally, this is a popular clinical method for people with ovulation disorders[ 4 ]. However, there are few studies comparing the two regimens in women with ovulation disorders, and the existing ones focus mostly on clinical outcomes, such as the clinical pregnancy rate or LBR[ 8 , 16 ]. Moreover, few studies have focused on or compared the safety of the two regimens for offspring. To the best of our knowledge, only one study has investigated the safety of the two regimens for offspring, but the study did not implement restrictions of the inclusion of patients; that is, patients with either normal or abnormal ovulation were included. Additionally, the study was limited by its lack of important information, including the dose and duration of letrozole[ 17 ]. Therefore, the purpose of this study was to explore the clinical outcomes and safety to offspring of L-FET and HRT for patients with ovulation disorders and provide evidence to guide the choice of clinical protocol. Materials And Methods Study design and population This was a retrospective cohort study approved by the review board of the Third Affiliated Hospital of Zhengzhou University. All patients who initiated the first FET of whole-embryo-cycle transfer with IVF/ICSI at the Reproductive Center of Third Affiliated Hospital of Zhengzhou University between January 2016 and January 2020 were analyzed for potential inclusion. We included FET cycles of oligo-anovulation or anovulation with L-FET or HRT, and only single blastocyst transfer cycles were included. Cycles with maternal age > 40 years were excluded, and cases with adenomyosis, uterine malformations, endometrial polyps, and PGD or PGS were excluded. Endometrial preparation protocols Beginning on menstrual cycle day 3, 4 or 5, 2.5 mg of letrozole (Hengrui Medicine Co., China) was administered daily for 5 consecutive days. Then, follicle growth was monitored by vaginal ultrasound and, if necessary, combined with serum estradiol analysis on day 10. If the diameter of the dominant follicle was greater than 14 mm, there was no need to add HMG to the regimen; otherwise, HMG (Lizhu Pharmaceutical Trading Co., China) 37.5–75 IU daily was added according to the development of the follicle. When the diameter of the dominant follicle was greater than 18 mm, the endometrial thickness was greater than 7 mm, serum estradiol was > 150 pg/ml and the occurrence of an LH surge was evident, 10 000 IU urinary hCG was injected (Lizhu Pharmaceutical Trading Co., China). FET was cancelled for cycles with insufficient thickness (< 7 mm) or insufficient follicle development . For HRT cycles, vaginal ultrasound examination was performed on the 3rd day of the menstrual cycle, 2–3 mg of estradiol valerate was taken orally three times daily (Bayer Co. Germany), and vaginal ultrasound examination was performed 7 days later. The drug dose was adjusted according to the thickness of the endometrium (up to 9 mg per day). When the medication was taken for > 12 days, the endometrial thickness was ≥ 7 mm, and the serum estrogen level was greater than 150 pg/ml, endometrial transformation was performed. FET was cancelled for Cycles with insufficient thickness ( 12 days in the HRT cycle, an endometrial thickness of ≥ 7 mm was verified, and routine corpus luteum support, namely oral dydrogesterone (2 times daily, 10 mg once) (Abbott Co. America) and intravaginal administration of 90 mg of a progesterone sustained-release vaginal gel (Merck Co. Germany), was given. Five days after endometrial development with corpus luteum support, single blastocyst transplantation was carried out by abdominal ultrasound. Corpus luteum support was performed at least until 55 days after transplantation if pregnancy occurred. Outcome measures and definition The primary outcome measure was LBR, defined as at least one live birth after ≥ 28 gestational weeks. The secondary outcome measures were the miscarriage rate (defined as a loss of clinical pregnancy before 28 gestational weeks) and offspring safety, which was assessed by examining the neonatal birth weight of singleton live births as follows: low birthweight (LBW, birthweight < 2500 g), small-for-gestational age (SGA, 90th percentile for gestational age)[ 18 ]. Statistical analysis All statistical management and analyses were performed using SPSS software, version 22.0. The one-sample K-S test was used to check for normality. Continuous variables with abnormal distributions are expressed as the mean ± SD, and Student’s t test was used to assess between-group differences. Categorical variables are represented as the number of cases (n) and percentage (%). The means from chi-square analyses were used to assess the differences between groups with Fisher’s exact test when necessary. For outcome measures (LBR, miscarriage rate, preterm birth, LBW, SGA, macrosomia, LGA), multiple logistic regression was used to adjust for the baseline characteristics. Unadjusted odds ratios and adjusted odds ratios (AORs) with 95% confidence intervals (CIs) were calculated. Statistical significance was set at p < 0.05. Results Study population From January 2016 to January 2020, a total of 2782 FET cycles, including 502 L-FET and 2280 HRT cycles, met the eligibility criteria for analysis. There were 1178 FET cycles with singleton births, including 245 cycles from L-FET cycles and 933 from HRT cycles. Baseline characteristics Table 1 lists the cycle baseline characteristics. There were no significant between-group differences in maternal age, paternal age, body mass index, duration of infertility, type of infertility, infertility diagnosis, basal serum FSH level, basal antral follicle count, fertilization method or developmental stage of the blastocyst. However, the endometrial thickness on the day of embryo transfer in the L-FET group was significantly higher than that in the HRT group (P < .001). Reproductive outcomes As shown in Table 2, the clinical pregnancy rate was 58.4% for the L-FET group and 54.5% for the HRT group, with no statistical significance (P = .116). The miscarriage rate was higher in the HRT group than in the L-FET group (21.7% vs. 14.3%, P = .005). Additionally, the LBR was significantly higher in the L-FET group than in the HRT group (49.6% vs. 41.7%, P = .001); similarly, the singleton LBR was higher in the L-FET group (48.8% vs. 40.9%, P = .001). The twin pregnancy rates were comparable between the two groups (0.8% vs. 0.8%, P = .987). Neonatal outcomes, including the newborn sex ratio and rates of preterm birth, normal neonatal birthweight, LBW, SGA, macrosomia and LGA, were similar between groups. The specific values are presented in Table 3. Regarding the main outcome measures, to adjust for the influence of confounding factors, we conducted a multiple logistic regression analysis. The included factors were maternal age, body mass index, duration of infertility, type of infertility (primary/secondary infertility), infertility diagnosis (tubal/male/others), basal antral follicle count, fertilization method (IVF/ICSI) and developmental stage of blastocysts (D5/D6). The unadjusted OR and adjusted OR value with their 95% CIs are presented in Table 4. After adjustments for confounding factors, the LBR was higher in the L-FET group (aOR 1.30, 95% CI 1.06–1.58). The specific multiple logistic regression data on LBW are presented in Supplemental Table 1. The rate of miscarriage was lower in the L-FET group (aOR 0.63, 95% CI 0.44–0.90). Furthermore, the rates of preterm birth, LBW, SGA, macrosomia and LGA remained consistent with the unadjusted rates, and the rates were comparable between the two groups. Discussion In summary, the results of this study demonstrate that the L-FET group has a higher LBR and lower miscarriage rate than the HRT group of patients with abnormal ovulation with a single blastocyst transfer. However, the offspring outcomes, including the rates of preterm birth, normal neonatal birthweight, LBW, SGA, macrosomia and LGA, were comparable between the two groups. Comparisons with other reports Regarding clinical outcomes, to the best of our knowledge, few studies have explored L-FET and HRT for patients with abnormal ovulation, including polycystic ovary syndrome (PCOS). The first study was published in 2014 and included only 116 PCOS cycles[ 19 ]. The results of the study showed that compared with those of the HRT group, the clinical pregnancy rate and ongoing pregnancy rate were significantly higher in the L-FET group. In the same year, Li et al.[ 20 ] evaluated the clinical efficacy of L-FET on ovulation induction and HRT during endometrial preparation in patients with ovulation disorders. This study suggested that the LBR of patients in the L-FET group (44.6%) was significantly higher than that of patients in the HRT group (32.5%, P < 0.05), while the miscarriage rate (12.0%) was significantly lower than that in the HRT group (21.0%, P < 0.05). A recent study published in 2019. Zhang et al.[ 8 ] further explored the clinical outcomes of L-FET and HRT among women with PCOS, and the results suggested that letrozole use for endometrial preparation was associated with higher LBR than use of HRT. However, one randomized controlled trial of 177 infertile PCOS patients had a different result. After analysis, there were no significant between-group differences in the implantation rate; the chemical, ectopic, and clinical pregnancy rates; the miscarriage rate; or the ongoing pregnancy rate[ 16 ]. To the best of our knowledge, only one study has explored both clinical outcomes and offspring outcomes. The study was a large retrospective cohort study from Japan published in 2017 (with 110 772 FET cycles included)[ 17 ]. Compared to those in the HRT group, the clinical pregnancy rate, clinical pregnancy with fetal heartbeat rate, and LBR were significantly higher in the L-FET group, while the miscarriage rate was significantly lower. Neonatal outcomes with the different regimens were mostly similar, which is consistent with our findings. However, the study did not strictly limit the inclusion of patients. According to the description in the article, in Japan, letrozole is used mainly for unexplained infertility, not for people with ovulation disorders. The important limitations of the study are the lack of information concerning the reasons for selecting the specific FET method, parity, the number of previous ART failures, embryo quality and the dose and duration of letrozole intake. Moreover, the study did not limit the type of ET, including cleavage-stage or blastocyst-stage ET, or the number of transferred embryos. According to current research, there may be differences in clinical and neonatal outcomes between cleavage-stage and blastocyst-stage embryo transfers[ 21 – 23 ]. Moreover, the effect of the number of transferred embryos on pregnancy outcome is relatively clear[ 24 , 25 ]. Therefore, to exclude the confounding effects of embryo developmental stage and number of transferred embryos on outcomes, we included only single blastocyst transfer on day 5 or day 6. Plausible biological mechanisms There are two possible mechanisms underlying the significant increase in the LBR and decrease in the miscarriage rate. One is that letrozole is a specific third-generation aromatase inhibitor; when the aromatase is inhibited, the conversion of androgens to estrogens decreases, and the decrease in peripheral estrogen leads to increased expression of estrogen receptors and, thus, increased sensitivity to subsequently high estrogen levels, resulting in faster endometrial proliferation and increased blood flow in the uterus and endometrium, with positive effects on implantation[ 17 , 26 , 27 ]. Our study also shows that the thickness of the endometrium in the L-FET group was higher than that in the HRT group, which may be related to this mechanism. Another possible mechanism is that letrozole might increase endometrial receptivity by increasing the expression of uterine receptivity such as integrin, L-selectin, leukemia inhibitory factor and pinopods during the implantation window[ 28 ], which is beneficial for improving the success rate of frozen embryo transfer. Strengths and limitations The strengths of this study are twofold. First, we included single-center cycles with full follow-up, cycles performed during the same period, and first transfer cycles, and this study included only the single blastocyst transfer cycle, to control the number of embryos transferred for the assessment of the pregnancy outcomes, as the consequent reduction in twin pregnancies had an impact on neonatal outcomes, which minimized potential bias. Second, our study explored not only the clinical outcomes of the two regimens but also their safety for the offspring, which has always been the focus of research and has always been of profound importance. Our study also has several limitations. First, it is limited by its retrospective nature, and thus, a further prospective study is needed. Second, we did not explore the relevant biological mechanism. In conclusion, for patients with abnormal ovulation, the L-FET regimen has a higher LBR and lower miscarriage rate than HRT. The neonatal outcomes, including the rates of preterm birth, normal neonatal birthweight, LBW, SGA, macrosomia and LGA, were similar between the two groups. Therefore, these findings imply that letrozole might be a better regimen for FET among women with abnormal ovulation, but further randomized controlled studies with large samples are needed. List Of Abbreviations IVF, in vitro fertilization; ICSI, intracytoplasmic sperm injection; FET, frozen embryo transfer; LBR, live birth rate; LBW, low birth weight; SGA, small-for-gestational age; LGA, large-for-gestational age Declarations Acknowledgments We acknowledge the patients who participated in the study. We also thank American Journal Experts for their professional manuscript editing service. Authors' contributions ZJW and DMZ designed the study and selected the population to be included and excluded. ZJW and LZ were involved in the data extraction and analysis. SLJ and GYC reviewed the data. ZJW was involved in drafting this article. All authors have approved the final version of the manuscript. Funding We did not receive any funding for this study Availability of data and material All data are included in this article and its additional files. Ethics approval and consent to participate This study was approved by the ethics committee of The Third Affiliated Hospital of Zhengzhou University (2020 Medical Ethics Review No. 126). Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. References Pereira N, Rosenwaks Z. A fresh(er) perspective on frozen embryo transfers. Fertil Steril 2016, 106: 257-258. 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Tables Table 1 Basic characteristics for cycles from 2017 through 2019 Characteristics L-FET(n = 502) HRT (n = 2280) P value Maternal age(y) 30.95 ± 4.56 31.20 ± 4.97 .062 Paternal age(y) 31.67 ± 5.14 32.33 ± 5.72 .058 Body mass index(kg/m2) 23.88 ± 2.99 23.97 ± 3.18 .548 Duration of Infertility (y) 3.26 ± 2.83 3.39 ± 2.75 .374 Type of infertility .239 Primary infertility 46.6(234/502) 43.7(997/2280) Secondary infertility 53.4(268/502) 56.3(1283/2280) Infertility diagnosis .322 Tubal factor 32.9(165/502) 35.4(807/2280) Male factor 21.7(109/502) 19.0(434/2280) Others 45.4(228/502) 45.6(1039/2280) Basal serum FSH level(IU/L) 5.5 ± 1.7 5.8 ± 2.1 .077 Basal antral follicle count 19.97 ± 7.03 18.90 ± 7.52 .072 Fertilization method .609 IVF 73.5(369/502) 74.6(1701/2280) ICSI 26.5(133/502) 25.4(579/2280) Endometrial thickness on day of embryo transfer (mm) 9.72 ± 1.83 8.99 ± 2.10 < .001 Development stage of blastocysts .323 D5 63.9(321/502) 61.1(1404/2280) D6 36.1(181/502) 38.4(876/2280) Note: Data are presented as mean ± SD for continuous variable and % (n/N) for categorical variable. Student t test was used for continuous variables, and the Pearson χ 2 test was used for categorical variables with Fisher's exact test when necessary. Table 2 Comparison of pregnancy outcome between the two groups L-FET(n = 502) HRT (n = 2280) P value Clinical pregnancy rate 58.4(293/502) 54.5(1243/2280) .116 Abortion rate 14.3(42/293) 21.7(270/1243) .005 Live birth rate 49.6(249/502) 41.7(951/2280) .001 Singletons 48.8(245/502) 40.9(933/2280) .001 Twins 0.8(4/502) 0.8(18/2280) .987 Note: Data are presented as % (n/N) for categorical variable. Pearson χ 2 test was used for categorical variables with Fisher's exact test when necessary. Table 3 Comparison of singleton neonatal outcome between the two groups L-FET(n = 245) HRT (n = 933) P value Gender of newborn .570 Male 53.1(130/245) 55.1(514/933) Female 46.9(115/245) 44.9(419/933) Preterm birth 6.5(16/245) 6.6(62/933) .949 Neonatal birthweight 3401.67 ± 498.97 3468.91 ± 561.27 .088 Low birthweight 4.9(12/245) 4.8(45/933) .961 Small for gestational age 12.2(30/245) 10.5(98/933) .436 Macrosomia 13.9(34/245) 16.1(150/933) .399 Large for gestational age 13.5(33/245) 18.5(173/933) .063 Congenital malformations rate 0.4(1/245) 0.6(6/933) .670 Note: Data are presented as mean ± SD for continuous variable and % (n/N) for categorical variable. Student t test was used for continuous variables, and the Pearson χ 2 test was used for categorical variables with Fisher's exact test when necessary. Table 4 Unadjusted and adjusted odds ratios of reproductive outcomes of blastocysts transfer following L-FET versus HRT cycles. Unadjusted OR (95%CI ) Adjusted OR (95%CI ) Live birth rate 1.37(1.13–1.67) 1.30(1.06–1.58) Abortion rate 0.60 (0.42–0.86) 0.63(0.44–0.90) Preterm birth 0.98 (0.56–1.73) 0.99(0.56–1.77) Low birthweight 0.98(0.51–1.89) 0.97(0.50–1.87) Small for gestational age 0.84(0.54–1.30) 0.84(0.54–1.29) Macrosomia 1.19(0.80–1.78) 1.18(0.79–1.78) Large for gestational age 1.46(0.97–2.19) 1.45(0.97–2.17) Note: Analysis were adjusted for maternal age, body mass index, duration of infertility, type of infertility(Primary/ Secondary infertility), infertility diagnosis(Tubal/ Male/ Others), basal antral follicle count, fertilization method(IVF/ICSI) and development stage of blastocysts(D5/D6) .CI = confidence interval Supplementary Files SupplementaryTable1.docx 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 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-204446","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research","associatedPublications":[],"authors":[{"id":10653907,"identity":"0b4a5164-7a4b-48d5-b2c3-2cacf4a190b1","order_by":0,"name":"Junwei Zhang","email":"","orcid":"","institution":"The Third Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Junwei","middleName":"","lastName":"Zhang","suffix":""},{"id":10653908,"identity":"7e437c8c-d17a-492b-ba91-4d6fd704798b","order_by":1,"name":"Zhen Li","email":"","orcid":"","institution":"The Third Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zhen","middleName":"","lastName":"Li","suffix":""},{"id":10653909,"identity":"545e56ee-82d9-42f0-a046-ba4b763b30bc","order_by":2,"name":"Lijun Sun","email":"","orcid":"","institution":"The Third Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Lijun","middleName":"","lastName":"Sun","suffix":""},{"id":10653910,"identity":"c10a1006-f3f3-41cc-8281-fc9de612f114","order_by":3,"name":"Yichun Guan","email":"","orcid":"","institution":"The Third Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yichun","middleName":"","lastName":"Guan","suffix":""},{"id":10653911,"identity":"3a7c0a3c-b1d2-405c-9dd3-7950359d41ef","order_by":4,"name":"Mingze Du","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4klEQVRIiWNgGAWjYDCCA2DEwMDG3tj44IOBjRzxWvh4DjcbzihIMyZKCxjISbi3CfN8OJxIUAffjezEwwW/6uTYJBjbmG0MmBMY2A8f3YBPi+SN3A2HZ/axGbNJN7Y9zjFgy2PgSUu7gU+LAUgLbw9PYpvMwXbjHAOeYgYJHjNitEjUt0kktklbGEgkNhClheeHQQIbSAuDgQFhLZJn3gJtaUgwbOM52GzYY5BgzEbIL3zHczd/5vlTJy/f3v7wwY8//+X42Q8fw6sFDBjbkDhsBJWDwR/ilI2CUTAKRsEIBQAeUE9sEggdwQAAAABJRU5ErkJggg==","orcid":"","institution":"The Third Affiliated Hospital of Zhengzhou University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Mingze","middleName":"","lastName":"Du","suffix":""}],"badges":[],"createdAt":"2021-02-04 03:04:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-204446/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-204446/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":13661307,"identity":"01e58a22-38ca-4c41-88a4-acffdfe51d3a","added_by":"auto","created_at":"2021-09-17 10:28:45","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":906467,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-204446/v1/4775132b-3ce5-4678-a7bd-55accc7f33ae.pdf"},{"id":6029422,"identity":"d5fcfa6c-7f65-48b6-9581-760959d541f9","added_by":"auto","created_at":"2021-02-16 22:32:41","extension":"docx","order_by":8,"title":"","display":"","copyAsset":false,"role":"supplement","size":15073,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTable1.docx","url":"https://assets-eu.researchsquare.com/files/rs-204446/v1/16a434eff1510119c7174d89.docx"}],"financialInterests":"","formattedTitle":"\u003cp\u003eComparison of Pregnancy and Neonatal Outcomes of Single Frozen Blastocyst Transfer Between Letrozole-induction and HRT Cycles in Patients With Abnormal Ovulation\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eOver the past decade, the use of frozen embryo transfer (FET) cycles has dramatically risen with the development of vitrification technology, and a rapid rise in single embryo transfer (ET), combined with the development of preimplantation genetic screening (PGS) and preimplantation genetic diagnosis (PGD), has increased the number of embryos available for freezing[\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e]. FET increases the cumulative live birth rate (LBR), reduces cost, is relatively simple to undertake and can be accomplished in a shorter time period than repeated in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles with fresh ET. Currently, for every 2 embryos transferred, one is a FET[\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e]. In some countries, the number of FET cycles far exceeds the number of fresh ET cycles[\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eThe optimal endometrial preparation method for women undergoing FET is of utmost importance to provide the optimal chances of pregnancy. There are different FET cycle regimens used to prepare the endometrium, including natural cycles, hormone replacement therapy (HRT) with estrogen and progesterone, cycles in which ovulation is induced by drugs, and gonadotrophin-releasing hormone agonist (GnRH-a) cycles. Although there are many options for the preparation of the endometrium, there is still no uniform recommendation for the preparation of the FET endometrium for different groups of women to date[\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e]. For patients with abnormal ovulation in particular, there have been few studies on FET protocols; notably, most of these studies focus only on the clinical pregnancy rate or LBR[\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e] and pay little attention to the regimen\u0026rsquo;s safety for offspring. The most frequently used regimens for patients with abnormal ovulation are ovulation induction by letrozole and HRT.\u003c/p\u003e\n\u003cp\u003eLetrozole is a third-generation aromatase inhibitor that is used mainly for the treatment of postmenopausal breast cancer. Recent studies have shown that letrozole can be used effectively for ovulation induction. Letrozole has a short half-life and has both peripheral and central effects[\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e]. Similar to clomiphene, Letrozole has no antiestrogen effect, is effective at promoting ovulation and has little effect on the cervical mucus, endometrium and sex hormone levels[\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e]. Furthermore, there are no obvious teratogenic effects on the fetus[\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e]. HRT can be used to prepare the endometrium, and then, the date of transplantation can be arranged and the number of monitoring procedures reduced; additionally, this is a popular clinical method for people with ovulation disorders[\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eHowever, there are few studies comparing the two regimens in women with ovulation disorders, and the existing ones focus mostly on clinical outcomes, such as the clinical pregnancy rate or LBR[\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e]. Moreover, few studies have focused on or compared the safety of the two regimens for offspring. To the best of our knowledge, only one study has investigated the safety of the two regimens for offspring, but the study did not implement restrictions of the inclusion of patients; that is, patients with either normal or abnormal ovulation were included. Additionally, the study was limited by its lack of important information, including the dose and duration of letrozole[\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e]. Therefore, the purpose of this study was to explore the clinical outcomes and safety to offspring of L-FET and HRT for patients with ovulation disorders and provide evidence to guide the choice of clinical protocol.\u003c/p\u003e"},{"header":"Materials And Methods","content":"\u003cp\u003eStudy design and population\u003c/p\u003e\n\u003cp\u003eThis was a retrospective cohort study approved by the review board of the Third Affiliated Hospital of Zhengzhou University. All patients who initiated the first FET of whole-embryo-cycle transfer with IVF/ICSI at the Reproductive Center of Third Affiliated Hospital of Zhengzhou University between January 2016 and January 2020 were analyzed for potential inclusion. We included FET cycles of oligo-anovulation or anovulation with L-FET or HRT, and only single blastocyst transfer cycles were included. Cycles with maternal age\u0026thinsp;\u0026gt;\u0026thinsp;40 years were excluded, and cases with adenomyosis, uterine malformations, endometrial polyps, and PGD or PGS were excluded.\u003c/p\u003e\n\u003cp\u003eEndometrial preparation protocols\u003c/p\u003e\n\u003cp\u003eBeginning on menstrual cycle day 3, 4 or 5, 2.5 mg of letrozole (Hengrui Medicine Co., China) was administered daily for 5 consecutive days. Then, follicle growth was monitored by vaginal ultrasound and, if necessary, combined with serum estradiol analysis on day 10. If the diameter of the dominant follicle was greater than 14 mm, there was no need to add HMG to the regimen; otherwise, HMG (Lizhu Pharmaceutical Trading Co., China) 37.5\u0026ndash;75 IU daily was added according to the development of the follicle. When the diameter of the dominant follicle was greater than 18 mm, the endometrial thickness was greater than 7 mm, serum estradiol was \u0026gt;\u0026thinsp;150 pg/ml and the occurrence of an LH surge was evident, 10 000 IU urinary hCG was injected (Lizhu Pharmaceutical Trading Co., China). FET was cancelled for cycles with insufficient thickness (\u0026lt;\u0026thinsp;7 mm) or insufficient follicle development .\u003c/p\u003e\n\u003cp\u003eFor HRT cycles, vaginal ultrasound examination was performed on the 3rd day of the menstrual cycle, 2\u0026ndash;3 mg of estradiol valerate was taken orally three times daily (Bayer Co. Germany), and vaginal ultrasound examination was performed 7 days later. The drug dose was adjusted according to the thickness of the endometrium (up to 9 mg per day). When the medication was taken for \u0026gt;\u0026thinsp;12 days, the endometrial thickness was \u0026ge;\u0026thinsp;7 mm, and the serum estrogen level was greater than 150 pg/ml, endometrial transformation was performed. FET was cancelled for Cycles with insufficient thickness (\u0026lt;\u0026thinsp;7 mm).\u003c/p\u003e\n\u003cp\u003eAfter the hCG injection in the L-FET cycle or after a medication time of \u0026gt;\u0026thinsp;12 days in the HRT cycle, an endometrial thickness of \u0026ge;\u0026thinsp;7 mm was verified, and routine corpus luteum support, namely oral dydrogesterone (2 times daily, 10 mg once) (Abbott Co. America) and intravaginal administration of 90 mg of a progesterone sustained-release vaginal gel (Merck Co. Germany), was given. Five days after endometrial development with corpus luteum support, single blastocyst transplantation was carried out by abdominal ultrasound. Corpus luteum support was performed at least until 55 days after transplantation if pregnancy occurred.\u003c/p\u003e\n\u003cp\u003eOutcome measures and definition\u003c/p\u003e\n\u003cp\u003eThe primary outcome measure was LBR, defined as at least one live birth after \u0026ge;\u0026thinsp;28 gestational weeks.\u003c/p\u003e\n\u003cp\u003eThe secondary outcome measures were the miscarriage rate (defined as a loss of clinical pregnancy before 28 gestational weeks) and offspring safety, which was assessed by examining the neonatal birth weight of singleton live births as follows: low birthweight (LBW, birthweight\u0026thinsp;\u0026lt;\u0026thinsp;2500 g), small-for-gestational age (SGA, \u0026lt;\u0026thinsp;10th percentile for gestational age)[\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e], macrosomia (birthweight\u0026thinsp;\u0026ge;\u0026thinsp;4000 g), and large-for-gestational age (LGA, \u0026gt;\u0026thinsp;90th percentile for gestational age)[\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eStatistical analysis\u003c/p\u003e\n\u003cp\u003eAll statistical management and analyses were performed using SPSS software, version 22.0.\u003c/p\u003e\n\u003cp\u003eThe one-sample K-S test was used to check for normality. Continuous variables with abnormal distributions are expressed as the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, and Student\u0026rsquo;s t test was used to assess between-group differences. Categorical variables are represented as the number of cases (n) and percentage (%). The means from chi-square analyses were used to assess the differences between groups with Fisher\u0026rsquo;s exact test when necessary. For outcome measures (LBR, miscarriage rate, preterm birth, LBW, SGA, macrosomia, LGA), multiple logistic regression was used to adjust for the baseline characteristics. Unadjusted odds ratios and adjusted odds ratios (AORs) with 95% confidence intervals (CIs) were calculated. Statistical significance was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eStudy population\u003c/p\u003e\n\u003cp\u003eFrom January 2016 to January 2020, a total of 2782 FET cycles, including 502 L-FET and 2280 HRT cycles, met the eligibility criteria for analysis. There were 1178 FET cycles with singleton births, including 245 cycles from L-FET cycles and 933 from HRT cycles.\u003c/p\u003e\n\u003cp\u003eBaseline characteristics\u003c/p\u003e\n\u003cp\u003eTable\u0026nbsp;1 lists the cycle baseline characteristics. There were no significant between-group differences in maternal age, paternal age, body mass index, duration of infertility, type of infertility, infertility diagnosis, basal serum FSH level, basal antral follicle count, fertilization method or developmental stage of the blastocyst. However, the endometrial thickness on the day of embryo transfer in the L-FET group was significantly higher than that in the HRT group (P\u0026thinsp;\u0026lt;\u0026thinsp;.001).\u003c/p\u003e\n\u003cp\u003eReproductive outcomes\u003c/p\u003e\n\u003cp\u003eAs shown in Table\u0026nbsp;2, the clinical pregnancy rate was 58.4% for the L-FET group and 54.5% for the HRT group, with no statistical significance (P\u0026thinsp;=\u0026thinsp;.116). The miscarriage rate was higher in the HRT group than in the L-FET group (21.7% vs. 14.3%, P\u0026thinsp;=\u0026thinsp;.005). Additionally, the LBR was significantly higher in the L-FET group than in the HRT group (49.6% vs. 41.7%, P\u0026thinsp;=\u0026thinsp;.001); similarly, the singleton LBR was higher in the L-FET group (48.8% vs. 40.9%, P\u0026thinsp;=\u0026thinsp;.001). The twin pregnancy rates were comparable between the two groups (0.8% vs. 0.8%, P\u0026thinsp;=\u0026thinsp;.987). Neonatal outcomes, including the newborn sex ratio and rates of preterm birth, normal neonatal birthweight, LBW, SGA, macrosomia and LGA, were similar between groups. The specific values are presented in Table\u0026nbsp;3.\u003c/p\u003e\n\u003cp\u003eRegarding the main outcome measures, to adjust for the influence of confounding factors, we conducted a multiple logistic regression analysis. The included factors were maternal age, body mass index, duration of infertility, type of infertility (primary/secondary infertility), infertility diagnosis (tubal/male/others), basal antral follicle count, fertilization method (IVF/ICSI) and developmental stage of blastocysts (D5/D6). The unadjusted OR and adjusted OR value with their 95% CIs are presented in Table\u0026nbsp;4. After adjustments for confounding factors, the LBR was higher in the L-FET group (aOR 1.30, 95% CI 1.06\u0026ndash;1.58). The specific multiple logistic regression data on LBW are presented in Supplemental Table\u0026nbsp;1. The rate of miscarriage was lower in the L-FET group (aOR 0.63, 95% CI 0.44\u0026ndash;0.90). Furthermore, the rates of preterm birth, LBW, SGA, macrosomia and LGA remained consistent with the unadjusted rates, and the rates were comparable between the two groups.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn summary, the results of this study demonstrate that the L-FET group has a higher LBR and lower miscarriage rate than the HRT group of patients with abnormal ovulation with a single blastocyst transfer. However, the offspring outcomes, including the rates of preterm birth, normal neonatal birthweight, LBW, SGA, macrosomia and LGA, were comparable between the two groups.\u003c/p\u003e\n\u003cp\u003eComparisons with other reports\u003c/p\u003e\n\u003cp\u003eRegarding clinical outcomes, to the best of our knowledge, few studies have explored L-FET and HRT for patients with abnormal ovulation, including polycystic ovary syndrome (PCOS). The first study was published in 2014 and included only 116 PCOS cycles[\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e]. The results of the study showed that compared with those of the HRT group, the clinical pregnancy rate and ongoing pregnancy rate were significantly higher in the L-FET group. In the same year, Li et al.[\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e] evaluated the clinical efficacy of L-FET on ovulation induction and HRT during endometrial preparation in patients with ovulation disorders. This study suggested that the LBR of patients in the L-FET group (44.6%) was significantly higher than that of patients in the HRT group (32.5%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), while the miscarriage rate (12.0%) was significantly lower than that in the HRT group (21.0%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). A recent study published in 2019. Zhang et al.[\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e] further explored the clinical outcomes of L-FET and HRT among women with PCOS, and the results suggested that letrozole use for endometrial preparation was associated with higher LBR than use of HRT.\u003c/p\u003e\n\u003cp\u003eHowever, one randomized controlled trial of 177 infertile PCOS patients had a different result. After analysis, there were no significant between-group differences in the implantation rate; the chemical, ectopic, and clinical pregnancy rates; the miscarriage rate; or the ongoing pregnancy rate[\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e]. To the best of our knowledge, only one study has explored both clinical outcomes and offspring outcomes. The study was a large retrospective cohort study from Japan published in 2017 (with 110 772 FET cycles included)[\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e]. Compared to those in the HRT group, the clinical pregnancy rate, clinical pregnancy with fetal heartbeat rate, and LBR were significantly higher in the L-FET group, while the miscarriage rate was significantly lower. Neonatal outcomes with the different regimens were mostly similar, which is consistent with our findings. However, the study did not strictly limit the inclusion of patients. According to the description in the article, in Japan, letrozole is used mainly for unexplained infertility, not for people with ovulation disorders. The important limitations of the study are the lack of information concerning the reasons for selecting the specific FET method, parity, the number of previous ART failures, embryo quality and the dose and duration of letrozole intake.\u003c/p\u003e\n\u003cp\u003eMoreover, the study did not limit the type of ET, including cleavage-stage or blastocyst-stage ET, or the number of transferred embryos. According to current research, there may be differences in clinical and neonatal outcomes between cleavage-stage and blastocyst-stage embryo transfers[\u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e]. Moreover, the effect of the number of transferred embryos on pregnancy outcome is relatively clear[\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e]. Therefore, to exclude the confounding effects of embryo developmental stage and number of transferred embryos on outcomes, we included only single blastocyst transfer on day 5 or day 6.\u003c/p\u003e\n\u003cp\u003ePlausible biological mechanisms\u003c/p\u003e\n\u003cp\u003eThere are two possible mechanisms underlying the significant increase in the LBR and decrease in the miscarriage rate. One is that letrozole is a specific third-generation aromatase inhibitor; when the aromatase is inhibited, the conversion of androgens to estrogens decreases, and the decrease in peripheral estrogen leads to increased expression of estrogen receptors and, thus, increased sensitivity to subsequently high estrogen levels, resulting in faster endometrial proliferation and increased blood flow in the uterus and endometrium, with positive effects on implantation[\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e27\u003c/span\u003e]. Our study also shows that the thickness of the endometrium in the L-FET group was higher than that in the HRT group, which may be related to this mechanism. Another possible mechanism is that letrozole might increase endometrial receptivity by increasing the expression of uterine receptivity such as integrin, L-selectin, leukemia inhibitory factor and pinopods during the implantation window[\u003cspan class=\"CitationRef\"\u003e28\u003c/span\u003e], which is beneficial for improving the success rate of frozen embryo transfer.\u003c/p\u003e\n\u003cp\u003eStrengths and limitations\u003c/p\u003e\n\u003cp\u003eThe strengths of this study are twofold. First, we included single-center cycles with full follow-up, cycles performed during the same period, and first transfer cycles, and this study included only the single blastocyst transfer cycle, to control the number of embryos transferred for the assessment of the pregnancy outcomes, as the consequent reduction in twin pregnancies had an impact on neonatal outcomes, which minimized potential bias. Second, our study explored not only the clinical outcomes of the two regimens but also their safety for the offspring, which has always been the focus of research and has always been of profound importance. Our study also has several limitations. First, it is limited by its retrospective nature, and thus, a further prospective study is needed. Second, we did not explore the relevant biological mechanism.\u003c/p\u003e\n\u003cp\u003eIn conclusion, for patients with abnormal ovulation, the L-FET regimen has a higher LBR and lower miscarriage rate than HRT. The neonatal outcomes, including the rates of preterm birth, normal neonatal birthweight, LBW, SGA, macrosomia and LGA, were similar between the two groups. Therefore, these findings imply that letrozole might be a better regimen for FET among women with abnormal ovulation, but further randomized controlled studies with large samples are needed.\u003c/p\u003e"},{"header":"List Of Abbreviations","content":"\u003cp\u003eIVF, in vitro fertilization; ICSI, intracytoplasmic sperm injection; FET, frozen embryo transfer; LBR, live birth rate; LBW, low birth weight; SGA, small-for-gestational age; LGA, large-for-gestational age\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe acknowledge the patients who participated in the study. We also thank American Journal Experts for their professional manuscript editing service.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eZJW and DMZ designed the study and selected the population to be included and excluded. ZJW and LZ were involved in the data extraction and analysis. SLJ and GYC reviewed the data. ZJW was involved in drafting this article. All authors have approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe did not receive any funding for this study\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data are included in this article and its additional files.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the ethics committee of The Third Affiliated Hospital of Zhengzhou University (2020 Medical Ethics Review No. 126).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003ePereira N, Rosenwaks Z.\u003cstrong\u003eA fresh(er) perspective on frozen embryo transfers.\u003c/strong\u003e \u003cem\u003eFertil Steril \u003c/em\u003e2016, \u003cstrong\u003e106:\u003c/strong\u003e257-258.\u003c/li\u003e\n\u003cli\u003eGliozheni O, Calhaz-Jorge C, De Geyter C, Kupka MS, de Mouzon J, Erb K, Mocanu E, Motrenko T, Scaravelli G, Wyns C, et al.\u003cstrong\u003eAssisted reproductive technology in Europe, 2013: results generated from European registers by ESHRE.\u003c/strong\u003e \u003cem\u003eHuman Reproduction \u003c/em\u003e2017, \u003cstrong\u003e32:\u003c/strong\u003e1957-1973.\u003c/li\u003e\n\u003cli\u003eRienzi L, Gracia C, Maggiulli R, LaBarbera AR, Kaser DJ, Ubaldi FM, Vanderpoel S, Racowsky C.\u003cstrong\u003eOocyte, embryo and blastocyst cryopreservation in ART: systematic review and meta-analysis comparing slow-freezing versus vitrification to produce evidence for the development of global guidance.\u003c/strong\u003e \u003cem\u003eHum Reprod Update \u003c/em\u003e2017, \u003cstrong\u003e23:\u003c/strong\u003e139-155.\u003c/li\u003e\n\u003cli\u003eGroenewoud ER, Cohlen BJ, Macklon NS.\u003cstrong\u003eProgramming the endometrium for deferred transfer of cryopreserved embryos: hormone replacement versus modified natural cycles.\u003c/strong\u003e \u003cem\u003eFertil Steril \u003c/em\u003e2018, \u003cstrong\u003e109:\u003c/strong\u003e768-774.\u003c/li\u003e\n\u003cli\u003eDe Geyter C, Calhaz-Jorge C, Kupka MS, Wyns C, Mocanu E, Motrenko T, Scaravelli G, Smeenk J, Vidakovic S, Goossens V.\u003cstrong\u003eART in Europe, 2014: results generated from European registries by ESHRE: The European IVF-monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE).\u003c/strong\u003e \u003cem\u003eHum Reprod \u003c/em\u003e2018, \u003cstrong\u003e33:\u003c/strong\u003e1586-1601.\u003c/li\u003e\n\u003cli\u003eGhobara T, Gelbaya TA, Ayeleke RO.\u003cstrong\u003eCycle regimens for frozen-thawed embryo transfer.\u003c/strong\u003e \u003cem\u003eCochrane Database Syst Rev \u003c/em\u003e2017, \u003cstrong\u003e7:\u003c/strong\u003eCD003414.\u003c/li\u003e\n\u003cli\u003eGlujovsky D, Pesce R, Sueldo C, Quinteiro Retamar AM, Hart RJ, Ciapponi A.\u003cstrong\u003eEndometrial preparation for women undergoing embryo transfer with frozen embryos or embryos derived from donor oocytes.\u003c/strong\u003e \u003cem\u003eCochrane Database of Systematic Reviews \u003c/em\u003e2020.\u003c/li\u003e\n\u003cli\u003eZhang J, Liu H, Wang Y, Mao X, Kuang Y.\u003cstrong\u003eLetrozole use during frozen embryo transfer cycles in women with polycystic ovary syndrome.\u003c/strong\u003e \u003cem\u003eFertility and Sterility \u003c/em\u003e2019, \u003cstrong\u003e112:\u003c/strong\u003e371-377.\u003c/li\u003e\n\u003cli\u003eHu YJ, Chen YZ, Zhu YM, Huang HF.\u003cstrong\u003eLetrozole stimulation in endometrial preparation for cryopreserved-thawed embryo transfer in women with polycystic ovarian syndrome: a pilot study.\u003c/strong\u003e \u003cem\u003eClinical Endocrinology \u003c/em\u003e2014, \u003cstrong\u003e80:\u003c/strong\u003e283-289.\u003c/li\u003e\n\u003cli\u003eSamsami A, Ghasmpour L, Davoodi S, Alamdarloo SM, Homayoon H.\u003cstrong\u003eFrozen embryo transfer: Endometrial preparation by letrozole versus hormone replacement cycle: A randomized clinical trial.\u003c/strong\u003e \u003cem\u003eInternational Journal of Reproductive BioMedicine (IJRM) \u003c/em\u003e2019, \u003cstrong\u003e17\u003c/strong\u003e.\u003c/li\u003e\n\u003cli\u003eFranik S, Kremer JA, Nelen WL, Farquhar C.\u003cstrong\u003eAromatase inhibitors for subfertile women with polycystic ovary syndrome.\u003c/strong\u003e \u003cem\u003eCochrane Database Syst Rev \u003c/em\u003e2014\u003cstrong\u003e:\u003c/strong\u003eCd010287.\u003c/li\u003e\n\u003cli\u003eFranik S, Eltrop SM, Kremer JA, Kiesel L, Farquhar C.\u003cstrong\u003eAromatase inhibitors (letrozole) for subfertile women with polycystic ovary syndrome.\u003c/strong\u003e \u003cem\u003eCochrane Database Syst Rev \u003c/em\u003e2018, \u003cstrong\u003e5:\u003c/strong\u003eCd010287.\u003c/li\u003e\n\u003cli\u003eBrown J, Farquhar C.\u003cstrong\u003eClomiphene and other antioestrogens for ovulation induction in polycystic ovarian syndrome.\u003c/strong\u003e \u003cem\u003eCochrane Database of Systematic Reviews \u003c/em\u003e2016, \u003cstrong\u003e12:\u003c/strong\u003eCD002249.\u003c/li\u003e\n\u003cli\u003eTulandi T, Martin J, Al-Fadhli R, Kabli N, Forman R, Hitkari J, Librach C, Greenblatt E, Casper RF.\u003cstrong\u003eCongenital malformations among 911 newborns conceived after infertility treatment with letrozole or clomiphene citrate.\u003c/strong\u003e \u003cem\u003eFertility and Sterility \u003c/em\u003e2006.\u003c/li\u003e\n\u003cli\u003eElizur SE, Tulandi T.\u003cstrong\u003eDrugs in infertility and fetal safety.\u003c/strong\u003e \u003cem\u003eFertil Steril \u003c/em\u003e2008, \u003cstrong\u003e89:\u003c/strong\u003e1595-1602.\u003c/li\u003e\n\u003cli\u003eHosseini-Najarkolaei A, Moini A.\u003cstrong\u003eThe effect of letrozole versus artificial hormonal endometrial preparation on pregnancy outcome after frozen-thawed embryos transfer cycles: a randomized clinical trial.\u003c/strong\u003e 2020, \u003cstrong\u003e18:\u003c/strong\u003e115.\u003c/li\u003e\n\u003cli\u003eTatsumi T, Jwa SC, Kuwahara A, Irahara M, Kubota T, Saito H.\u003cstrong\u003ePregnancy and neonatal outcomes following letrozole use in frozen-thawed single embryo transfer cycles.\u003c/strong\u003e \u003cem\u003eHum Reprod \u003c/em\u003e2017, \u003cstrong\u003e32:\u003c/strong\u003e1244-1248.\u003c/li\u003e\n\u003cli\u003eDai L, Deng C, Li Y, Zhu J, Mu Y, Deng Y, Mao M, Wang Y, Li Q, Ma S, et al.\u003cstrong\u003eBirth weight reference percentiles for Chinese.\u003c/strong\u003e \u003cem\u003ePLoS One \u003c/em\u003e2014, \u003cstrong\u003e9:\u003c/strong\u003ee104779.\u003c/li\u003e\n\u003cli\u003eHu YJ, Chen YZ, Zhu YM, Huang HF.\u003cstrong\u003eLetrozole stimulation in endometrial preparation for cryopreserved-thawed embryo transfer in women with polycystic ovarian syndrome: a pilot study.\u003c/strong\u003e \u003cem\u003eClin Endocrinol (Oxf) \u003c/em\u003e2014, \u003cstrong\u003e80:\u003c/strong\u003e283-289.\u003c/li\u003e\n\u003cli\u003eLi SJ, Zhang YJ, Chai XS, Nie MF, Zhou YY, Chen JL, Tao GS.\u003cstrong\u003eLetrozole ovulation induction: an effective option in endometrial preparation for frozen-thawed embryo transfer.\u003c/strong\u003e \u003cem\u003eArch Gynecol Obstet \u003c/em\u003e2014, \u003cstrong\u003e289:\u003c/strong\u003e687-693.\u003c/li\u003e\n\u003cli\u003eWang X, Du M, Guan Y, Wang B, Zhang J, Liu Z.\u003cstrong\u003eComparative neonatal outcomes in singleton births from blastocyst transfers or cleavage-stage embryo transfers: a systematic review and meta-analysis.\u003c/strong\u003e \u003cem\u003eReprod Biol Endocrinol \u003c/em\u003e2017, \u003cstrong\u003e15:\u003c/strong\u003e36.\u003c/li\u003e\n\u003cli\u003eGlujovsky D, Farquhar C, Quinteiro Retamar AM, Alvarez Sedo CR, Blake D.\u003cstrong\u003eCleavage stage versus blastocyst stage embryo transfer in assisted reproductive technology.\u003c/strong\u003e \u003cem\u003eCochrane Database Syst Rev \u003c/em\u003e2016\u003cstrong\u003e:\u003c/strong\u003eCd002118.\u003c/li\u003e\n\u003cli\u003eKontopoulos G, Simopoulou M, Zervomanolakis I, Prokopakis T, Dimitropoulos K, Dedoulis E, Grigorakis S, Agapitou K, Nikitos E, Rapani A, Vlahos N.\u003cstrong\u003eCleavage Stage versus Blastocyst Stage Embryo Transfer in Oocyte Donation Cycles.\u003c/strong\u003e \u003cem\u003eMedicina (Kaunas) \u003c/em\u003e2019, \u003cstrong\u003e55\u003c/strong\u003e.\u003c/li\u003e\n\u003cli\u003eBhandari S, Ganguly I, Agarwal P, Munaganuru N, Gupta N, Singh A.\u003cstrong\u003eRelationship of Number of Embryos Transferred with Perinatal Outcome of Singleton Pregnancy.\u003c/strong\u003e \u003cem\u003eJ Reprod Infertil \u003c/em\u003e2017, \u003cstrong\u003e18:\u003c/strong\u003e179-184.\u003c/li\u003e\n\u003cli\u003eBalen AH, MacDougall J, Tan SL.\u003cstrong\u003eThe influence of the number of embryos transferred in 1060 in-vitro fertilization pregnancies on miscarriage rates and pregnancy outcome.\u003c/strong\u003e \u003cem\u003eHum Reprod \u003c/em\u003e1993, \u003cstrong\u003e8:\u003c/strong\u003e1324-1328.\u003c/li\u003e\n\u003cli\u003eCasper RF, Mitwally MF.\u003cstrong\u003eUse of the aromatase inhibitor letrozole for ovulation induction in women with polycystic ovarian syndrome.\u003c/strong\u003e \u003cem\u003eClin Obstet Gynecol \u003c/em\u003e2011, \u003cstrong\u003e54:\u003c/strong\u003e685-695.\u003c/li\u003e\n\u003cli\u003eGarcia-Velasco JA.\u003cstrong\u003eThe use of aromatase inhibitors in in\u0026nbsp;vitro fertilization.\u003c/strong\u003e \u003cem\u003eFertil Steril \u003c/em\u003e2012, \u003cstrong\u003e98:\u003c/strong\u003e1356-1358.\u003c/li\u003e\n\u003cli\u003eGanesh A, Chauhan N, Das S, Chakravarty B, Chaudhury K.\u003cstrong\u003eEndometrial receptivity markers in infertile women stimulated with letrozole compared with clomiphene citrate and natural cycles.\u003c/strong\u003e \u003cem\u003eSystems Biology in Reproductive Medicine \u003c/em\u003e2014, \u003cstrong\u003e60:\u003c/strong\u003e105-111.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eBasic characteristics for cycles from 2017 through 2019\u003c/div\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eCharacteristics\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eL-FET(n\u0026thinsp;=\u0026thinsp;502)\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eHRT (n\u0026thinsp;=\u0026thinsp;2280)\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\"\u003eP\u003c/span\u003e value\u003c/div\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eMaternal age(y)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e30.95\u0026thinsp;\u0026plusmn;\u0026thinsp;4.56\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e31.20\u0026thinsp;\u0026plusmn;\u0026thinsp;4.97\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.062\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003ePaternal age(y)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e31.67\u0026thinsp;\u0026plusmn;\u0026thinsp;5.14\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e32.33\u0026thinsp;\u0026plusmn;\u0026thinsp;5.72\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.058\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eBody mass index(kg/m2)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e23.88\u0026thinsp;\u0026plusmn;\u0026thinsp;2.99\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e23.97\u0026thinsp;\u0026plusmn;\u0026thinsp;3.18\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.548\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eDuration of Infertility (y)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e3.26\u0026thinsp;\u0026plusmn;\u0026thinsp;2.83\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e3.39\u0026thinsp;\u0026plusmn;\u0026thinsp;2.75\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.374\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eType of infertility\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.239\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003ePrimary infertility\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e46.6(234/502)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e43.7(997/2280)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eSecondary infertility\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e53.4(268/502)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e56.3(1283/2280)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eInfertility diagnosis\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.322\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eTubal factor\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e32.9(165/502)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e35.4(807/2280)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eMale factor\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e21.7(109/502)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e19.0(434/2280)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eOthers\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e45.4(228/502)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e45.6(1039/2280)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eBasal serum FSH level(IU/L)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e5.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e5.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.077\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eBasal antral follicle count\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e19.97\u0026thinsp;\u0026plusmn;\u0026thinsp;7.03\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e18.90\u0026thinsp;\u0026plusmn;\u0026thinsp;7.52\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.072\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eFertilization method\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.609\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eIVF\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e73.5(369/502)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e74.6(1701/2280)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eICSI\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e26.5(133/502)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e25.4(579/2280)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eEndometrial thickness on day of embryo transfer (mm)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e9.72\u0026thinsp;\u0026plusmn;\u0026thinsp;1.83\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e8.99\u0026thinsp;\u0026plusmn;\u0026thinsp;2.10\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eDevelopment stage of blastocysts\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.323\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eD5\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e63.9(321/502)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e61.1(1404/2280)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eD6\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e36.1(181/502)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e38.4(876/2280)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"4\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eNote: Data are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD for continuous variable and % (n/N) for categorical variable. Student t test was used for continuous variables, and the Pearson\u0026nbsp;\u003cspan class=\"Italic\"\u003e\u0026chi;\u003c/span\u003e\u003csup\u003e\u003cspan class=\"Italic\"\u003e2\u003c/span\u003e\u003c/sup\u003e test was used for categorical variables with Fisher's exact test when necessary.\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eComparison of pregnancy outcome between the two groups\u003c/div\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eL-FET(n\u0026thinsp;=\u0026thinsp;502)\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eHRT (n\u0026thinsp;=\u0026thinsp;2280)\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\"\u003eP\u003c/span\u003e value\u003c/div\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eClinical pregnancy rate\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e58.4(293/502)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e54.5(1243/2280)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.116\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eAbortion rate\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e14.3(42/293)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e21.7(270/1243)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.005\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eLive birth rate\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e49.6(249/502)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e41.7(951/2280)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.001\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eSingletons\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e48.8(245/502)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e40.9(933/2280)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.001\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eTwins\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.8(4/502)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.8(18/2280)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.987\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"4\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eNote: Data are presented as % (n/N) for categorical variable. Pearson\u0026nbsp;\u003cspan class=\"Italic\"\u003e\u0026chi;\u003c/span\u003e\u003csup\u003e\u003cspan class=\"Italic\"\u003e2\u003c/span\u003e\u003c/sup\u003e test was used for categorical variables with Fisher's exact test when necessary.\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eComparison of singleton neonatal outcome between the two groups\u003c/div\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eL-FET(n\u0026thinsp;=\u0026thinsp;245)\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eHRT (n\u0026thinsp;=\u0026thinsp;933)\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\"\u003eP\u003c/span\u003e value\u003c/div\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eGender of newborn\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.570\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eMale\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e53.1(130/245)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e55.1(514/933)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eFemale\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e46.9(115/245)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e44.9(419/933)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003ePreterm birth\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e6.5(16/245)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e6.6(62/933)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.949\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eNeonatal birthweight\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e3401.67\u0026thinsp;\u0026plusmn;\u0026thinsp;498.97\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e3468.91\u0026thinsp;\u0026plusmn;\u0026thinsp;561.27\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.088\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eLow birthweight\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e4.9(12/245)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e4.8(45/933)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.961\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eSmall for gestational age\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e12.2(30/245)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e10.5(98/933)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.436\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eMacrosomia\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e13.9(34/245)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e16.1(150/933)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.399\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eLarge for gestational age\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e13.5(33/245)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e18.5(173/933)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.063\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eCongenital malformations rate\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.4(1/245)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.6(6/933)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e.670\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"4\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eNote: Data are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD for continuous variable and % (n/N) for categorical variable. Student t test was used for continuous variables, and the Pearson\u0026nbsp;\u003cspan class=\"Italic\"\u003e\u0026chi;\u003c/span\u003e\u003csup\u003e\u003cspan class=\"Italic\"\u003e2\u003c/span\u003e\u003c/sup\u003e test was used for categorical variables with Fisher's exact test when necessary.\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab4\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eUnadjusted and adjusted odds ratios of reproductive outcomes of blastocysts transfer following L-FET versus HRT cycles.\u003c/div\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eUnadjusted OR\u003c/div\u003e\n\u003cdiv class=\"SimplePara\"\u003e(95%CI )\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eAdjusted OR\u003c/div\u003e\n\u003cdiv class=\"SimplePara\"\u003e(95%CI )\u003c/div\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eLive birth rate\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.37(1.13\u0026ndash;1.67)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.30(1.06\u0026ndash;1.58)\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eAbortion rate\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.60 (0.42\u0026ndash;0.86)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.63(0.44\u0026ndash;0.90)\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003ePreterm birth\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.98 (0.56\u0026ndash;1.73)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.99(0.56\u0026ndash;1.77)\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eLow birthweight\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.98(0.51\u0026ndash;1.89)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.97(0.50\u0026ndash;1.87)\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eSmall for gestational age\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.84(0.54\u0026ndash;1.30)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.84(0.54\u0026ndash;1.29)\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eMacrosomia\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.19(0.80\u0026ndash;1.78)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.18(0.79\u0026ndash;1.78)\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eLarge for gestational age\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.46(0.97\u0026ndash;2.19)\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.45(0.97\u0026ndash;2.17)\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eNote: Analysis were adjusted for maternal age, body mass index, duration of infertility, type of infertility(Primary/ Secondary infertility), infertility diagnosis(Tubal/ Male/ Others), basal antral follicle count, fertilization method(IVF/ICSI) and development stage of blastocysts(D5/D6) .CI\u0026thinsp;=\u0026thinsp;confidence interval\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\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":"Letrozole, frozen embryo transfer, live birth rate, miscarriage, neonatal outcomes","lastPublishedDoi":"10.21203/rs.3.rs-204446/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-204446/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eThe use of frozen embryo transfer (FET) cycles has dramatically risen. The optimal endometrial preparation method for women undergoing FET is of utmost importance to provide the optimal chances of pregnancy. For patients with abnormal ovulation in particular, there have been few studies on FET protocols; notably, most of these studies focus only on the clinical pregnancy rate or live birth rate (LBR) and pay little attention to the regimen’s safety for offspring.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eIt was a retrospective cohort study. First FET cycle with a single blastocyst from whole embryo frozen IVF/ICSI at the Reproductive Center of Third Affiliated Hospital of Zhengzhou University between January 2016 and January 2020. The LBR was the primary outcome of interest. The secondary outcome measures were miscarriage rate and offspring safety, including preterm birth, low birthweight (LBW), small-for-gestational age (SGA), macrosomia and large-for-gestational age (LGA).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e In total, 2782 FET cycles met the eligibility criteria for analysis. Additionally, there were 1178 singleton births from FET cycles. The clinical pregnancy rate was 58.4% in the L-FET group and 54.5% in the HRT group, with no statistical significance (P=.116). The miscarriage rate was higher in the HRT group than in the L-FET group (21.7% vs. 14.3%, P=.005). The LBR was significantly higher in the L-FET group than in the HRT group (49.6% vs. 41.7%, P=.001). Neonatal outcomes were similar between the two groups. After adjustments for confounding factors, the LBR was higher in the L-FET group (aOR 1.30, 95% CI 1.06-1.58). The rate of miscarriage was lower in the L-FET group (aOR 0.63, 95% CI 0.44-0.90). \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e For patients with abnormal ovulation, the L-FET regimen has a higher LBR and lower miscarriage rate than HRT. The neonatal outcomes were similar between the two groups.\u003c/p\u003e","manuscriptTitle":"Comparison of Pregnancy and Neonatal Outcomes of Single Frozen Blastocyst Transfer Between Letrozole-induction and HRT Cycles in Patients With Abnormal Ovulation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-02-16 22:32:40","doi":"10.21203/rs.3.rs-204446/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":"6cbe1b6f-d310-4ef9-bee0-f12e6e28bbf9","owner":[],"postedDate":"February 16th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":2446788,"name":"Endocrinology \u0026 Metabolism"}],"tags":[],"updatedAt":"2021-02-16T22:35:41+00:00","versionOfRecord":[],"versionCreatedAt":"2021-02-16 22:32:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-204446","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-204446","identity":"rs-204446","version":["v1"]},"buildId":"GqpaHPwrfC8PjnIFayRh5","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}